The relationship between aldosterone, oxidative stress, and inflammation in chronic, stable human heart failure

Background: Aldosterone antagonists reduce morbidity and mortality in patients with severe heart failure, but the mechanisms responsible are not fully understood. Observations in animal models suggest that elevated levels of aldosterone promote oxidative stress and inflammation in the myocardium. It is unknown if these findings are relevant to heart failure patients who may have much lower aldosterone levels. Methods and Results: We therefore examined the relationship of plasma aldosterone levels to markers of oxidative stress, inflammation and matrix turnover in 58 patients with chronic, stable heart failure from systolic dysfunction (LV ejection fraction < 0.40) who were not receiving aldosterone antagonists. Chronic, stable heart failure patients had modestly elevated levels of aldosterone. Additionally, these patients had elevated levels of 8-isoprostaglandin F-2 alpha, C-reactive protein, soluble intercellular adhesion molecule-1, osteopontin, brain natriuretic peptide, procollagen type III aminoterminal peptide, and tissue inhibitor of metalloproteinase-1. Among these patients with heart failure, aldosterone levels correlated with 8-iso-PGF(2 alpha) (P = .003), ICAM-1 (P = .008), and TIMP-1 (P = .006) after adjustment for age, gender, race, diabetes, smoking, heart rate, left ventricular mass, and body mass index. Conclusion: In chronic, stable heart failure patients on standard therapy, higher aldosterone levels are associated with systemic evidence of oxidative stress, inflammation, and matrix turnover.