Arnold, J. Malcolm O.

Background: Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality. We assessed the association between albuminuria and death or cardiovascular events among patients with stable coronary disease. Methods: 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 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 (eGFR) and outcomes. Results: The majority of patients (73%) had a baseline albumin/creatinine ratio within the normal range. Independent of the eGFR and other baseline covariates, a higher albumin/creatinine ratio 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 significantly modified by the level of albuminuria. Nevertheless, trandolapril therapy was associated with a significantly lower mean follow-up ACR (12.5 ug/mg vs 14.6 ug/mg, p = 0.0002), after adjusting for baseline ACR, time between collections and other covariates. An increase in ACR over time was associated with increased risk of cardiovascular death (HR per log ACR 1.74, 95% confidence intervals 1.08–2.82). Conclusions: Albuminuria, even in low levels within the normal range, is an independent predictor of cardiovascular and all-cause mortality.

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.