Prognostic Value of Aldosterone and Cortisol in Patients Hospitalized for Acutely Decompensated Chronic Heart Failure With and Without Mineralocorticoid Receptor Antagonism

• We model the prognostic value of aldosterone and cortisol in systolic heart failure (HF)
• Analyses were stratified according to mineralocorticoid receptor blocker (MRA) intake
• In MRA-naïve patients, high levels of both aldosterone and cortisol predicted death
• In patients on MRA, only aldosterone, but not cortisol, levels predicted death
• The prognosis-mediating effect of MRA supports a causal role of cortisol in HF

BackgroundSerum aldosterone and cortisol independently predict an increased mortality risk in heart failure (HF), and mineralocorticoid receptor antagonism (MRA) improves survival. The prognostic relevance of aldosterone and cortisol with MRA is unclear.Methods and ResultsIn this post hoc analysis of a prospective cohort, study serum levels of aldosterone and cortisol were measured at baseline in 842 patients with systolic HF. The mean age was 68 ± 12 years (27% female, 45% in New York Heart Association functional class III/IV, 43% with MRA; median follow-up 38 months [interquartile range 30–43 mo]). Crude mortality in the total cohort was 43% (patients with vs without MRA: 34% vs 41%; P = .052). In MRA-naïve patients, higher levels of both aldosterone and cortisol were predictive of increased mortality risk in multivariable Cox regression: hazard ratio (HR) with 95% confidence interval of highest vs lowest tertile for aldosterone: 1.51 [1.02–2.24] (P = .040); and for cortisol: 1.94 [1.28–2.93] (P = .002). In MRA-treated patients, aldosterone (highest vs lowest tertile: HR 1.65 [1.01–2.71]; P = .048) but not cortisol (HR 0.77 [0.44–1.27]; P = .33) was associated with all-cause mortality. Further subgroup analysis revealed that particularly patients with low cortisol and high aldosterone levels had the worst prognosis (HR 5.01 [2.22–11.3]; P < .001), compared with the reference of low cortisol and low aldosterone. Subjects with this profile had larger ventricles and more often coronary artery disease.ConclusionsIn systolic HF, the prognostic value of aldosterone and cortisol levels differs in dependency of MRA intake. The pathophysiologic link between low cortisol, high aldosterone, and increased mortality risk in patients with MRA needs to be clarified.