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Cardiovascular Illness Collection
Content published since 1 January 1999
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Roy P, Durieux P, Gillaizeau F, et al.
Roy and colleagues developed a program to guide diagnosis of pulmonary embolism for use on a mobile, handheld device. The
investigators randomly assigned 20 emergency departments in France to activation of either the decision-support system on
the devices or posters and pocket cards that showed diagnostic strategies. The device-based program improved appropriate testing
of patients with suspected pulmonary embolism more than paper guidelines alone.
Bosworth HB, Olsen MK, Grubber JM, et al.
In this trial, 636 patients with hypertension were randomly assigned to receive usual care; a telephone-delivered, nurse-administered
behavioral self-management intervention; home blood pressure self-monitoring; or both of the latter 2 interventions. Compared
with usual care, the adjusted improvement in the proportion of patients with blood pressure control at 24 months was 4.3%
for the behavioral intervention group, 7.6% for the blood pressure monitoring group, and 11.0% for the combined intervention
group. The combined intervention improved blood pressure control and systolic and diastolic blood pressures more than usual
care.
Rothschild JM
In this issue, Roy and colleagues studied the use of a handheld clinical decision-support system to improve the diagnosis
of pulmonary embolism in 20 French emergency departments. Handheld computers could provide a key resource that improves access
to decision-support tools and leads to better management decisions. Roy and colleagues' work represents a promising start
toward this essential goal.
Jafar TH, Hatcher J, Poulter N, et al.
Jafar and colleagues assessed the effectiveness of community-based interventions on blood pressure in 1341 hypertensive adults
in Karachi, Pakistan. Participants received home health education (HHE) every 3 months from lay health workers, with or without
care from general practitioners (GPs) specially trained in hypertension management, or no intervention. Patients who received
HHE plus GP care had greater decreases in systolic blood pressure (10.8 mm Hg vs. 5.8 mm Hg in the other 3 groups).
Sharma M, Ansari MT, Abou-Setta AM, et al.
This systematic review of 102 studies compared the benefits and harms of high-dose statin monotherapy with those of combination
therapy in adults at high risk for coronary disease. Limited evidence suggested that combinations of lipid-lowering agents
did not improve clinical outcomes more than high-dose statin monotherapy.
Arrhythmias (46 articles)
Singer DE, Chang Y, Fang MC, et al.
Guidelines for prescribing anticoagulants in atrial fibrillation should balance treatment benefits and harms. Singer and colleagues
calculated 6-year ischemic stroke rates (benefit) and intracranial hemorrhage rates (harm) in 13 359 adults receiving and
not receiving warfarin. Net treatment benefit was highest in patients with previous stroke, age older than 84 years, and others
with high stroke risk. Risk assessment that incorporates risk for both thromboembolism and intracranial hemorrhage can advance
decision making about antithrombotic therapy in patients with atrial fibrillation.
Hart RG, Halperin JL
In this issue, Singer and colleagues question the net clinical benefit of adjusted-dose warfarin for at least half of patients
with atrial fibrillation, including the one third deemed to have moderate stroke risk. If their findings are confirmed in
other large cohorts, recommendations should be modified to ensure that patients with atrial fibrillation for whom anticoagulation
is advocated are likely to accrue net clinical benefit when the small risk for catastrophic cerebral hemorrhage is taken into
account.
Terasawa T, Balk EM, Chung M, et al.
Terasawa and colleagues performed a systematic review to determine whether radiofrequency catheter ablation is better than
medical therapy for patients with atrial fibrillation. They found that radiofrequency ablation after a failed drug course
maintained sinus rhythm more often than continuation of drug therapy alone. Some studies indicated that ablation improved
quality of life but did not necessarily reduce stroke rates compared with medical therapy. Fewer than 5% of patients undergoing
ablation reportedly experienced major adverse events, such as pulmonary-vein stenosis or cardiac tamponade.
Krantz MJ, Martin J, Stimmel B, et al.
An expert panel met to develop safety recommendations for prescribing methadone, which can be associated with prolongation
of the QT interval and an increased risk for torsade de pointes. Panelists recommended that clinicians inform patients of
arrhythmia risk when they prescribe methadone and ask about a history of heart disease. They also recommend that patients
have pretreatment and follow-up electrocardiography. Possible actions if the rate-corrected QT interval is greater than 450
ms or 500 ms include discussion of the risks and benefits of methadone, more frequent monitoring, dose reduction, or stopping
methadone treatment. Finally, clinicians should learn about interactions between methadone and other drugs that can prolong
the QT interval or slow elimination of methadone.
Gourevitch MN
An expert panel convened to discuss how to incorporate methadone's possible effect on the QT interval into clinical practice.
The findings and recommendations of some of the panel members appear in this issue. They wade into controversial territory
by recommending that physicians obtain electrocardiograms before treatment initiation, at 30 days, and annually thereafter
in all patients receiving methadone. Before guidelines are implemented, research methods, such as decision analysis, should
be applied to permit clear appreciation of the tradeoffs, benefits, and harms of alternative screening strategies.
Crowther MA, Ageno W, Garcia D, et al.
Crowther and colleagues measured the effect of oral vitamin K or placebo on prevention of bleeding in 724 patients with international
normalized ratios (INRs) of 4.5 to 10.0 who were receiving warfarin. They found that 15.8% of vitamin K recipients and 16.3%
of placebo recipients had at least 1 bleeding complication; 2.5% and 1.1%, respectively, had major bleeding events; and 1.1%
and 0.8% experienced thromboembolism. Low-dose oral vitamin K lowered the INR but did not reduce bleeding in overanticoagulated
patients.
Eckman MH, Rosand J, Greenberg SM, et al.
Eckman and coworkers evaluated the cost-effectiveness of genotype-guided warfarin dosing for patients with nonvalvular atrial
fibrillation. For the standard base case (a man age 69 years with no contraindications to warfarin therapy and the current
cost of genotyping of about $400), it costs $170 000 more per quality-adjusted life-year gained than standard warfarin dosing.
At its current cost, routine genotyping before warfarin dosing is unlikely to be cost-effective.
Eckart RE, Field ME, Hruczkowski TW, et al.
The prognostic value of exercise-induced ventricular arrhythmia (EIVA) is uncertain, and outcomes may depend on QRS morphology.
Among 585 patients with and 2340 patients without EIVA who were matched by age, sex, and risk factor and underwent exercise
testing, 5.3% and 1.8%, respectively, died over 24 months. However, only patients with right bundle-branch block morphology
had a higher risk for death than those without EIVA.
Ezekowitz JA, Rowe BH, Dryden DM, et al.
This systematic review summarizes the evidence on the benefits and harms of implantable cardioverter defibrillators (ICDs)
in adult patients with left ventricular systolic dysfunction. The ICDs reduced all-cause mortality by 20% (95% CI, 10% to
29%) in 12 randomized trials and were associated with a 46% reduction (CI, 32% to 57%) in 76 observational studies. Death
associated with ICD implantation occurred in 1.2% (CI, 0.9% to 1.5%) of procedures.
Hart RG, Pearce LA, Aguilar MI
Hart and colleagues provide an update of a previous meta-analysis of antithrombotic agents for stroke prevention in patients
with atrial fibrillation. The updated meta-analysis shows that, compared with placebo, adjusted-dose warfarin reduces stroke
risk by 64% (6 trials) and antiplatelet agents reduce stroke risk by 22% (8 trials). Adjusted-dose warfarin is more effective
than antiplatelet therapy, but it doubles the risk for major extracranial hemorrhage and intracranial hemorrhage (12 trials).
However, the rates of these serious adverse events were only 0.2% per year.
O'Donnell MJ, Kearon C, Johnson J, et al.
When patients on long-term warfarin therapy require surgery, low-molecular-weight heparins are often used as bridging therapy
between full anticoagulation with warfarin and no anticoagulation during surgery. Because of safety concerns, the authors
measured heparin activity after an evening dose of low-molecular-weight heparin. They found that two thirds of 94 patients—who
received their last dose of enoxaparin 14 hours before surgery—had elevated heparin levels when surgery was scheduled to begin.
They suggest a longer interval between the last dose of heparin and the time of surgery.
Lim W, Dentali F, Eikelboom JW, et al.
The authors analyzed studies of bleeding rates in patients who were taking low-molecular-weight heparin. Patients who have
a creatinine clearance of 30 mL/min or less and are taking enoxaparin have an increased risk for major bleeding relative to
patients with a creatinine clearance of more than 30 mL/min. Empirical dose adjustment of enoxaparin may be indicated in patients
with severe renal insufficiency. The evidence was not adequate to form conclusions about other low-molecular-weight heparins.
Cummings JE, Schweikert RA, Saliba WI, et al.
The authors report 9 patients who developed an atrial–esophageal fistula within several weeks after radiofrequency catheter
ablation around the pulmonary vein for atrial fibrillation. All died. Only 3 patients received correct diagnoses before death,
although all patients presented to a physician. This disorder may have an indolent presentation that mimics other disease
states, such as stroke or sepsis.
Aasbo JD, Lawrence AT, Krishnan K, et al.
This meta-analysis of 10 randomized, double-blind trials involving 1744 patients showed that amiodarone prophylaxis substantially
decreased the occurrence of atrial fibrillation, ventricular tachyarrhythmias, and stroke and length of stay after open-heart
surgery. The value of adding amiodarone when a patient is taking β-blocker prophylaxis perioperatively is not known.
Fang MC, Chang Y, Hylek EM, et al.
The risk for intracranial hemorrhage increases at age 85 years. In this study, international normalized ratios (INRs) less
than 2.0 and INRs of 2.0 to 3.0 were associated with the same risk for intracranial hemorrhage. The risk increases with INRs
of 3.5 or greater. Therefore, in elderly patients with atrial fibrillation, clinicians should maintain INRs in the 2.0 to
3.0 range.
Marshall DA, Levy AR, Vidaillet H, et al.
In the Atrial Fibrillation Follow-up Investigation of Rhythm Management randomized trial, a strategy of controlling the rate
of atrial fibrillation was less costly than trying to achieve and maintain normal sinus rhythm. Since the 2 strategies led
to similar clinical outcomes, rate control is the preferred initial management approach from an economic perspective.
Zimetbaum P, Josephson ME
The patients in randomized trials comparing rate control with antiarrhythmic therapy were highly selected and did not receive
a uniform approach to rhythm control. Therefore, although the trials showed no advantage to achieving and maintaining sinus
rhythm, this strategy remains appropriate in selected patients.
Bahnson TD, Grant AO
Two papers in this issue raise questions about managing atrial fibrillation: Does rhythm control have any role in treating
patients similar to the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study sample? Is it useful
in any other patients? Does being in normal sinus rhythm provide significant benefits? If so, why didn't the rhythm control
group in AFFIRM have better outcomes? Finally, what is a reasonable approach to treating patients with atrial fibrillation?
Nichol G, Kaul P, Huszti E, et al.
The incremental cost per quality-adjusted life-year for cardiac resynchronization is similar to that of other commonly used
interventions but is sensitive to changes in several key variables. Clinicians should not recommend resynchronization therapy
for patients with comorbid illness that shortens life expectancy.
McAlister FA, Ezekowitz JA, Wiebe N, et al.
In selected patients with heart failure, cardiac resynchronization therapy improves functional and hemodynamic status, reduces
heart failure hospitalizations, and may reduce all-cause mortality.
Hlatky MA, Massie BM
In this issue, McAlister and associates summarize the evidence on cardiac resynchronization therapy for heart failure, and
Nichol and coworkers analyze the cost-effectiveness of this therapy. Cardiac resynchronization therapy may be worth its high
cost if it substantially improves patient survival, quality of life, or both. The weight of current evidence suggests that
this therapy does improve functional status and quality of life.
Possick SE, Barry M
In the context of a case presentation, the authors review the data on safe air travel after myocardial infarction and common
complications of air travel after coronary artery revascularization; provide recommendations on safe air travel after myocardial
infarction; discuss the safety of preflight screening and the in-flight environment for patients with pacemakers and implantable
automatic defibrillators; and provide recommendations to prevent in-flight deep venous thrombosis.
Halligan SC, Gersh BJ, Brown RD, et al.
Lone atrial flutter has a stroke risk at least as high as lone atrial fibrillation. The risk for atrial fibrillation is higher
in patients with lone atrial flutter than in the general population. Physicians should consider long-term anticoagulation
for all patients with atrial flutter who are older than 65 years of age.
Snow V, Weiss KB, LeFevre M, et al.
This paper summarizes the recommendations of the Joint Panel of the American Academy of Family Physicians and the American
College of Physicians for managing a first episode of atrial fibrillation in adults.
McNamara RL, Tamariz LJ, Segal JB, et al.
This review, which supports the recommendations of the American Academy of Family Physicians and the American College of Physicians,
summarizes the available evidence about the efficacy of medications used for ventricular rate control, stroke prevention,
acute rhythm conversion, and maintenance of sinus rhythm. The review also discusses the efficacy of electrical cardioversion
and the use of echocardiography in patients with atrial fibrillation.
Hart RG, Halperin JL, Pearce LA, et al.
The Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and warfarin plus aspirin
for preventing stroke. This review presents the major results and implications of the six multicenter trials involving 3950
participants. Collectively, these trials offer unique perspectives on antithrombotic therapies for stroke prevention in patients
with atrial fibrillation.
Saad EB, Marrouche NF, Saad CP, et al.
Severe pulmonary vein stenosis after catheter ablation of atrial fibrillation is associated with respiratory symptoms that
often mimic more common diseases.
Ezekowitz JA, Armstrong PW, McAlister FA
Implantable cardioverter defibrillators prevent sudden cardiac death regardless of baseline risk. However, their impact on
total mortality is sensitive to baseline risk for arrhythmic death. Decisions about resource allocation for these devices
depend on accurate stratification of patients according to risk.
Buxton AE
In this issue, Ezekowitz and colleagues summarize mortality data from eight recent trials of implantable cardioverter defibrillators.
Although the patients included in these studies (coronary disease and ejection fraction < 0.3) were at high risk for sudden
death, more than 56% of patients with myocardial infarction who later die suddenly have an ejection fraction greater than
0.3. The real challenge lies in identifying potential victims in this large reservoir of lower-risk patients.
Biondi B, Palmieri EA, Lombardi G, et al.
Because the heart responds to the minimal but persistent changes in circulating thyroid hormone levels, subclinical thyroid
dysfunction is not simply a compensated biochemical change. Physicians should consider timely treatment of subclinical thyroid
dysfunction to avoid adverse cardiovascular effects.
Krantz MJ, Lewkowiez L, Hays H, et al.
The authors describe 17 methadone-treated patients who developed torsade de pointes. Given the likely expansion of methadone
treatment into primary care, further investigation of these findings is warranted.
Maisel WH, Rawn JD, Stevenson WG
Atrial fibrillation frequently complicates cardiac surgery, but many cases can be prevented with appropriate prophylactic
therapy. A strategy of rhythm management for symptomatic patients and rate management for all other patients usually results
in reversion to sinus rhythm within 6 weeks of discharge.
Takata TS, Page RL, Joglar JA
The authors provide general information on the technology and operation of automated external defibrillators, summarize the
experience of trials of these devices (in emergency medical systems and in special environments), and discuss legislative
and legal concerns.
Bryce M, Spielman SR, Greenspan AM, et al.
The authors review the current clinical experience and future trends in cardiac pacing in four specific areas: 1) hypertrophic
cardiomyopathy, 2) dilated cardiomyopathy and heart failure, 3) neurocardiogenic syncope, and 4) the prevention of atrial
fibrillation.
Rathore SS, Weinfurt KP, Gersh BJ, et al.
Patients with paced rhythms were less likely than those without to receive treatment for acute myocardial infarction and had
poorer short- and long-term outcomes. However, this mortality risk diminished after adjustment for treatment. This suggests
that improved recognition and treatment of myocardial infarction may improve outcomes, particularly in the short term.
Gage BF, Fihn SD, White RH
This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old
man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy.
Cheng CH, Sanders GD, Hlatky MA, et al.
Radiofrequency ablation substantially improves quality of life and reduces costs when it is used to treat highly symptomatic
patients with supraventricular tachycardia. Although the benefit of radiofrequency ablation has not been studied in less symptomatic
patients, a small improvement in quality of life is sufficient to give preference to this therapy over drug therapy.
Ohnishi K, Yoshida H, Shigeno K, et al.
Cardiac toxicity occurs during arsenic trioxide therapy in patients with acute promyelocytic leukemia. Such patients should
be monitored for prolonged QT intervals and ventricular arrhythmia.
Beyth RJ, Quinn L, Landefeld CS
A multicomponent program of warfarin management reduced the frequency of major bleeding in older patients. These findings
support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin
therapy in older patients.
Chua JD, Wilkoff BL, Lee I, et al.
For infections related to implantable electrophysiologic devices, complete device removal and antimicrobial therapy allow
timely, successful reimplantation at a remote anatomic site without substantial risk for surgical mortality or recurrent infection.
Go AS, Hylek EM, Borowsky LH, et al.
In a large cohort of ambulatory patients with atrial fibrillation who received care in a health maintenance organization,
warfarin use was considerably higher than that reported in other studies.
Hart RG, Benavente O, McBride R, et al.
Adjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more
efficacious than aspirin. The benefit of antithrombotic therapy was not offset by the occurrence of major hemorrhage among
participants in randomized trials.
Ezekowitz MD
Hart and colleagues' meta-analysis in this issue reemphasizes the value of anticoagulation in patients with atrial fibrillation,
especially those at highest risk for stroke. These findings may lead to increased use of antithrombotic therapy in elderly
patients, who have the greatest risk for stroke but also are a group for whom the fear of bleeding complications with anticoagulation
is greatest.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Catherwood E, Fitzpatrick WD, Greenberg ML, et al.
Cardioversion alone should be the initial management strategy for persistent nonvalvular atrial fibrillation. On relapse of
arrhythmia, repeated cardioversion plus low-dose amiodarone is cost-effective for patients at moderate to high risk for ischemic
stroke.
Pauker SG, Eckman MH
Over the past decade, the management of patients with nonvalvular atrial fibrillation has been the subject of more papers
than any clinician has time to digest. In this issue, Catherwood and colleagues extend their previous model to offer a new
cost-effectiveness analysis of therapies for nonvalvular fibrillation.
Cardiac arrest (9 articles)
Ezekowitz JA, Rowe BH, Dryden DM, et al.
This systematic review summarizes the evidence on the benefits and harms of implantable cardioverter defibrillators (ICDs)
in adult patients with left ventricular systolic dysfunction. The ICDs reduced all-cause mortality by 20% (95% CI, 10% to
29%) in 12 randomized trials and were associated with a 46% reduction (CI, 32% to 57%) in 76 observational studies. Death
associated with ICD implantation occurred in 1.2% (CI, 0.9% to 1.5%) of procedures.
Messerli FH, Mancia G, Conti CR, et al.
Because blood flow in the coronary arteries takes place largely during diastole, an increase in risk for coronary artery disease
with excessive lowering of diastolic blood pressure is plausible, although unproven. In this secondary analysis of data from
a large randomized trial of 2 antihypertensive drugs in patients with coronary artery disease, the risk for the primary outcome,
all-cause death, and myocardial infarction increased with low diastolic blood pressure. This relationship did not occur for
stroke.
Kanaya AM, Herrington D, Vittinghoff E, et al.
The authors evaluated the association between cardiovascular outcomes and fasting glucose using 2 definitions for impaired
fasting glucose: the 1997 definition (6.1 to 6.9 mmol/L [110 to 125 mg/dL]) and the 2003 definition of the American Diabetes
Association (5.6 to 6.9 mmol/L [100 to 125 mg/dL]). Women identified with the 2003 definition but not the 1997 definition
(those with blood glucose levels between 5.6 mmol/L and 6.0 mmol/L [100 mg/dL and 109 mg/dL]) had the cardiac risk of normal
women. The 1997 definition is preferable.
Takata TS, Page RL, Joglar JA
The authors provide general information on the technology and operation of automated external defibrillators, summarize the
experience of trials of these devices (in emergency medical systems and in special environments), and discuss legislative
and legal concerns.
Joshipura KJ, Hu FB, Manson JE, et al.
Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C–rich fruits and vegetables, appears
to have a protective effect against coronary heart disease.
Su Y, Swift M
Carriers of mutations at the ataxia-telangiectasia locus, who make up 1.4% to 2% of the general population, have a higher
mortality rate and an earlier age at death from cancer and ischemic heart disease than noncarriers.
Grønbæk M, Becker U, Johansen D, et al.
This study suggests that wine intake may have a beneficial effect on all-cause mortality that is additive to the effect of
alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer.
Gilbert K, Larocque BJ, Patrick LT
Existing indices for prediction of cardiac complications performed better than chance, but no index is significantly superior. There
is room for improvement in our ability to predict such complications.
Bach DS, Eagle KA
In this issue, Gilbert and colleagues report on the relatively low accuracy of existing perioperative risk indices in predicting
adverse perioperative events. However, in a low-risk population, the accurate prediction of few adverse events is to be expected. Thus,
risk scores above a given threshold should not be relied on as a guide to preventive interventions.
Cardiomyopathy (14 articles)
Okin PM, Devereux RB, Harris KE, et al.
Regression of left ventricular hypertrophy (LVH) has been associated with reductions in various cardiovascular outcomes, but
heart failure outcomes have not been carefully studied. Okin and colleagues found that regression of LVH by Cornell product
electrocardiographic criteria was associated with fewer hospitalizations for new-onset heart failure. This relationship appeared
to be separate from blood pressure reduction and type of therapy. Whether clinicians should adjust antihypertensive therapy
on the basis of electrocardiographic findings of LVH is not yet known.
Fett JD, Christie LG, Murphy JG
The authors documented clinical outcomes of subsequent pregnancy in 15 Haitian women with peripartum cardiomyopathy. Half
of the 15 women experienced worsening heart failure and long-term systolic dysfunction, while the other half experienced no
deterioration and eventually regained normal left ventricular systolic function.
Viotti R, Vigliano C, Lococo B, et al.
The authors assigned alternate patients with chronic Chagas disease to treatment with benznidazole or to no treatment and
followed them for a mean of approximately 10 years. The patients had no evidence of cardiac disease at baseline. Compared
with no treatment, benznidazole was associated with reduced progression to advanced stages of cardiac disease: 4.2% in the
treated group versus 14.1% in the untreated group. On the basis of these findings, a randomized, controlled trial is warranted.
Dias JC
In this issue, Viotti and colleagues evaluated benznidazole in patients with chronic Chagas disease. The study was an advance
over previous work because of the large number of patients, systematic assignment to study groups, and standardization of
drug dose. Fewer treated patients had progression of cardiomyopathy, and more patients became serologically nonreactive. These
results are new, positive evidence that specific treatment of chronic Chagas disease can ameliorate the most important effect
of the infection: evolution to severe chronic cardiomyopathy.
McGavock JM, Victor RG, Unger RH, et al.
Obesity is a major risk factor for heart disease, and physicians must be aware of emerging research of novel mechanisms through
which adiposity adversely affects the heart. The purpose of this review is to highlight a novel mechanism by which obesity
causes heart disease, whereby excessive lipid accumulation within the myocardium causes left ventricular remodeling and dilated
cardiomyopathy.
Mahon NG, Murphy RT, MacRae CA, et al.
The authors examined 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy. Approximately
5% had treatable asymptomatic cases of the disorder. Left ventricular enlargement or depressed fractional shortening was common
and was associated with an increased medium-term risk for disease progression. Relatives of patients with cardiomyopathy need
cardiac evaluation.
Bybee KA, Kara T, Prasad A, et al.
Some people who do not have coronary artery obstruction experience transient wall-motion abnormalities involving the left
ventricular apex and mid-ventricle. They have transient left ventricular apical ballooning syndrome. The authors review case
series of patients with this syndrome.
Fernández-Solà J, Nicolás JM, Oriola J, et al.
Vulnerability to cardiomyopathy among chronic alcohol abusers is partially genetic and is related to presence of the angiotensin-converting
enzyme DD genotype. This finding demonstrates genetic susceptibility to alcohol-induced myocardial damage.
Nicolás JM, Fernández-Solà J, Estruch R, et al.
In patients with alcoholic cardiomyopathy, both abstinence and controlled drinking of up to 60 g of ethanol per day (four
standard drinks) helped promote improvement in cardiac function.
Wynne J
Given the widespread use of alcoholic beverages in the western world, let us hope that the provocative studies by Walsh and
Nicolás and their colleagues reported in this issue will stir researchers to gain further understanding of the cardiovascular
effects of alcohol.
Bryce M, Spielman SR, Greenspan AM, et al.
The authors review the current clinical experience and future trends in cardiac pacing in four specific areas: 1) hypertrophic
cardiomyopathy, 2) dilated cardiomyopathy and heart failure, 3) neurocardiogenic syncope, and 4) the prevention of atrial
fibrillation.
Raymondos K, Panning B, Leuwer M, et al.
This prospective study demonstrates that administration of adrenaline into the airways is hemodynamically effective and increases
adrenaline plasma levels in adults with severe cardiac disease.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Pelliccia A, Culasso F, Di Paolo FM, et al.
In a sample of highly trained athletes, left ventricular cavity dimension varied widely but was strikingly increased to a
degree compatible with primary dilated cardiomyopathy in almost 15% of patients. When systolic dysfunction is absent, this
dilatation is probably an extreme physiologic adaptation to intensive athletic conditioning.
Congenital heart disease (3 articles)
Mahon NG, Murphy RT, MacRae CA, et al.
The authors examined 767 asymptomatic relatives of 189 consecutive unselected patients with dilated cardiomyopathy. Approximately
5% had treatable asymptomatic cases of the disorder. Left ventricular enlargement or depressed fractional shortening was common
and was associated with an increased medium-term risk for disease progression. Relatives of patients with cardiomyopathy need
cardiac evaluation.
Ammash NM, Warnes CA
Because congenital ventricular septal defects are of different sizes and locations, their clinical presentation, natural history,
and treatment vary greatly. This review discusses the different types of ventricular septal defects commonly seen in adults.
Schwerzmann M, Seiler C, Lipp E, et al.
In divers, the significance of a patent foramen ovale and its potential relation to paradoxical gas emboli remain uncertain.
This study found that regardless of whether a diver has a patent foramen ovale, diving is associated with ischemic brain lesions.
Congestive heart failure (59 articles)
Meta-analysis: β-Blocker Dose, Heart Rate Reduction, and Death in Patients With Heart Failure (2009)
McAlister FA, Wiebe N, Ezekowitz JA, et al.
The reasons why β-blockade reduces mortality from heart failure remain elusive. In a review of 23 trials of β-blockade in
heart failure, the authors sought to determine whether heart rate reduction, β-blocker dose, or both predicted the outcome.
For every reduction in heart rate of 5 beats/min with β-blocker treatment, the risk for death was 18% lower. In contrast,
β-blocker dosing did not predict all-cause mortality.
Schneider H, Lam L, Lokuge A, et al.
B-type natriuretic peptide (BNP) testing is commonly used to distinguish cardiac from noncardiac causes of dyspnea. In this
randomized trial, BNP testing did not reduce health services utilization or improve health outcomes for dyspneic patients
who visited emergency departments. Measuring BNP in all dyspneic patients to see whether heart failure is a cause of their
symptoms may not be justified.
Jeger RV, Radovanovic D, Hunziker PR, et al.
This analysis of hospital registry data from Switzerland showed that rates of cardiogenic shock in patients with acute coronary
syndromes decreased from 1997 to 2006. This decline was due to a decrease in the incidence of cardiogenic shock during hospitalization
rather than a change in the prevalence of cardiogenic shock at admission. In patients with cardiogenic shock, use of percutaneous
coronary intervention increased and in-hospital mortality decreased.
Hebert PL, Sisk JE, Wang JJ, et al.
Although nurse-led case management improves clinical outcomes for patients with heart failure, the cost- effectiveness of
these programs is not clearly established. Using data on costs from a randomized trial of 12 months of case management versus
usual care for socioeconomically disadvantaged patients with heart failure, Hebert and coworkers estimated the cost-effectiveness
of case management to be less than $20 000 per quality-adjusted life-year. This program was a reasonably cost-effective way
to reduce the burden of heart failure in this setting.
Okin PM, Devereux RB, Harris KE, et al.
Regression of left ventricular hypertrophy (LVH) has been associated with reductions in various cardiovascular outcomes, but
heart failure outcomes have not been carefully studied. Okin and colleagues found that regression of LVH by Cornell product
electrocardiographic criteria was associated with fewer hospitalizations for new-onset heart failure. This relationship appeared
to be separate from blood pressure reduction and type of therapy. Whether clinicians should adjust antihypertensive therapy
on the basis of electrocardiographic findings of LVH is not yet known.
Ahmad J, Bryce CL, Cacciarelli T, et al.
Sicker patients with liver disease get higher priority for liver transplants under the current system of organ allocation.
Ahmad and colleagues wanted to determine whether disease severity scores and waiting times of liver transplant recipients
differed by transplantation center. They found that patients waiting for transplants at higher-volume transplantation centers
(which performed ≥100 transplantations in 2005) had lower disease severity scores at the time of transplantation and had shorter
waiting times than did patients waiting for transplants at lower-volume centers. Differences in priority still exist by center,
despite the current system being need-based.
Baker DW, Persell SD, Thompson JA, et al.
In this study, Baker and colleagues compared automated review of electronic health record (EHR) fields with automated review
followed by manual review of the EHR to assess the quality of care of out patients with heart failure. Automated review of
EHR data was similar to hybrid review for measuring left ventricular ejection fraction, prescription of β-blockers, and prescription
of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. However, automated queries often underestimated
provider performance for prescribing warfarin for atrial fibrillation because the queries did not detect documentation of
legitimate reasons for not prescribing warfarin.
Dentali F, Douketis JD, Gianni M, et al.
Anticoagulant prophylaxis for hospitalized medical inpatients at risk for venous thromboembolism (VTE) is underutilized.
The goal of this meta-analysis of randomized trials was to assess the effects of anticoagulant prophylaxis in reducing VTE
in hospitalized medical patients. The authors found that prophylaxis with anticoagulants (unfractionated heparin, low-molecular-weight
heparin, or fondaparinux) is effective in preventing symptomatic VTE.
Bibbins-Domingo K, Fernandez A
In 2005, the U.S. Food and Drug Administration (FDA) approved the first racially or ethnically targeted medication for treating
heart failure in black patients, citing the need to address racial disparities in health as a factor in their decision. The
authors of this article contend that the FDA decision incorrectly interpreted trial results that claimed differential drug
response by race, while ignoring a substantial body of evidence on the causes of racial disparities in health and health care.
Temple R, Stockbridge NL
Some critics of the FDA's approval of the fixed combination of hydralazine hydrochloride and isosorbide dinitrate do not
recognize that the decision to approve the drug only for black patients reflected careful analyses of 2 previous trials in
racially mixed, but mostly white, patient populations. Both of these trials showed little or no overall effect of hydralazine
hydrochloride–isosorbide dinitrate but hinted at a substantial effect in subsets of black patients.
Shlipak MG, Katz R, Sarnak MJ, et al.
In this longitudinal study involving 4663 elderly persons without known kidney disease (estimated glomerular filtration rate
≥ 60 mL/min per 1.73 m2), increasing cystatin C concentration was associated with increased risks for death, stroke, myocardial
infarction, heart failure, and progression to chronic kidney disease. These associations were much stronger for cystatin C
than for creatinine.
Sisk JE, Hebert PL, Horowitz CR, et al.
This 12-month trial of assistance with managing systolic-dysfunction heart failure randomly assigned 406 ethnically diverse
adults from Harlem, New York, to usual care or nurse management. Nurse management patients received counseling about sodium
intake, fluid buildup, medication adherence, and self-management of symptoms. Nurses also regularly called patients and served
as a bridge between patients and physicians. Compared with patients who received usual care, nurse management patients had
fewer hospitalizations and better functioning.
Coresh J, Astor B
In this issue, Shlipak and colleagues show that 2 markers of decreased kidney function, estimated glomerular filtration rate
and cystatin C, are strong risk factors for noncardiovascular death as well as cardiovascular death and incidence. The most
urgent next step is to evaluate these markers in combination with data on albuminuria.
Ärnlöv J, Pencina MJ, Amin S, et al.
A total of 2084 men from 2 Framingham Heart Study cohorts had 1 measurement of total serum estrogen, testosterone, and dehydroepiandrosterone
sulfate (DHEA-S), followed by 10 years of monitoring for cardiovascular disease (CVD) outcomes. Testosterone and DHEA-S levels
were not associated with CVD risk, but high estrogen levels were associated with low risk. The risk for CVD in men whose estrogen
levels were in the highest quartile was 0.68 times (95% CI, 0.50 to 0.92 times) that in the lowest quartile.
McGavock JM, Victor RG, Unger RH, et al.
Obesity is a major risk factor for heart disease, and physicians must be aware of emerging research of novel mechanisms through
which adiposity adversely affects the heart. The purpose of this review is to highlight a novel mechanism by which obesity
causes heart disease, whereby excessive lipid accumulation within the myocardium causes left ventricular remodeling and dilated
cardiomyopathy.
Leff B, Burton L, Mader SL, et al.
This 3-site quasi-experiment enrolled patients who required hospital-level care for pneumonia, cellulitis, chronic obstructive
pulmonary disease, and heart failure. In the 3 sites, 69%, 69%, and 29% of patients who were offered hospital-at-home care
chose it over acute hospital care. Patients received fewer invasive procedures in hospital-at-home care and had a shorter
stay (3.2 days vs. 4.9 days) and less delirium. Hospital-at-home care was less expensive.
Barr DA
Some of the population groups identified through genetic analyses have resembled what have been historically categorized as
“races.” Some argue that a patient's race predicts underlying genetic traits well enough to predict outcomes of treatment.
Others argue that racially defined groups are too heterogeneous to make useful predictions for individuals. Physicians must
translate this scientific debate into individualized clinical decisions. Is it appropriate to use a patient's self-identified
“race” to help decide treatment?
Shepperd S
In their quasi-experimental study, which is reported in this issue, Leff and colleagues attempted to obtain robust data about
the effectiveness of hospital at home in several U.S. settings. However, their results have not shifted the weight of evidence
toward (or away from) the conclusion that hospital-at-home care offers worthy net benefits. Despite increasing interest in
the potential of such services, the objective evidence is insufficient to gauge the health or economic benefits of this type
of care.
Ammann P, Sticherling C, Kalusche D, et al.
Cardiac resynchronization devices use a bipolar electrode to depolarize the right and left ventricles synchronously. Loss
of left ventricular capture may cause worsening heart failure and can be difficult to diagnose without special equipment.
An algorithm that analyzes the R–S ratio on leads V1 and I of the surface electrocardiogram accurately diagnoses failure to
capture the left ventricle.
Kanaya AM, Herrington D, Vittinghoff E, et al.
The authors evaluated the association between cardiovascular outcomes and fasting glucose using 2 definitions for impaired
fasting glucose: the 1997 definition (6.1 to 6.9 mmol/L [110 to 125 mg/dL]) and the 2003 definition of the American Diabetes
Association (5.6 to 6.9 mmol/L [100 to 125 mg/dL]). Women identified with the 2003 definition but not the 1997 definition
(those with blood glucose levels between 5.6 mmol/L and 6.0 mmol/L [100 mg/dL and 109 mg/dL]) had the cardiac risk of normal
women. The 1997 definition is preferable.
Sarnak MJ, Katz R, Stehman-Breen CO, et al.
Cystatin C, a cysteine proteinase inhibitor produced by all nucleated cells, is a new and promising marker of kidney dysfunction.
Its serum concentration is an independent risk factor for onset of heart failure in older adults and provides a better measure
of risk than serum creatinine.
Levin A
In this issue, Sarnak and colleagues underscore what we know about the association between chronic kidney disease and cardiovascular
disease, what we need to know (the mechanisms by which chronic kidney disease affects cardiovascular disease), and what we
can do with what we currently know (improve the accuracy of chronic kidney disease measures and use cystatin C as a novel
prognostic indicator for heart failure).
Yan AT, Yan RT, Liu PP
Clinical trials over the past 2 decades have revolutionized the care of patients with systolic heart failure. Substantial
evidence supports the use of angiotensin-converting enzyme inhibitors, β-blockers, angiotensin-receptor blockers, and aldosterone
blockers for managing this serious condition. This article reviews the evidence on the pharmacologic treatment of heart failure,
with emphasis on recent clinical trials.
Lee VC, Rhew DC, Dylan M, et al.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers have similar efficacy for reducing all-cause
mortality and rates of rehospitalization for heart failure in patients with chronic heart failure or high-risk acute myocardial
infarction. Angiotensin-receptor blockers are suitable alternatives to ACE inhibitors.
DeBusk RF, Miller NH, Parker KM, et al.
In this clinical trial, nurse care management for patients with heart failure at low risk for rehospitalization did not reduce
rehospitalizations for heart failure or for any cause. Most care management programs have targeted patients at high risk for
rehospitalization. These programs may be less effective for patients at low risk.
Wagner EH
The nurses in the heart failure disease management intervention tested in DeBusk and colleagues' study contacted the patients
only by telephone. The failure of this program to alter congestive heart failure outcomes should cause policymakers to question
the rush to telephone-only disease management programs.
Piantadosi CA, Schwartz DA
This review describes the clinical, etiologic, and physiologic basis of the acute respiratory distress syndrome and summarizes
how its molecular pathogenesis leads to respiratory failure. The authors describe a physiologic basis for the respiratory
management of patients with this syndrome.
Nichol G, Kaul P, Huszti E, et al.
The incremental cost per quality-adjusted life-year for cardiac resynchronization is similar to that of other commonly used
interventions but is sensitive to changes in several key variables. Clinicians should not recommend resynchronization therapy
for patients with comorbid illness that shortens life expectancy.
McAlister FA, Ezekowitz JA, Wiebe N, et al.
In selected patients with heart failure, cardiac resynchronization therapy improves functional and hemodynamic status, reduces
heart failure hospitalizations, and may reduce all-cause mortality.
Hlatky MA, Massie BM
In this issue, McAlister and associates summarize the evidence on cardiac resynchronization therapy for heart failure, and
Nichol and coworkers analyze the cost-effectiveness of this therapy. Cardiac resynchronization therapy may be worth its high
cost if it substantially improves patient survival, quality of life, or both. The weight of current evidence suggests that
this therapy does improve functional status and quality of life.
Huddleston JM, Long KH, Naessens JM, et al.
A hospitalist–orthopedic surgeon comanagement team model reduced minor postoperative complication rates. Length of stay, cost,
and major complications did not change. The nurses and surgeons preferred the comanagement model over standard care.
Davis BR, Furberg CD, Wright JT, et al.
This paper reviews key aspects of the design, analyses, findings, and conclusions of the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT). The authors also address several frequent comments about heart failure and
diabetes outcomes.
Merli GJ
In this issue, Huddleston and colleagues report on the first step toward a new approach to the perioperative care of surgical
patients: the hospitalist–orthopedic surgeon comanagement team. The expansion of hospitalist care into comanagement of perioperative
care is the direction of the future.
The Editors
The opinion of an expert has value. The problem is finding a way to maximize the benefits of that expertise while minimizing
the risk for harm resulting from real or perceived bias due to a potential conflict of interest. The safest place to try is
a peer-reviewed journal with vigilant editors.
Vasan RS, Sullivan LM, D'Agostino RB, et al.
In this prospective, community-based study, serum insulin-like growth factor I level was inversely related to the risk for
congestive heart failure in elderly people without a previous myocardial infarction.
Kwon HJ, Cot TR, Cuffe MS, et al.
Some patients treated with tumor necrosis factor antagonists experience new or worsening heart failure.
Haider AW, Larson MG, Franklin SS, et al.
Although each component of blood pressure was associated with risk for congestive heart failure, pulse pressure and systolic
pressure conferred greater risk than diastolic pressure. Increased pulse pressure may help identify hypertensive patients
who, because they are at high risk for congestive heart failure, are candidates for aggressive blood pressure control.
Goldstein DS, Robertson D, Esler M, et al.
The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The authors discuss
chronic autonomic failure; autonomic function in chronic orthostatic intolerance, essential hypertension, panic disorder,
and congestive heart failure; and dysautonomia and the chronic fatigue syndrome and neurocardiology.
Gottdiener JS, McClelland RL, Marshall R, et al.
Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for
death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function
because left ventricular function is more often normal than impaired in elderly persons with heart failure.
Davis BR, Cutler JA, Furberg CD, et al.
In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone
is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure
does not explain this increased risk.
Walsh CR, Larson MG, Evans JC, et al.
In the community, alcohol consumption is not associated with increased risk for congestive heart failure, even among heavy
drinkers (≥ 15 drinks/wk in men and ≥ 8 drinks/wk in women). To the contrary, when consumed in moderation, alcohol appears
to protect against congestive heart failure.
Wynne J
Given the widespread use of alcoholic beverages in the western world, let us hope that the provocative studies by Walsh and
Nicolás and their colleagues reported in this issue will stir researchers to gain further understanding of the cardiovascular
effects of alcohol.
Bryce M, Spielman SR, Greenspan AM, et al.
The authors review the current clinical experience and future trends in cardiac pacing in four specific areas: 1) hypertrophic
cardiomyopathy, 2) dilated cardiomyopathy and heart failure, 3) neurocardiogenic syncope, and 4) the prevention of atrial
fibrillation.
Brophy JM, Joseph L, Rouleau JL
β-Blocker therapy is associated with clinically meaningful reductions in mortality and morbidity in patients with stable congestive
heart failure and should be routinely offered to all patients who are similar to those included in trials.
Feenstra H, Grobbee RE, in't Veld BA, et al.
Outcomes may differ in treated and untreated patients as a result of a contraindication for treatment in untreated patients
that is independently associated with the outcome of interest. This study evaluated the effects of confounding by contraindication
on risk factors for death in patients taking ibopamine after use of the drug was restricted in the Netherlands.
Gilbert K, Larocque BJ, Patrick LT
Existing indices for prediction of cardiac complications performed better than chance, but no index is significantly superior. There
is room for improvement in our ability to predict such complications.
Bach DS, Eagle KA
In this issue, Gilbert and colleagues report on the relatively low accuracy of existing perioperative risk indices in predicting
adverse perioperative events. However, in a low-risk population, the accurate prediction of few adverse events is to be expected. Thus,
risk scores above a given threshold should not be relied on as a guide to preventive interventions.
Poses RM, McClish DK, Smith WR, et al.
Results of outcome report cards for simulated survival in patients with congestive heart failure depend on the method used
to adjust for severity. Relying on report cards that use one of the currently available risk adjustment methods may lead to
erroneous conclusions about the quality of care at particular hospitals.
Goraya TY, Jacobsen SJ, Pellikka PA, et al.
In elderly patients, treadmill exercise testing provided prognostic information that was incremental to clinical data. After
adjustment for clinical factors, workload was the only treadmill exercise testing variable strongly associated with outcome,
and its prognostic effect was of the same magnitude in elderly and younger persons.
Ayus JC, Varon J, Arieff AI
In seven healthy marathon runners, noncardiogenic pulmonary edema was associated with hyponatremic encephalopathy. The condition
may be fatal if it is not diagnosed, and it can be successfully treated with hypertonic NaCl.
Khatta M, Alexander BS, Krichten CM, et al.
In a randomized, controlled trial, coenzyme Q10 did not affect ejection fraction, peak oxygen consumption, or exercise duration
in patients with congestive heart failure receiving standard medical therapy.
Auerbach AD, Hamel MB, Davis RB, et al.
In this observational study of patients hospitalized with congestive heart failure, cardiologist care was associated with
greater costs and resource use and no difference in survival at 30 days of follow-up compared with generalist care. Whether
the trend toward better survival at 1-year follow-up represents differences in care or unadjusted illness severity is uncertain.
Morris DL, Petruccelli DF
In this issue, Auerbach and colleagues report that care by cardiologists may be associated with a marginal survival benefit
but is also associated with higher costs and greater resource utilization. However, without information on appropriateness
of care, the reason for cost differences and resource utilization cannot be attributed to overuse of resources by cardiologists
or underuse of resources by generalists.
Hamel MB, Davis RB, Teno JM, et al.
This study found a modest association between patient age and short-term survival of serious illness. This age effect was
not explained by the current practice of providing less aggressive care to elderly patients.
Schroeder SA
Few clinical research projects have generated as much public interest or as many published articles as SUPPORT (the Study
to Understand Prognoses and Preferences for Outcomes and Risks of Treatment). The latest of these articles appears in this
issue. What accounts for SUPPORT's impact?
Culleton BF, Larson MG, Kannel WB, et al.
Despite previous suggestions to the contrary, uric acid does not have a causal role in the development of coronary heart disease,
death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due
to the association of uric acid level with other risk factors.
Vaccarino V, Krumholz HM
In this issue, Culleton and colleagues from the Framingham Heart Study resolve the long-standing controversy surrounding the
role of uric acid as a risk factor for cardiovascular disease. Enthusiasm for new cardiovascular risk factors should be accompanied
by efforts to evaluate their independent association with the incidence of cardiovascular disease and their practical clinical
utility.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Matsumoto A, Momomura S, Sugiura S, et al.
In this study, nitric oxide inhalation improved gas exchange in patients with congestive heart failure. This treatment may
be useful as supportive therapy when other conventional vasodilators worsen gas exchange.
Coronary artery disease (205 articles)
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force (USPSTF) has issued a recommendation statement on the use of 9 nontraditional risk
factors (high-sensitivity C-reactive protein [CRP], ankle–brachial index, leukocyte count, fasting blood glucose level, periodontal
disease, carotid intima–media thickness, coronary artery calcification on electron-beam computed tomography, homocysteine
level, and lipoprotein[a] level) in assessing coronary heart disease (CHD) risk in asymptomatic persons. It concludes that
the current evidence is insufficient to assess the balance of benefits and harms of using these nontraditional risk factors
to screen asymptomatic men and women with no history of CHD to prevent CHD events (I statement).
Buckley DI, Fu R, Freeman M, et al.
To support the USPSTF recommendation statement in this issue, Buckley and colleagues systematically reviewed evidence on the
use of CRP in assessing CHD risk in persons at intermediate risk based on traditional risk factors. They found strong evidence
that CRP is associated with CHD events and moderate, consistent evidence that adding CRP to risk prediction models among initially
intermediate-risk persons improves risk stratification. Evidence was insufficient to assess whether reducing CRP levels prevents
CHD events.
Helfand M, Buckley DI, Freeman M, et al.
To support the USPSTF recommendation statement in this issue, Helfand and associates evaluated the clinical usefulness of
9 new risk factors for CHD. Available evidence varied among these factors. Although CRP was the best candidate for use in
screening, evidence that changes in CRP level lead to primary prevention of CHD events is inadequate. Thus, the current evidence
does not support routine use of any of the 9 risk factors for further stratification of intermediate-risk persons.
McGeechan K, Liew G, Macaskill P, et al.
Retinal vessel caliber may be a novel marker of coronary heart disease (CHD) risk. However, the sex-specific effect, magnitude
of association, and effect independent of traditional CHD disease risk factors remain unclear. In this meta-analysis of 21 428
participants from 6 population-based studies, variations in retinal vessel caliber (both wider venules and narrower arterioles)
were associated with an increased risk for incident CHD in women but not in men. The risk associated with changes in retinal
vessel caliber was higher among women without diabetes or hypertension.
Mann JF, Schmieder RE, Dyal L, et al.
Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but
without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated
glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome
results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased
more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.
Auerbach AD, Hilton JF, Maselli J, et al.
The authors sought to measure the contribution of better quality of care to better outcomes of coronary artery bypass surgery
in hospitals that do a larger volume of surgery. The highest surgeon volume and highest hospital volume were associated with
lower 30-day mortality rates and lower readmission risk, respectively. Adjustment for individual quality measures did not
change these associations. However, if no quality measures were missed, mortality rates at the lowest-volume centers and highest-volume
centers were similar. High overall quality seems to be more important than volume.
Bach PB
Auerbach and colleagues' findings in this issue are an important contribution to the literature on both quality of care and
the relation between volume and outcome, but their study is another grim reminder of how often hospitals do not take the most
basic steps to enhance patient outcomes after a frequently performed major procedure.
McWilliams JM, Meara E, Zaslavsky AM, et al.
Improving the quality of care and expanding insurance coverage can reduce differences in outcomes experienced by different
sociodemographic groups. McWilliams and colleagues used blood pressure, hemoglobin A1c, and total cholesterol measurements
obtained from participants in a national survey to measure changes in chronic disease control. Over 8 years, disease control
improved but gaps between white and nonwhite patients did not change. The gaps narrowed after age 65 years, when universal
Medicare insurance begins.
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians
should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products (grade
A recommendation). For pregnant women, clinicians should ask about tobacco use and provide augmented, pregnancy-tailored counseling
for those who smoke (grade A recommendation).
Ip S, Lichtenstein AH, Chung M, et al.
Low-density lipoprotein (LDL) subfractions differ in size and may differ in the strength of association with cardiovascular
disease. The authors reviewed 24 published studies that reported relationships between LDL subfractions and cardiovascular
outcomes. Higher LDL particle concentration is consistently associated with increased risk for cardiovascular disease, independent
of other lipid measurements. The LDL particle size is generally not associated with cardiovascular disease. Routine use of
clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.
Steinhubl SR, Bhatt DL, Brennan DM, et al.
This post hoc analysis of data from a randomized trial suggests that the dose of aspirin used to prevent cardiovascular events
does not affect efficacy or safety. However, in patients randomly assigned to clopidogrel, higher aspirin doses seemed to
be associated with reduced efficacy and increased harm. Lower aspirin doses (75 to 81 mg/d) seem to optimize efficacy and
safety for patients requiring aspirin for long-term prevention, especially those taking clopidogrel.
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force (USPSTF) recommends encouraging men age 45 to 79 years and women age 55 to 79 years
to use aspirin when the potential benefit of a reduction in myocardial infarctions and ischemic strokes, respectively, outweighs
the potential harm of increased risk for gastrointestinal hemorrhage (A recommendations). It discourages men and women younger
than these ages from using aspirin for cardiovascular disease prevention (D recommendation). Evidence is insufficient to assess
the balance of benefits and harms of aspirin use for cardiovascular disease prevention in men and women older than 79 years
(I statement).
Wolff T, Miller T, Ko S
To support the USPSTF recommendation in this issue, Wolff and colleagues reviewed new evidence on the benefits and harms of
aspirin for the primary prevention of cardiovascular disease. They conclude that aspirin reduces the risk for myocardial infarction
in men and strokes in women but increases the risk for serious bleeding events, primarily gastrointestinal bleeding events.
Mehta SR
In this issue, 2 studies shed light on key questions related to aspirin use. Steinhubl and colleagues investigated the optimal
dose of aspirin for prevention and treatment of cardiovascular disease, and they found that higher doses do not lead to improved
efficacy and may be associated with more bleeding. The updated USPSTF recommendation on the use of aspirin for the primary
prevention of coronary heart disease is an important and user-friendly document for the busy clinician.
Spertus JA, Jones PG, Masoudi FA, et al.
Among 1849 U.S. patients who had myocardial infarction, the 28% who were black had higher unadjusted mortality and rehospitalization
rates, more angina, and worse quality of life. However, many of these differences did not persist after statistical adjustment
to make patient risk factors and site of care comparable in black and white patients. The results suggest that differences
in baseline cardiac risk and hospital factors are more important determinants of outcome than are differences in treatments
received for myocardial infarction.
Pletcher MJ, Lazar L, Bibbins-Domingo K, et al.
Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk. The authors used a probabilistic
model to show that the Adult Treatment Panel III guidelines, which recommend treatment based on cholesterol level and estimated
CHD risk, are reasonably cost-effective if statins cost about $1.50 to $2.20 per pill. At costs lower than $0.10 per pill,
treating everyone with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL), regardless of other
CHD risk factors, could be a better strategy.
Wong JB, Mulrow C, Sox HC
Pletcher and colleagues' cost-effectiveness analysis in this issue found that some statin strategies had acceptable economic
value in preventing CHD. Wong and associates provide a brief introduction to cost-effectiveness analyses and discuss whether
the U.S. federal government should use them to inform its policy decisions about health care.
Marenzi G, Assanelli E, Campodonico J, et al.
Percutaneous coronary intervention (PCI) can cause contrast-induced nephropathy (CIN). Understanding the relationship among
CIN, contrast volume, and patient characteristics could help to minimize this complication. Marenzi and coworkers found that
20% of 561 patients with ST-segment elevation myocardial infarction who had primary PCI developed CIN. Patients with CIN were
more likely to die in the hospital. Higher contrast volume and a higher ratio of contrast used to the ideal dose (contrast
ratio) were associated with CIN and in-hospital death.
Paynter NP, Chasman DI, Buring JE, et al.
Paynter and colleagues compared cardiovascular risk prediction using a genetic variation at chromosome 9p21.3 plus conventional
risk factors—such as family history of early cardiovascular disease, smoking, blood pressure, and cholesterol and C-reactive
protein levels—with risk prediction using conventional risk factors alone. Using a sample of 22 129 white, female health professionals
observed for a median of 10 years, the investigators found that adding genetic information to conventional risk factors did
not improve the accuracy of classifying cardiovascular risk.
El Harchaoui K, Arsenault BJ, Franssen R, et al.
High-density lipoprotein (HDL) particles are heterogeneous in size and composition. This nested case–control study found that
both HDL size and particle concentration were associated with risk for coronary artery disease (CAD). Larger size was strongly
associated with risk factors of the metabolic syndrome, such as triglyceride and apolipoprotein B levels. Adjustment for those
factors weakened the association, suggesting that they mediate the effect of HDL particle size on CAD risk. On the other hand,
HDL particle concentration seems to be an independent predictor of CAD risk.
Lim E, Brown A, Helmy A, et al.
The authors evaluated the contribution of individual end points to composite outcomes in 304 recent cardiovascular trials.
In these trials, composite outcomes commonly comprised 3 or 4 individual end points ranging in significance from angina to
death. Because individual outcomes do not necessarily occur at the same rate, readers should not assume that the overall estimate
of effect for a composite measure applies equally to each of its component outcomes.
Jeger RV, Radovanovic D, Hunziker PR, et al.
This analysis of hospital registry data from Switzerland showed that rates of cardiogenic shock in patients with acute coronary
syndromes decreased from 1997 to 2006. This decline was due to a decrease in the incidence of cardiogenic shock during hospitalization
rather than a change in the prevalence of cardiogenic shock at admission. In patients with cardiogenic shock, use of percutaneous
coronary intervention increased and in-hospital mortality decreased.
Hemingway H, Chen R, Junghans C, et al.
Can patient-specific appropriateness criteria developed by experts identify which patients with suspected angina should undergo
coronary angiography? In Hemingway and colleagues' study, expert panels scored hundreds of patient-specific scenarios as inappropriate,
uncertain, or appropriate indications for coronary angiography. Researchers matched these appropriateness indications to 9356
clinic patients with recent-onset chest pain. Many patients judged as appropriate candidates did not undergo angiography and
more had subsequent coronary events than did patients who “appropriately” had angiography.
Faxon DP
In this issue, Hemingway and associates assessed the reliability and validity of patient-specific appropriateness criteria
for coronary angiography in patients with suspected stable angina pectoris. The study provides valuable new insights into
the validity and potential application of appropriateness ratings.
Ochs N, Auer R, Bauer DC, et al.
The authors systematically reviewed 12 prospective cohort studies to determine whether subclinical thyroid dysfunction increases
risk for coronary heart disease and death. Both subclinical hypothyroidism and hyperthyroidism may be associated with increased
risk for coronary heart disease and death. However, the risk estimates are imprecise, and higher-quality studies found a lower
risk associated with subclinical hypothyroidism. Whether the increased risk is real and clinically important may only be determined
by randomized, placebo-controlled trials of treatment for subclinical thyroid dysfunction.
Ladenson PW
In this issue, Ochs and colleagues report a meta-analysis of population-based cohort studies in which researchers examined
whether disorders of thyroid function increase coronary heart disease events and mortality. Subclinical hypothyroidism poses
minimal risk. Relative risks seemed to be larger among younger adults than older adults; however, a recent study argues that
the true upper limit of normal serum thyroid-stimulating hormone level changes with age. We need an appropriately powered
prospective, randomized, controlled, double-blind interventional trial of thyroxine therapy for subclinical hypothyroidism.
Qayyum R, Khalid MR, Adomaityte J, et al.
Qayyum and associates performed a systematic review of 10 randomized trials to compare the effects of managing all patients
with non–ST-segment elevation acute coronary syndrome invasively or selectively. Of 10 648 patients, 15.9% of those assigned
to a routine invasive strategy died or had nonfatal myocardial infarction, compared with 17.5% of those assigned to a selective
invasive strategy. The trial evidence does not establish the superiority of routine invasive management over a selective approach.
Jeremias A, Kirtane A
Some cardiologists have questioned the safety of drug-eluting stents because of an apparent increase in late stent thrombosis.
However, the current evidence seems to say that the net clinical benefit of drug-eluting stents may outweigh their risks.
Patients who are candidates for drug-eluting stents should be screened for their ability to tolerate uninterrupted antiplatelet
therapy for longer than is necessary with bare-metal stents, and all patients should take antiplatelet and other optimal medical
therapies. Full assessment of the net clinical effects of drug-eluting stents compared with bare-metal stents will require
randomized trials that are larger than past studies.
Lauer MS, Pothier CE, Magid DJ, et al.
In a large prospective cohort study, Lauer and colleagues developed a post–treadmill test prediction rule to determine mortality
in adults with normal electrocardiograms and suspected coronary artery disease. Their model used clinical and treadmill variables
coupled with a nomogram to predict all-cause mortality. The nomogram better discriminated between those who die and those
who survive than did the standard Duke treadmill score, which uses only treadmill test variables to predict outcome. It gave
good results when used to predict all-cause mortality in an independent population of patients from a large HMO.
Bravata DM, Gienger AL, McDonald KM, et al.
The relative benefits and harms of coronary artery bypass graft surgery (CABG) versus percutaneous coronary intervention (PCI)
are sometimes unclear. Bravata and colleagues systematically reviewed 23 randomized trials that found that survival at 10
years was similar for CABG and PCI, even among diabetic patients. Procedural strokes and angina relief were more common after
CABG (risk difference, 0.6% and about 5% to 8%, respectively), whereas repeated revascularization procedures were more common
after PCI (risk difference, 24% at 1 year).
Gibbons RJ, Fihn SD
In this issue, the meta-analysis by Bravata and colleagues found that early procedural mortality rates (1.15% vs. 1.8%) and
5-year survival rates (89.7% vs. 90.7%) are similar after percutaneous coronary intervention and coronary artery bypass grafting.
This editorial discusses the most immediate implications of these findings for the practicing internist.
Diamond GA, Bax L, Kaul S
Diamond and colleagues discuss the recent, widely publicized meta-analysis of 42 clinical trials, which concluded that rosiglitazone
was associated with an approximately 43% increased risk for myocardial infarction and an approximately 64% increased risk
for cardiovascular death. They describe the limitations of the analysis, use alternative ways to examine the data, and do
other analyses. They conclude that the risk for myocardial infarction and death from cardiovascular disease for diabetic patients
taking rosiglitazone is uncertain: The evidence is insufficient to establish either an increased or a decreased risk.
Mulrow CD, Cornell J, Localio AR
In this issue, Diamond and coworkers explicate some weaknesses of the evidence that the U.S. Food and Drug Administration
(FDA)–approved rosiglitazone increases the risk for ischemic heart disease. The analyses by GlaxoSmithKline, Nissen and Wolski,
Diamond and colleagues, and the FDA teach us the difficulties of reliably summarizing data about scarce adverse events. In
the end, it is deplorable that we have so little reliable information about important macrovascular clinical events in patients
taking any FDA-approved pharmacotherapy for type 2 diabetes. Better studies, not meta-analyses, are the answer to this problem.
Tirosh A, Rudich A, Shochat T, et al.
Triglyceride levels measured at a single time point may not reliably indicate risk for coronary heart disease (CHD). Tirosh
and colleagues measured triglyceride levels and performed stress electrocardiography 5 years apart on 13 593 young Israeli
male career soldiers and did coronary angiography if the stress test was abnormal. They identified 158 new cases of incident
CHD. The changes in triglycerides between the 2 measurements strongly predicted incident CHD after adjustment for CHD risk
factors and lifestyle variables. A decrease in initially elevated triglyceride levels was associated with a decrease in CHD
risk, and CHD risk was lowest when triglyceride levels at both time points were low.
Criqui MH
In this issue, Tirosh and colleagues examined the association of triglyceride levels with incident CHD in 13 953 men age 26
to 45 years. Their results are striking: Triglycerides were strongly associated with CHD risk. The results complement the
growing body of evidence that triglycerides have an independent effect on the incidence of CHD and emphasize the importance
of “rediscovering” triglycerides as a cardiovascular risk factor.
Fox KA, Bassand J, Mehta SR, et al.
Fox and associates compared fondaparinux with enoxaparin for non–ST-segment acute coronary syndromes when the risk for bleeding
was increased because of renal dysfunction. Among patients with a glomerular filtration rate (GFR) less than 58 mL/min per
1.73 m2, fondaparinux had lower rates of combined death, major bleeding, myocardial infarction, or refractory angina than
enoxaparin. The advantage of fondaparinux was largest among patients with a GFR less than 58 mL/min per 1.73 m2.
Wenger NK, Lewis SJ, Herrington DM, et al.
The benefits of intensive lipid-lowering treatment for elderly persons with heart disease are largely unknown. In a secondary
analysis of a randomized trial, Wenger and associates examined outcomes of 3809 adults age 65 years or older with coronary
heart disease after 4.9 years of receiving atorvastatin, 80 mg/d or 10 mg/d. Patients achieved average low-density lipoprotein
cholesterol levels of approximately 1.81 mmol/L (70 mg/dL) and 2.59 mmol/L (100 mg/dL), respectively. The absolute reduction
in risk for serious cardiovascular events was 2% in patients who received 80 mg of atorvastatin relative to those who received
10 mg.
Sipahi I, Tuzcu EM, Wolski KE, et al.
The mechanisms by which β-blockers prevent recurrent myocardial infarction are not clear. In a pooled analysis of individual
patient data, Sipahi and coworkers examined changes in coronary atheroma volume as measured by serial intravascular ultrasonography
in 4 randomized trials. The trials followed 1515 patients with coronary artery disease for 18 to 24 months. Atheroma volume
decreased in patients who were receiving β-blockers but stayed the same in those not receiving β-blockers. β-Blockers appear
to slow progression of coronary atherosclerosis.
Halvorsen PA, Selmer R, Kristiansen IS
Patients respond differently when given equivalent but different descriptions of the outcomes of a treatment. Halvorsen and
colleagues randomly assigned 1754 healthy people to receive 1 of 3 surveys with equal but different descriptions of the outcome
of a hypothetical drug to prevent either myocardial infarction (MI) or hip fracture. Respondents consented to treatment more
frequently when the outcome was described as the number of people who needed to take the drug for 5 years to prevent 1 MI
or hip fracture. They consented less frequently when the description said that the treatment delayed the outcome.
Sox HC
In this issue, Halvorsen and colleagues remind us about framing effects. They report that the way in which an outcome is described
strongly influences whether a patient will consent to an intervention. But how should physicians use this knowledge? It is
hoped that this study will remind researchers, medical students, and practicing physicians that talking time is more than
a pleasurable exercise of clinical skills—it can change people's lives.
van der Steeg WA, Boekholdt SM, Stein EA, et al.
The apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio is a strong risk factor for atherosclerotic cardiovascular disease.
The researchers performed a case–control analysis of persons 45 to 79 years of age. They found that the apo B–apo A-I ratio
is no better than conventional measures of risk prediction in distinguishing between people who later developed atherosclerotic
cardiovascular disease and people who did not.
Berkwits M, Guallar E
van der Steeg and colleagues show that the apolipoprotein B–apolipoprotein A-I ratio does not improve overall prediction of
coronary artery disease in a general population. In fact, newer risk factors rarely add much to predictions that use established
risk measures, which is why clinicians should require rigorous proof of added value of any new risk factor before recommending
widespread testing for it in routine clinical practice.
Eshaghian S, Kaul S, Amin S, et al.
The available evidence from randomized trials indicates that dual therapy with clopidogrel and aspirin is modestly but significantly
more effective than aspirin alone in preventing serious vascular events. It is also associated with a favorable benefit–risk
profile in patients at high risk, but the bleeding risk exceeds potential cardiovascular benefit in low-risk patients.
O'Donnell MJ, Kearon C, Johnson J, et al.
When patients on long-term warfarin therapy require surgery, low-molecular-weight heparins are often used as bridging therapy
between full anticoagulation with warfarin and no anticoagulation during surgery. Because of safety concerns, the authors
measured heparin activity after an evening dose of low-molecular-weight heparin. They found that two thirds of 94 patients—who
received their last dose of enoxaparin 14 hours before surgery—had elevated heparin levels when surgery was scheduled to begin.
They suggest a longer interval between the last dose of heparin and the time of surgery.
Beulens JW, Rimm EB, Ascherio A, et al.
In this 16-year prospective study, 11 711 male health professionals with hypertension reported their average alcohol consumption
every 4 years. Hypertensive men who consumed 10 to 14 grams of alcohol (about 1 drink) or more per day had a lower risk for
myocardial infarction than those abstaining from alcohol. Alcohol intake did not predict all-cause mortality or deaths due
to cardiovascular disease.
Thiébaut AC, Freedman LS, Carroll RJ, et al.
Relationships between diet and chronic disease have become the focus of many analytic studies in nutritional epidemiology
over the past several decades. In this issue, Beulens and colleagues present a prospective analysis of the relationship between
alcohol intake and cardiovascular events among men with hypertension in the Health Professionals Follow-Up Study.
Calvin JE, Roe MT, Chen AY, et al.
The authors studied the care received for non–ST-segment elevation acute coronary syndromes by 37 345 patients younger than
age 65 years and 59 550 patients age 65 years or older. Compared with privately insured patients, Medicaid patients received
fewer guideline-recommended services at admission or discharge and experienced greater delays in receiving invasive procedures.
Differences for Medicare patients were fewer and smaller, although delays were common. The in-hospital mortality rate was
higher in Medicaid patients but not Medicare patients.
Ting HH, Yang EH, Rihal CS
Optimal treatment for ST-segment elevation myocardial infarction depends on early diagnosis and rapid selection of the appropriate
reperfusion strategy. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at PCI-capable
hospitals, but transferring patients to a hospital that does primary PCI may cause clinically important delays. The authors
present a systematic, evidence-based approach to selecting a reperfusion strategy.
Shlipak MG, Katz R, Sarnak MJ, et al.
In this longitudinal study involving 4663 elderly persons without known kidney disease (estimated glomerular filtration rate
≥ 60 mL/min per 1.73 m2), increasing cystatin C concentration was associated with increased risks for death, stroke, myocardial
infarction, heart failure, and progression to chronic kidney disease. These associations were much stronger for cystatin C
than for creatinine.
Coresh J, Astor B
In this issue, Shlipak and colleagues show that 2 markers of decreased kidney function, estimated glomerular filtration rate
and cystatin C, are strong risk factors for noncardiovascular death as well as cardiovascular death and incidence. The most
urgent next step is to evaluate these markers in combination with data on albuminuria.
Ärnlöv J, Pencina MJ, Amin S, et al.
A total of 2084 men from 2 Framingham Heart Study cohorts had 1 measurement of total serum estrogen, testosterone, and dehydroepiandrosterone
sulfate (DHEA-S), followed by 10 years of monitoring for cardiovascular disease (CVD) outcomes. Testosterone and DHEA-S levels
were not associated with CVD risk, but high estrogen levels were associated with low risk. The risk for CVD in men whose estrogen
levels were in the highest quartile was 0.68 times (95% CI, 0.50 to 0.92 times) that in the lowest quartile.
Rosenberg IH, Mulrow CD
Several large trials have examined the reduction of total homocysteine levels as secondary stroke prevention in patients with
vascular disease. In the Vitamin Intervention for Stroke Prevention (VISP) trial, a moderate reduction of total homocysteine
levels had no statistically significant effect on vascular outcomes. Two larger, double-blind, placebo-controlled trials with
longer follow-up were subsequently done: the Heart Outcomes Prevention Evaluation (HOPE) 2 and the Norwegian Vitamin (NORVIT)
trial. What did these landmark trials show, and how will their findings affect clinical practice?
The Effect of Including C-Reactive Protein in Cardiovascular Risk Prediction Models for Women (2006)
Cook NR, Buring JE, Ridker PM
Adding high-sensitivity C-reactive protein (hsCRP) to a global risk prediction model improves cardiovascular risk classification,
mostly for women at intermediate risk. However, since most of this apparently healthy population of women had a low cardiovascular
disease risk, adding hsCRP reclassified relatively few women.
Lloyd-Jones DM, Liu K, Tian L, et al.
In this review, the authors describe what is known about the gain in ability to predict the incidence of cardiovascular disease
(CVD) by adding C-reactive protein (CRP) to prediction models that use traditional CVD risk factors. They did not find definitive
evidence that CRP improves prediction in most individuals. They define several research questions that must be answered before
deciding whether to incorporate CRP into risk prediction algorithms and whether to recommend universal screening with CRP.
Messerli FH, Mancia G, Conti CR, et al.
Because blood flow in the coronary arteries takes place largely during diastole, an increase in risk for coronary artery disease
with excessive lowering of diastolic blood pressure is plausible, although unproven. In this secondary analysis of data from
a large randomized trial of 2 antihypertensive drugs in patients with coronary artery disease, the risk for the primary outcome,
all-cause death, and myocardial infarction increased with low diastolic blood pressure. This relationship did not occur for
stroke.
Tung R, Kaul S, Diamond GA, et al.
Interventional cardiologists have stopped using bare metal stents for percutaneous angioplasty in favor of drug-eluting stents.
The authors argue that the evidence about the long-term incremental risks, benefits, and costs is not adequate to conclude
that drug-eluting stents are superior to bare metal stents.
Diez Roux AV, Ranjit N, Powell L, et al.
The authors examined the association between psychosocial factors and subclinical coronary atherosclerosis in a multiethnic,
community-based sample of adults. The prevalence and extent of coronary calcification were essentially the same across the
full range of anxiety and depressive symptom scores and chronic stress burden in both men and women. Depressive symptoms,
anger, anxiety, and chronic stress burden were not associated with coronary calcification in asymptomatic adults.
Whooley MA
In this issue, Diez Roux and colleagues examined the relationship between psychological factors (depressive symptoms, anxiety,
anger, and chronic burden) and coronary artery calcium and found no association. Given the substantial evidence supporting
an association between psychological factors and coronary heart disease events, are these negative findings surprising? Do
they contradict more than a century of epidemiologic observations? How do they improve our understanding of the link between
psychological factors and coronary heart disease events?
Lim W, Dentali F, Eikelboom JW, et al.
The authors analyzed studies of bleeding rates in patients who were taking low-molecular-weight heparin. Patients who have
a creatinine clearance of 30 mL/min or less and are taking enoxaparin have an increased risk for major bleeding relative to
patients with a creatinine clearance of more than 30 mL/min. Empirical dose adjustment of enoxaparin may be indicated in patients
with severe renal insufficiency. The evidence was not adequate to form conclusions about other low-molecular-weight heparins.
McGavock JM, Victor RG, Unger RH, et al.
Obesity is a major risk factor for heart disease, and physicians must be aware of emerging research of novel mechanisms through
which adiposity adversely affects the heart. The purpose of this review is to highlight a novel mechanism by which obesity
causes heart disease, whereby excessive lipid accumulation within the myocardium causes left ventricular remodeling and dilated
cardiomyopathy.
Pignone M, Earnshaw S, Tice JA, et al.
In this cost–utility analysis of the effects of aspirin and statins for primary prevention of coronary heart disease (CHD),
aspirin was less costly and more effective than no treatment in middle-aged men whose 10-year risk for CHD was 7.5% or higher.
Adding a statin to aspirin therapy is cost-effective only when the patient's 10-year CHD risk exceeds 10%.
Go AS, Iribarren C, Chandra M, et al.
This case–control study of 1384 adults from a large prepaid group practice evaluated the effect of current use of statins
or β-blockers at first presentation of coronary heart disease. Use of these drugs was associated with lower odds of presenting
with an acute myocardial infarction and higher odds of presenting with stable angina. Additional studies are needed to prove
that these therapies protect against unstable, higher-risk clinical presentations of coronary disease.
Smith SC
In this issue, Go and colleagues suggest that the use of statin and β-blocker therapy might favorably alter the initial clinical
presentation of coronary heart disease. We need to perform randomized clinical trials to confirm these findings in appropriate
patient groups and investigate their mechanisms. If confirmed by such trials, these findings could have a substantial effect
on patient care.
Alter DA, Chong A, Austin PC, et al.
The true causes of income-related health disparities are not known. In 3407 Canadian patients who were hospitalized for acute
myocardial infarction, high income was associated with a lower 2-year mortality rate (crude hazard ratio, 0.45 [95% CI, 0.35
to 0.57]; P < 0.001). However, adjusting for income-related differences in age and the prevalence of preexisting cardiovascular
events or risk factors substantially reduced the effect of high income (adjusted hazard ratio, 0.77 [CI, 0.54 to 1.10]; P =
0.150).
Kaplan GA
Do we really need another paper on socioeconomic inequalities in health? Alter and colleagues have added to our knowledge,
but the assumption that we can reduce socioeconomic inequalities in survival after cardiovascular disease (CVD) by reducing
morbidity and risk factors in poor people begs the key question. We must integrate our knowledge of the upstream social determinants
that lead to differential burdens of CVD and its risk factors and the downstream, proximal biological factors that drive health
outcomes. Building a bridge between these bodies of knowledge could provide a way to decrease socioeconomic inequalities in
survival.
Witt BJ, Brown RD, Jacobsen SJ, et al.
This study examined the relationship between myocardial infarction (MI) and subsequent stroke in persons living in Olmsted
County, Minnesota. Myocardial infarction was associated with a marked increase in the risk for stroke, particularly early
after MI, compared with the risk in a population without MI. The risk for death after MI was much higher in patients who had
had a stroke.
Clark AM, Hartling L, Vandermeer B, et al.
The authors reviewed 63 randomized trials that measured the effect of adding an exercise program to secondary cardiac prevention
programs. Programs that promoted exercise reduced all-cause mortality (summary risk ratio, 0.85 [95% CI, 0.77 to 0.94]) relative
to programs that did not promote exercise. Exercise-promoting programs had no added benefit 1 year after patients began them
but reduced mortality substantially after 2 years.
Combination Pharmacotherapy and Public Health Research Working Group*
Rather than screening for risk factors for cardiovascular disease (CVD), Wald and Law proposed that everyone take a “polypill”
containing a statin, a diuretic, a β-blocker, an angiotensin-converting enzyme inhibitor, aspirin, and folic acid. This type
of combination pharmacotherapy may prove to be efficacious, but may also have harms that outweigh the benefits in a population
in which relatively few persons are destined to develop CVD.
Meine TJ, Patel MR, DePuy V, et al.
People have speculated that patients who have an acute myocardial infarction in December have worse outcomes because evidence-based
therapies are less available during the holiday season. The authors compared patients hospitalized with acute myocardial infarction
in December and in other months. Patients hospitalized in December received evidence-based therapies at the same rate as in
other months but had higher 30-day mortality rates (21.7% vs. 20.1%).
Rothberg MB, Celestin C, Fiore LD, et al.
After acute coronary syndromes, warfarin plus aspirin was associated with fewer myocardial infarctions, ischemic strokes,
and revascularization procedures. Warfarin was associated with an increase in major bleeding, but mortality did not differ.
For patients who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding
risks.
Mulrow C, Pignone M
In 2002, Annals published a systematic review of aspirin for the primary prevention of cardiovascular disease for the U.S.
Preventive Services Task Force. Because few women participated in previous trials, the evidence that women benefit was inconclusive
until the March 2005 publication of the Women's Health Study. We explain how this study clarifies the use of aspirin to prevent
cardiovascular disease in women.
Kanaya AM, Herrington D, Vittinghoff E, et al.
The authors evaluated the association between cardiovascular outcomes and fasting glucose using 2 definitions for impaired
fasting glucose: the 1997 definition (6.1 to 6.9 mmol/L [110 to 125 mg/dL]) and the 2003 definition of the American Diabetes
Association (5.6 to 6.9 mmol/L [100 to 125 mg/dL]). Women identified with the 2003 definition but not the 1997 definition
(those with blood glucose levels between 5.6 mmol/L and 6.0 mmol/L [100 mg/dL and 109 mg/dL]) had the cardiac risk of normal
women. The 1997 definition is preferable.
U.S. Preventive Services Task Force*
This statement summarizes the U.S. Preventive Services Task Force recommendations on hormone therapy for the prevention of
chronic conditions in postmenopausal women and the supporting scientific evidence, and updates the Task Force's 2002 recommendations
on hormone replacement therapy.
Jeremias A, Gibson CM
An elevated troponin level is an important criterion for diagnosing non–ST-segment elevation myocardial infarction (MI). While
normal troponin levels essentially “rule out” non–ST-segment elevation MI, elevated levels are not specific for acute coronary
syndromes. However, even when a thrombotic acute coronary syndrome is not present, troponin elevation has prognostic value.
Al-Khatib SM, Anstrom KJ, Eisenstein EL, et al.
The Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II showed that the implantable cardioverter defibrillator
(ICD) prolongs life in patients with a history of myocardial infarction and an ejection fraction of 0.3 or less. Implanting
defibrillators in everyone who meets these criteria will be expensive, but it is cost-effective because ICD therapy had such
a large effect on survival in MADIT-II.
Pauker SG, Estes NA, Salem DN
Although implantable cardioverter defibrillators (ICDs) can prevent sudden cardiac death, the United States may not be able
to afford the cost. Al-Khatib and colleagues' cost-effectiveness analysis supports using ICDs in patients similar to participants
in the Multicenter Automatic Defibrillator Implantation Trial-II. However, we must continue to refine methods to select patients
for ICDs in order to keep the costs in line with the benefits.
Vasan RS, Sullivan LM, Wilson PW, et al.
These researchers estimated the 10-year coronary heart disease event rate for each person in a nationally representative sample
by using the individual's risk factors and the Framingham Study risk equation. The findings suggest that in the United States,
borderline levels of risk factors account for a small proportion of coronary heart disease events.
Mulrow C, Kussmaul W
Researchers have proposed that physicians should advise all of their patients over age 55 to take a polypill containing treatments
for many cardiovascular risk factors rather than testing them for risk factors and treating selectively. In this issue, Vasan
and colleagues describe the prevalence of risk factors for cardiovascular disease in the United States. This evidence, along
with other data, suggests that a preventive polypill is the wrong approach for this population.
Schleinitz MD, Heidenreich PA
In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin followed by life-long
aspirin results in greater life expectancy than life-long aspirin alone. The cost-effectiveness of adding clopidogrel—$15 400
per quality-adjusted life-year—is similar to that of many well-accepted interventions.
Whitney EJ, Krasuski RA, Personius BE, et al.
The authors compared a combination drug regimen designed to increase high-density lipoprotein cholesterol levels (gemfibrozil,
niacin, and cholestyramine) plus counseling about diet and exercise to counseling alone. The drug regimen improved cholesterol
profiles; slowed angiographic progression of coronary stenosis; reduced cardiovascular events; and led to more skin rashes,
flushing, and abdominal symptoms.
Lee VC, Rhew DC, Dylan M, et al.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers have similar efficacy for reducing all-cause
mortality and rates of rehospitalization for heart failure in patients with chronic heart failure or high-risk acute myocardial
infarction. Angiotensin-receptor blockers are suitable alternatives to ACE inhibitors.
Snow V, Barry P, Fihn SD, et al.
This paper summarizes the treatment and follow-up recommendations of the 2002 American College of Cardiology/American Heart
Association guideline. It covers patients with chronic stable angina who have not had a recent acute myocardial infarction
or revascularization procedure and asymptomatic patients with known or suspected coronary disease based on electrocardiographic
evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests.
Khaw K, Wareham N, Bingham S, et al.
In this study of patients recruited from general practice, the risk for cardiovascular disease and total mortality rose continuously
throughout the range of hemoglobin A1c concentrations seen in the general population. Seventy-five percent of the excess population
mortality risk associated with a hemoglobin A1c concentration greater than 5.0% occurred in persons with concentrations between
5.0% and 6.9%.
Selvin E, Marinopoulos S, Berkenblit G, et al.
This meta-analysis of observational studies in patients with diabetes shows that increased serum hemoglobin A1c levels are
associated with an increased risk for cardiovascular disease in both type 1 and type 2 diabetes.
Gerstein HC
What can we conclude from the reports by Khaw and Selvin and colleagues in this issue? First, the glycosylated hemoglobin
level is an independent progressive risk factor for cardiovascular events, regardless of diabetes status. Second, glycosylated
hemoglobin belongs on the list of cardiovascular risk factors. Third, these studies highlight the importance of ongoing clinical
trials of reducing glycosylated hemoglobin levels to reduce cardiovascular risk.
Brophy JM, Bogaty P
This review critically analyzes the evidence comparing primary percutaneous coronary intervention (PCI) with thrombolytic
therapy and concludes that reasonable health care professionals may still find considerable uncertainty about the superiority
of primary PCI for all situations.
Keeley EC, Grines CL
The authors contend that because primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction
has superior outcomes, it should be available to all patients with ST-segment elevation myocardial infarction. They outline
obstacles to instituting PCI as the universal treatment and propose strategies to increase its availability.
Bach RG, Cannon CP, Weintraub WS, et al.
After acute coronary syndromes, older people have a larger risk for poor ischemic outcomes than younger people. Despite this
increased risk, a routine early invasive strategy can significantly improve ischemic outcomes in elderly patients with unstable
angina and non–ST-segment elevation myocardial infarction.
Pilote L, Abrahamowicz M, Rodrigues E, et al.
Survival benefits in the first year after acute myocardial infarction in patients 65 years of age or older seem to differ
according to the specific angiotensin-converting enzyme inhibitor prescribed. Ramipril was associated with lower mortality
than most other drugs in this class.
Song Y, Stampfer MJ, Liu S
Previous studies on apolipoprotein E (apoE) ε4 allele as a risk factor for coronary heart disease have had conflicting results.
This meta-analysis found that the apoE ε4 allele is strongly implicated as a risk factor for coronary heart disease.
Possick SE, Barry M
In the context of a case presentation, the authors review the data on safe air travel after myocardial infarction and common
complications of air travel after coronary artery revascularization; provide recommendations on safe air travel after myocardial
infarction; discuss the safety of preflight screening and the in-flight environment for patients with pacemakers and implantable
automatic defibrillators; and provide recommendations to prevent in-flight deep venous thrombosis.
Hennessy S, Kimmel SE
Pilote and colleagues' study in this issue indicates that in the absence of head-to-head randomized trials that test survival
benefits of different angiotensin-converting enzyme inhibitors, the current level of scientific evidence is not sufficient
to justify the selection of one proven drug in this class over another.
Davis BR, Furberg CD, Wright JT, et al.
This paper reviews key aspects of the design, analyses, findings, and conclusions of the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT). The authors also address several frequent comments about heart failure and
diabetes outcomes.
Snow V, Barry P, Fihn SD, et al.
This guideline is an update of the 1999 guidelines on chronic stable angina published by the American College of Physicians
and the American College of Cardiology/American Heart Association. It covers diagnosis and risk stratification for patients
with symptomatic chronic stable angina who have not had an acute myocardial infarction or revascularization procedure in the
previous 6 months.
The Editors
The opinion of an expert has value. The problem is finding a way to maximize the benefits of that expertise while minimizing
the risk for harm resulting from real or perceived bias due to a potential conflict of interest. The safest place to try is
a peer-reviewed journal with vigilant editors.
Rauramaa R, Halonen P, Väisänen SB, et al.
Aerobic exercise did not slow progression of atherosclerosis at the carotid artery bifurcation in middle-aged men. In a subgroup
analysis, exercise reduced the rate of progression of atherosclerosis in men who did not take statins.
Spencer FA, Allegrone J, Goldberg RJ, et al.
Statin therapy can modulate early pathophysiologic processes in patients with acute coronary syndromes. In this observational
study, patients taking statins before admission for acute coronary syndromes and patients who started taking statins after
admission had better outcomes than patients who did not take statins.
Laupacis A, Mamdani M
The current evidence leaves us uncertain about whether starting statin therapy at the time of admission for an acute coronary
syndrome is more effective than starting this therapy later. While we wait for the results of large randomized trials, we
can reflect on the many reasons for caution in drawing firm conclusions from observational studies of treatment effectiveness.
Lee MS, Makkar RR
In principle, stem cells could rapidly regenerate contracting myocardium and improve immediate and long-term prognosis after
acute myocardial infarction. This article describes the formidable obstacles to achieving this goal.
Snow V, Aronson MD, Hornbake ER, et al.
The American College of Physicians makes 4 recommendations for lipid control in patients with type 2 diabetes: 1) Use lipid-lowering
therapy for secondary prevention of cardiovascular mortality and morbidity for all patients with known coronary artery disease
and type 2 diabetes; 2) use a statin for primary prevention of macrovascular complications in patients with type 2 diabetes
and other cardiovascular risk factors; 3) patients with type 2 diabetes who take statins should take at least moderate doses;
4) for patients with type 2 diabetes who are taking statins, routine monitoring of liver function tests or muscle enzymes
is unnecessary except in specific circumstances.
Vijan S, Hayward RA
In patients with type 2 diabetes, treatment with lipid-lowering agents reduces the risk for cardiovascular disease. Statins
reduce cardiovascular disease risk in most patients, including those whose baseline low-density lipoprotein cholesterol levels
are below 2.97 mmol/L (<115 mg/dL), and possibly below 2.59 mmol/L (<100 mg/dL). Most patients with diabetes should receive
at least moderate doses of these drugs.
U.S. Preventive Services Task Force*
Among other recommendations, the U.S. Preventive Services Task Force recommends against routine screening with resting electrocardiography,
exercise treadmill test, or electron-beam computerized tomography for coronary calcium for either the presence of severe coronary
artery stenosis or predicting coronary heart disease events in adults at low risk for coronary heart disease events.
Fowler-Brown A, Pignone M, Pletcher M, et al.
Murabito JM, Nam B, D'Agostino RB, et al.
It is difficult to interpret a family history of cardiovascular disease because the accuracy of patient reports of family
history is unknown. Using Framingham Heart Study data spanning 2 generations, the authors compared patient reports of parental
history with their parents' Framingham Study records. A positive family history item is probably accurate and a negative family
history item is often inaccurate.
Howard AA, Arnsten JH, Gourevitch MN
Moderate alcohol consumption is associated with a decreased risk for developing diabetes mellitus and a decreased risk for
heart disease in persons with diabetes. The long-term effects of alcohol consumption on glycemic control and noncardiac complications
in persons with diabetes are poorly understood.
Soinio M, Marniemi J, Laakso M, et al.
High plasma homocysteine level has been associated with increased risk for coronary heart disease (CHD) events in nondiabetic
individuals, especially in those with previously diagnosed CHD. In this large cohort of patients with type 2 diabetes, plasma
homocysteine level was a strong and independent risk factor for CHD events.
Henrikson CA, Howell EE, Bush DE, et al.
Contrary to common belief, relief of chest pain with nitroglycerin did not predict active coronary artery disease in patients
admitted for acute chest pain.
Goldman L, Kirtane AJ
The basis of this article is a patient who was sent home from the emergency department after presenting with chest pain. Later
events proved that the patient had a myocardial infarction. The authors discuss the diagnosis and triage of patients presenting
with acute chest pain or with symptoms consistent with possible cardiac ischemia.
Gibbons RJ
The study by Henrikson and colleagues in this issue is an important addition to the evidence on the diagnostic value of chest
pain relief by nitroglycerin. The response to sublingual nitroglycerin had no diagnostic value in patients who developed chest
pain (presumably at rest) under medical supervision after admission. Do these findings mean that we should stop using the
response to nitroglycerin to help diagnose patients with chronic chest pain?
Wachtell K, Ibsen H, Olsen MH, et al.
An increased urine albumincreatinine ratio (UACR) is associated with increasing cardiovascular risk in hypertensive patients
with left ventricular hypertrophy. The authors found no UACR values where risk was not affected by UACR.
Pastor-Barriuso R, Banegas JR, Damin J, et al.
Increasing systolic blood pressure increases all-cause and cardiovascular mortality over a wide range of blood pressure. In
older people, the relationship of diastolic blood pressure to mortality is J-shaped. Therefore, the association of pulse pressure
with mortality is complex, which makes it less useful as a guide to treatment or prognosis.
Messerli FH
In the recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the incidence of the primary
end point was identical in the chlorthalidone, lisinopril, and amlodipine groups. The authors based their widely publicized
major conclusionthat thiazide diuretics are the preferred first-line antihypertensive therapysolely on secondary end points
and cost.
U.S. Preventive Services Task Force*
According to the U.S. Preventive Services Task Force, the evidence is insufficient to recommend for or against the use of
supplements of vitamins A, C, or E; multivitamins with folic acid; or antioxidant combinations to prevent cancer or cardiovascular
disease. The Task Force recommends against the use of beta-carotene supplements, either alone or in combination, for preventing
cancer or cardiovascular disease.
Morris CD, Carson S
This systematic review evaluates the evidence that routine vitamin supplementation reduces the risk for cancer and cardiovascular
disease.
Brophy JM, Belisle P, Joseph L
In published clinical trials, routinely stenting all significant stenoses was safe but probably did not reduce death, acute
myocardial infarction, or coronary artery bypass surgery rates below those after stenting only for complications or an unsatisfactory
result of standard percutaneous transluminal coronary angioplasty (PTCA). Coronary stenting reduced angiographic restenosis
rates and the need for repeated PTCA, although the true benefit may be smaller than that seen in the clinical trials.
Hart RG, Halperin JL, Pearce LA, et al.
The Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and warfarin plus aspirin
for preventing stroke. This review presents the major results and implications of the six multicenter trials involving 3950
participants. Collectively, these trials offer unique perspectives on antithrombotic therapies for stroke prevention in patients
with atrial fibrillation.
King III SB
In their meta-analysis in this issue, Brophy and colleagues measured the added benefit of routinely stenting each lesion treated
with percutaneous transluminal coronary angioplasty (PTCA) rather than using stents only for complications or unsatisfactory
results of PTCA (provisional stenting). Rates of death and myocardial infarction for the two strategies did not differ substantially.
The clinical trials results don't help much in choosing between routine stenting or provisional stenting for an individual
lesion, which emphasizes the role of the clinical judgment of a highly experienced physician.
Grayburn PA, Hillis LD
The paradigm is shifting from predicting which patient is at high risk for a perioperative cardiac event to minimizing the
likelihood of such an event with specific perioperative pharmacologic therapy.
Vittinghoff E, Shlipak MG, Varosy PD, et al.
Women with coronary disease are at high risk for myocardial infarction or death from coronary heart disease even in the absence
of other risk factors, and their risk increases up to sixfold when they have many risk factors. Physicians frequently fail
to prescribe established drugs for secondary prevention, including aspirin, -blockers, and lipid-lowering agents, for these
women at especially high risk.
Tonelli M, Moy L, Sacks FM, et al.
Pravastatin is effective and appears safe for secondary prevention of cardiovascular events in persons with mild chronic renal
insufficiency. Since statins may be underused in this setting, physicians should consider prescribing them for patients with
chronic renal insufficiency and known coronary disease.
Miller AP, Oparil S
In this issue, Vittinghoff and colleagues analyze data from the Heart and Estrogen/progestin Replacement Study to identify
risk factors for myocardial infarction and death from coronary heart disease and describe the participants' use of secondary
prevention strategies. The most striking aspect of this analysis is the alarming underuse of proven therapies for secondary
prevention of cardiovascular disease in women.
Biondi B, Palmieri EA, Lombardi G, et al.
Because the heart responds to the minimal but persistent changes in circulating thyroid hormone levels, subclinical thyroid
dysfunction is not simply a compensated biochemical change. Physicians should consider timely treatment of subclinical thyroid
dysfunction to avoid adverse cardiovascular effects.
Forrester JS
The author describes the steps in plaque destabilization and links them to a set of clinical strategies that may substantially
decrease the incidence of acute coronary syndromes.
U.S. Preventive Services Task Force*
The U.S. Preventive Services Task Force recommends against the routine use of estrogen and progestin for the prevention of
chronic conditions in postmenopausal women. It concludes that the evidence is insufficient to recommend for or against the
use of unopposed estrogen for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy.
Shlipak MG, Heidenreich PA, Noguchi H, et al.
Renal insufficiency was an independent risk factor for death in elderly patients after myocardial infarction. Targeted interventions
may be needed to improve treatment for this high-risk population.
Wright RS, Reeder GS, Herzog CA, et al.
Patients with renal failure are at increased risk for death after acute myocardial infarction and receive less aggressive
treatment compared with patients who have normal renal function.
Townsend RR
In this issue, Shlipak and Wright and colleagues address the role of impaired kidney function as a risk factor for myocardial
infarction. Their findings suggest that clinicians underuse available treatments in patients presenting with acute myocardial
infarction and impaired kidney function.
Rathore SS, Wang Y, Radford MJ, et al.
Among elderly persons, women have lower rates of cardiac catheterization use after an acute myocardial infarction than men.
However, this difference was attenuated after multivariable adjustment, and it occurred primarily in patients with equivocal
indications. The authors found no sex variations in procedure use among patients who had strong indications for cardiac catheterization.
Rea TD, Heckbert SR, Kaplan RC, et al.
In patients who had myocardial infarction, smoking was associated with an elevated risk for recurrent coronary events. In
persons who quit smoking after infarction, the risk declined to equal that of nonsmokers by 3 years after cessation.
Humphrey LL, Chan BK, Sox HC
This meta-analysis discusses postmenopausal hormone replacement therapy and the primary prevention of cardiovascular disease.
Laine C
The early stoppage and release of the main results of the estrogen plus progestin component of the Women's Health Initiative
have caused millions of postmenopausal women to confront their medicine cabinets in confusion. In this issue, Humphrey and
colleagues summarize data that pointed toward a sizable reduction in the risk for coronary events in women who took hormone
replacement therapy after menopause.
Selker HP, Beshansky JR, Griffith JL
Although its effect was minimal on patients with high baseline reperfusion rates, the electrocardiograph-based Thrombolytic
Predictive Instrument increased use and timeliness of reperfusion in often-missed groups and when involved physicians were
off site.
Ghali WA, Faris PD, Galbraith PD, et al.
Clinical variables fully explained sex differences in rates of revascularization after cardiac catheterization. Extreme caution
is needed in interpreting reports on access to care that use sparsely detailed clinical data sources.
Rifai N, Buring JE, Lee I, et al.
C-reactive protein (CRP) predicts risk for future cardiovascular events in asymptomatic persons. However, because CRP also
predicts total mortality, its specificity for vascular disease is uncertain. This study found that CRP level appears to independently
predict cardiovascular events but not cancer.
Koenig W, Pepys MB
Consistent results from more than 15 well-conducted prospective studies in initially healthy persons have shown a strong and
independent association between the circulating C-reactive protein level and cardiovascular end points. As Rifai and colleagues
show in this issue, the empirical measurement of C-reactive protein is a powerful predictor of cardiovascular risk regardless
of the underlying mechanisms.
Roger VL, Jacobsen SJ, Weston SA, et al.
Over time, the incidence of hospitalized myocardial infarction decreased in men but increased in women and elderly persons.
Survival benefits were clustered among younger persons. These results suggest that both incidence and survival contribute
to the contrasting mortality trends by age and sex and that the burden of coronary disease has shifted toward elderly persons.
Sox HC
This issue marks the first of a series of articles describing the state of the art and science of disease prevention, as interpreted
by the U.S. Preventive Services Task Force. Annals will publish these reports because we believe that internists should have
convenient access to the best evidence about disease prevention, a core activity for most internists.
U.S. Preventive Services Task Force*
The U.S. Preventive Services Task Force strongly recommends that clinicians discuss aspirin chemoprevention with adults who
are at increased risk for coronary heart disease. Discussions with patients should address both the potential benefits and
harms of aspirin therapy.
Hayden M, Pignone M, Phillips C, et al.
This systematic review supports the U.S. Preventive Services Task Force's position on aspirin chemoprevention for adults at
risk for coronary heart disease.
Freedman SB, Isner JM
This review discusses the biology of angiogenesis that forms the basis for clinical studies of patients with coronary artery
disease, and it summarizes information from clinical trials of therapeutic angiogenesis for myocardial ischemia.
Furberg CD, Psaty BM, Pahor M, et al.
The authors address three questions: 1) Is blood pressure reduction a reliable marker for health benefits of antihypertensive
drugs? 2) Does it matter how elevated blood pressure is decreased? 3) What types of antihypertensive clinical trials are needed
in the future?
Mulrow C
In this issue, two perspectives highlight recent evolutions of thought regarding pharmacologic treatment for people with hypertension.
In addition to pharmacologic advice, this issue also features an important report from Vollmer and colleagues on a long-debated
lifestyle intervention: dietary salt restriction.
Kawano H, Motoyama T, Ohgushi M, et al.
In premenopausal women with variant angina, the authors documented a cyclic variation in endothelial function and the frequency
of myocardial ischemia that was associated with the variation in estrogen levels.
Charney P
In this issue, Kawano and colleagues elegantly explore the relationship of endogenous hormone levels to arterial function
and coronary ischemic symptoms. Consideration of the interaction of the menstrual cycle and coronary artery disease may affect
clinical practice in the not-distant future.
Sanders GD, Hlatky MA, Every NR, et al.
Use of implantable cardioverter defibrillators (ICDs) or amiodarone in patients with past myocardial infarction and severely
depressed left ventricular function may provide substantial clinical benefit at an acceptable cost. These results highlight
the importance of clinical trials of ICDs in patients with low ejection fractions who have had myocardial infarction.
Sheifer SE, Manolio TA, Gersh BJ
This review of myocardial infarctions that escape clinical recognition focuses on the prevalence, predisposing factors, and
prognosis, and incorporates data from relevant epidemiologic studies, basic science investigations, and review articles.
Simon JA, Hunninghake DB, Agarwal SK, et al.
Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a small, marginally significant
increase in the risk for biliary tract surgery.
Schneider EC, Leape LL, Weissman JS, et al.
Among a large and diverse sample of Medicare beneficiaries in five U.S. states, overuse of percutaneous transluminal coronary
angioplasty was greater in white men than in other groups, but this difference did not fully explain overall disparities in
revascularization by race. Overuse of cardiac revascularization varied significantly by geographic region.
Kressin NR, Petersen LA
This review found racial differences in invasive cardiac procedure use even after adjustment for disease severity. Future
studies should comprehensively and simultaneously examine the full range of patient, physician, and health care system variables
related to racial differences in the provision of invasive cardiac procedures.
Ridker PM, Danesh J, Youngman L, et al.
In a socioeconomically homogeneous population, there was limited evidence of association between Helicobacter pylori exposure
and risk for future myocardial infarction.
Bostom AG, Selhub J, Jacques PF, et al.
Fortification of cereal grain flour with folic acid has dramatically affected the occurrence of mild hyperhomocysteinemia
and responsiveness to total homocysteine–lowering treatment in people with cardiovascular disease who are free of chronic
renal insufficiency. As a result, ongoing trials of total homocysteine–lowering therapy for the potential reduction of cardiovascular
disease outcomes may be underpowered.
Grodstein F, Manson JE, Stampfer MJ
The risk for recurrent major coronary events seems to increase among women with previous coronary disease who have used hormone
replacement therapy for a short period but appears to decrease with longer-term hormone use.
Joshipura KJ, Hu FB, Manson JE, et al.
Consumption of fruits and vegetables, particularly green leafy vegetables and vitamin C–rich fruits and vegetables, appears
to have a protective effect against coronary heart disease.
Shlipak MG, Elmouchi DA, Herrington DM, et al.
In this study, the incidence of unrecognized myocardial infarction in women with known coronary disease was much lower than
that noted in previous studies of populations without established coronary heart disease.
Hunt D, Young P, Simes J, et al.
In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced
the risk for all major cardiovascular events and all-cause mortality. Since older patients are at higher risk than younger
patients for these events, the absolute benefit of treatment is significantly greater in older patients.
Sethi AA, Tybjærg-Hansen A, Grønholdt MM, et al.
In six large case–control studies, the M235T and T174M angiotensinogen mutations were not consistently associated with increased
(or decreased) risk for ischemic heart disease, myocardial infarction, or ischemic cerebrovascular disease. Statistically
significant associations may represent chance findings rather than real phenomena.
Mann JF, Gerstein HC, Pogue J, et al.
In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild
renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular
risk without increasing adverse effects.
Rathore SS, Weinfurt KP, Gersh BJ, et al.
Patients with paced rhythms were less likely than those without to receive treatment for acute myocardial infarction and had
poorer short- and long-term outcomes. However, this mortality risk diminished after adjustment for treatment. This suggests
that improved recognition and treatment of myocardial infarction may improve outcomes, particularly in the short term.
Kasiske BL
In this issue, Mann and colleagues report that ramipril safely reduced risk for cardiovascular disease in patients with mild
renal insufficiency and that mild renal insufficiency is an independent risk factor for cardiovascular disease. It may be
more than coincidental that angiotensin-converting enzyme inhibitors seem both renoprotective and cardioprotective. Understanding
the link between cardiovascular risk factors and kidney damage may be key to finding better ways to prevent and treat kidney
and cardiovascular disease.
Navas-Nacher EL, Colangelo L, Beam C, et al.
Major coronary disease risk factors, many of which are modifiable, are strong contributors to prediction of future risk, even
in young men. These data may help in formulating appropriate strategies to identify young men at heightened risk for death
from coronary heart disease in later adulthood.
Solomon SD, Glynn RJ, Greaves S, et al.
Significant myocardial stunning with subsequent improvement of ventricular function occurred in most study patients after
Q-wave anterior myocardial infarction. A lower peak creatine kinase level, an estimate of the extent of necrosis, is independently
predictive of recovery of function. Early functional assessment had limited ability to predict recovery of ventricular function.
Girardi AM, Pyenson LR, Morris J, et al.
Incidence of and death from coronary heart disease among office-holding world leaders has decreased over the past 30 years,
possibly because of increased use of cardiac procedures. A coronary event in a world leader is unlikely to presage a change
in government.
Hurst JW
Girardi and colleagues' report in this issue suggests that most world leaders remain in power after a coronary event. In the
United States, a president's physician, along with a White House physician and consultants, decides whether the president
is disabled.
Vaccarino V, Krumholz HM, Yarzebski J, et al.
Younger, but not older, women who survive hospitalization for myocardial infarction have a higher long-term mortality rate
than men. This finding provides additional evidence that younger women who sustain a myocardial infarction are at greater
risk for death than men.
Newman AB, Arnold AM, Burke GL, et al.
Total mortality, cardiovascular disease mortality, and rate of incident cardiovascular disease were higher in patients with
abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease,
and extent of atherosclerosis detected by noninvasive testing.
Rauch U, Osende JI, Fuster V, et al.
Long-term treatment with potent antithrombotic drugs, such as tissue factor or factor Xa inhibitors, that effectively block
thrombosis without causing bleeding complications could help reduce death from cardiovascular disease.
Ayanian JZ
Amid growing efforts to understand and improve the treatment of heart disease in women, Vaccarino and colleagues, in this
issue, provide sobering evidence regarding the adverse long-term consequences of acute myocardial infarction in middle-aged
women.
Hu FB, Stampfer MJ, Solomon C, et al.
Among diabetic women, increased physical activity, including regular walking, is associated with substantially reduced risk
for cardiovascular events.
Grodstein F, Manson JE, Colditz GA, et al.
Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore,
0.3 mg of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625
mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increase risk for stroke.
Grady D, Hulley SB
Despite strong observational evidence from the Nurses' Health Study (including that reported by Grodstein and colleagues in
this issue) and others, the disappointing results of three recent trials indicate that clinicians should not use hormone therapy
for prevention of coronary disease until this practice is supported by evidence from randomized trials.
Su Y, Swift M
Carriers of mutations at the ataxia-telangiectasia locus, who make up 1.4% to 2% of the general population, have a higher
mortality rate and an earlier age at death from cancer and ischemic heart disease than noncarriers.
Jacobson TA
The robust findings of trials examining lipid-lowering drug therapy do not necessarily justify targeting low-density lipoprotein
cholesterol to its lowest possible level, and the argument expressed by the phrase “the lower the better” is clearly not evidence
based.
Grønbæk M, Becker U, Johansen D, et al.
This study suggests that wine intake may have a beneficial effect on all-cause mortality that is additive to the effect of
alcohol. This effect may be attributable to a reduction in death from both coronary heart disease and cancer.
Gilbert K, Larocque BJ, Patrick LT
Existing indices for prediction of cardiac complications performed better than chance, but no index is significantly superior. There
is room for improvement in our ability to predict such complications.
Bach DS, Eagle KA
In this issue, Gilbert and colleagues report on the relatively low accuracy of existing perioperative risk indices in predicting
adverse perioperative events. However, in a low-risk population, the accurate prediction of few adverse events is to be expected. Thus,
risk scores above a given threshold should not be relied on as a guide to preventive interventions.
Arthur HM, Daniels C, McKelvie R, et al.
The waiting period for elective procedures, such as coronary artery bypass grafting, may be used to enhance in-hospital and
early-phase recovery, improving patients' functional abilities and quality of life while reducing their hospital stay.
Saito I, Folsom AR, Brancati FL, et al.
In this study, predictors of coronary heart disease among patients with diabetes were levels of albumin, fibrinogen, and von
Willebrand factor; factor VIII activity; and leukocyte count.
Fonseca VA
The study by Saito and colleagues in this issue highlights the importance of several nontraditional risk factors in the pathogenesis
of increased cardiovascular disease associated with diabetes.
Seto TB, Taira DA, Berezin R, et al.
Elderly patients who were selected for participation in a trial of percutaneous coronary intervention had substantial improvements
in health-related quality of life after this intervention that were similar to improvements in younger patients.
Ganz DA, Kuntz KM, Jacobson GA, et al.
The cost-effectiveness ratios of statin therapy in older patients who have previously had myocardial infarction are reasonable
under a variety of assumptions about drug efficacy, drug cost, and rates of cardiac and cerebrovascular events. Pending results
of randomized, controlled trials of secondary prevention in patients in this age group, statin therapy seems to be as cost-effective
as many routinely accepted medical interventions in this setting.
Raymondos K, Panning B, Leuwer M, et al.
This prospective study demonstrates that administration of adrenaline into the airways is hemodynamically effective and increases
adrenaline plasma levels in adults with severe cardiac disease.
Garber AM
The studies by Ganz and Prosser and their colleagues in this issue evaluate statin therapy in clinically important populations
that were not studied adequately in randomized trials. These studies reinforce the message that lipid management for secondary
prevention should be a high priority, regardless of whether the patient is female or male, young or old.
Hak AE, Pols HA, Visser TJ, et al.
Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.
Polanczyk CA, Kuntz KM, Sacks DB, et al.
Measurement of creatine kinase–MB mass plus early exercise testing is a cost-effective initial strategy for younger patients
and those with a low to moderate probability of myocardial infarction. Troponin I measurement can be a cost-effective second
test in higher-risk patients if the creatine kinase–MB level is normal and early exercise testing is not an option.
Fox AC, Levin RI
In this issue, Polanczyk and colleagues used relatively new markers of myocardial necrosis—creatine kinase–MB and troponin
I—to formulate triage strategies for acute chest pain in the emergency department. Do the results of their cost-effectiveness
analysis challenge the prevailing algorithm for diagnosis?
Suwaidi JA, Velianou JL, Gertz MA, et al.
Cardiac amyloidosis can present as angina pectoris associated with coronary flow reserve abnormalities despite normal coronary
angiograms. This finding may have major therapeutic and prognostic implications in patients with this disorder.
Krumholz HM, Radford MJ, Wang Y, et al.
In this study, early β-blocker therapy was not used for 51% of elderly patients who were hospitalized with an acute myocardial
infarction and did not have a contraindication to this therapy. Increasing β-blocker use for these patients would provide
an excellent opportunity to improve their care and outcomes.
Hunink MG, Kuntz KM, Fleischmann KE, et al.
New imaging techniques, such as magnetic resonance imaging and electron-beam computed tomography, must be relatively inexpensive
and have excellent sensitivity and specificity to be cost-effective compared with other techniques that are already available
for the diagnosis of coronary artery disease.
Ridker PM, Hennekens CH, Buring JE, et al.
In apparently healthy postmenopausal women, little evidence was found to support the notion that previous infection (as measured
by IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus) is associated
with subsequent risk for cardiovascular disease.
Herrington DM
The Heart and Estrogen/progestin Replacement Study (HERS) showed no overall effect of long-term use of estrogen plus progestin
for secondary prevention of coronary heart disease in postmenopausal women. The key to understanding this finding, which contradicts
previous research, may rest in the explanation of the time-trend data.
Kark JD, Selhub J, Adler B, et al.
A mildly to moderately elevated nonfasting total homocysteine level is a substantial risk marker for death from any cause.
The association seems to be stronger during the first 5 years of follow-up.
Eikelboom JW, Lonn E, Genest J, et al.
This paper reviews the relation between homocyst(e)ine levels and risk for cardiovascular disease and the potential cardiovascular
risk reduction associated with therapy to decrease homocyst(e)ine levels.
Harjai KJ
Recent studies have identified several potential new cardiovascular risk factors, including left ventricular hypertrophy,
homocysteinemia, lipoprotein(a) excess, hypertriglyceridemia, oxidative stress, and hyperfibrinogenemia. This review summarizes
the current literature that supports these conditions as risk factors.
Graham I
Is an elevated plasma homocysteine level bad for you? Although the association between genetic hyperhomocysteinemia and vascular
disease would clearly indicate that an increased homocysteine level precedes the disease, these issues have not been definitively
resolved. Several papers in this issue address this topic.
Culleton BF, Larson MG, Kannel WB, et al.
Despite previous suggestions to the contrary, uric acid does not have a causal role in the development of coronary heart disease,
death from cardiovascular disease, or death from all causes. Any apparent association with these outcomes is probably due
to the association of uric acid level with other risk factors.
Hollenberg SM, Kavinsky CJ, Parrillo JE
Improved understanding of the pathophysiology of shock and myocardial infarction has led to improved treatment. If cardiogenic
shock is managed with rapid evaluation and prompt initiation of supportive measures and definitive therapy, outcomes can improve.
Vaccarino V, Krumholz HM
In this issue, Culleton and colleagues from the Framingham Heart Study resolve the long-standing controversy surrounding the
role of uric acid as a risk factor for cardiovascular disease. Enthusiasm for new cardiovascular risk factors should be accompanied
by efforts to evaluate their independent association with the incidence of cardiovascular disease and their practical clinical
utility.
Ridker PM
When considering the clinical utility of screening for a new marker of cardiovascular disease, physicians should determine
whether a standardized and reproducible assay for the marker is available, whether a consistent series of prospective studies
indicate that baseline elevations of the marker predict future risk, and whether assessment of the marker adds to the predictive
value of other plasma-based risk factors.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Kuntz KM, Fleischmann KE, Hunink MG, et al.
Exercise electrocardiography or exercise echocardiography resulted in reasonable diagnostic cost-effectiveness ratios for
patients at mild to moderate risk for coronary artery disease in terms of age, sex, and type of chest pain. Coronary angiography
without previous noninvasive testing resulted in reasonable cost-effectiveness ratios for patients with a high pretest probability
of coronary artery disease.
Garber AM, Solomon NA
Echocardiography, single-photon emission computed tomography, and immediate angiography are cost-effective diagnostic alternatives
to positron emission tomography and other diagnostic approaches. Test selection should reflect local variation in test accuracy.
von Schacky C, Angerer P, Kothny W, et al.
Dietary intake of ω-3 fatty acids modestly mitigates the course of coronary atherosclerosis in humans.
Locatelli ER, Varghese JP, Shuaib A, et al.
This report describes three patients with asystole or bradycardia associated with complex partial seizures and reviews the
relevant literature.
Daumit GL, Hermann JA, Coresh J, et al.
Differences between ethnic groups in use of cardiovascular procedures narrowed markedly once a serious illness developed and
adequate insurance coverage was ensured. The disparity was eliminated in patients with previous Medicare insurance or a stronger
indication for a procedure.
Hasdai D, Lerman A, Grill DE, et al.
In this study, successful percutaneous coronary revascularization did not substantially supplant the use of antianginal medications,
which were commonly used despite the marked improvement in anginal status. This finding may reflect reluctance to alter therapy
once symptoms of angina subside.
Endocarditis (6 articles)
Morpeth S, Murdoch D, Cabell CH, et al.
Endocarditis caused by non-HACEK organisms (species other than Haemophilus species, Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, and Kingella species) has long been thought to be associated with injection
drug use. Morpeth and coworkers described the clinical characteristics and outcomes of 2761 cases of patients with infective
endocarditis from 61 hospitals. Non-HACEK organisms accounted for fewer than 2% of cases. Most non-HACEK endocarditis infections
were associated with health care: 59% of patients had implanted endovascular devices or prosthetic valves and only 4% were
injection drug users. More than half of the patients with non-HACEK infections had cardiac surgery; 24% died.
Gavaldà J, Len O, Miró JM, et al.
A 4- to 6-week course of penicillin or ampicillin plus an aminoglycoside is currently recommended for treating enterococcal
endocarditis. However, this regimen is ineffective against Enterococcus faecalis organisms with high-level aminoglycoside
resistance (HLAR). Gavaldà and colleagues evaluated the efficacy and safety of ampicillin plus ceftriaxone for treating E.
faecalis endocarditis in patients who could not tolerate aminoglycosides because of nephrotoxicity. Twenty- one patients had
HLAR organisms and 22 patients did not. A 6-week course effectively treated both groups.
Gubler JG, Kuster M, Dutly F, et al.
Cardiac manifestations of Whipple disease are rarely diagnosed before autopsy. In four patients with culture-negative endocarditis,
the absence of clinical, microscopic, or microbiological evidence of gastrointestinal disease did not rule out Tropheryma
whippelii.
Raoult D
In this issue, Gubler and colleagues report that chronic afebrile endocarditis could be caused by Whipple disease bacterium
in patients whose clinical picture does not suggest classic infective endocarditis. Our knowledge of Whipple disease is growing
rapidly, but culture of the bacterium is necessary to develop a serologic test and to determine whether the bacterium is a
unique pathotype.
Rosen AB, Fowler VG, Corey GR, et al.
Within the limitations of existing empirical data, this study suggests that for patients with clinically uncomplicated catheter-associated
Staphylococcus aureus bacteremia, the use of transesophageal echocardiography to determine therapy duration is a cost-effective
alternative to 2- or 4-week empirical therapy.
Weinstein MC
The cost-effectiveness papers by Rosen and Gould and their colleagues in this issue show that some cost-increasing technologies
do indeed represent good value for money in the clinical uses for which they are evaluated.
Hypertension (90 articles)
Bosworth HB, Olsen MK, Grubber JM, et al.
In this trial, 636 patients with hypertension were randomly assigned to receive usual care; a telephone-delivered, nurse-administered
behavioral self-management intervention; home blood pressure self-monitoring; or both of the latter 2 interventions. Compared
with usual care, the adjusted improvement in the proportion of patients with blood pressure control at 24 months was 4.3%
for the behavioral intervention group, 7.6% for the blood pressure monitoring group, and 11.0% for the combined intervention
group. The combined intervention improved blood pressure control and systolic and diastolic blood pressures more than usual
care.
Jafar TH, Hatcher J, Poulter N, et al.
Jafar and colleagues assessed the effectiveness of community-based interventions on blood pressure in 1341 hypertensive adults
in Karachi, Pakistan. Participants received home health education (HHE) every 3 months from lay health workers, with or without
care from general practitioners (GPs) specially trained in hypertension management, or no intervention. Patients who received
HHE plus GP care had greater decreases in systolic blood pressure (10.8 mm Hg vs. 5.8 mm Hg in the other 3 groups).
Mann JF, Schmieder RE, Dyal L, et al.
Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but
without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated
glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome
results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased
more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.
Sowers JR, Whaley-Connell A, Epstein M
Obesity, insulin resistance, and hypertension and other risk factors for cardiovascular and chronic kidney disease form the
metabolic syndrome. This review discusses emerging evidence that aldosterone promotes insulin resistance and participates
in the pathogenesis of the metabolic syndrome and resistant hypertension.
McWilliams JM, Meara E, Zaslavsky AM, et al.
Improving the quality of care and expanding insurance coverage can reduce differences in outcomes experienced by different
sociodemographic groups. McWilliams and colleagues used blood pressure, hemoglobin A1c, and total cholesterol measurements
obtained from participants in a national survey to measure changes in chronic disease control. Over 8 years, disease control
improved but gaps between white and nonwhite patients did not change. The gaps narrowed after age 65 years, when universal
Medicare insurance begins.
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians
should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products (grade
A recommendation). For pregnant women, clinicians should ask about tobacco use and provide augmented, pregnancy-tailored counseling
for those who smoke (grade A recommendation).
Baid SK, Lai EW, Wesley RA, et al.
Contrast media are widely thought to induce hypertensive crisis in patients with pheochromocytoma. However, in a series of
22 patients with pheochromocytoma undergoing computed tomography with low-osmolar contrast media, Baid and associates observed
no instances of catecholamine surge or hypertensive crisis. Contemporary low-osmolar computed tomography contrast seems to
be safe for patients with pheochromocytoma.
Bryson CL, Au DH, Sun H, et al.
Alcohol misuse may be a risk factor for failing to adhere to medication regimens. Bryson and colleagues found a graded, linear
decrease in adherence to statins and hypertension medications with increasing levels of alcohol misuse among patients at 7
Veterans Affairs primary care clinics. At 1 year, the percentage of patients adherent to statins was lower in the 2 highest
alcohol misuse groups than in nondrinkers. Similarly, the percentage of patients adherent to antihypertensive regimens was
lower in the 3 highest alcohol misuse groups than in nondrinkers.
Golin C
In this issue, Bryson and colleagues report a direct, dose-related association between alcohol misuse and medication nonadherence
for antihypertensives and statins but not oral hypoglycemics. This well-designed, nicely executed prospective study is a major
step forward in understanding the relationship between substance abuse and medication nonadherence, and as many classic studies
do, it raises more questions than it answers.
Wilper AP, Woolhandler S, Lasser KE, et al.
Some claim that U.S. persons without health insurance do not typically have ongoing health care needs. Using data from the
National Health and Nutrition Examination Survey, Wilper and associates estimate that more than 11 million working-age Americans
without health insurance have cardiovascular disease, hypertension, diabetes, dyslipidemia, obstructive lung disease, or previous
cancer. Chronically ill patients without insurance were less likely than those with coverage to visit a health professional
and were more likely to identify an emergency department as their standard site of care.
Vickers AJ, Basch E, Kattan MW
Cut-points for defining a diagnosis have substantial limitations. Risk prediction, in which patient risk factors are combined
into a single model and the results used in shared decision making about treatments, may offer an alternative to diagnosis.
The authors compare the diagnostic and risk prediction approaches and attempt to identify for which types of medical problem
each is best suited.
Chin MH
The article by Wilper and colleagues in this issue tells us that chronic disease is rampant among uninsured persons. This
editorial identifies opportunities for policy reforms and outlines what every practice, hospital, and health plan can do now
to improve outcomes for vulnerable patients with chronic disease.
Pletcher MJ, Bibbins-Domingo K, Lewis CE, et al.
In their prospective cohort study, Pletcher and colleagues found that prehypertension before age 35 years, especially systolic
prehypertension, showed a graded association with coronary calcium later in life. This association remained strong after adjustment
for differences in blood pressure elevation after age 35 years and other coronary risk factors and participant characteristics.
Kerr EA, Zikmund-Fisher BJ, Klamerus ML, et al.
Clinicians often fail to intensify antihypertensive therapy when their patient's blood pressure is elevated. Kerr and colleagues
sought the reasons for this practice by studying 1169 diabetic patients with elevated triage blood pressure during routine
primary care visits at 9 Veterans Affairs facilities. Half of the patients did not have an increase in antihypertensive drug
dosage, which was associated with patient reports of taking their blood pressure at home, rechecking the blood pressure during
the clinical visit, and discussing of antihypertensive medication. Uncertainty about the patient's true blood pressure may
contribute to failure to intensify antihypertensive therapy.
Phillips LS, Twombly JG
When blood pressure levels are above goal, clinicians often fail to intensify therapy—a practice called clinical inertia.
Two recent Annals articles, one in this issue, provide information about the factors that contribute to clinical inertia in
hypertension management. The studies suggest that clinical uncertainty about a patient's true blood pressure is a more important
cause of clinical inertia than many comorbid conditions that require attention in a 15-minute visit. Clinicians will need
a new paradigm to guide them in treating high blood pressure—it's time to overcome clinical inertia.
Turner BJ, Hollenbeak CS, Weiner M, et al.
Little is known about the quality of care received by patients with multiple unrelated comorbid conditions. The authors examined
the electronic medical records of 15 459 patients with uncontrolled hypertension at 6 primary care practices. Most patients
had 2 or more comorbid conditions unrelated to hypertension, such as arthritis, gastroesophageal reflux, or thyroid disease.
At office visits, clinicians were less likely to intensify treatment for uncontrolled hypertension in patients with multiple
unrelated conditions.
Kestenbaum B, Rudser KD, de Boer IH, et al.
Kestenbaum and associates tested the hypothesis that early kidney dysfunction, as measured by serum cystatin C levels and
urinary albumin excretion, predates hypertension in adults without clinically recognized kidney or cardiovascular disease.
During a median follow-up of 3.1 years, 545 (19.7%) of 2767 adults age 45 to 84 years developed hypertension. Higher baseline
levels of cystatin C—but not the spot baseline urine albumin–creatinine ratio—were associated with higher incidence of hypertension,
independent of other risk factors. These population-based findings complement experimental work implicating early kidney damage
in the pathogenesis of essential hypertension.
Bakris GL, Berkwits M
The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicon-MR Controlled Evaluation) trial tested whether
perindopril, 2 mg/d, and indapamide, 0.625 mg/d, plus standard antihypertensive treatment reduced both the microvascular and
macrovascular complications of diabetes. Compared with placebo, participants taking the drug combination had a statistically
significant mean reduction in systolic and diastolic blood pressure and a borderline statistically significant reduction in
major macrovascular and microvascular events. Because the mean blood pressure of participants was lower than that of participants
in previous trials, the ADVANCE trial provides new evidence that starting antihypertensives at a prehypertensive stage in
patients with type 2 diabetes is beneficial.
Parikh NI, Pencina MJ, Wang TJ, et al.
Identifying normotensive adults who have a high probability of developing hypertension could help target nonpharmacologic
preventive measures. Using data from the Framingham cohort study, the investigators devised a simple risk score that identified
adults without diabetes who had low (10%) probability of developing hypertension within 4 years. If this risk score gives
similar results in other populations, it could help clinicians identify high-risk patients who could benefit from preventive
interventions.
Matchar DB, McCrory DC, Orlando LA, et al.
The authors systematically reviewed trials that directly compared angiotensin-converting enzyme (ACE) inhibitors with angiotensin-receptor
blockers (ARBs) in adults with essential hypertension. They found good evidence that the 2 classes of agents had similar long-term
effects on blood pressure, with no consistent differences in mortality, cardiovascular events, progression to diabetes, left
ventricular function, and kidney disease. The ACE inhibitors caused chronic cough more often than ARBs.
Parfrey PS
The most important contribution of the systematic reviews by Matchar and colleagues and Kunz and associates is that they tell
us what we do not know, which is the adverse effects of long-term therapy with these agents. We need a large, long-term, 3-group,
randomized, controlled trial involving monotherapy and combination therapy with angiotensin-receptor blockers and angiotensin-converting
enzyme inhibitors. Until then, physicians should closely monitor patients with late-stage kidney disease who are using combination
therapy with these 2 drug classes.
U.S. Preventive Services Task Force
A targeted literature search sought new evidence on the direct benefits and harms of screening, and on the harms of treating
screen-detected or mild to moderate hypertension. The U.S. Preventive Services Task Force (USPSTF) found no new substantial
evidence that would lead it to change its 2003 recommendation. It therefore reaffirms its recommendation that clinicians screen
for high blood pressure in adults age 18 years or older.
Wolff T, Miller T
This evidence update supports the USPSTF recommendation on screening for high blood pressure. The only new evidence was about
the harms of treatment of early hypertension: Although pharmacologic therapy is associated with common side effects, serious
adverse events are uncommon.
Okin PM, Devereux RB, Harris KE, et al.
Regression of left ventricular hypertrophy (LVH) has been associated with reductions in various cardiovascular outcomes, but
heart failure outcomes have not been carefully studied. Okin and colleagues found that regression of LVH by Cornell product
electrocardiographic criteria was associated with fewer hospitalizations for new-onset heart failure. This relationship appeared
to be separate from blood pressure reduction and type of therapy. Whether clinicians should adjust antihypertensive therapy
on the basis of electrocardiographic findings of LVH is not yet known.
Beulens JW, Rimm EB, Ascherio A, et al.
In this 16-year prospective study, 11 711 male health professionals with hypertension reported their average alcohol consumption
every 4 years. Hypertensive men who consumed 10 to 14 grams of alcohol (about 1 drink) or more per day had a lower risk for
myocardial infarction than those abstaining from alcohol. Alcohol intake did not predict all-cause mortality or deaths due
to cardiovascular disease.
Thiébaut AC, Freedman LS, Carroll RJ, et al.
Relationships between diet and chronic disease have become the focus of many analytic studies in nutritional epidemiology
over the past several decades. In this issue, Beulens and colleagues present a prospective analysis of the relationship between
alcohol intake and cardiovascular events among men with hypertension in the Health Professionals Follow-Up Study.
Roumie CL, Elasy TA, Greevy R, et al.
The authors randomly assigned providers caring for hypertensive patients to 1 of 3 interventions: 1) a Web link to the Seventh
Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; 2) the
Web link and a computer reminder of the patient's blood pressure; or 3) the Web link, the computer alert, and a letter to
their patients about ways to control their blood pressure. Patients of providers assigned to the third group had better blood
pressure control.
Boudville N, Ramesh Prasad GV, Knoll G, et al.
This review found 10 studies that compared the blood pressure of kidney donors and healthy adults of similar age, sex, and
ethnicity. Within 5 to 10 years of donation, the average blood pressure of kidney donors was 5 mm Hg higher than that anticipated
with normal aging.
Childress JF
There are many “opportunities for action” to increase the supply of transplantable organs. The media tend to focus on the
most controversial proposals, such as buying and selling organs, rather than the less dramatic but potentially very effective
proposals, such as donation after circulatory determination of death. Furthermore, although living donation will be an important
continuing source of organs—mainly kidneys—it clearly needs much more attention and oversight because of incomplete information
about risks to donors and other ethical concerns.
Estruch R, Martínez-González MÁ, Corella D, et al.
The authors assigned 772 participants to a low-fat diet or to 1 of 2 Mediterranean diets that emphasized consumption of either
olive oil or nuts. They then measured changes in body weight, blood pressure, lipid profile, glucose levels, and inflammatory
molecules. Compared with the low-fat diet, the 2 Mediterranean diets had a beneficial effect on most of these outcomes at
3 months.
Messerli FH, Mancia G, Conti CR, et al.
Because blood flow in the coronary arteries takes place largely during diastole, an increase in risk for coronary artery disease
with excessive lowering of diastolic blood pressure is plausible, although unproven. In this secondary analysis of data from
a large randomized trial of 2 antihypertensive drugs in patients with coronary artery disease, the risk for the primary outcome,
all-cause death, and myocardial infarction increased with low diastolic blood pressure. This relationship did not occur for
stroke.
Rodondi N, Peng T, Karter AJ, et al.
The authors assessed the care of 253 238 adults who had poorly controlled hypertension, dyslipidemia, or diabetes. The objective
was to determine whether poor control triggered changes in treatment and whether these changes were successful. The authors
found that many patients with poorly controlled systolic blood pressure (64%), diastolic blood pressure (71%), low-density
lipoprotein cholesterol level (56%), or diabetes (66%) did have clinically appropriate changes in their treatment.
Elmer PJ, Obarzanek E, Vollmer WM, et al.
The authors randomly assigned 810 adults with prehypertension or early-stage hypertension to receive advice on changing diet
and exercise, a behavioral intervention, or the behavioral intervention plus the Dietary Approaches to Stop Hypertension (DASH)
diet. Relative to the advice only group, the odds ratios for having hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04)
for the behavioral intervention group and 0.77 (CI, 0.62 to 0.97) for the behavioral intervention plus DASH group. Absolute
blood pressure at 18 months was lower in the behavioral intervention groups, but the difference was not statistically significant.
McGavock JM, Victor RG, Unger RH, et al.
Obesity is a major risk factor for heart disease, and physicians must be aware of emerging research of novel mechanisms through
which adiposity adversely affects the heart. The purpose of this review is to highlight a novel mechanism by which obesity
causes heart disease, whereby excessive lipid accumulation within the myocardium causes left ventricular remodeling and dilated
cardiomyopathy.
Perlin JB, Pogach LM
Clinical trials have shown that better control of glycemia, blood pressure, and low-density lipoprotein cholesterol level
leads to better outcomes of diabetes, hypertension, and dyslipidemia. Guidelines have incorporated new evidence very quickly,
and national public education programs and professional societies have disseminated these evidence-based recommendations to
the public and to professionals. Has this unprecedented momentum created by publicizing evidence and measuring outcomes resulted
in translation of evidence into practice? And if not, why? Two studies in this issue provide us with a progress report from
both the public health and managed health care plan perspectives.
Barr DA
Some of the population groups identified through genetic analyses have resembled what have been historically categorized as
“races.” Some argue that a patient's race predicts underlying genetic traits well enough to predict outcomes of treatment.
Others argue that racially defined groups are too heterogeneous to make useful predictions for individuals. Physicians must
translate this scientific debate into individualized clinical decisions. Is it appropriate to use a patient's self-identified
“race” to help decide treatment?
Chodosh J, Morton SC, Mojica W, et al.
The authors examined studies of the effectiveness of self-management programs for osteoarthritis, hypertension, and diabetes
mellitus. Self-management programs appear to produce clinically important benefits for patients with hypertension and diabetes,
but the evidence is not sufficient to identify the program elements that are most responsible for improved outcomes.
Lawrence DM
The care of patients with chronic disease is one of the most urgent medical challenges facing the United States. Although
the articles by Chodosh and colleagues and Wolff and Boult are useful, studies of one intervention divert attention from underlying
issues. The bigger picture combines health care providers and their interactions, support staff, care pathways, diagnostic
and therapeutic technologies, information and communications infrastructure, clinical decision-making systems, and real-time
evaluation and learning loops, all applied over the lifetime of a chronic illness. A silver bullet won't cure what ails us.
He J, Gu D, Wu X, et al.
The authors examined the effect of soybean supplements to the diet in 302 participants with an initial untreated systolic
blood pressure of 130 to 159 mm Hg, diastolic blood pressure of 80 to 99 mm Hg, or both. Systolic and diastolic blood pressure
both decreased. Increasing soybean protein intake may help to prevent and treat hypertension.
Cutler JA, Obarzanek E
The evidence on the environmental determinants of increased blood pressure supports 4 recommendations for lifestyle intervention:
controlling body weight, reducing dietary salt, increasing physical activity, and maintaining moderate alcohol use. Our editorial
summarizes several studies of another factor, dietary protein.
Levey AS, Mulrow CD
Several recent studies have tried to characterize the effects of a lower-than-usual target blood pressure on progression of
nondiabetic kidney disease. An observational study, the Modification of Diet in Renal Disease Study, showed long-term benefit.
The randomized African-American Study of Kidney Disease and Hypertension showed no benefit, nor did the recently published
Ramipril Efficacy in Nephropathy 2 Trial. Here's our take on these conflicting study results.
Eisen SA, Kang HK, Murphy FM, et al.
The authors compared the prevalence of medical conditions in 2 groups of veterans of U.S. military service: One served in
the Gulf War, and the other did not. Physical health was similar in the 2 groups, except Gulf War veterans had a higher prevalence
of fibromyalgia, the chronic fatigue syndrome, certain skin conditions, and dyspepsia.
Komaroff AL
Eisen and his colleagues provide robust evidence that armed forces personnel deployed to the Gulf War in the early 1990s are
more likely to report a constellation of debilitating symptoms than armed forces personnel deployed elsewhere at the same
time. However, no one has shown that these symptoms have a specific cause or even constitute a syndrome unique to Gulf War
service.
Sarnak MJ, Greene T, Wang X, et al.
The optimal blood pressure to slow progression of chronic kidney disease is not known. In this report of long-term follow-up
of patients with a moderately to severely decreased glomerular filtration rate in the Modification of Diet in Renal Disease
Study, random assignment to a low target blood pressure slowed the progression of nondiabetic kidney disease.
Vasbinder GB, Nelemans PJ, Kessels AG, et al.
Computed tomographic angiography and magnetic resonance angiography are not sufficiently reproducible or sensitive to rule
out renal artery stenosis in hypertensive patients. Therefore, digital subtraction angiography is still the best diagnostic
test for renal artery stenosis.
Textor SC
Vasbinder and colleagues' study of noninvasive tests for diagnosing renal artery stenosis reminds us that vascular imaging
methods are fallible. While clinicians must know what they can reasonably expect from diagnostic imaging, it is even more
important for them to decide whether the results of the imaging procedures would change their management of the patient.
Brewster LM, van Montfrans GA, Kleijnen J
Although some antihypertensive drugs affect blood pressure differently in black patients and white patients, efficacy for
reducing morbidity and mortality is the same once patients achieve a blood pressure goal.
Davis BR, Furberg CD, Wright JT, et al.
This paper reviews key aspects of the design, analyses, findings, and conclusions of the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT). The authors also address several frequent comments about heart failure and
diabetes outcomes.
The Editors
The opinion of an expert has value. The problem is finding a way to maximize the benefits of that expertise while minimizing
the risk for harm resulting from real or perceived bias due to a potential conflict of interest. The safest place to try is
a peer-reviewed journal with vigilant editors.
Visceral Adiposity Is an Independent Predictor of Incident Hypertension in Japanese Americans (2004)
Hayashi T, Boyko EJ, Leonetti DL, et al.
This prospective study used computed tomography to measure body fat in 300 normotensive Japanese Americans. Ninety-two participants
developed hypertension within 10 to 11 years. Greater visceral adiposity was associated with increased risk for hypertension
even after adjustment for baseline differences in risk factors for hypertension.
Hoerger TJ, Harris R, Hicks KA, et al.
Diabetes screening targeted to people with hypertension is more cost-effective than universal screening. The most cost-effective
strategy is to screen people at age 55 to 75 years because hypertension is more common and cardiovascular death rates are
higher in older people.
Nathan DM, Herman WH
Hoerger and colleagues have used decision modeling to advance our understanding of the benefit of screening for diabetes in
people with and without hypertension. However, without optimized management of hypertension and hyperglycemia after the diagnosis
of diabetes, no screening program can be effective or cost-effective.
Wong TY, Klein R, Sharrett AR, et al.
Researchers have speculated that narrowing of the small arterioles contributes to the pathogenesis of hypertension. In this
prospective study, patients who were normotensive at baseline but had narrowed retinal arterioles were more likely to develop
hypertension later in life. Arteriolar narrowing may be an early stage of hypertension.
Wachtell K, Ibsen H, Olsen MH, et al.
An increased urine albumincreatinine ratio (UACR) is associated with increasing cardiovascular risk in hypertensive patients
with left ventricular hypertrophy. The authors found no UACR values where risk was not affected by UACR.
Pastor-Barriuso R, Banegas JR, Damin J, et al.
Increasing systolic blood pressure increases all-cause and cardiovascular mortality over a wide range of blood pressure. In
older people, the relationship of diastolic blood pressure to mortality is J-shaped. Therefore, the association of pulse pressure
with mortality is complex, which makes it less useful as a guide to treatment or prognosis.
Oparil S, Zaman MA, Calhoun DA
Increased recognition of specific causes of hypertension may lead to therapies that address specific pathophysiologic mechanisms
and cause fewer adverse effects. Research to identify such therapies will use powerful new techniques of genetics, genomics,
and proteomics in conjunction with systems physiology and population studies.
Messerli FH
In the recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the incidence of the primary
end point was identical in the chlorthalidone, lisinopril, and amlodipine groups. The authors based their widely publicized
major conclusionthat thiazide diuretics are the preferred first-line antihypertensive therapysolely on secondary end points
and cost.
Jafar TH, Stark PC, Schmid CH, et al.
Achieving a systolic blood pressure between 110 and 129 mm Hg may slow the progression of nondiabetic kidney disease when
the urinary protein excretion exceeds 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher
risk for progression.
Mulrow CD, Townsend RR
In this issue, Jafar and colleagues address three questions about the management of patients with nondiabetic kidney disease
and hypertension: Does the amount of urinary protein affect outcomes? Are blood pressure targets less than 130/80 mm Hg too
high? Should clinicians use both urinary protein and blood pressure levels during follow-up to guide management?
Devereux RB, Dahlf B, Kjeldsen SE, et al.
In hypertensive patients without clinically evident vascular disease, losartan and atenolol were equally effective in reducing
blood pressure, but losartan was more effective in preventing cardiovascular death and morbidity (predominantly from stroke).
Berl T, Hunsicker LG, Lewis JB, et al.
Treatment with irbesartan, amlodipine, or placebo led to the same composite cardiovascular event rate (cardiovascular death,
myocardial infarction, congestive heart failure, strokes, and coronary revascularization) in patients with type 2 diabetes
and overt nephropathy who also received conventional antihypertensive therapy.
Snow V, Weiss KB, Mottur-Pilson C
This article describes the American College of Physicians' guidelines for managing hypertension in patients with type 2 diabetes
mellitus. It answers the following questions: 1) What are the benefits of tight blood pressure control in type 2 diabetes?
2) What are appropriate target levels of systolic blood pressure and diastolic blood pressure for patients with type 2 diabetes?
and 3) Are certain antihypertensive agents more effective in patients with diabetes?
Vijan S, Hayward RA
The authors use the accumulated results of research on the effects of blood pressure on the complications of type 2 diabetes
to recommend optimal blood pressure goals and preferred antihypertensive drugs. This paper provides the rationale for the
American College of Physicians' clinical guidelines and provides an evidence base to guide clinicians in setting hypertension
treatment goals and priorities in patients with type 2 diabetes.
Haider AW, Larson MG, Franklin SS, et al.
Although each component of blood pressure was associated with risk for congestive heart failure, pulse pressure and systolic
pressure conferred greater risk than diastolic pressure. Increased pulse pressure may help identify hypertensive patients
who, because they are at high risk for congestive heart failure, are candidates for aggressive blood pressure control.
Strazzullo P, Iacone R, Iacoviello L, et al.
The angiotensin-converting enzyme I/D polymorphism was a significant predictor of overweight and abdominal adiposity in men.
DD homozygosity was associated with larger age-related increases in body weight and blood pressure, as well as with higher
incidence of overweight and abdominal adiposity.
Davis BR, Cutler JA, Furberg CD, et al.
In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone
is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure
does not explain this increased risk.
Kivipelto M, Helkala E, Laakso MP, et al.
The association between the apolipoprotein E (apoE) ε4 allele and Alzheimer disease does not seem to be mediated by vascular
factors. The apoE ε4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent
risk factors for Alzheimer disease. The risk for Alzheimer disease from treatable factors—elevated total cholesterol level
and blood pressure—appears to be greater than that from the apoE ε4 allele.
U.S. Preventive Services Task Force*
The U.S. Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against behavioral
counseling in primary care settings to promote physical activity.
Eden KB, Orleans CT, Mulrow CD, et al.
This systematic review supports the U.S. Preventive Services Task Force's position on behavioral counseling to promote physical
activity.
Whelton SP, Chin A, Xin X, et al.
Exercise reduces blood pressure in both hypertensive and normotensive persons. An increase in aerobic physical activity should
be considered an important component of lifestyle modification for prevention and treatment of high blood pressure.
Boutitie F, Gueyffier F, Pocock S, et al.
Several studies in hypertensive patients receiving treatment have described the relationship between blood pressure and mortality
as J-shaped, with an increased risk for events in patients with low blood pressure. This study found that the increased risk
for events in patients with low blood pressure was not related to antihypertensive treatment and was not specific to blood
pressure–related events. Poor health conditions leading to low blood pressure and an increased risk for death probably explain
the J-shaped curve.
Vollmer WM, Sacks FM, Ard J, et al.
The DASH (Dietary Approaches to Stop Hypertension) diet plus reduced sodium intake is recommended to control blood pressure
in diverse subgroups of patients with hypertension.
Furberg CD, Psaty BM, Pahor M, et al.
The authors address three questions: 1) Is blood pressure reduction a reliable marker for health benefits of antihypertensive
drugs? 2) Does it matter how elevated blood pressure is decreased? 3) What types of antihypertensive clinical trials are needed
in the future?
Kaplan NM
Achieving therapy goals in diabetic patients with hypertension usually requires several antihypertensive drugs. On the basis
of their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors should probably be
the first choice. Second and third choices should be a long-acting diuretic and a calcium-channel blocker or a β-blocker,
respectively.
Mulrow C
In this issue, two perspectives highlight recent evolutions of thought regarding pharmacologic treatment for people with hypertension.
In addition to pharmacologic advice, this issue also features an important report from Vollmer and colleagues on a long-debated
lifestyle intervention: dietary salt restriction.
Vasbinder GB, Nelemans PJ, Kessels AG, et al.
Computed tomography angiography and gadolinium-enhanced three-dimensional magnetic resonance angiography seem to be preferred
in patients referred for evaluation of renovascular hypertension. However, because few studies of these tests have been published,
further research is recommended.
Scuteri A, Bos AJ, Brant LJ, et al.
Postmenopausal women taking hormone replacement therapy have a smaller increase in systolic blood pressure over time than
those not taking this therapy. This difference is intensified at older ages.
Sawka AM, Young WF, Thompson GB, et al.
Resolution of hypertension after adrenalectomy for primary aldosteronism is independently associated with a lack of family
history of hypertension and preoperative use of two or fewer antihypertensive agents.
Jafar TH, Schmid CH, Landa M, et al.
Antihypertensive regimens that include angiotensin-converting enzyme (ACE) inhibitors are more effective than regimens without
these drugs in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by
factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria.
Angiotensin-converting enzyme inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and
proteinuria and, possibly, those without proteinuria.
Schrier RW, Estacio RO
Jafar and colleagues' meta-analysis in this issue contributes evidence on strategies to slow nondiabetic renal progression
by use of angiotensin-converting enzyme inhibitors. However, the authors' conclusion, although perhaps correct, must be considered
tentative.
Rogers MA, Small D, Buchan DA, et al.
Use of a telecommunication service that consisted of automatic transmission of blood pressure data over telephone lines and
weekly electronic transmission of reports to physicians reduced the mean arterial pressure of patients with established essential
hypertension.
Stevens VJ, Obarzanek E, Cook NR, et al.
Even modest weight loss can lead to clinically significant long-term reductions in blood pressure and reduced risk for hypertension.
Pickering TG
As highlighted in Stevens and colleagues' article in this issue, there is no simple solution to the problem of obesity. Dealing
with it will require action at several levels: policy, education (of both the public and heath care providers), and incorporation
of a team approach to patient care that involves dietitians and health educators.
Lester SJ, Baggott M, Welm S, et al.
Modest oral doses of MDMA (the psychoactive stimulant commonly known as ecstasy) increase heart rate, blood pressure, and
myocardial oxygen consumption in a magnitude similar to that seen with dobutamine, 20 to 40 µg/kg per minute. Unlike dobutamine,
MDMA has no measurable inotropic effects.
Mi J, Law C, Zhang K, et al.
This study found that infants with low birthweight were at increased risk for developing elements of the insulin resistance
syndrome in adult life. This increase in risk was associated with mothers' low body mass index during pregnancy and seems
independent of the offspring's high adult body mass index.
Smulyan H, Safar ME
Normal or low diastolic blood pressure is the characteristic that makes isolated systolic hypertension clinically different
from essential hypertension. The elevated systolic pressure requires therapy, but large reductions in cuff diastolic pressures,
especially in patients with known coronary artery disease, should probably be avoided.
Liu JE, Roman MJ, Pini R, et al.
“White coat normotension”—elevated ambulatory blood pressure but normal office blood pressure—is associated with left ventricular
mass and carotid wall thickness similar to those in patients with sustained hypertension. The association of white coat normotension
with prognostically important target organ damage may partly explain the ability of high normal left ventricular mass and
high normal clinical blood pressure to predict subsequent hypertension in patients with clinical normotension.
Ghose RP, Hall PM, Bravo EL
Medical management of aldosterone-producing adenomas is a viable option for controlling blood pressure and serum potassium
levels.
Hayashi T, Tsumura K, Suematsu C, et al.
Walking to work and other types of physical activity decreased the risk for hypertension in Japanese men. These findings suggest
that regular exercise can slow the development of hypertension.
McLaughlin VV, Genthner DE, Panella MM, et al.
Intravenous prostacyclin may be effective in the treatment of certain types of secondary pulmonary hypertension.
Lipid disorders (53 articles)
Sharma M, Ansari MT, Abou-Setta AM, et al.
This systematic review of 102 studies compared the benefits and harms of high-dose statin monotherapy with those of combination
therapy in adults at high risk for coronary disease. Limited evidence suggested that combinations of lipid-lowering agents
did not improve clinical outcomes more than high-dose statin monotherapy.
Angell SY, Silver LD, Goldstein GP, et al.
Cholesterol control efforts have focused on consumer education and medical treatment. An approach is to change the makeup
of food—a route the New York City Department of Health and Mental Hygiene took when it restricted artificial trans fat in
restaurants. Preliminary analyses suggest that replacement of artificial trans fat has resulted in products with more healthful
fatty acid profiles. Angell and colleagues describe the rationale and process that led to this ruling and the Department's
experience in implementing it.
Safer Fats for Healthier Hearts: The Case for Eliminating Dietary Artificial Trans Fat Intake (2009)
Gerberding JL
In this issue, Angell and colleagues describe the New York City Department of Health and Mental Hygiene's trans fat restriction
program. The successful intervention raises a key policy question: Is it time to institute broader federal government efforts
to assure that people in all communities experience the potential health benefits of safer dietary fats? To answer this question,
we must assess the evidence of health benefits, the feasibility of national elimination, and the need for federal government
intervention.
Becker DJ, Gordon RY, Halbert SC, et al.
Red yeast rice is a dietary supplement that can decrease low-density lipoprotein (LDL) cholesterol levels and could be a treatment
option for patients with statin-associated myopathy. Investigators randomly assigned 62 patients with dyslipidemia and a history
of intolerance to at least 1 statin to receive red yeast rice, 1800 mg twice daily, or placebo. After 12 and 24 weeks, LDL
and total cholesterol levels improved more in the red yeast rice group than in the placebo group. Pain, creatinine phosphokinase,
and liver enzyme levels did not differ between the groups.
Joy TR, Hegele RA
Statin-related myopathy is a clinically important cause of statin intolerance and discontinuation. In this overview, Joy and
Hegele cover the pathophysiology, epidemiology, clinical features, and management of statin-related myopathy. They discuss
options for managing statin myopathy, including statin switching, nondaily dosing regimens, nonstatin alternatives, and coenzyme
Q10 supplementation.
Phillips PS
Two articles in this issue apply the best available methodologies to statin myopathy. Joy and Hegele's systematic review of
statin myopathy emphasizes findings from randomized, controlled trials. Becker and colleagues' randomized, controlled trial
suggests that red yeast rice, a nutraceutical form of statin, may be safe for patients who cannot tolerate statins. Both articles
give priority to controlled trials and deemphasize anecdote.
McWilliams JM, Meara E, Zaslavsky AM, et al.
Improving the quality of care and expanding insurance coverage can reduce differences in outcomes experienced by different
sociodemographic groups. McWilliams and colleagues used blood pressure, hemoglobin A1c, and total cholesterol measurements
obtained from participants in a national survey to measure changes in chronic disease control. Over 8 years, disease control
improved but gaps between white and nonwhite patients did not change. The gaps narrowed after age 65 years, when universal
Medicare insurance begins.
Schwartz LM, Woloshin S, Welch HG
Direct-to-consumer drug advertisements do not provide standardized information about the benefits and harms of the drugs.
Schwartz and coworkers tested whether adding a “drug facts box” to consumer-directed drug advertisements would improve consumer
knowledge and judgment. The box contained a comparison of outcomes that might occur with 2 drugs. In a randomized experiment,
consumers who were shown advertisements that included the box knew more about drug benefits and side effects than consumers
shown the advertisements without the box.
U.S. Preventive Services Task Force
The U.S. Preventive Services Task Force reaffirms its 2003 recommendation on counseling to prevent tobacco use. Clinicians
should ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products (grade
A recommendation). For pregnant women, clinicians should ask about tobacco use and provide augmented, pregnancy-tailored counseling
for those who smoke (grade A recommendation).
Avorn J, Shrank WH
In this issue, Schwartz and colleagues found that the quality of information transfer with conventional direct-to-consumer
drug advertisements was inferior to their own coherently designed drug boxes. Their studies have drawn our attention to the
need for more creative thinking about how to communicate drug benefits and risks effectively and the need to study possible
solutions in a methodologically rigorous manner.
Ip S, Lichtenstein AH, Chung M, et al.
Low-density lipoprotein (LDL) subfractions differ in size and may differ in the strength of association with cardiovascular
disease. The authors reviewed 24 published studies that reported relationships between LDL subfractions and cardiovascular
outcomes. Higher LDL particle concentration is consistently associated with increased risk for cardiovascular disease, independent
of other lipid measurements. The LDL particle size is generally not associated with cardiovascular disease. Routine use of
clinically available LDL subfraction tests to estimate cardiovascular disease risk is premature.
Silverberg MJ, Leyden W, Hurley L, et al.
Silverberg and colleagues compared the effectiveness and safety of lipid-lowering therapy in 829 HIV-infected patients receiving
antiretroviral therapy and 6941 patients without HIV infection. Reductions in low-density lipoprotein cholesterol and triglyceride
levels were smaller in HIV-infected patients than in uninfected patients. The effect was larger for the triglyceride response
to gemfibrazole than for the low-density lipoprotein cholesterol response to statins. Dyslipidemia is more difficult to treat
in patients with HIV infection than in the general population.
Atlas SJ, Grant RW, Ferris TG, et al.
The effect of “connectedness” (whether a patient goes to a particular physician or practice) on measures of clinical performance
is unknown. Using a recently validated measure, the authors found that patients who were more connected to a primary care
physician were more likely to receive recommended prevention services. This measure of patient–physician connectedness may
be a good indicator of adherence to the patient-centered medical home model of primary care.
Pletcher MJ, Lazar L, Bibbins-Domingo K, et al.
Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk. The authors used a probabilistic
model to show that the Adult Treatment Panel III guidelines, which recommend treatment based on cholesterol level and estimated
CHD risk, are reasonably cost-effective if statins cost about $1.50 to $2.20 per pill. At costs lower than $0.10 per pill,
treating everyone with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL), regardless of other
CHD risk factors, could be a better strategy.
Wong JB, Mulrow C, Sox HC
Pletcher and colleagues' cost-effectiveness analysis in this issue found that some statin strategies had acceptable economic
value in preventing CHD. Wong and associates provide a brief introduction to cost-effectiveness analyses and discuss whether
the U.S. federal government should use them to inform its policy decisions about health care.
El Harchaoui K, Arsenault BJ, Franssen R, et al.
High-density lipoprotein (HDL) particles are heterogeneous in size and composition. This nested case–control study found that
both HDL size and particle concentration were associated with risk for coronary artery disease (CAD). Larger size was strongly
associated with risk factors of the metabolic syndrome, such as triglyceride and apolipoprotein B levels. Adjustment for those
factors weakened the association, suggesting that they mediate the effect of HDL particle size on CAD risk. On the other hand,
HDL particle concentration seems to be an independent predictor of CAD risk.
Bryson CL, Au DH, Sun H, et al.
Alcohol misuse may be a risk factor for failing to adhere to medication regimens. Bryson and colleagues found a graded, linear
decrease in adherence to statins and hypertension medications with increasing levels of alcohol misuse among patients at 7
Veterans Affairs primary care clinics. At 1 year, the percentage of patients adherent to statins was lower in the 2 highest
alcohol misuse groups than in nondrinkers. Similarly, the percentage of patients adherent to antihypertensive regimens was
lower in the 3 highest alcohol misuse groups than in nondrinkers.
Golin C
In this issue, Bryson and colleagues report a direct, dose-related association between alcohol misuse and medication nonadherence
for antihypertensives and statins but not oral hypoglycemics. This well-designed, nicely executed prospective study is a major
step forward in understanding the relationship between substance abuse and medication nonadherence, and as many classic studies
do, it raises more questions than it answers.
Wilper AP, Woolhandler S, Lasser KE, et al.
Some claim that U.S. persons without health insurance do not typically have ongoing health care needs. Using data from the
National Health and Nutrition Examination Survey, Wilper and associates estimate that more than 11 million working-age Americans
without health insurance have cardiovascular disease, hypertension, diabetes, dyslipidemia, obstructive lung disease, or previous
cancer. Chronically ill patients without insurance were less likely than those with coverage to visit a health professional
and were more likely to identify an emergency department as their standard site of care.
Vickers AJ, Basch E, Kattan MW
Cut-points for defining a diagnosis have substantial limitations. Risk prediction, in which patient risk factors are combined
into a single model and the results used in shared decision making about treatments, may offer an alternative to diagnosis.
The authors compare the diagnostic and risk prediction approaches and attempt to identify for which types of medical problem
each is best suited.
Chin MH
The article by Wilper and colleagues in this issue tells us that chronic disease is rampant among uninsured persons. This
editorial identifies opportunities for policy reforms and outlines what every practice, hospital, and health plan can do now
to improve outcomes for vulnerable patients with chronic disease.
Pletcher MJ, Bibbins-Domingo K, Lewis CE, et al.
In their prospective cohort study, Pletcher and colleagues found that prehypertension before age 35 years, especially systolic
prehypertension, showed a graded association with coronary calcium later in life. This association remained strong after adjustment
for differences in blood pressure elevation after age 35 years and other coronary risk factors and participant characteristics.
Glasziou PP, Irwig L, Heritier S, et al.
Visit-to-visit changes in the serum cholesterol level while monitoring the effects of cholesterol-lowering medication are
due to random variation and to real changes over time. The authors analyzed data from a trial that compared pravastatin with
placebo in patients with coronary heart disease. Most of the visit-to-visit change in serum cholesterol was due to random
variation, which should not trigger dose adjustment. To increase the contribution of real long-term change, the authors propose
monitoring patients receiving stable cholesterol-lowering treatment every 3 to 5 years rather than every few months or annually.
Tirosh A, Rudich A, Shochat T, et al.
Triglyceride levels measured at a single time point may not reliably indicate risk for coronary heart disease (CHD). Tirosh
and colleagues measured triglyceride levels and performed stress electrocardiography 5 years apart on 13 593 young Israeli
male career soldiers and did coronary angiography if the stress test was abnormal. They identified 158 new cases of incident
CHD. The changes in triglycerides between the 2 measurements strongly predicted incident CHD after adjustment for CHD risk
factors and lifestyle variables. A decrease in initially elevated triglyceride levels was associated with a decrease in CHD
risk, and CHD risk was lowest when triglyceride levels at both time points were low.
Criqui MH
In this issue, Tirosh and colleagues examined the association of triglyceride levels with incident CHD in 13 953 men age 26
to 45 years. Their results are striking: Triglycerides were strongly associated with CHD risk. The results complement the
growing body of evidence that triglycerides have an independent effect on the incidence of CHD and emphasize the importance
of “rediscovering” triglycerides as a cardiovascular risk factor.
Wenger NK, Lewis SJ, Herrington DM, et al.
The benefits of intensive lipid-lowering treatment for elderly persons with heart disease are largely unknown. In a secondary
analysis of a randomized trial, Wenger and associates examined outcomes of 3809 adults age 65 years or older with coronary
heart disease after 4.9 years of receiving atorvastatin, 80 mg/d or 10 mg/d. Patients achieved average low-density lipoprotein
cholesterol levels of approximately 1.81 mmol/L (70 mg/dL) and 2.59 mmol/L (100 mg/dL), respectively. The absolute reduction
in risk for serious cardiovascular events was 2% in patients who received 80 mg of atorvastatin relative to those who received
10 mg.
van der Steeg WA, Boekholdt SM, Stein EA, et al.
The apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio is a strong risk factor for atherosclerotic cardiovascular disease.
The researchers performed a case–control analysis of persons 45 to 79 years of age. They found that the apo B–apo A-I ratio
is no better than conventional measures of risk prediction in distinguishing between people who later developed atherosclerotic
cardiovascular disease and people who did not.
Berkwits M, Guallar E
van der Steeg and colleagues show that the apolipoprotein B–apolipoprotein A-I ratio does not improve overall prediction of
coronary artery disease in a general population. In fact, newer risk factors rarely add much to predictions that use established
risk measures, which is why clinicians should require rigorous proof of added value of any new risk factor before recommending
widespread testing for it in routine clinical practice.
Estruch R, Martínez-González MÁ, Corella D, et al.
The authors assigned 772 participants to a low-fat diet or to 1 of 2 Mediterranean diets that emphasized consumption of either
olive oil or nuts. They then measured changes in body weight, blood pressure, lipid profile, glucose levels, and inflammatory
molecules. Compared with the low-fat diet, the 2 Mediterranean diets had a beneficial effect on most of these outcomes at
3 months.
Rodondi N, Peng T, Karter AJ, et al.
The authors assessed the care of 253 238 adults who had poorly controlled hypertension, dyslipidemia, or diabetes. The objective
was to determine whether poor control triggered changes in treatment and whether these changes were successful. The authors
found that many patients with poorly controlled systolic blood pressure (64%), diastolic blood pressure (71%), low-density
lipoprotein cholesterol level (56%), or diabetes (66%) did have clinically appropriate changes in their treatment.
McGavock JM, Victor RG, Unger RH, et al.
Obesity is a major risk factor for heart disease, and physicians must be aware of emerging research of novel mechanisms through
which adiposity adversely affects the heart. The purpose of this review is to highlight a novel mechanism by which obesity
causes heart disease, whereby excessive lipid accumulation within the myocardium causes left ventricular remodeling and dilated
cardiomyopathy.
Perlin JB, Pogach LM
Clinical trials have shown that better control of glycemia, blood pressure, and low-density lipoprotein cholesterol level
leads to better outcomes of diabetes, hypertension, and dyslipidemia. Guidelines have incorporated new evidence very quickly,
and national public education programs and professional societies have disseminated these evidence-based recommendations to
the public and to professionals. Has this unprecedented momentum created by publicizing evidence and measuring outcomes resulted
in translation of evidence into practice? And if not, why? Two studies in this issue provide us with a progress report from
both the public health and managed health care plan perspectives.
van Wijk JP, de Koning EJ, Cabezas MC, et al.
The authors compared the effects of the peroxisome proliferator–activated receptor-γ agonist rosiglitazone (8 mg/d) and metformin
(2 g/d) for treating HIV lipodystrophy. Their findings emphasize the importance of tailoring the choice of medication to the
needs of the individual patient. Although rosiglitazone may partly correct lipoatrophy, metformin reduces cardiovascular risk
factors by reducing visceral fat accumulation and improving fasting lipid profile and endothelial function.
Choudhry NK, Avorn J
The British government recently decided to permit over-the-counter sale of a statin. The U.S. Food and Drug Administration
decided not to allow it. Many questions remain about statin effectiveness at the lower doses in over-the-counter use, the
ability of patients to appropriately self-select to take statins, and the social and economic implications of this approach
to disease prevention.
Tonelli M, Moy L, Sacks FM, et al.
Pravastatin is effective and appears safe for secondary prevention of cardiovascular events in persons with mild chronic renal
insufficiency. Since statins may be underused in this setting, physicians should consider prescribing them for patients with
chronic renal insufficiency and known coronary disease.
Phillips PS, Haas RH, Bannykh S, et al.
Some patients who develop muscle symptoms while receiving statin therapy have demonstrable weakness and histopathologic findings
of myopathy despite normal serum creatine kinase levels. These findings resolve after discontinuation of statin therapy and
recur with resumption of therapy.
Grundy SM
Phillips and colleagues' report in this issue on low-grade myopathy associated with statin use in a few patients highlights
the need for further study on the actions of statins on muscle metabolism and structure.
Kivipelto M, Helkala E, Laakso MP, et al.
The association between the apolipoprotein E (apoE) ε4 allele and Alzheimer disease does not seem to be mediated by vascular
factors. The apoE ε4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent
risk factors for Alzheimer disease. The risk for Alzheimer disease from treatable factors—elevated total cholesterol level
and blood pressure—appears to be greater than that from the apoE ε4 allele.
Rodondi N, Darioli R, Ramelet A, et al.
Persons who develop hypertriglyceridemia during isotretinoin therapy for acne, as well as their parents, are at increased
risk for future hyperlipidemia and the metabolic syndrome.
Fuentes F, López-Miranda J, Sánchez E, et al.
In hypercholesterolemic men, diets low in fat (especially saturated fat) and diets rich in monounsaturated fats improve endothelial
function.
Hunt D, Young P, Simes J, et al.
In older patients with coronary heart disease and average or moderately elevated cholesterol levels, pravastatin therapy reduced
the risk for all major cardiovascular events and all-cause mortality. Since older patients are at higher risk than younger
patients for these events, the absolute benefit of treatment is significantly greater in older patients.
Binder EF, Williams DB, Schechtman KB, et al.
In women 75 years of age or older, hormone replacement therapy improved the lipoprotein profile to the extent observed previously
in younger postmenopausal women. Further studies are needed to evaluate whether these effects protect against coronary heart
disease in this population.
Jacobson TA
The robust findings of trials examining lipid-lowering drug therapy do not necessarily justify targeting low-density lipoprotein
cholesterol to its lowest possible level, and the argument expressed by the phrase “the lower the better” is clearly not evidence
based.
Stevinson C, Pittler MH, Ernst E
The available data suggest that garlic is superior to placebo in reducing total cholesterol levels. However, the size of the
effect is modest, and its robustness is debatable. The use of garlic for hypercholesterolemia is therefore of questionable
value.
Arioglu E, Duncan-Morin J, Sebring N, et al.
Troglitazone therapy improved metabolic control and increased body fat in patients with lipoatrophic diabetes. The substantial
benefits of troglitazone must be balanced against the risk for hepatotoxicity, which can occur relatively late in the treatment
course.
Ganda OP
In this issue, Arioglu and colleagues report that troglitazone led to better metabolic control and increased body fat in patients
with lipoatrophic diabetes. What are the mechanisms of the efficacy of troglitazone in these patients?
Prosser LA, Stinnett AA, Goldman PA, et al.
Cost-effectiveness of cholesterol-lowering treatments was found to vary significantly when adjusted for sex, age, and the
presence or absence of additional risk factors. Primary prevention with a step I diet seems to be cost-effective for most
risk subgroups but not for otherwise healthy young women. Primary prevention with a statin may not be cost-effective for younger
men and women with few risk factors, given the option of secondary prevention and of primary prevention in older age ranges.
Garber AM
The studies by Ganz and Prosser and their colleagues in this issue evaluate statin therapy in clinically important populations
that were not studied adequately in randomized trials. These studies reinforce the message that lipid management for secondary
prevention should be a high priority, regardless of whether the patient is female or male, young or old.
Zambón D, Sabaté J, Muñoz S, et al.
Previous studies have reported that walnuts decrease serum cholesterol levels in young men. In this study of men and women
with polygenic hypercholesterolemia, substituting walnuts for part of the monounsaturated fat in a cholesterol-lowering Mediterranean
diet further reduced total fat and low-density lipoprotein cholesterol levels.
Cole CR, Foody JM, Blackstone EH, et al.
Abnormal heart rate recovery after symptom-limited exercise is an important prognostic factor. This study found that even
after submaximal exercise in patients in good cardiovascular health, abnormal heart rate recovery predicts death.
Mi J, Law C, Zhang K, et al.
This study found that infants with low birthweight were at increased risk for developing elements of the insulin resistance
syndrome in adult life. This increase in risk was associated with mothers' low body mass index during pregnancy and seems
independent of the offspring's high adult body mass index.
Balasekaran R, Porter JL, Santa Ana CA, et al.
Consumption of olestra can cause false-positive results on tests for steatorrhea and may therefore lead to an erroneous diagnosis
of the malabsorption syndrome.
Bellentani S, Saccoccio G, Masutti F, et al.
Steatosis frequently occurs in healthy persons and is almost always present in obese persons who drink more than 60 g of alcohol
per day. This condition is more strongly associated with obesity than with heavy drinking.
Myocardial disease (3 articles)
Lim E, Brown A, Helmy A, et al.
The authors evaluated the contribution of individual end points to composite outcomes in 304 recent cardiovascular trials.
In these trials, composite outcomes commonly comprised 3 or 4 individual end points ranging in significance from angina to
death. Because individual outcomes do not necessarily occur at the same rate, readers should not assume that the overall estimate
of effect for a composite measure applies equally to each of its component outcomes.
Viotti R, Vigliano C, Lococo B, et al.
The authors assigned alternate patients with chronic Chagas disease to treatment with benznidazole or to no treatment and
followed them for a mean of approximately 10 years. The patients had no evidence of cardiac disease at baseline. Compared
with no treatment, benznidazole was associated with reduced progression to advanced stages of cardiac disease: 4.2% in the
treated group versus 14.1% in the untreated group. On the basis of these findings, a randomized, controlled trial is warranted.
Dias JC
In this issue, Viotti and colleagues evaluated benznidazole in patients with chronic Chagas disease. The study was an advance
over previous work because of the large number of patients, systematic assignment to study groups, and standardization of
drug dose. Fewer treated patients had progression of cardiomyopathy, and more patients became serologically nonreactive. These
results are new, positive evidence that specific treatment of chronic Chagas disease can ameliorate the most important effect
of the infection: evolution to severe chronic cardiomyopathy.
Pericardial disease (1 articles)
Ling LH, Oh JK, Breen JF, et al.
In contrast to common belief, pericardial calcification was noted to be a frequent finding in patients with constrictive pericarditis.
It is often associated with idiopathic disease and other markers of disease chronicity and is an independent predictor of
increased perioperative mortality rates.
Sudden death (4 articles)
Ezekowitz JA, Rowe BH, Dryden DM, et al.
This systematic review summarizes the evidence on the benefits and harms of implantable cardioverter defibrillators (ICDs)
in adult patients with left ventricular systolic dysfunction. The ICDs reduced all-cause mortality by 20% (95% CI, 10% to
29%) in 12 randomized trials and were associated with a 46% reduction (CI, 32% to 57%) in 76 observational studies. Death
associated with ICD implantation occurred in 1.2% (CI, 0.9% to 1.5%) of procedures.
Eckart RE, Scoville SL, Campbell CL, et al.
Anomalous origin of the left coronary artery and myocarditis are the leading identifiable causes of sudden death among military
recruits. More than one third of sudden deaths remain unexplained after detailed medical investigation and autopsy.
Balady GJ
In this issue, Eckart and colleagues show that cardiovascular conditions account for most sudden deaths in basic military
training. These conditions are very difficult to detect with noninvasive tests in a low-risk population. A history of chest
pain, syncope, or unusual dyspnea before or during basic training should alert physicians to military recruits at relatively
high risk.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Syncope (4 articles)
Bryce M, Spielman SR, Greenspan AM, et al.
The authors review the current clinical experience and future trends in cardiac pacing in four specific areas: 1) hypertrophic
cardiomyopathy, 2) dilated cardiomyopathy and heart failure, 3) neurocardiogenic syncope, and 4) the prevention of atrial
fibrillation.
Fenton AM, Hammill SC, Rea RF, et al.
Vasovagal syncope is a common, difficult to manage clinical syndrome. Advancements are being made in laboratory investigations
of its triggering mechanisms. Randomized, controlled trials of pharmacologic and nonpharmacologic interventions are needed.
Maurer MS, Karmally W, Rivadeneira H, et al.
Meal ingestion and head-up tilt-table testing are associated with increasing occurrences of symptomatic hypotension; 22% of
functionally independent elderly persons in this study had symptomatic hypotension after eating a meal and undergoing tilt-table
testing.
Zimetbaum PJ, Josephson ME
Ambulatory electrocardiographic monitors, particularly transtelephonic continuous-loop event recorders, aid in the diagnosis
of symptomatic arrhythmias. These devices are also useful for monitoring the effectiveness and safety of antiarrhythmic medications.
Valvular heart disease (7 articles)
Avierinos J, Inamo J, Grigioni F, et al.
Mitral valve prolapse is more common in women than in men, but men more frequently undergo surgery for severe mitral regurgitation.
Avierinos and colleagues sought to determine the reason for these sex-specific differences. Among 4461 women and 3768 men
with mitral valve prolapse diagnosed on echocardiography, women had severe regurgitation less frequently. However, women with
severe regurgitation were less likely to have surgery and had worse survival than men. Among patients who had surgery, survival
did not differ between men and women.
Lim E, Brown A, Helmy A, et al.
The authors evaluated the contribution of individual end points to composite outcomes in 304 recent cardiovascular trials.
In these trials, composite outcomes commonly comprised 3 or 4 individual end points ranging in significance from angina to
death. Because individual outcomes do not necessarily occur at the same rate, readers should not assume that the overall estimate
of effect for a composite measure applies equally to each of its component outcomes.
O'Donnell MJ, Kearon C, Johnson J, et al.
When patients on long-term warfarin therapy require surgery, low-molecular-weight heparins are often used as bridging therapy
between full anticoagulation with warfarin and no anticoagulation during surgery. Because of safety concerns, the authors
measured heparin activity after an evening dose of low-molecular-weight heparin. They found that two thirds of 94 patients—who
received their last dose of enoxaparin 14 hours before surgery—had elevated heparin levels when surgery was scheduled to begin.
They suggest a longer interval between the last dose of heparin and the time of surgery.
Babu AN, Kymes SM, Carpenter Fryer SM
For more than a century, eponymous signs of aortic regurgitation have occupied a prominent place in medical textbooks. The
evidence that these signs are accurate indicators of aortic regurgitation is weak. To sustain the place of these signs in
the traditions of clinical diagnosis, we need better evidence about their accuracy.
Mast ST, Jollis JG, Ryan T, et al.
In 50 patients who had developed at least mild mitral regurgitation or aortic regurgitation after exposure to fenfluramines,
serial echocardiography showed that valvular regurgitation improved or remained stable in most patients after therapy was
discontinued. Worsening of valvular regurgitation was uncommon.
Weissman NJ, Panza JA, Tighe JF, et al.
The findings of this study suggest that after dexfenfluramine therapy is taken for 2 to 3 months and then discontinued, development
or progression of any valvular regurgitation over the following year is unlikely. Echocardiographic evidence indicates that
aortic regurgitation regresses in some previously treated patients.
St John Sutton M
The studies by Weissman and Mast and their colleagues in this issue clarify two important issues concerning anorexogen-induced
valvulopathy: that progressive valvulopathy is uncommon and that valvular regurgitation may spontaneously resolve in some
patients after cessation of anorexogen therapy.
Vascular disease (122 articles)
Roy P, Durieux P, Gillaizeau F, et al.
Roy and colleagues developed a program to guide diagnosis of pulmonary embolism for use on a mobile, handheld device. The
investigators randomly assigned 20 emergency departments in France to activation of either the decision-support system on
the devices or posters and pocket cards that showed diagnostic strategies. The device-based program improved appropriate testing
of patients with suspected pulmonary embolism more than paper guidelines alone.
Rothschild JM
In this issue, Roy and colleagues studied the use of a handheld clinical decision-support system to improve the diagnosis
of pulmonary embolism in 20 French emergency departments. Handheld computers could provide a key resource that improves access
to decision-support tools and leads to better management decisions. Roy and colleagues' work represents a promising start
toward this essential goal.
Rosove MH, Grody WW
In 2007, the U.S. Food and Drug Administration modified warfarin prescribing information to suggest, but not to mandate, pharmacogenetic
testing to guide dosing. Rosove and Grody ask whether we should now be applying warfarin pharmacogenetics routinely to clinical
practice. They discuss that results predict only one third of all dosing variation, the value of testing in reducing bleeding
and thrombosis rates remains unproved, and cost-effectiveness is not established.
Murad SD, Plessier A, Hernandez-Guerra M, et al.
Darwish Murad and colleagues describe 163 patients with newly diagnosed hepatic venous outflow obstruction (the Budd–Chiari
syndrome). Most of the patients had identifiable risk factors for clot, most commonly myeloproliferative disorders. About
half were managed noninvasively with diuretics and anticoagulation, while half were managed with transjugular shunting, recanalization,
and liver transplantation. Survival rates were good and were better than previously described.
Chandra D, Parisini E, Mozaffarian D
The body of evidence regarding associations between long-distance travel and risk for venous thromboembolism (VTE) is heterogeneous
and inconclusive. Chandra and colleagues sought to clarify the risk for VTE in travelers and identify reasons for the contradictory
results of previous studies. Among 14 eligible studies, the pooled relative risk for VTE was 2.0 (95% CI, 1.5 to 2.7). After
6 case–control studies were eliminated, the relative risk was 2.8 (CI, 2.2 to 3.7). The excluded studies had control participants
with a different risk for VTE than the source population for the case patients.
Vandenbroucke JP, Cannegieter SC, Rosendaal FR
In this issue, Chandra and colleagues present a meta-analysis that is based on case–control studies. This editorial discusses
the selection of controls for case–control studies, using Chandra and colleagues' study as an example.
Chan W, Lee A, Spencer FA, et al.
The clinical predictors of deep venous thrombosis (DVT) are well known in the general population but not in pregnant women.
Over 7 years, clinical thrombosis experts enrolled 194 pregnant women with suspected DVT in 5 Canadian centers, evaluated
them, and did leg vein compression ultrasonography. Seventeen (8.8%) women had DVT. All had at least 1 of the following clinical
predictors: left leg symptoms, difference in calf circumference of 2 cm or more, and presentation during the first trimester
of pregnancy. These 3 variables may improve the accuracy of DVT diagnosis in pregnancy.
Mann JF, Schmieder RE, Dyal L, et al.
Mann and colleagues compared the long-term renal effects of telmisartan and placebo in 5927 adults with vascular disease but
without macroalbuminuria. They used a composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated
glomerular filtration rate (GFR), and changes in albuminuria. Patients receiving telmisartan had the same composite outcome
results as those receiving placebo. Albuminuria increased less with telmisartan than with placebo, whereas estimated GFR decreased
more with telmisartan. On balance, telmisartan had the same effects as placebo on major renal outcomes.
Prandoni P, Prins MH, Lensing AW, et al.
Prandoni and colleagues randomly assigned 538 patients with proximal deep venous thrombosis (DVT) who had completed 3 months
of anticoagulation to receive anticoagulation for a fixed duration or for a flexible duration that depended on results of
ultrasonography. During follow-up, 17% versus 12% of the fixed-duration therapy and ultrasonography-guided groups, respectively,
had recurrent thromboembolism, whereas 0.7% versus 1.5% had major bleeding events. Individualizing the duration of anticoagulation
therapy for DVT may reduce the rate of recurrent venous thromboembolism (VTE).
Goldhaber SZ
In this issue, Prandoni and coworkers report a lower rate of recurrent VTE when anticoagulation was continued until the veins
had recanalized. However, the results are not sufficiently definitive to justify changing medical practice. For now, the most
practical strategy is to follow current guidelines: time-limited anticoagulation for provoked and indefinite therapy for idiopathic
VTE.
Crowther MA, Ageno W, Garcia D, et al.
Crowther and colleagues measured the effect of oral vitamin K or placebo on prevention of bleeding in 724 patients with international
normalized ratios (INRs) of 4.5 to 10.0 who were receiving warfarin. They found that 15.8% of vitamin K recipients and 16.3%
of placebo recipients had at least 1 bleeding complication; 2.5% and 1.1%, respectively, had major bleeding events; and 1.1%
and 0.8% experienced thromboembolism. Low-dose oral vitamin K lowered the INR but did not reduce bleeding in overanticoagulated
patients.
Büller HR, ten Cate-Hoek AJ, Hoes AW, et al.
Office-based methods to rule out suspected deep venous thrombosis (DVT) are needed to reduce the number of avoidable referrals
for ultrasonography. Büller and colleagues conducted a management trial of a prediction rule that uses clinical findings and
a point-of-care d-dimer test to identify patients at very low risk for suspected DVT. Among 1028 patients from approximately
300 primary care practices, nearly half (49%) were at low enough risk to withhold imaging tests and anticoagulation treatment.
In 3 months, 1.4% had venous thromboembolism.
Reilly BM, Evans AT
In this issue, Büller and colleagues present the results of a study designed to reduce unnecessary diagnostic testing (ultrasonography)
for primary care patients with suspected DVT. We are cautiously optimistic that the use of the AMUSE rule can improve clinicians'
decisions by reducing unnecessary care.
Kahn SR, Shrier I, Julian JA, et al.
Chronic leg symptoms after deep venous thrombosis (DVT) (the postthrombotic syndrome) are common but difficult to predict.
By using a standardized scale, Kahn and coworkers evaluated leg symptoms in 387 patients for 2 years after DVT. Mild, moderate,
and severe postthrombotic syndrome occurred in 30%, 10%, and 3% of patients, respectively, at all study intervals, but severity
fluctuated over time in many patients. Age, previous DVT, and severity at 1 month were the best predictors of long-term severity.
Verhovsek M, Douketis JD, Yi Q, et al.
A test to identify persons at low risk for recurrent venous thromboembolism (VTE) could help with the decision to continue
or stop anticoagulant treatment. This systematic review identified 7 studies that measured d-dimer 3 to 6 weeks after stopping
treatment for a first unprovoked VTE. Recurrence rates within approximately 2 years were 8.9% and 3.5% in patients with a
positive and negative d-dimer test result, respectively.
Carrier M, Le Gal G, Wells PS, et al.
In a systematic review, Carrier and colleagues summarized 36 studies of the prevalence of previously undiagnosed cancer at
diagnosis and various time points after unprovoked venous thromboembolism (VTE). They also measured the number of cases detected
by limited and extensive occult cancer screening at the time of VTE diagnosis. The prevalence of occult cancer was 6.1% at
VTE diagnosis and increased to 10.0% 12 months after VTE diagnosis. Extensive screening increased the proportion of cases
that were detected at baseline (from 49.4% to 69.7% with limited screening) but still missed many cases.
Ornstein DL
In this issue, Carrier and colleagues report the period prevalence of cancer in patients with VTE at 3 time points and confirm
that unprovoked VTE is more commonly associated with cancer than provoked VTE, and that extensive screening finds more cases
of cancer at baseline than usual care. These findings demonstrate that if we look hard enough, we can find hidden cancer in
a sizeable proportion of patients with idiopathic VTE. However, the search for cancer is expensive, and we do not know whether
finding it changes survival.
Camporese G, Bernardi E, Prandoni P, et al.
In this trial, 1761 adults who had knee arthroscopy were randomly assigned to receive 7 or 14 days of low-molecular-weight
heparin (LMWH) or to wear a full-length graduated compression stocking on the operated leg for 1 week. Fewer than 1% of the
patients in any group had significant postsurgical bleeding complications. Fewer patients in the 7-day LMWH group experienced
a composite outcome of deep venous thrombosis, pulmonary embolism, or death.
Hull RD
In this issue, Camporese and colleagues report the findings of a large randomized trial of LMWH prophylaxis in adults undergoing
knee arthroscopy. The study adds substantive information on the efficacy and safety of LMWH prophylaxis for this indication,
and the findings support using LMWH to prevent venous thromboembolism in knee arthroscopy patients undergoing meniscectomy.
Vidula H, Tian L, Liu K, et al.
Changes in thrombogenic and inflammatory biomarkers might predict near-term cardiovascular disease events. The authors measured
d-dimer, amyloid A protein, and C-reactive protein annually for 3.4 years in 377 patients with peripheral arterial disease.
Elevated levels were associated with all-cause and cardiovascular disease–related deaths occurring 1 to 2 years after their
measurement but not with deaths occurring after 2 years. A similar pattern occurred after increases in these levels: increased
risk for death for a few years but not later. This observation requires confirmation in a larger sample.
U.S. Preventive Services Task Force
In this update to a previous recommendation, the U.S. Preventive Services Task Force recommends that clinicians not screen
for asymptomatic carotid artery stenosis in the general adult population. This recommendation applies to adults without neurologic
signs or symptoms or a history of transient ischemic attacks or stroke.
Wolff T, Guirguis-Blake J, Miller T, et al.
This evidence update supports the U.S. Preventive Services Task Force recommendations on screening for carotid artery stenosis.
Douketis JD, Gu CS, Schulman S, et al.
The decision to discontinue anticoagulation for venous thromboembolism (VTE) depends in part on the risk for a fatal recurrence
after stopping. In cohorts from 2 source studies that monitored 2052 patients for an average of 5 years after discontinuing
anticoagulation for a first episode of VTE, the annual risk for any fatal pulmonary embolism was 0.43 event per 100 patient-years,
and the risk for definite or probable fatal recurrent VTE was 0.17 event per 100 patient-years. Decision makers must take
these rates into account if they decide to stop anticoagulant therapy.
Glynn RJ, Ridker PM, Goldhaber SZ, et al.
Short-term aspirin therapy can lower the risk for venous thromboembolism (VTE) in high-risk patients, but whether long-term,
low-dose aspirin therapy reduces risk in healthy adults is uncertain. In a secondary analysis of the Women's Health Study,
Glynn and colleagues measured VTE rates in 39 876 female health professionals who were randomly assigned to low-dose aspirin
or placebo for 10 years. Low-dose aspirin did not affect overall VTE rates or those in women with increased rates because
of inherited thrombophilia.
Ray JG, Kearon C, Yi Q, et al.
In observational studies, elevated plasma homocysteine levels were associated with venous thromboembolism. Ray and colleagues
investigated the effect of homocysteine lowering on venous thromboembolism in a multicenter trial of folic acid and B vitamins
to reduce cardiovascular events. Five years of therapy with folic acid and vitamins B6 and B12 decreased homocysteine levels
compared with placebo, but the incidence of venous thromboembolism was the same in both groups, even in participants with
the highest levels of homocysteine.
Qaseem A, Snow V, Barry P, et al.
This guideline, a companion to the recommendation statement and systematic review on management of venous thromboembolism
(VTE) that were published in the 6 February 2007 issue of Annals, summarizes current approaches to diagnosis of VTE. Its purpose
is to present recommendations based on current evidence to aid clinicians in diagnosis of deep venous thrombosis and pulmonary
embolism.
Dentali F, Douketis JD, Gianni M, et al.
Anticoagulant prophylaxis for hospitalized medical inpatients at risk for venous thromboembolism (VTE) is underutilized.
The goal of this meta-analysis of randomized trials was to assess the effects of anticoagulant prophylaxis in reducing VTE
in hospitalized medical patients. The authors found that prophylaxis with anticoagulants (unfractionated heparin, low-molecular-weight
heparin, or fondaparinux) is effective in preventing symptomatic VTE.
O'Donnell MJ, Kearon C, Johnson J, et al.
When patients on long-term warfarin therapy require surgery, low-molecular-weight heparins are often used as bridging therapy
between full anticoagulation with warfarin and no anticoagulation during surgery. Because of safety concerns, the authors
measured heparin activity after an evening dose of low-molecular-weight heparin. They found that two thirds of 94 patients—who
received their last dose of enoxaparin 14 hours before surgery—had elevated heparin levels when surgery was scheduled to begin.
They suggest a longer interval between the last dose of heparin and the time of surgery.
Snow V, Qaseem A, Barry P, et al.
Venous thromboembolism is a common condition affecting 7.1 community residents per 10 000 person-years. Incidence rates are
higher for men and African Americans and increase substantially with age. The target audience for the guidelines in this issue
is all clinicians who care for patients with deep venous thromboembolism or pulmonary embolism.
Segal JB, Streiff MB, Hofmann LV, et al.
New treatments are available for venous thromboembolism. This background paper to the guidelines on treatment of venous thromboembolism
from the American College of Physicians and the American Academy of Family Physicians in this issue reviews the evidence on
the efficacy of interventions for treatment of deep venous thrombosis and pulmonary embolism.
Goldhaber SZ, Berkwits M
There were few questions about the advantages of subcutaneous unfractionated heparin (UFH) relative to low-molecular-weight
heparin (LMWH) for venous thromboembolism until publication of the Fixed Dose (FIDO) heparin trial in August 2006. The investigators
found no statistically or clinically significant difference in recurrent venous thromboembolism in those receiving UFH and
those receiving LMWH. The trial's most important contribution is its suggestion that a new weight-based dosing regimen for
subcutaneous UFH is safe and effective for treatment of acute venous thromboembolism.
Brouwer JP, Veeger NJ, Kluin-Nelemans HC, et al.
The authors studied first-degree relatives of persons with protein S, protein C, or antithrombin deficiency who had had venous
thromboembolism (VTE). They assessed each relative for environmental exposures and additional thrombophilic defects. Risk
for VTE in first-degree relatives increased with the number of defects and with exposure to environmental risk factors.
Ärnlöv J, Pencina MJ, Amin S, et al.
A total of 2084 men from 2 Framingham Heart Study cohorts had 1 measurement of total serum estrogen, testosterone, and dehydroepiandrosterone
sulfate (DHEA-S), followed by 10 years of monitoring for cardiovascular disease (CVD) outcomes. Testosterone and DHEA-S levels
were not associated with CVD risk, but high estrogen levels were associated with low risk. The risk for CVD in men whose estrogen
levels were in the highest quartile was 0.68 times (95% CI, 0.50 to 0.92 times) that in the lowest quartile.
Kearon C, Ginsberg JS, Douketis J, et al.
In patients with a low clinical probability of pulmonary embolism who also have negative d-dimer test results, withholding
additional diagnostic testing does not increase the frequency of venous thromboembolism during follow-up. Low clinical probability
and negative d-dimer test results occur in 50% of outpatients and in 20% of inpatients who have suspected pulmonary embolism.
Ahimastos AA, Lawler A, Reid CM, et al.
The authors randomly assigned 40 older adults with symptomatic peripheral arterial disease to ramipril, 10 mg/d, or to placebo.
After adjustment for between-group baseline differences, mean pain-free walking time after ramipril treatment was 227 seconds
(95% CI, 175 seconds to 278 seconds; P < 0.001) longer than after placebo treatment. Similarly, maximum walking time improved
by 451 seconds in the ramipril group (CI, 367 seconds to 536 seconds; P < 0.001) but did not change in the placebo group.
No adverse events were reported.
Lim W, Dentali F, Eikelboom JW, et al.
The authors analyzed studies of bleeding rates in patients who were taking low-molecular-weight heparin. Patients who have
a creatinine clearance of 30 mL/min or less and are taking enoxaparin have an increased risk for major bleeding relative to
patients with a creatinine clearance of more than 30 mL/min. Empirical dose adjustment of enoxaparin may be indicated in patients
with severe renal insufficiency. The evidence was not adequate to form conclusions about other low-molecular-weight heparins.
Tillie-Leblond I, Marquette C, Perez T, et al.
Pulmonary embolism (PE) is common in patients with chronic obstructive pulmonary disease who present with a severe exacerbation
of unknown origin. In this study, 49 of 197 such patients met diagnostic criteria for PE. Pulmonary embolism was associated
with a history of thromboembolic disease, active cancer, and a decrease in Paco2 of at least 5 mm Hg from baseline levels.
Roy P, Meyer G, Vielle B, et al.
The authors compared the diagnostic management of suspected pulmonary embolism (PE) with evidence-based criteria. The decision
to rule in PE was in accord with established criteria in 92% of 429 patients. The decision to rule out PE was in accord with
the criteria in only 43% of 1100 patients. In 39 of the 44 patients who had venous thromboembolism during follow-up, the physician
had not used appropriate criteria to rule out PE.
Sox HC
This issue contains 2 articles about the management of suspected pulmonary embolism (PE). One shows that physicians frequently
fail to use evidence-based diagnostic guidelines, especially when interpreting negative test results. The companion article
describes a clinical prediction rule for classifying patients with suspected PE into low-, medium-, and high-risk categories.
These studies are representative of the very high-quality body of evidence to guide decision making for suspected PE. We have
a wide gap between our abundant knowledge and its application. Computer-based decision support for diagnosing suspected PE
is an idea whose time is at hand, if not long overdue.
McDermott MM, Liu K, Ferrucci L, et al.
The natural history of symptomatic peripheral arterial disease (PAD) involves a decline in physical performance. In this observational
study, physical performance of patients who were not in a supervised exercise program declined more slowly if they walked
for exercise at least 3 times weekly. These findings may be particularly important for the many patients with PAD who do not
have access to an organized walking exercise program.
Heit JA, Kobbervig CE, James AH, et al.
The incidence of venous thromboembolism during pregnancy has remained constant in the past 30 years. While the incidence of
pulmonary embolism has been much higher in the postpartum period, it has decreased sharply in the past decade. Women younger
than age 20 years and older than age 35 years are at greatest risk. The benefits and harms of prophylaxis with anticoagulants
are not known in these patients.
Lee RV
In this issue, Heit and colleagues provide solid clinical evidence to confirm current clinical wisdom: Pregnancy increases
the risk for thromboembolism. No time during pregnancy is without thromboembolic risk.
Oudega R, Hoes AW, Moons KG
This study aimed to validate the diagnostic accuracy of the Wells rule for deep venous thrombosis (DVT) in 1295 consecutive
primary care patients with suspected DVT. Twelve percent of patients in the low-risk group had DVT (only 3%; had DVT in the
original study by Wells). In low-risk people who had negative results on d-dimer tests, the prevalence of DVT was 2.9% (0.9%
had DVT in the original study). The Wells rule did not accurately estimate the prevalence of DVT in low-risk primary care
patients.
Goodacre S, Sutton AJ, Sampson FC
The authors summarized published research on the sensitivity and specificity of clinical findings, risk scores, and physicians'
empirical judgments for deep venous thrombosis (DVT). Only malignancy, previous DVT, recent immobilization, difference in
calf circumference, and recent surgery were useful for ruling in DVT. Only symmetry in calf circumference or absence of calf
swelling was useful for ruling out DVT. Assessment of clinical probability by using the Wells score is more useful than individual
clinical features.
Douketis JD
In this issue, 2 articles assess a low Wells score as a predictor of deep venous thrombosis (DVT). Goodacre and colleagues
concluded that a low Wells score and negative results on a d-dimer test made venous ultrasonography unnecessary. In contrast,
Oudega and coworkers found that 3% of patients with a low Wells score plus negative d-dimer test results had DVT. To reconcile
these apparently discordant findings, we might start by considering the criteria that a clinical prediction score should satisfy
before using it in everyday practice.
U.S. Preventive Services Task Force*
This statement summarizes the U.S. Preventive Services Task Force recommendations on hormone therapy for the prevention of
chronic conditions in postmenopausal women and the supporting scientific evidence, and updates the Task Force's 2002 recommendations
on hormone replacement therapy.
Tzou WS, Douglas PS, Srinivasan SR, et al.
In this study, advanced lipoprotein testing using vertical-spin density-gradient ultracentrifugation did not improve prediction
of carotid intima–media thickness in 311 young adults compared with models using total cholesterol, low-density lipoprotein
cholesterol, and high-density lipoprotein cholesterol. Advanced testing does not improve cardiovascular risk assessment in
this population.
Merkel PA, Lo GH, Holbrook JT, et al.
The authors measured the rate of venous thromboembolism in a cohort of 180 patients with active Wegener granulomatosis. The
annual rate is 7.0 per 100 persons in these patients. A population of healthy people of similar age had an annual rate of
0.31 per 100 persons. Active Wegener granulomatosis is a risk factor for venous thromboembolism.
Kearon C, Ginsberg JS, Douketis J, et al.
This randomized study compared two diagnostic strategies for suspected deep venous thrombosis. The starting point is a normal
result on ultrasonography of the proximal leg veins. A strategy based on d-dimer testing followed by no further testing if
the results were negative and venography if the results were positive identified substantially more cases than a strategy
of repeated ultrasonography in 1 week. The rates of late venous thromboembolism were the same, however.
Hull RD
The article in this issue by Kearon and colleagues compares two strategies for being sure that patients with suspected deep
venous thrombosis are successfully diagnosed and treated. One of them involves contrast venography, a seldom-used test that
offers a complete one-visit diagnostic strategy but also a small added risk.
U.S. Preventive Services Task Force*
The U.S. Preventive Services Task Force recommends one-time screening for abdominal aortic aneurysm (AAA) by ultrasonography
in men who have ever smoked. It makes no recommendation for or against screening for AAA in 65- to 75-year-old men who have
never smoked and recommends against routine screening for AAA in women.
Fleming C, Whitlock EP, Beil TL, et al.
According to the best-quality evidence on screening for abdominal aortic aneurysm (AAA), inviting men age 65 years and older
to attend AAA screening reduces AAA-related mortality.
Menéndez-Jándula B, Souto JC, Oliver A, et al.
The authors randomly assigned patients to self-management of anticoagulation or to conventional clinic management. Self-managed
patients had equally good control of anticoagulation and fewer adverse events. Major complications and minor hemorrhages were
less common in the self-management group.
Beyth RJ
Menéndez-Jándula and colleagues' study in this issue provides further evidence that patient self-management of anticoagulation
leads to better reliability, better quality, and reduced risks and is therefore a valuable model of care for the long-term
management of anticoagulation.
Rathbun SW, Whitsett TL, Raskob GE
A negative d-dimer test result can obviate the need for further testing or anticoagulation in many patients with a suspected
first episode of deep venous thrombosis. This management trial extends this concept to patients with suspected recurrent venous
thrombosis by showing a very low rate of deep venous thrombosis after a negative d-dimer test result in up to two thirds of
such patients.
Moores LK, Jackson WL, Shorr AF, et al.
Patients with suspected pulmonary embolism seldom have subsequent venous thromboembolism after negative results on computed
tomographic pulmonary angiography (CTPA). Withholding anticoagulation after negative CTPA results seems to be safe.
Vasbinder GB, Nelemans PJ, Kessels AG, et al.
Computed tomographic angiography and magnetic resonance angiography are not sufficiently reproducible or sensitive to rule
out renal artery stenosis in hypertensive patients. Therefore, digital subtraction angiography is still the best diagnostic
test for renal artery stenosis.
Textor SC
Vasbinder and colleagues' study of noninvasive tests for diagnosing renal artery stenosis reminds us that vascular imaging
methods are fallible. While clinicians must know what they can reasonably expect from diagnostic imaging, it is even more
important for them to decide whether the results of the imaging procedures would change their management of the patient.
Selvin E, Marinopoulos S, Berkenblit G, et al.
This meta-analysis of observational studies in patients with diabetes shows that increased serum hemoglobin A1c levels are
associated with an increased risk for cardiovascular disease in both type 1 and type 2 diabetes.
Gerstein HC
What can we conclude from the reports by Khaw and Selvin and colleagues in this issue? First, the glycosylated hemoglobin
level is an independent progressive risk factor for cardiovascular events, regardless of diabetes status. Second, glycosylated
hemoglobin belongs on the list of cardiovascular risk factors. Third, these studies highlight the importance of ongoing clinical
trials of reducing glycosylated hemoglobin levels to reduce cardiovascular risk.
Prandoni P, Lensing AW, Prins MH, et al.
Chronic post-thrombotic sequelae develop in almost half of patients with proximal deep venous thrombosis. Ready-made below-knee
elastic compression stockings reduce this rate by 50%.
Ginsberg JS
What is a clinician to do to prevent long-term complications of acute symptomatic deep venous thrombosis? Should all patients
routinely use elastic compression stockings over the long term, or can clinicians use a “wait-and-see” approach? The safest
approach, on the evidence from the randomized trial reported in this issue, is routine stocking therapy.
Possick SE, Barry M
In the context of a case presentation, the authors review the data on safe air travel after myocardial infarction and common
complications of air travel after coronary artery revascularization; provide recommendations on safe air travel after myocardial
infarction; discuss the safety of preflight screening and the in-flight environment for patients with pacemakers and implantable
automatic defibrillators; and provide recommendations to prevent in-flight deep venous thrombosis.
Stevens SM, Elliott CG, Chan KJ, et al.
These researchers withheld anticoagulation from 375 patients who had negative results on comprehensive (ankle to groin) duplex
ultrasonography for a first episode of suspected symptomatic deep venous thrombosis of the leg. The rate of subsequently diagnosed
deep venous thrombosis was 0.8% (95% CI, 0.16% to 2.3%).
El Kheir D, Büller H
Ultrasonography limited to the common femoral and popliteal veins has been the gold standard for diagnosing symptomatic deep
venous thrombosis. After a negative examination, many centers repeat the study 1 week later to exclude propagation of calf
vein thrombosis into the thigh. Stevens and colleagues report on the safety of withholding anticoagulation after normal results
on a single ankle-to-groin ultrasonographic examination. Will this test become the new gold standard?
Büller HR, Davidson BL, Decousus H, et al.
Once-daily subcutaneous fondaparinux was at least as effective and safe as twice-daily, body weight–adjusted enoxaparin in
the initial treatment of symptomatic deep venous thrombosis.
Prandoni P
After almost 50 years without any substantial progress, antithrombotic treatment of patients with venous thromboembolism has
finally evolved. Factor Xa or thrombin inhibitors will probably allow antithrombotic treatment that is effective, safe, and
simple enough for all physicians to use in most outpatients.
Stein PD, Hull RD, Patel KC, et al.
Excluding a diagnosis from consideration requires a test result that will reduce its probability to below a threshold. Among
tests for d-dimer, enzyme-linked immunosorbent assays (ELISAs) had the highest sensitivity and lowest negative likelihood
ratio, which makes ELISA the best d-dimer test for excluding deep venous thrombosis and pulmonary embolism.
Juul K, Tybjærg-Hansen A, Schnohr P, et al.
In the adult Danish population, heterozygotes for the factor V Leiden mutation had a hazard ratio of 3 for venous thromboembolism
relative to noncarriers of the mutation. For homozygotes, the hazard ratio was 18. When smoking, obesity, and old age were
all present, the absolute 10-year thromboembolic risk was 10% in heterozygotes and 51% in homozygotes.
Quinlan DJ, McQuillan A, Eikelboom JW
Fixed-dose low-molecular-weight heparin appears to be as effective and safe as dose-adjusted intravenous unfractionated heparin
for the initial treatment of pulmonary embolism. This conclusion does not necessarily apply to patients with massive pulmonary
embolism because the trials excluded them.
Linkins L, Choi PT, Douketis JD
The authors found that anticoagulant-related major bleeding has a major impact in patients with venous thromboembolism, a
factor that clinicians should take into account when deciding about long-term oral anticoagulant therapy in an individual
patient.
Agnelli G, Prandoni P, Becattini C, et al.
Patients with pulmonary embolism have a substantial risk for recurrence after stopping oral anticoagulation, regardless of
the length of treatment. Physicians should try to identify patients who may benefit from indefinite oral anticoagulation because
of their high risk for recurrent venous thromboembolism.
Kruip MJ, Leclercq MG, Heul Cv, et al.
A normal perfusion lung scan or normal D-dimer levels in a patient with a low clinical probability safely excludes pulmonary
embolism. When these tests do not exclude pulmonary embolism, second-level diagnostic strategies include spiral computed tomography,
tests for deep venous thrombosis, and pulmonary angiography.
Bates SM, Kearon C, Crowther M, et al.
A negative result on a quantitative latex D-dimer assay safely eliminates the need for anticoagulants and further testing
in patients with low or moderate pretest probability of deep venous thrombosis.
Kovacs MJ, Rodger M, Anderson DR, et al.
A dosing nomogram for starting warfarin anticoagulation achieves a therapeutic international normalized ratio more quickly
if the first dose is 10 mg rather than 5 mg.
Raschke R, Hirsh J, Guidry JR
Few published randomized, controlled trials comparing low-molecular-weight heparin with unfractionated heparin used validated
therapeutic ranges for adjusted partial thromboplastin time or standardized protocols for adjusting unfractionated heparin
dose. This departure from good clinical trials practice may have biased the results of previous trials in favor of low-molecular-weight
heparin.
Saad EB, Marrouche NF, Saad CP, et al.
Severe pulmonary vein stenosis after catheter ablation of atrial fibrillation is associated with respiratory symptoms that
often mimic more common diseases.
de Araujo T, Valencia I, Federman DG, et al.
This case-based review discusses potential causes of leg ulcers, clinical characteristics suggesting that leg ulcers are due
to venous disease, diagnostic procedures, therapy (including compression therapy, growth factors and other medical treatments,
and surgery), and specialist referral.
Desnick RJ, Brady R, Barranger J, et al.
Fabry disease is an X-linked recessive lysosomal storage disorder. Although the disease presents in childhood and culminates
in cardiac, cerebrovascular, and end-stage renal disease, diagnosis is often delayed or missed. This paper reviews the key
signs and symptoms of Fabry disease and provides expert recommendations for diagnosis, follow-up, medical management, and
enzyme replacement therapy.
Crowther MA, Kelton JG
This review summarizes current knowledge of the congenital prothrombotic states and proposes a simple classification system
that divides them into two broad groups: those associated with reduced levels of the inhibitors of the coagulation cascade
and those associated with increased levels or function of the coagulation factors.
Prandoni P, Lensing AW, Prins MH, et al.
Residual venous thrombosis after discontinuing anticoagulation is an important risk factor for recurrent thromboembolism.
Assessing residual venous thrombosis with ultrasonography may help clinicians to identify patients who need prolonged anticoagulation.
U.S. Preventive Services Task Force*
The U.S. Preventive Services Task Force recommends against the routine use of estrogen and progestin for the prevention of
chronic conditions in postmenopausal women. It concludes that the evidence is insufficient to recommend for or against the
use of unopposed estrogen for the prevention of chronic conditions in postmenopausal women who have had a hysterectomy.
Francis CW, Davidson BL, Berkowitz SD, et al.
For prophylaxis of venous thromboembolism, fixed-dose ximelagatran started the morning after total knee arthroplasty is well
tolerated and at least as effective as warfarin, but it does not require coagulation monitoring or dose adjustment.
Crowther MA, Douketis JD, Schnurr T, et al.
Oral vitamin K lowers the international normalized ratio more rapidly than subcutaneous vitamin K in asymptomatic patients
who had supratherapeutic international normalized ratio values while receiving warfarin.
Baarslag H, van Beek EJ, Koopman MM, et al.
Duplex ultrasonography may be the method of choice for initial diagnosis of patients with suspected thrombosis of the upper
extremities. However, in patients with isolated flow abnormalities, contrast venography should be performed.
McDermott MM, Greenland P, Liu K, et al.
The ankle brachial index is more closely associated with leg function in persons with peripheral arterial disease than is
intermittent claudication or other leg symptoms. These data support the use of the ankle brachial index to identify abnormal
lower-extremity function.
Miller J, Chan BK, Nelson HD
Postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism, and this risk may be
highest in the first year of use.
Goldhaber SZ
Echocardiography is useful for identifying patients with pulmonary embolism who may have a poor prognosis. Further research
will clarify and more precisely define the utility and limitations of echocardiography in the management of pulmonary embolism.
Rice L, Attisha WK, Drexler A, et al.
Delayed-onset heparin-induced thrombocytopenia is increasingly being recognized. To avoid disastrous outcomes, physicians
must consider heparin-induced thrombocytopenia whenever a recently hospitalized patient returns with thromboembolism; therapy
with alternative anticoagulants, not heparin, should be initiated.
Fraser DG, Moody AR, Morgan PS, et al.
Magnetic resonance direct thrombus imaging (MRDTI) is an accurate noninvasive test for diagnosis of deep venous thrombosis,
and its accuracy is maintained below the knee. Comparison of individual venous segments showed that results of MRDTI agreed
strongly with findings on venography. Scanning was well tolerated, and interpretation was highly reproducible.
Obernosterer A, Aschauer M, Schnedl W, et al.
An anomaly of the inferior vena cava should be suspected if thrombosis involving the iliac veins occurs in patients 30 years
of age or younger. Patients with an anomaly and thrombosis may be at higher risk for thrombotic recurrence.
Ernst E
The author outlines risk–benefit profiles for the most commonly used herbal medicines. These profiles are based on systematic
reviews where possible.
Hodis HN, Mack WJ, Lobo RA, et al.
Overall, the average rate of progression of subclinical atherosclerosis was slower in healthy postmenopausal women taking
unopposed estrogen replacement therapy with 17β-estradiol than in women taking placebo. Progression of subclinical atherosclerosis
decreased in women who did not take lipid-lowering medication but not in those who took these medications.
Hull RD, Pineo GF, Stein PD, et al.
Extended prophylaxis with low-molecular-weight heparin showed consistent effectiveness and safety in the trials included in
this systematic review (regardless of study variations in clinical practice and length of hospital stay) for venographic deep
venous thrombosis and symptomatic venous thromboembolism. The aggregate findings support the need for extended out-of-hospital
prophylaxis in patients undergoing hip arthroplasty surgery.
Warkentin TE
Warfarin may contribute to the pathogenesis of cancer-associated venous limb gangrene by leading to severe depletion of protein
C while at the same time failing to reduce thrombin generation.
Middeldorp S, Meinardi JR, Koopman MM, et al.
The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation
is low and does not justify routine screening of the families of symptomatic patients.
Bauer KA
The author focuses on which patients should be screened for hereditary and other thrombophilias and on the implications of
such a diagnosis on patient management.
Perrier A, Howarth N, Didier D, et al.
Helical computed tomography should not be used alone for suspected pulmonary embolism but could replace angiography in combined
strategies that include ultrasonography and lung scanning.
Wells PS, Anderson DR, Rodger M, et al.
Managing patients for suspected pulmonary embolism on the basis of pretest probability and d-dimer test result is safe and
decreases the need for diagnostic imaging.
Kearon C, Ginsberg JS, Douketis J, et al.
The combination of a low pretest probability of deep venous thrombosis and a negative result on a whole-blood d-dimer test
rules out deep venous thrombosis in a large proportion of symptomatic outpatients.
Newman AB, Arnold AM, Burke GL, et al.
Total mortality, cardiovascular disease mortality, and rate of incident cardiovascular disease were higher in patients with
abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease,
and extent of atherosclerosis detected by noninvasive testing.
Merli G, Spiro TE, Olsson C, et al.
Subcutaneous enoxaparin given once or twice daily is as effective and safe as dose-adjusted, continuously infused unfractionated
heparin for preventing recurrent symptomatic venous thromboembolic disease.
Lakka TA, Laukkanen JA, Rauramaa R, et al.
Good cardiorespiratory fitness is associated with slower progression of early atherosclerosis in middle-aged men. These findings
are important because they emphasize that middle-aged men can be evaluated for cardiorespiratory fitness to estimate their
future risk for atherosclerotic vascular diseases.
Beyth RJ, Quinn L, Landefeld CS
A multicomponent program of warfarin management reduced the frequency of major bleeding in older patients. These findings
support the premise that efforts to reduce the likelihood of major bleeding will lead to safe and effective use of warfarin
therapy in older patients.
Suzuki T, Katoh H, Tsuchio Y, et al.
Levels of smooth-muscle myosin heavy-chain protein can be used to diagnose aortic dissection soon after symptom onset. This
assay had the greatest diagnostic value in patients with proximal lesions.
Heit JA, Elliott CG, Trowbridge AA, et al.
Among patients who had total knee or total hip replacement and received 4 to 10 days of postoperative ardeparin prophylaxis,
the cumulative incidence of symptomatic venous thromboembolism or death after hospital discharge was not significantly reduced
by extended out-of hospital ardeparin prophylaxis.
Baumgartner I, Rauh G, Pieczek A, et al.
Vascular endothelial growth factor (VEGF) may enhance vascular permeability in humans. In this study, 34% of patients undergoing
VEGF gene transfer developed lower-extremity edema. This condition responded to oral diuretic therapy and did not seem to
be associated with serious sequelae.
Davidson BL, Lensing AW
In this issue, Heit and colleagues report on their important study of prolonged ardeparin sodium prophylaxis against venous
thromboembolism after joint replacement surgery. What additional guidance for assessing the value of this treatment can be
gained from this report?
Grady D, Wenger NK, Herrington D, et al.
Postmenopausal therapy with estrogen plus progestin increases risk for venous thromboembolism in women with coronary heart
disease. This risk should be considered when the risks and benefits of therapy are being weighed.
Rathbun SW, Raskob GE, Whitsett TL
Use of helical computed tomography (CT) in the diagnosis of pulmonary embolism has not been adequately evaluated. The safety
of withholding anticoagulation in patients with negative findings on helical CT is uncertain. Definitive large, prospective
studies should be conducted to assess the sensitivity, specificity, and safety of helical CT for diagnosing suspected pulmonary
embolism.
Bates SM, Ginsberg JS
Rathbun and colleagues' systematic review in this issue evaluates prospective studies on helical computed tomography (CT)
for diagnosing pulmonary embolism. The authors correctly conclude that helical CT has not been adequately assessed for the
diagnosis of pulmonary embolism. The role of this new technology remains controversial, and further studies are needed.
Héron E, Lozinguez O, Emmerich J, et al.
The overall clinical outcome of spontaneous axillary–subclavian venous thrombosis is good, and no relation exists between
the severity of late symptoms and ultrasonographic sequelae.
Lee AY, Julian JA, Levine MN, et al.
A negative D-dimer test result in patients with cancer does not reliably exclude deep venous thrombosis because the negative
predictive value of the test is significantly lower in these patients than in patients without cancer.
Eikelboom JW, Lonn E, Genest J, et al.
This paper reviews the relation between homocyst(e)ine levels and risk for cardiovascular disease and the potential cardiovascular
risk reduction associated with therapy to decrease homocyst(e)ine levels.
Graham I
Is an elevated plasma homocysteine level bad for you? Although the association between genetic hyperhomocysteinemia and vascular
disease would clearly indicate that an increased homocysteine level precedes the disease, these issues have not been definitively
resolved. Several papers in this issue address this topic.
Tahirkheli NK, Greipp PR
A regimen of terbutaline and theophylline seems to be effective prophylaxis against the systemic capillary leak syndrome.
In this series of eight patients, maintenance of therapeutic drug levels was associated with favorable results.
Gould MK, Dembitzer AD, Sanders GD, et al.
Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thromboembolism. This treatment
reduces cost when small numbers of patients are eligible for outpatient management.
Gould MK, Dembitzer AD, Doyle RL, et al.
Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be
as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing
thromboembolic recurrences.
Weinstein MC
The cost-effectiveness papers by Rosen and Gould and their colleagues in this issue show that some cost-increasing technologies
do indeed represent good value for money in the clinical uses for which they are evaluated.
Rodeghiero F, Tosetto A
The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism.
Phenotypic evaluation of resistance to activated protein C should be encouraged in patients with venous thromboembolism.
The ICAI Study Group*
Short-term treatment with alprostadil-α-cyclodextrine provides patients with critical leg ischemia a clinically worthwhile
benefit that is apparent in the short term but decreases over time.
Schainfeld RM, Isner JM
Prognosis for patients with critical leg ischemia is often poor, and no pharmacotherapy has been effective. In this issue,
the ICAI Study Group reports that prostaglandin E1 used to treat this condition had initial benefits that disappeared with
time. Another potential medical approach to critical leg ischemia that has shown early promise is the use of gene transfer
to repair the vascular system.
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