Spectrum of Primary Aldosteronism and Risk of Cardiovascular Outcomes

Importance: Mounting evidence suggests that renin-independent aldosteronism is common and often underrecognized. Yet, whether aldosteronism across this broader spectrum is associated with incident cardiovascular disease (CVD) has not, to the authors' knowledge, been comprehensively evaluated. Objective: To determine whether aldosterone measures are associated with incident CVD events in community-dwelling older adults. Design, Setting, and Participants: This prospective cohort analysis included participants from the Atherosclerosis Risk in Communities (ARIC) study with serum aldosterone and renin levels measured in 2011 to 2013. Longitudinal analyses were conducted in March to September 2025 using Cox regression to assess associations between aldosterone parameters and incident CVD among participants free of heart failure (HF), myocardial infarction (MI), stroke, and potassium-sparing diuretic use at ARIC visit 5 (2011-2013). Exposures: Serum aldosterone level and aldosterone-renin ratio (ARR). Main Outcomes and Measures: Incident HF hospitalization, atrial fibrillation (AF), ischemic stroke, MI, and a composite of these events plus all-cause death. Results: Among 3477 individuals free of baseline CVD (mean [SD] age, 74.8 [4.9] years; 2139 female [61.5%]), the median (IQR) aldosterone level was 5.1 (3.0-8.3) ng/dL (to convert to picomoles per liter, multiply by 27.74), renin activity was 0.78 (0.41-1.90) ng/mL per hour, and ARR was 5.9 (2.2-12.3) ng/dL per ng/mL/h. Over 9 years of follow-up, higher ARR was associated with the composite outcome (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.08 per doubling), stroke (aHR, 1.13; 95% CI, 1.02-1.26), and AF (aHR, 1.10; 95% CI, 1.05-1.15) but not with incident HF hospitalization (aHR, 1.02; 95% CI, 0.96-1.07) or MI (aHR, 1.01; 95% CI, 0.92-1.12). Conclusions and Relevance: The findings of this cohort study underscore a spectrum of primary aldosteronism, in which higher ARR was independently associated with increased risks of AF and ischemic stroke among older adults, supporting the aldosterone pathway as a potential target for CVD prevention.