Complementary and Incremental Mortality Risk Prediction by Cortisol and Aldosterone in Chronic Heart Failure

BACKGROUND: In patients with systolic heart failure, high levels of circulating aldosterone are associated with an adverse prognosis, and mineralocorticoid receptor blockade improves survival. The prognostic significance of cortisol that may also bind and activate the mineralocorticoid receptor in chronic heart failure is unknown. METHODS AND RESULTS: Serum levels of cortisol and aldosterone were quantified in a prospective cohort study of 294 consecutive patients with chronic heart failure 48% were in New York Heart Association functional class III or IV; 58% had systolic heart failure. During a median follow-up of 803 days (interquartile range, 314 to 1098), 79 patients died (27.3% mortality rate). Cortisol and aldosterone were independent predictors of increased mortality risk in Cox regression analyses adjusted for age, sex, New York Heart Association functional class, C-reactive protein, N-terminal pro-brain natriuretic peptide, sodium, and hypercholesterolemia. The hazard ratio for highest versus lowest tertile of cortisol was 2.72 95% confidence interval [CI, 1.38 to 5.36; P=0.004], and the hazard ratio for aldosterone was 2.19 (95% CI, 1.23 to 3.93; P=0.008). Patients with both cortisol and aldosterone levels above the respective medians had a 3.4-fold higher mortality risk compared with subjects with both corticosteroids below the median (95% CI, 1.54 to 7.46; P=0.0001). Addition of cortisol and aldosterone levels to the fully adjusted model significantly improved the discriminatory power increase in Harrell's C-statistic from 0.80 (95% CI, 0.70 to 0.90) to 0.86 (95% CI, 0.79 to 0.94; P<0.001 for change. CONCLUSIONS: In patients with chronic heart failure, higher serum levels of both cortisol and aldosterone were independent predictors of increased mortality risk that conferred complementary and incremental prognostic value.