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1 October 2002 | Volume 137 Issue 7 | Pages 555-562
Background: Patients with end-stage renal disease are known to have decreased survival after myocardial infarction, but the association of less severe renal dysfunction with survival after myocardial infarction is unknown.
Objectives: To determine how patients with renal insufficiency are treated during hospitalization for myocardial infarction and to determine the association of renal insufficiency with survival after myocardial infarction.
Design: Cohort study.
Setting: All nongovernment hospitals in the United States.
Patients: 130 099 elderly patients with myocardial infarction hospitalized between April 1994 and July 1995.
Measurements: Patients were categorized according to initial serum creatinine level: no renal insufficiency (creatinine level < 1.5 mg/dL [<132 µmol/L]; n = 82 455), mild renal insufficiency (creatinine level, 1.5 to 2.4 mg/dL [132 to 212 µmol/L]; n = 36 756), or moderate renal insufficiency (creatinine level, 2.5 to 3.9 mg/dL [221 to 345 µmol/L]; n = 10 888). Vital status up to 1 year after discharge was obtained from Social Security records.
Results: Compared with patients with no renal insufficiency, patients with moderate renal insufficiency were less likely to receive aspirin, ß-blockers, thrombolytic therapy, angiography, and angioplasty during hospitalization. One-year mortality was 24% in patients with no renal insufficiency, 46% in patients with mild renal insufficiency, and 66% in patients with moderate renal insufficiency (P < 0.001). After adjustment for patient and treatment characteristics, mild (hazard ratio, 1.68 [95% CI, 1.63 to 1.73]) and moderate (hazard ratio, 2.35 [CI, 2.26 to 2.45]) renal insufficiency were associated with substantially elevated risk for death during the first month of follow-up. This increased mortality risk continued until 6 months after myocardial infarction.
Conclusions: 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.
Contribution
Implications
–The Editors
Patients with end-stage renal disease who require dialysis have markedly increased mortality after myocardial infarction compared with other patients. One-year mortality in these patients is approximately 60% (1-3). After myocardial infarction, these patients are also unlikely to receive aggressive therapy, such as thrombolytic therapy and primary angioplasty, although these treatments have been associated with improved survival in these patients (4).
Patients with renal insufficiency have a greater risk for cardiovascular disease events (5, 6), but the association between mild and moderate renal insufficiency and survival after myocardial infarction has not been evaluated in-depth (1, 7). Two earlier studies have included measures of renal function in prediction models for death after myocardial infarction. Normand and colleagues (8) incorporated both blood urea nitrogen and creatinine levels into a multivariate prediction model for 30-day mortality after myocardial infarction. Jacobs and colleagues included urea nitrogen levels as one of seven categories of predictors for death after hospital admission for acute coronary syndromes (9). However, studies have not compared survival after myocardial infarction among patients with and without renal insufficiency. In addition, the use of medical treatments and procedures after myocardial infarction among patients with and without renal insufficiency, and their association with survival, has not been studied.
We hypothesized that patients with mild and moderate renal insufficiency would have substantially greater 1-year mortality than patients with no renal insufficiency. We also hypothesized that patients with renal insufficiency would be less likely to receive therapeutic interventions known to improve survival after myocardial infarction, such as ß-blockers, aspirin, angiotensin-converting enzyme (ACE) inhibitors, thrombolytic therapy, and primary angioplasty. Using data from the Cooperative Cardiovascular Project, we evaluated the treatment of patients with no renal insufficiency and patients with mild and moderate renal insufficiency. We also determined the independent association of renal insufficiency with survival after myocardial infarction.
The Cooperative Cardiovascular Project collected data from all elderly (age
Measurements
Within the Cooperative Cardiovascular Project, trained medical record abstracters collected the following data for each patient: date and location of hospitalization, demographic characteristics, comorbid conditions, severity of illness measures, electrocardiogram findings, laboratory values, results from invasive and noninvasive cardiac studies, contraindications to therapy, in-hospital treatments, and discharge medications (9). The reliability of the data abstraction process has been demonstrated (10, 12).
We classified renal function using both the admission serum creatinine level and the estimated creatinine clearance. We defined no renal insufficiency as a serum creatinine level less than 1.5 mg/dL (<132 µmol/L), mild renal insufficiency as a serum creatinine level between 1.5 and 2.4 mg/dL (132 to 212 µmol/L), and moderate renal insufficiency as a serum creatinine level between 2.5 and 3.9 mg/dL (221 to 345 µmol/L). We estimated creatinine clearance by using the Cockroft–Gault equation (13) and divided patients into tertiles. Data on serum creatinine levels were available for all patients. Data on mortality during the first year after hospital admission were obtained from Social Security Administration records.
Statistical Analysis
We compared the characteristics and treatments of patients with no renal insufficiency, mild renal insufficiency, and moderate renal insufficiency using analysis of variance and chi-square tests. We compared the proportions of patients treated with ß-blockers among all patients in each category of renal function and in just the patients without relative contraindications to ß-blockers (previous heart failure, diabetes, chronic obstructive pulmonary disease, and pulmonary edema at presentation). We compared use of ACE inhibitors among all patients and then restricted the comparison to patients with hypertension or diabetes. For thrombolytic therapy, we compared treatment as a proportion of all patients treated and as a proportion of "ideal" patients treated. Ideal candidates were defined by ST-segment elevation or left bundle-branch block on the electrocardiogram; onset of chest pain within 6 hours of presentation; age of 80 years or younger; and the absence of peptic ulcer disease, chronic liver disease, metastatic cancer, and terminal illness (14).
To determine the association of renal function with survival after myocardial infarction, we constructed Kaplan–Meier curves for the three groups of serum creatinine levels (and the tertiles of creatinine clearance); statistical significance was assessed by using the log-rank test. We repeated these analyses within subgroups of patients who presented without pulmonary edema or cardiogenic shock (Killip class I and class II) to determine whether the association of renal function with 1-year survival persisted among patients with less severe myocardial infarctions.
We used Cox proportional-hazards models to determine whether mild and moderate renal insufficiency were independent predictors of 1-year mortality (15). These models were adjusted for patient demographic characteristics (age, sex, race, rural or urban setting, and region of the United States); comorbid conditions (history of diabetes mellitus, hypertension, hypercholesterolemia, tobacco use, congestive heart failure, stroke, peripheral vascular disease, angina, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, chronic obstructive pulmonary disease, dementia, inability to ambulate, depression, and incontinence); severity of clinical presentation (Killip class, electrocardiogram findings, heart rate, mean arterial blood pressure, alertness and orientation according to the Glasgow coma scale, duration of chest pain, and blood urea nitrogen level [< 30 mg/dL; <10.7 mmol/L as urea or
We tested the validity of the proportional hazards assumption by determining whether the risk estimates for the renal function categories varied significantly over time. Because we found a significant interaction of the risk for renal function over time, we elected to explore stratified models over time. We separately evaluated the association of our renal function categories with survival after myocardial infarction for the following time intervals: months 1, 2 to 3, 4 to 6, 7 to 9, and 10 to 12. Because the association of renal insufficiency with mortality was the same for months 7 to 9 and 10 to 12, we combined these follow-up intervals. We confirmed that there were no residual violations of the proportional hazards assumption within each time strata by again testing for the presence of an interaction of each renal function predictor with time in predicting mortality during that time strata. We used Martingale and deviance residuals to check the overall fit of each model and found no evidence for a lack of fit.
We evaluated the association of medication use with aspirin, ß-blockers, and ACE inhibitors with survival during the first month after myocardial infarction—overall and stratified by baseline renal function. Because of the large sample size, we found statistically significant interactions for renal function with aspirin and ACE inhibitors, although the point estimates were very similar. Because we did not believe that these statistical interactions had clinical relevance, we did not include these interactions in the models estimating the effect of renal function on survival after myocardial infarction.
Because mortality follow-up was complete, informative censoring could be ruled out for this analysis. Information on discharge medications was available for all patients. Hot-deck imputation, which imputed values by cluster, was used for other missing variables (16, 17). We repeated our analyses when missing variables were not imputed and verified that the results were essentially unchanged. Statistical analysis was performed by using the SAS statistical package, version 6.12 (SAS Institute, Inc., Cary, North Carolina). Statistical significance was set at a two-sided P value of less than 0.05.
Role of the Funding Source
This study was supported by a research grant from the Centers for Medicare & Medical Services (formerly the Health Care Financing Administration) and the National Institute on Aging. The funding source had no role in the collection, analysis, and interpretation of the data or in the decision to submit the paper for publication. ARTICLE
Association of Renal Insufficiency with Treatment and Outcomes after Myocardial Infarction in Elderly Patients
Editors' Notes
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Editors' Notes
Methods
Results
Discussion
Author & Article Info
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Context
Methods
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Methods
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Discussion
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Patients
65 years) Medicare beneficiaries who were admitted between April 1994 and July 1995 to an acute-care hospital and discharged with the diagnosis of acute myocardial infarction (International Classification of Diseases, Ninth Revision, diagnosis code 410) (10). The diagnosis was confirmed by review of the medical records for each patient and required a serum creatine kinase–MB index greater than 5%; an elevated serum lactate dehydrogenase level with lactate dehydrogenase-1 greater than or equal to lactate dehydrogenase-2; or two of the following three criteria: chest pain, serum creatine kinase level more than twice the normal value, or electrocardiographic evidence of acute myocardial infarction (11). A total of 139 567 patients had confirmed myocardial infarction. Only the initial hospitalization for myocardial infarction during the period of evaluation was included. We excluded 6790 patients with severe renal insufficiency (serum creatinine level 4.0 mg/dL [354 µmol/L]) or estimated creatinine clearance less than 0.17 mL/sec. We also excluded 10 570 patients (8.1%) for whom information on body weight was not available to estimate creatinine clearance. 30 mg/dL; 10.7 mmol/L as urea]); hospital characteristics (capability to do coronary angiography and revascularization; volume of myocardial infarction admissions); in-hospital treatments (aspirin, ß-blockers, ACE inhibitors, thrombolytic therapy, intravenous nitroglycerin, coronary angiography, percutaneous transluminal coronary angioplasty, and coronary artery bypass graft surgery); and discharge medications (aspirin, ß-blockers, calcium-channel blockers, and ACE inhibitors). We evaluated the inclusion of a categorical variable for each hospital (n = 4200) in a 10% sample of our data set, but it had little effect on the association of renal function with survival after myocardial infarction. We also checked for violations of linearity by examining augmented models, which included quadratic terms for continuous predictors.
Results
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Methods
Results
Discussion
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Of the 130 099 elderly patients with myocardial infarction in our sample, 36 756 (28.3%) met the definition of mild renal insufficiency based on serum creatinine level and 10 888 (8.4%) met the criteria for moderate renal insufficiency. Patients with renal insufficiency were older and more likely to be male and black compared with patients who had relatively preserved renal function (Table 1). Several chronic disease conditions, including diabetes, hypertension, chronic heart failure, peripheral vascular disease, and dementia, were more prevalent among patients with renal insufficiency. Smoking, however, was less common.
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Myocardial infarction was more severe for patients with renal insufficiency (Table 1). More than half of patients with mild and moderate renal insufficiency presented with Killip class III or IV compared with 30% of patients with preserved renal function. Patients with renal insufficiency also had higher heart rates and lower systolic blood pressures; however, presenting electrocardiogram findings were similar.
Treatment
In-hospital treatment differed substantially among the groups of patients (Table 2). Patients with no renal insufficiency were treated with aspirin and ß-blockers 20% more often (on an absolute scale) than patients with moderate renal insufficiency. In addition, patients with no renal insufficiency were more than twice as likely to receive thrombolytic therapy, coronary angiography, and angioplasty than patients with moderate renal insufficiency but were only slightly more likely to have coronary artery bypass graft surgery. Use of ACE inhibitors, in contrast, was greatest in patients with mild renal insufficiency, followed by patients with moderate renal insufficiency, and lowest in patients with no renal insufficiency. A similar pattern was observed when analyses were restricted to patients with hypertension or diabetes.
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Among patients surviving to hospital discharge, those with no renal insufficiency were most likely to be prescribed aspirin and ß-blockers, those with mild renal insufficiency most often received ACE inhibitors, and those with moderate renal insufficiency most often received calcium-channel blockers. Indeed, calcium-channel blockers were prescribed more often for patients with moderate renal insufficiency than either ACE inhibitors or ß-blockers.
Serum Creatinine Level and Survival after Myocardial Infarction
In unadjusted analyses, renal insufficiency was strongly associated with survival after myocardial infarction (Figure 1). At 1 month after hospital admission, mortality for patients with moderate renal insufficiency was 44% compared with 13% for patients who had relatively normal renal function. At 1 year, almost three times as many patients with moderate renal insufficiency had died compared with patients without renal insufficiency (Figure 1). Among patients who presented without pulmonary edema (Killip class I and class II), the unadjusted relative hazard was 1.60 (95% CI, 1.56 to 1.66) for patients with mild renal insufficiency and 2.56 (CI, 2.45 to 2.67) for patients with moderate renal insufficiency. We also repeated these analyses among patients who underwent echocardiography with measurement of left ventricular ejection fraction (LVEF) during hospitalization and survived to hospital discharge (n = 84 948); 34% (n = 28 545) of these patients had an LVEF less than 0.40. Left ventricular ejection fraction and renal insufficiency had no statistical interaction with 1-year survival, and the relative risk associated with renal insufficiency was similar in both LVEF subgroups.
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Because of the time interaction of renal insufficiency and survival after myocardial infarction, we conducted separate multivariate proportional hazards models for months 1, 2 to 3, 4 to 6, and 7 to 12. After adjustment for both patient characteristics and treatments, moderate renal insufficiency was associated with a more than twofold risk for death in month 1, a 60% increased risk for death in months 2 to 3, and a 25% increased risk for death in months 3 to 6 (Table 3) . Mild renal insufficiency was also associated with a significantly elevated mortality risk in each of these time intervals. However, during months 7 to 12 of follow-up, the mortality risks were similar and low in all three groups of patients.
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Estimated Creatinine Clearance and Survival after Myocardial Infarction
We found an inverse association between renal function as measured by tertiles of estimated creatinine clearance and 1-year mortality (Figure 2). Compared with patients in the highest tertile (creatinine clearance > 0.92 mL/sec), those in the lowest tertile (<0.55 mL/sec) had a 2.6-fold higher mortality and those in the middle tertile (0.55 to 0.92 mL/sec) had a 1.5-fold higher mortality for the entire year of follow-up.
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After multivariate adjustment, patients in the lowest tertile of creatinine clearance had a high mortality risk during the first month of follow-up (Table 3). However, after 6 months of follow-up, this high risk disappeared. Patients in the middle tertile of creatinine clearance were primarily at increased mortality risk during the first month after myocardial infarction compared with patients in the highest tertile.
Association of Medication Use with 1-Month Survival after Myocardial Infarction
Because aspirin, ß-blockers, and ACE inhibitor use differed among patients according to their renal function, we evaluated the association of these medications with 1-month survival after stratification by renal function (Table 4). All three medications seemed to be associated with a substantial survival benefit in patients with no renal insufficiency as well as those with mild and moderate renal insufficiency. Although these associations seemed similar across renal function subgroups, the relative hazard for aspirin was significantly lower in patients with no renal insufficiency than in patients with renal insufficiency; the relative hazard for ACE inhibitor use was significantly greater.
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Discussion
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Although 1-year mortality is known to be greater than 60% among patients receiving renal dialysis, the effects of mild and moderate renal insufficiency on mortality after myocardial infarction have not been well described (2). Earlier investigations have incorporated the serum creatinine or blood urea nitrogen levels into predictive models for mortality (8, 9). Increased serum creatinine levels have also predicted cardiac complications and mortality after noncardiac and cardiac surgery (18-21). We found that serum creatinine level and estimated creatinine clearance were strongly associated with early mortality after myocardial infarction in elderly patients.
The association of renal insufficiency with mortality after myocardial infarction was strongest in the initial few months and disappeared after 6 months. However, by 6 months after myocardial infarction, half of the patients with moderate renal insufficiency had already died; relatively few patients died during months 7 to 12 of follow-up in all of the patient subgroups. Appropriate secondary prevention for patients with renal insufficiency should therefore be initiated immediately after myocardial infarction. Treatment with aspirin, ß-blockers, and ACE inhibitors seemed to be associated with substantial benefit in the first month after myocardial infarction for patients with or without renal insufficiency.
In light of the substantially increased mortality risk for patients with renal insufficiency, their undertreatment is of concern. The low use of certain treatments, such as aspirin and ACE inhibitors, in patients with renal insufficiency may result from fear of adverse effects. However, two recent observational studies of elderly patients with reduced LVEF after myocardial infarction found that ACE inhibitors and ß-blockers were associated with greater benefit in patients with renal insufficiency than in patients with preserved renal function (22, 23). Similarly, aspirin therapy has been recommended for the treatment and secondary prevention of myocardial infarction in patients with renal insufficiency (24).
It is not clear why patients with renal insufficiency—even those considered ideal candidates—received thrombolytic therapy less often. Similarly, we noted a lower rate of ß-blocker use in patients with renal insufficiency, even among those without chronic obstructive pulmonary disease, heart failure, and diabetes. In some of these patients, the treating physician may have been aware of potential contraindications not contained in the medical record and, thus, unknown to us. More likely, patients with renal insufficiency receive less aspirin, ß-blockers, and thrombolytic therapy because they are thought to be frail and less likely to benefit or more likely to experience side effects. Patients with the highest mortality risk, however, such as those with renal insufficiency, should gain the greatest survival benefit from medications that reduce their risk (25). Unfortunately, clinicians who evaluate this risk–benefit tradeoff may emphasize the tangible risk for short-term side effects rather than the long-term benefits of reduced mortality.
One strength of our study is that we analyzed a national sample of elderly patients with myocardial infarction; thus, our findings should be generalizable (10). Although our data set relied on chart abstraction, the data collection process has been validated extensively. The primary predictors that we evaluated, serum creatinine level and estimated creatinine clearance, are routinely obtained in patients with myocardial infarction who are admitted to hospitals. These measures are much less precise than a true glomerular filtration rate for assessing renal function, but this imprecision would be expected to reduce the magnitude of the associations that we saw between renal insufficiency and mortality after myocardial infarction.
We cannot be certain that the serum creatinine levels measured at presentation indicated baseline renal function, because the severity of the myocardial infarction could have caused an acute elevation in the serum creatinine level. We did observe, however, similar relative risks associated with renal insufficiency among the patients with the least severe infarctions (Killip class I and class II); these patients would have been unlikely to present with acute renal failure. Another limitation is that the events evaluated in our study occurred in 1994 and 1995. Because the indications for the use of ß-blockers and ACE inhibitors have expanded since that time, treatment of persons with and without renal insufficiency may have changed (26-29). In addition, the treatment disparities that we observed may be less pronounced in younger patients with renal insufficiency; we cannot extend our findings to persons younger than 65 years of age.
In conclusion, we found mortality for elderly patients after myocardial infarction to be substantially greater in those with mild and moderate renal insufficiency than in patients who have relatively normal renal function. Undertreatment of these patients with proven medical therapies could contribute to their excess mortality. Interventions such as clinical practice guidelines should address the quality of care for this high-risk subgroup of patients with myocardial infarction.
Author and Article Information
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Acknowledgments: The authors thank Dr. Eric Vittinghoff for his contributions to this manuscript.
Grant Support: By the Centers for Medicare & Medicaid Services (formerly the Health Care Financing Administration) (500-96-P535) and the National Institute on Aging. Dr. Shlipak and Dr. Heidenreich are Research Career Development Awardees from the Health Research and Development Division of the Veterans Administration. Dr. Shlipak is also supported by the National Heart, Lung, and Blood Institute (RO3 HL68099-01).
Requests for Single Reprints: Michael G. Shlipak, MD, MPH, General Internal Medicine Section, Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121; e-mail, shlip{at}itsa.ucsf.edu.
Current Author Addresses: Dr. Shlipak: General Internal Medicine Section, Veterans Affairs Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121.
Dr. Heidenreich: Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304.
Dr. Noguchi: Toyo-Eiwa University, 32 Miho-cho, Midoritau, Yokohama, Kanagawa, Japan 226-0015.
Dr. Chertow: Division of Nephrology, University of California, San Francisco, 3333 California Street, Suite 430, San Francisco, CA 94118.
Dr. Browner: California Pacific Medical Center, 2340 Clay Street, Room 114, San Francisco, CA 94115.
Dr. McClellan: Council of Economics Advisor, The White House, Eisenhower Executive Building, Room 320, Washington, DC 20502.
Author Contributions: Conception and design: M.G. Shlipak, W.S. Browner, M.B. McClellan.
Analysis and interpretation of the data: M.G. Shlipak, P.A. Heidenreich, H. Noguchi, G.M. Chertow, W.S. Browner.
Drafting of the article: M.G. Shlipak, W.S. Browner.
Critical revision of the article for important intellectual content: M.G. Shlipak, P.A. Heidenreich, G.M. Chertow, W.S. Browner.
Final approval of the article: M.G. Shlipak, P.A. Heidenreich, G.M. Chertow, W.S. Browner, M.B. McClellan.
Provision of study materials or patients: M.B. McClellan.
Statistical expertise: M.G. Shlipak, H. Noguchi, W.S. Browner, M.B. McClellan.
Obtaining of funding: M.B. McClellan.
Collection and assembly of data: H. Noguchi.
References
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 M. Chonchol, H. Gnahn, and D. Sander Impact of subclinical carotid atherosclerosis on incident chronic kidney disease in the elderly Nephrol. Dial. Transplant., August 1, 2008; 23(8): 2593 - 2598. [Abstract] [Full Text] [PDF]
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 S. J. Shah, T. Thenappan, S. Rich, L. Tian, S. L. Archer, and M. Gomberg-Maitland Association of Serum Creatinine With Abnormal Hemodynamics and Mortality in Pulmonary Arterial Hypertension Circulation, May 13, 2008; 117(19): 2475 - 2483. [Abstract] [Full Text] [PDF]
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 C. R. Parikh, S. G. Coca, Y. Wang, F. A. Masoudi, and H. M. Krumholz Long-term Prognosis of Acute Kidney Injury After Acute Myocardial Infarction Arch Intern Med, May 12, 2008; 168(9): 987 - 995. [Abstract] [Full Text] [PDF]
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J. K. Inrig, U. D. Patel, L. P. Briley, L. She, B. S. Gillespie, J. D. Easton, E. J. Topol, and L. A. Szczech Mortality, kidney disease and cardiac procedures following acute coronary syndrome Nephrol. Dial. Transplant., March 1, 2008; 23(3): 934 - 940. [Abstract] [Full Text] [PDF]
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M. Chonchol, M. Cigolini, and G. Targher Association between 25-hydroxyvitamin D deficiency and cardiovascular disease in type 2 diabetic patients with mild kidney dysfunction Nephrol. Dial. Transplant., January 1, 2008; 23(1): 269 - 274. [Abstract] [Full Text] [PDF]
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M. Rudnick and H. Feldman Contrast-Induced Nephropathy: What Are the True Clinical Consequences? Clin. J. Am. Soc. Nephrol., January 1, 2008; 3(1): 263 - 272. [Abstract] [Full Text] [PDF]
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 G. L. Smith, F. A. Masoudi, M. G. Shlipak, H. M. Krumholz, and C. R. Parikh Renal Impairment Predicts Long-Term Mortality Risk after Acute Myocardial Infarction J. Am. Soc. Nephrol., January 1, 2008; 19(1): 141 - 150. [Abstract] [Full Text] [PDF]
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C. A. Schneider, E. Ferrannini, R. DeFronzo, G. Schernthaner, J. Yates, and E. Erdmann Effect of Pioglitazone on Cardiovascular Outcome in Diabetes and Chronic Kidney Disease J. Am. Soc. Nephrol., January 1, 2008; 19(1): 182 - 187. [Abstract] [Full Text] [PDF]
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 T. Sayin, S. Turhan, O. Akyurek, and M. Kilickap Gadolinium:Nonionic Contrast Media (1:1) Coronary Angiography in Patients With Impaired Renal Function Angiology, November 1, 2007; 58(5): 561 - 564. [Abstract] [PDF]
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J. Shepherd, J. J.P. Kastelein, V. Bittner, P. Deedwania, A. Breazna, S. Dobson, D. J. Wilson, A. Zuckerman, N. K. Wenger, and for the Treating to New Targets Investigators Effect of Intensive Lipid Lowering with Atorvastatin on Renal Function in Patients with Coronary Heart Disease: The Treating to New Targets (TNT) Study Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1131 - 1139. [Abstract] [Full Text] [PDF]
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C. O. Phillips, A. Kashani, D. K. Ko, G. Francis, and H. M. Krumholz Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction: A Quantitative Review of Data From Randomized Clinical Trials Arch Intern Med, October 8, 2007; 167(18): 1930 - 1936. [Abstract] [Full Text] [PDF]
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C. A. Herzog, K. Littrell, C. Arko, P. D. Frederick, and M. Blaney Clinical Characteristics of Dialysis Patients With Acute Myocardial Infarction in the United States: A Collaborative Project of the United States Renal Data System and the National Registry of Myocardial Infarction Circulation, September 25, 2007; 116(13): 1465 - 1472. [Abstract] [Full Text] [PDF]
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L. G. Glynn, D. Reddan, J. Newell, J. Hinde, B. Buckley, and A. W. Murphy Chronic kidney disease and mortality and morbidity among patients with established cardiovascular disease: a West of Ireland community-based cohort study Nephrol. Dial. Transplant., September 1, 2007; 22(9): 2586 - 2594. [Abstract] [Full Text] [PDF]
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E. L. Schiffrin, M. L. Lipman, and J. F.E. Mann Chronic Kidney Disease: Effects on the Cardiovascular System Circulation, July 3, 2007; 116(1): 85 - 97. [Abstract] [Full Text] [PDF]
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S. S. DeLoach and E. R. Mohler III Peripheral Arterial Disease: A Guide for Nephrologists Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 839 - 846. [Abstract] [Full Text] [PDF]
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 L. Zhang, L. Zuo, F. Wang, M. Wang, S. Wang, L. Liu, and H. Wang Metabolic Syndrome and Chronic Kidney Disease in a Chinese Population Aged 40 Years and Older Mayo Clin. Proc., July 1, 2007; 82(7): 822 - 827. [Abstract] [Full Text] [PDF]
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 K. A.A. Fox, E. M. Antman, G. Montalescot, S. Agewall, B. SomaRaju, F. W.A. Verheugt, J. Lopez-Sendon, H. Hod, S. A. Murphy, and E. Braunwald The Impact of Renal Dysfunction on Outcomes in the ExTRACT-TIMI 25 Trial J. Am. Coll. Cardiol., June 12, 2007; 49(23): 2249 - 2255. [Abstract] [Full Text] [PDF]
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J. H. Ix, M. G. Shlipak, G. M. Chertow, and M. A. Whooley Association of Cystatin C With Mortality, Cardiovascular Events, and Incident Heart Failure Among Persons With Coronary Heart Disease: Data From the Heart and Soul Study Circulation, January 16, 2007; 115(2): 173 - 179. [Abstract] [Full Text] [PDF]
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J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, R. Marin, P. Rodriguez, S. Tranche, J. V. Lozano, C. Filozof, et al. Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S236 - S245. [Abstract] [Full Text] [PDF]
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 S. G. Coca, H. M. Krumholz, A. X. Garg, and C. R. Parikh Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease. JAMA, September 20, 2006; 296(11): 1377 - 1384. [Abstract] [Full Text] [PDF]
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P. A. Sarafidis and G. L. Bakris Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease Nephrol. Dial. Transplant., September 1, 2006; 21(9): 2366 - 2374. [Full Text] [PDF]
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B. B. Newsome, W. M. McClellan, C. S. Coffey, J. J. Allison, C. I. Kiefe, and D. G. Warnock Survival Advantage of Black Patients with Kidney Disease after Acute Myocardial Infarction Clin. J. Am. Soc. Nephrol., September 1, 2006; 1(5): 993 - 999. [Abstract] [Full Text] [PDF]
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L. Zhang, L. Zuo, F. Wang, M. Wang, S. Wang, J. Lv, L. Liu, and H. Wang Cardiovascular Disease in Early Stages of Chronic Kidney Disease in a Chinese Population J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2617 - 2621. [Abstract] [Full Text] [PDF]
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W. C. Winkelmayer, D. M. Charytan, M. A. Brookhart, R. Levin, D. H. Solomon, and J. Avorn Kidney Function and Use of Recommended Medications after Myocardial Infarction in Elderly Patients Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 796 - 801. [Abstract] [Full Text] [PDF]
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M. Tonelli, N. Wiebe, B. Culleton, A. House, C. Rabbat, M. Fok, F. McAlister, and A. X. Garg Chronic Kidney Disease and Mortality Risk: A Systematic Review J. Am. Soc. Nephrol., July 1, 2006; 17(7): 2034 - 2047. [Abstract] [Full Text] [PDF]
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N. Pannu, N. Wiebe, M. Tonelli, and for the Alberta Kidney Disease Network Prophylaxis Strategies for Contrast-Induced Nephropathy JAMA, June 21, 2006; 295(23): 2765 - 2779. [Abstract] [Full Text] [PDF]
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M. Tonelli, P. Jose, G. Curhan, F. Sacks, E. Braunwald, M. Pfeffer, and Cholesterol and Recurrent Events (CARE) Trial Inve Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial BMJ, June 17, 2006; 332(7555): 1426. [Abstract] [Full Text] [PDF]
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G. L. Smith, M. G. Shlipak, E. P. Havranek, J. M. Foody, F. A. Masoudi, S. S. Rathore, and H. M. Krumholz Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease. Arch Intern Med, May 22, 2006; 166(10): 1134 - 1142. [Abstract] [Full Text] [PDF]
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M. E. Williams Coronary Revascularization in Diabetic Chronic Kidney Disease/End-Stage Renal Disease: A Nephrologist's Perspective Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 209 - 220. [Full Text] [PDF]
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 Y. Maaravi, M. Bursztyn, R. Hammerman-Rozenberg, A. Cohen, and J. Stessman Moderate renal insufficiency at 70 years predicts mortality QJM, February 1, 2006; 99(2): 97 - 102. [Abstract] [Full Text] [PDF]
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E. Suganuma, Y. Zuo, N. Ayabe, J. Ma, V. R. Babaev, M. F. Linton, S. Fazio, I. Ichikawa, A. B. Fogo, and V. Kon Antiatherogenic Effects of Angiotensin Receptor Antagonism in Mild Renal Dysfunction J. Am. Soc. Nephrol., February 1, 2006; 17(2): 433 - 441. [Abstract] [Full Text] [PDF]
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R. W. Schrier Role of Diminished Renal Function in Cardiovascular Mortality: Marker or Pathogenetic Factor? J. Am. Coll. Cardiol., January 3, 2006; 47(1): 1 - 8. [Abstract] [Full Text]
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M. Tonelli, A. Keech, J. Shepherd, F. Sacks, A. Tonkin, C. Packard, M. Pfeffer, J. Simes, C. Isles, C. Furberg, et al. Effect of Pravastatin in People with Diabetes and Chronic Kidney Disease J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3748 - 3754. [Abstract] [Full Text] [PDF]
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M. Shlipak and C. Stehman-Breen Observational Research Databases in Renal Disease J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3477 - 3484. [Abstract] [Full Text] [PDF]
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 M. J. Holzmann, S. Ahnve, N. Hammar, L. Jorgensen, K. Klerdal, K. Pehrsson, and T. Ivert Creatinine clearance and risk of early mortality in patients undergoing coronary artery bypass grafting J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 746 - 746. [Abstract] [Full Text] [PDF]
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M. Tonelli, C. Isles, T. Craven, A. Tonkin, M. A. Pfeffer, J. Shepherd, F. M. Sacks, C. Furberg, S. M. Cobbe, J. Simes, et al. Effect of Pravastatin on Rate of Kidney Function Loss in People With or at Risk for Coronary Disease Circulation, July 12, 2005; 112(2): 171 - 178. [Abstract] [Full Text] [PDF]
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R. Vanholder, Z. Massy, A. Argiles, G. Spasovski, F. Verbeke, N. Lameire, and for the European Uremic Toxin Work Group (EUTox) Chronic kidney disease as cause of cardiovascular morbidity and mortality Nephrol. Dial. Transplant., June 1, 2005; 20(6): 1048 - 1056. [Abstract] [Full Text] [PDF]
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 M. G. Shlipak, M. J. Sarnak, R. Katz, L. F. Fried, S. L. Seliger, A. B. Newman, D. S. Siscovick, and C. Stehman-Breen Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons N. Engl. J. Med., May 19, 2005; 352(20): 2049 - 2060. [Abstract] [Full Text] [PDF]
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 M. J. Sarnak, R. Katz, C. O. Stehman-Breen, L. F. Fried, N. S. Jenny, B. M. Psaty, A. B. Newman, D. Siscovick, M. G. Shlipak, and and the Cardiovascular Health Study* Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults Ann Intern Med, April 5, 2005; 142(7): 497 - 505. [Abstract] [Full Text] [PDF]
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R. N. Foley, A. M. Murray, S. Li, C. A. Herzog, A. M. McBean, P. W. Eggers, and A. J. Collins Chronic Kidney Disease and the Risk for Cardiovascular Disease, Renal Replacement, and Death in the United States Medicare Population, 1998 to 1999 J. Am. Soc. Nephrol., February 1, 2005; 16(2): 489 - 495. [Abstract] [Full Text] [PDF]
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H. Kramer, R. Toto, R. Peshock, R. Cooper, and R. Victor Association between Chronic Kidney Disease and Coronary Artery Calcification: The Dallas Heart Study J. Am. Soc. Nephrol., February 1, 2005; 16(2): 507 - 513. [Abstract] [Full Text] [PDF]
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A. M. O'Hare, D. Bertenthal, M. G. Shlipak, S. Sen, and M.-M. Chren Impact of Renal Insufficiency on Mortality in Advanced Lower Extremity Peripheral Arterial Disease J. Am. Soc. Nephrol., February 1, 2005; 16(2): 514 - 519. [Abstract] [Full Text] [PDF]
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M. P. Tokmakova, H. Skali, S. Kenchaiah, E. Braunwald, J. L. Rouleau, M. Packer, G. M. Chertow, L. A. Moye, M. A. Pfeffer, and S. D. Solomon Chronic Kidney Disease, Cardiovascular Risk, and Response to Angiotensin-Converting Enzyme Inhibition After Myocardial Infarction: The Survival And Ventricular Enlargement (SAVE) Study Circulation, December 14, 2004; 110(24): 3667 - 3673. [Abstract] [Full Text] [PDF]
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G. Marenzi, G. Lauri, E. Assanelli, J. Campodonico, M. De Metrio, I. Marana, M. Grazi, F. Veglia, and A. L. Bartorelli Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction J. Am. Coll. Cardiol., November 2, 2004; 44(9): 1780 - 1785. [Abstract] [Full Text] [PDF]
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J. Ezekowitz, F. A. McAlister, K. H. Humphries, C. M. Norris, M. Tonelli, W. A. Ghali, M. L. Knudtson, and APPROACH Investigators The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1587 - 1592. [Abstract] [Full Text] [PDF]
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R. Gupta, Y. Birnbaum, and B. F. Uretsky The renal patient with coronary artery disease: Current concepts and dilemmas J. Am. Coll. Cardiol., October 6, 2004; 44(7): 1343 - 1353. [Abstract] [Full Text] [PDF]
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N. S. Anavekar, J. J.V. McMurray, E. J. Velazquez, S. D. Solomon, L. Kober, J.-L. Rouleau, H. D. White, R. Nordlander, A. Maggioni, K. Dickstein, et al. Relation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction N. Engl. J. Med., September 23, 2004; 351(13): 1285 - 1295. [Abstract] [Full Text] [PDF]
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A. S. Go, G. M. Chertow, D. Fan, C. E. McCulloch, and C.-y. Hsu Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization N. Engl. J. Med., September 23, 2004; 351(13): 1296 - 1305. [Abstract] [Full Text] [PDF]
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M. Tonelli, C. Isles, G. C. Curhan, A. Tonkin, M. A. Pfeffer, J. Shepherd, F. M. Sacks, C. Furberg, S. M. Cobbe, J. Simes, et al. Effect of Pravastatin on Cardiovascular Events in People With Chronic Kidney Disease Circulation, September 21, 2004; 110(12): 1557 - 1563. [Abstract] [Full Text] [PDF]
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W. M. McClellan, R. D. Langston, and R. Presley Medicare Patients with Cardiovascular Disease Have a High Prevalence of Chronic Kidney Disease and a High Rate of Progression to End-Stage Renal Disease J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1912 - 1919. [Abstract] [Full Text] [PDF]
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R. Dikow, L. P. Kihm, M. Zeier, J. Kapitza, J. Tornig, K. Amann, C. Tiefenbacher, and E. Ritz Increased Infarct Size in Uremic Rats: Reduced Ischemia Tolerance? J. Am. Soc. Nephrol., June 1, 2004; 15(6): 1530 - 1536. [Abstract] [Full Text] [PDF]
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D. E. Weiner, H. Tighiouart, M. G. Amin, P. C. Stark, B. MacLeod, J. L. Griffith, D. N. Salem, A. S. Levey, and M. J. Sarnak Chronic Kidney Disease as a Risk Factor for Cardiovascular Disease and All-Cause Mortality: A Pooled Analysis of Community-Based Studies J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1307 - 1315. [Abstract] [Full Text] [PDF]
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 J. A. Joles and H. A. Koomans Causes and Consequences of Increased Sympathetic Activity in Renal Disease Hypertension, April 1, 2004; 43(4): 699 - 706. [Abstract] [Full Text] [PDF]
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E. Ritz and W. M. McClellan Overview: Increased Cardiovascular Risk in Patients with Minor Renal Dysfunction: An Emerging Issue with Far-Reaching Consequences J. Am. Soc. Nephrol., March 1, 2004; 15(3): 513 - 516. [Abstract] [Full Text] [PDF]
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H. A. Koomans, P. J. Blankestijn, and J. A. Joles Sympathetic Hyperactivity in Chronic Renal Failure: A Wake-up Call J. Am. Soc. Nephrol., March 1, 2004; 15(3): 524 - 537. [Abstract] [Full Text] [PDF]
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M. Sachdev, J. L. Sun, A. A. Tsiatis, C. L. Nelson, D. B. Mark, and J. G. Jollis The prognostic importance of comorbidity for mortality in patients with stable coronary artery disease J. Am. Coll. Cardiol., February 18, 2004; 43(4): 576 - 582. [Abstract] [Full Text] [PDF]
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A. M. O'Hare, J. Feinglass, G. E. Reiber, R. A. Rodriguez, J. Daley, S. Khuri, W. G. Henderson, and K. L. Johansen Postoperative Mortality after Nontraumatic Lower Extremity Amputation in Patients with Renal Insufficiency J. Am. Soc. Nephrol., February 1, 2004; 15(2): 427 - 434. [Abstract] [Full Text] [PDF]
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M. Trovati and F. Cavalot Optimization of Hypolipidemic and Antiplatelet Treatment in the Diabetic Patient with Renal Disease J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S12 - 20. [Abstract] [Full Text]
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G. Leoncini, F. Viazzi, D. Parodi, E. Ratto, S. Vettoretti, V. Vaccaro, M. Ravera, G. Deferrari, and R. Pontremoli Mild Renal Dysfunction and Cardiovascular Risk in Hypertensive Patients J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S88 - 90. [Abstract] [Full Text]
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H. M. Sadeghi, G. W. Stone, C. L. Grines, R. Mehran, S. R. Dixon, A. J. Lansky, M. Fahy, D. A. Cox, E. Garcia, J. E. Tcheng, et al. Impact of Renal Insufficiency in Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction Circulation, December 2, 2003; 108(22): 2769 - 2775. [Abstract] [Full Text] [PDF]
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J. H. Ix, M. G. Shlipak, H. H. Liu, N. B. Schiller, and M. A. Whooley Association between Renal Insufficiency and Inducible Ischemia in Patients with Coronary Artery Disease: The Heart and Soul Study J. Am. Soc. Nephrol., December 1, 2003; 14(12): 3233 - 3238. [Abstract] [Full Text] [PDF]
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C. M. Gibson, D. S. Pinto, S. A. Murphy, D. A. Morrow, H.-P. Hobbach, S. D. Wiviott, R. P. Giugliano, C. P. Cannon, E. M. Antman, E. Braunwald, et al. Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1535 - 1543. [Abstract] [Full Text] [PDF]
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W. J. French and R. S. Wright Renal insufficiency and worsened prognosis with STEMI: A call for action J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1544 - 1546. [Full Text] [PDF]
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M. J. Sarnak, A. S. Levey, A. C. Schoolwerth, J. Coresh, B. Culleton, L. L. Hamm, P. A. McCullough, B. L. Kasiske, E. Kelepouris, M. J. Klag, et al. Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention Hypertension, November 1, 2003; 42(5): 1050 - 1065. [Full Text] [PDF]
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M. J. Sarnak, A. S. Levey, A. C. Schoolwerth, J. Coresh, B. Culleton, L. L. Hamm, P. A. McCullough, B. L. Kasiske, E. Kelepouris, M. J. Klag, et al. Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: A Statement From the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention Circulation, October 28, 2003; 108(17): 2154 - 2169. [Full Text] [PDF]
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R. Dikow and E. Ritz Cardiovascular complications in the diabetic patient with renal disease: an update in 2003 Nephrol. Dial. Transplant., October 1, 2003; 18(10): 1993 - 1998. [Full Text] [PDF]
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C. A. Herzog How to Manage the Renal Patient with Coronary Heart Disease: The Agony and the Ecstasy of Opinion-Based Medicine J. Am. Soc. Nephrol., October 1, 2003; 14(10): 2556 - 2572. [Full Text] [PDF]
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A. O. Ojo, P. J. Held, F. K. Port, R. A. Wolfe, A. B. Leichtman, E. W. Young, J. Arndorfer, L. Christensen, and R. M. Merion Chronic Renal Failure after Transplantation of a Nonrenal Organ N. Engl. J. Med., September 4, 2003; 349(10): 931 - 940. [Abstract] [Full Text] [PDF]
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J J Santopinto, K A A Fox, R J Goldberg, A Budaj, G Pinero, A Avezum, D Gulba, J Esteban, J M Gore, J Johnson, et al. Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE) Heart, September 1, 2003; 89(9): 1003 - 1008. [Abstract] [Full Text] [PDF]
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K. C. Abbott, C. M. Yuan, A. J. Taylor, D. F. Cruess, and L. Y. C. Agodoa Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2358 - 2365. [Abstract] [Full Text] [PDF]
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D. A. Morrow and E. Braunwald Future of Biomarkers in Acute Coronary Syndromes: Moving Toward a Multimarker Strategy Circulation, July 22, 2003; 108(3): 250 - 252. [Full Text] [PDF]
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A. K. Berger, S. Duval, and H. M. Krumholz Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction J. Am. Coll. Cardiol., July 16, 2003; 42(2): 201 - 208. [Abstract] [Full Text] [PDF]
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C. R. Conti Management of patients with acute myocardial infarction and end-stage renal disease J. Am. Coll. Cardiol., July 16, 2003; 42(2): 209 - 210. [Full Text] [PDF]
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