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17 April 2001 | Volume 134 Issue 8 | Pages 629-636
Background: The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency.
Objective: To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk.
Design: Post hoc analysis.
Setting: The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers.
Patients: 980 patients with mild renal insufficiency (serum creatinine concentration
Measurements: The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke.
Results: Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference).
Conclusions: 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.
Author and Article Information
From McMaster University, Hamilton, Ontario, Canada; Schwabing General Hospital, Ludwig Maximilians University, Munchen, Germany; and the German Institute for High Blood Pressure Research, Heidelberg, Germany.
Grant Support: By the Medical Research Council of Canada, the Ontario Heart Foundation, Aventis, Astra-Zeneca, NEGMA, and the Natural Source Vitamin E Producers Association.
Requests for Single Reprints: Jackie Bosch, MA, HOPE Office, McMaster University, Hamilton General Hospital, 527 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Current Author Addresses: Dr. Mann: Department of Nephrology and Hypertension, Schwabing General Hospital, LMU, Kolner Platz 1, D-80804 Munchen, Germany.
Drs. Gerstein, Pogue, and Yusuf and Ms. Bosch: HOPE Office, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.
Author Contributions: Conception and design: J.F.E. Mann, H.C. Gerstein, S. Yusuf.
Analysis and interpretation of the data: J.F.E. Mann, H.C. Gerstein, J. Pogue.
Drafting of the article: J.F.E. Mann, H.C. Gerstein, S. Yusuf.
Critical revision of the article for important intellectual content: J.F.E. Mann, H.C. Gerstein, J. Pogue, J. Bosch, S. Yusuf.
Final approval of the article: J.F.E. Mann, H.C. Gerstein, J. Bosch, S. Yusuf.
Provision of study materials or patients: J.F.E. Mann, H.C. Gerstein, J. Bosch.
Statistical expertise: J. Pogue.
Obtaining of funding: H.C. Gerstein, S. Yusuf.
Collection and assembly of data: J.F.E. Mann, J. Bosch. ARTICLE
Renal Insufficiency as a Predictor of Cardiovascular Outcomes and the Impact of Ramipril: The HOPE Randomized Trial
124 µmol/L [ 1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 µmol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 µmol/L (2.3 mg/dL) were excluded.
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C. Meisinger, A. Doring, H. Lowel, and for the KORA Study Group Chronic kidney disease and risk of incident myocardial infarction and all-cause and cardiovascular disease mortality in middle-aged men and women from the general population Eur. Heart J., May 2, 2006; 27(10): 1245 - 1250. [Abstract] [Full Text] [PDF]
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M. Ravera, M. Re, L. Deferrari, S. Vettoretti, and G. Deferrari Importance of Blood Pressure Control in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2006; 17(4_suppl_2): S98 - S103. [Abstract] [Full Text] [PDF]
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M.K. Jayapaul, R. Messersmith, D.N. Bennett-Jones, P.A. Mead, and D.M. Large The joint diabetic-renal clinic in clinical practice: 10 years of data from a District General Hospital QJM, March 1, 2006; 99(3): 153 - 160. [Abstract] [Full Text] [PDF]
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A. M. O'Hare, D. Bertenthal, K. E. Covinsky, C. S. Landefeld, S. Sen, K. Mehta, M. A. Steinman, A. Borzecki, and L. C. Walter Mortality Risk Stratification in Chronic Kidney Disease: One Size for All Ages? J. Am. Soc. Nephrol., March 1, 2006; 17(3): 846 - 853. [Abstract] [Full Text] [PDF]
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M. Rahman, S. Pressel, B. R. Davis, C. Nwachuku, J. T. Wright Jr., P. K. Whelton, J. Barzilay, V. Batuman, J. H. Eckfeldt, M. A. Farber, et al. Cardiovascular Outcomes in High-Risk Hypertensive Patients Stratified by Baseline Glomerular Filtration Rate Ann Intern Med, February 7, 2006; 144(3): 172 - 180. [Abstract] [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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C. S. Fox, M. G. Larson, R. S. Vasan, C.-Y. Guo, H. Parise, D. Levy, E. P. Leip, C. J. O'Donnell, R. B. D'Agostino Sr., and E. J. Benjamin Cross-Sectional Association of Kidney Function with Valvular and Annular Calcification: The Framingham Heart Study J. Am. Soc. Nephrol., February 1, 2006; 17(2): 521 - 527. [Abstract] [Full Text] [PDF]
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W. Van Biesen, R. Vanholder, N. Veys, F. Verbeke, J. Delanghe, D. De Bacquer, and N. Lameire The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes Nephrol. Dial. Transplant., January 1, 2006; 21(1): 77 - 83. [Abstract] [Full Text] [PDF]
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N. A. Khan, I. Ma, C. R. Thompson, K. Humphries, D. N. Salem, M. J. Sarnak, and A. Levin Kidney Function and Mortality among Patients with Left Ventricular Systolic Dysfunction J. Am. Soc. Nephrol., January 1, 2006; 17(1): 244 - 253. [Abstract] [Full Text] [PDF]
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J. J. Brugts, A. M. Knetsch, F. U. S. Mattace-Raso, A. Hofman, and J. C. M. Witteman Renal Function and Risk of Myocardial Infarction in an Elderly Population: The Rotterdam Study Arch Intern Med, December 12, 2005; 165(22): 2659 - 2665. [Abstract] [Full Text] [PDF]
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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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D. N. Reddan, L. Szczech, M. V. Bhapkar, D. J. Moliterno, R. M. Califf, E. M. Ohman, P. B. Berger, J. S. Hochman, F. Van de Werf, R. A. Harrington, et al. Renal function, concomitant medication use and outcomes following acute coronary syndromes Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2105 - 2112. [Abstract] [Full Text] [PDF]
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C. S. Fox, M. G. Larson, E. P. Leip, J. B. Meigs, P. W.F. Wilson, and D. Levy Glycemic Status and Development of Kidney Disease: The Framingham Heart Study Diabetes Care, October 1, 2005; 28(10): 2436 - 2440. [Abstract] [Full Text] [PDF]
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R. N. Foley, C. Wang, and A. J. Collins Cardiovascular Risk Factor Profiles and Kidney Function Stage in the US General Population: The NHANES III Study Mayo Clin. Proc., October 1, 2005; 80(10): 1270 - 1277. [Abstract] [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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A. M. O'Hare, R. A. Rodriguez, and P. Bacchetti Low Ankle-Brachial Index Associated With Rise in Creatinine Level Over Time: Results From the Atherosclerosis Risk in Communities Study Arch Intern Med, July 11, 2005; 165(13): 1481 - 1485. [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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Z. T. Bloomgarden The European Association for the Study of Diabetes Diabetes Care, May 1, 2005; 28(5): 1250 - 1257. [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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K. Kalantar-Zadeh, K. C Abbott, A. K Salahudeen, R. D Kilpatrick, and T. B Horwich Survival advantages of obesity in dialysis patients Am. J. Clinical Nutrition, March 1, 2005; 81(3): 543 - 554. [Abstract] [Full Text] [PDF]
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 W. Koenig, D. Twardella, H. Brenner, and D. Rothenbacher Plasma Concentrations of Cystatin C in Patients with Coronary Heart Disease and Risk for Secondary Cardiovascular Events: More than Simply a Marker of Glomerular Filtration Rate Clin. Chem., February 1, 2005; 51(2): 321 - 327. [Abstract] [Full Text] [PDF]
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 C C Geddes and G M Baxter Renal impairment Imaging, January 1, 2005; 17(1): 1 - 18. [Abstract] [Full Text] [PDF]
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