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


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 >or= 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].


CONCLUSIONS
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 (www.ClinicalTrials.gov number NCT00308347).
Eijkelkamp
Wouter B A
WB
Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. eijkelkamp@cs.com
Zhang
Zhongxin
Z
Brenner
Barry M
BM
Cooper
Mark E
ME
Devereux
Richard B
RB
Dahlöf
Björn
B
Ibsen
Hans
H
Keane
William F
WF
Lindholm
Lars H
LH
Olsen
Michael H
MH
Parving
Hans-Henrik
HH
Remuzzi
Giuseppe
G
Shahinfar
Shahnaz
S
Snapinn
Steven M
SM
Wachtell
Kristian
K
de Zeeuw
Dick
D
D000368:Aged; D000419:Albuminuria / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism* / Q000503:physiopathology; D003404:Creatinine / Q000097:blood / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012307:Risk Factors
D015415:Biomarkers; D003404:Creatinine