Renal function and risk for cardiovascular events in type 2 diabetic patients with hypertension: The RENAAL and LIFE studies

Wouter B A Eijkelkamp, Zhongxin Zhang, Barry M. Brenner, Mark E. Cooper, Richard B. Devereux, Björn Dahlöf, Hans Ibsen, William F. Keane, Lars H. Lindholm, Michael H. Olsen, Hans Henrik Parving, Giuseppe Remuzzi, Shahnaz Shahinfar, Steven M. Snapinn, Kristian Wachtell, Dick De Zeeuw

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: To investigate whether a threshold exists for cardiovascular risk in type 2 diabetic patients with hypertension, the association between renal function and cardiovascular risk was examined across the entire physiological range of serum creatinine. DESIGN AND METHODS: The RENAAL and LIFE studies enrolled 1513 and 1195 patients with type 2 diabetes and hypertension, respectively. The relationship between baseline serum creatinine and the risk for a composite outcome of myocardial infarction, stroke or cardiovascular death was examined using Cox regression models. To adjust for heterogeneity between studies and treatment groups, these factors were included as strata when applicable. The analyses were conducted with adjustment for age, gender, smoking, alcohol use, blood pressure, heart rate, total and high-density lipoprotein (HDL) cholesterol, hemoglobin, albuminuria and prior cardiovascular disease. RESULTS: The hazard ratios across the baseline serum creatinine categories <0.9 mg/dl, 0.9-1.2 mg/dl, 1.2-1.6 mg/dl, 1.6-2.8 mg/dl and ≥ 2.8 mg/dl were 0.51 (95% confidence interval 0.34, 0.74), 0.74 (0.55, 1.00), 1.00 (reference), 1.24 (0.96, 1.59) and 1.67 (1.17, 2.91), respectively. Baseline serum creatinine (per mg/dl) strongly predicted the composite cardiovascular endpoint in LIFE [2.82(1.74,4.56), P <0.001], RENAAL [1.41(1.12,1.79), P <0.001], as well as the combined studies [1.51(1.21,1.87), P <0.001]. CONCLUSION: A progressively higher risk for the composite cardiovascular endpoint was observed with incremental baseline serum creatinine in type 2 diabetic patients with hypertension, even within the normal range. Thus, there appears to be no serum creatinine threshold level for an increased cardiovascular risk. Baseline serum creatinine was a major independent risk factor for cardiovascular disease ( number NCT00308347).

Original languageEnglish
Pages (from-to)871-876
Number of pages6
JournalJournal of Hypertension
Issue number4
Publication statusPublished - Apr 2007


  • Angiotensin II receptor blocker
  • Cardiovascular outcome
  • Hypertension
  • Intervention
  • Renal function
  • Serum creatinine
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology


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