Association of Plasma Aldosterone With Cardiovascular Mortality in Patients With Low Estimated GFR: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study

Background: We have previously shown that plasma aldosterone levels within the physiologic reference range predicted increased all-cause and cardiovascular disease (CVD) mortality in patients referred for coronary angiography. Decreased kidney function is associated with a marked increase in CVD mortality that is not explained fully by known cardiovascular risk factors. We hypothesized that level of kidney function might modify the association between plasma aldosterone level and CVD mortality. Study Design: Prospective cohort study. Setting & Participants: 3,153 patients (mean age, 62.7 +/- 10.6 years; 30.1% women) free of primary kidney disease at baseline were referred for coronary angiography in a tertiary-care center in Southwest Germany between 1997 and 2000. Predictors: Plasma aldosterone level, determined using radioimmunoassay. Tertiles of estimated glomerular filtration rate (eGFR) based on creatinine and cystatin C levels. Results: At baseline, median plasma aldosterone concentration was 79.0 (25th-75th percentile, 48.0-124.0) pg/mL. Mean eGFR was 83.8 +/- 20.1 (SD) mL/min/1.73 m(2), and mean eGFRs in tertiles 1-3 were 61.9 +/- 13.0, 84.7 +/- 4.4, and 104.7 +/- 10.3 mL/min/1.73 m2, respectively. After a median follow-up of 7.75 years, 454 (14.4%) patients died of cardiovascular causes and 179 (5.7%) died suddenly. Multivariate Cox proportional hazard analyses showed increased risks of CVD mortality (HR per 50-pg/mL increment in plasma aldosterone concentration, 1.08; 95% CI, 1.03-1.12; P = 0.001) and sudden cardiac death (HR, 1.11; 95% CI, 1.06-1.15; P < 0.001). In tertiles 1-3 of eGFR, adjusted HRs per 50-pg/mL increment in plasma aldosterone concentration for CVD mortality were 1.10 (95% CI, 1.05-1.14; P < 0.001), 1.00 (95% CI, 0.83-1.16; P = 0.8), and 0.97 (95% CI, 0.75-1.26; P = 0.8), respectively (product term for interaction, P = 0.001), and for sudden cardiac death were 1.13 (95% CI, 1.08-1.17; P < 0.001), 0.99 (95% CI, 0.75-1.29; P = 0.9), and 0.90 (95% CI, 0.60-1.34; P = 0.5), respectively (product term for interaction, P < 0.001). Limitations: No urinary analysis was performed to assess dietary salt intake and proteinuria. Conclusions: Our findings suggest that the association of higher plasma aldosterone concentration with overall CVD mortality and sudden cardiac death is stronger for patients with lower kidney function. Am J Kidney Dis. 57(3): 403-414. (C) 2011 by the National Kidney Foundation, Inc.