Published Online
on November 19, 2007

A more recent version of this article appeared on December 4, 2007

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Submitted on June 22, 2007
Accepted on September 27, 2007

Influence of Albuminuria on Cardiovascular Risk in Patients With Stable Coronary Artery Disease

Scott D. Solomon MD^*, Julie Lin MD, MPH, Caren G. Solomon MD, MPH, Kathleen A. Jablonski PhD, Madeline Murguia Rice PhD, Michael Steffes MD, Michael Domanski MD, Judith Hsia MD, Bernard J. Gersh MBChB, DPhil, J. Malcolm O. Arnold MD, Jean Rouleau MD, Eugene Braunwald MD, Marc A. Pfeffer MD, PhD, for the Prevention of Events With ACE Inhibition (PEACE) Investigators

From the Divisions of Cardiovascular Medicine, Renal Medicine, and General Medicine, Brigham and Women’s Hospital (S.D.S., J.L., C.G.S., E.B., M.A.P.), Boston, Mass; George Washington University Biostatistics Center (K.A.J., M.M.R., J.H.), Rockville, Md; University of Minnesota Medical Center (M.S.), Minneapolis, Minn; National Heart, Lung, and Blood Institute (M.D.), Bethesda, Md; Mayo Clinic College of Medicine (B.J.G.), Rochester, Minn; London Health Sciences Centre, (J.M.O.A.), London, Ontario, Canada; and University of Montreal (J.R.), Montreal, Quebec, Canada.

^* To whom correspondence should be addressed. E-mail: ssolomon{at}rics.bwh.harvard.edu.

Background—Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and the risks for death and cardiovascular events among patients with stable coronary disease.

Methods and Results—We studied patients enrolled in the Prevention of Events with an ACE inhibitor (PEACE) trial, in which patients with chronic stable coronary disease and preserved systolic function were randomized to trandolapril or placebo and followed up for a median of 4.8 years. The urinary albumin to creatinine ratio (ACR) assessed in a core laboratory in 2977 patients at baseline and in 1339 patients at follow-up (mean 34 months) was related to estimated glomerular filtration rate and outcomes. The majority of patients (73%) had a baseline ACR within the normal range (<17 µg/mg for men and <25 µg/mg for women). Independent of the estimated glomerular filtration rate and other baseline covariates, a higher ACR, even within the normal range, was associated with increased risks for all-cause mortality (P<0.001) and cardiovascular death (P=0.01). The effect of trandolapril therapy on outcomes was not modified significantly by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 versus 14.6 µg/mg, P=0.0002), after adjustment for baseline ACR, time between collections, and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (hazard ratio per log ACR 1.74, 95% CI 1.08 to 2.82).

Conclusions—Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

Key words: cardiovascular diseases • kidney • albuminuria

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