Key result
Higher aldosterone-to-renin ratio is linked to ~24% higher risk of incident cardiovascular disease.
Why the study?
Primary aldosteronism is linked with harmful metabolic and cardiovascular effects, but limited research has explored the impact of subclinical primary aldosteronism on long-term clinical outcomes and the risk of developing cardiovascular disease.
Does subclinical primary aldosteronism (measured by plasma renin activity and aldosterone to renin ratio) increase the long-term risk of incident cardiovascular disease and all-cause death in adults with hypertension?
Cohort (n=1,308)
Does subclinical primary aldosteronism (measured by plasma renin activity and aldosterone to renin ratio) increase the long-term risk of incident cardiovascular disease and all-cause death in adults with hypertension?
In hypertensive adults, lower plasma renin activity and higher aldosterone-to-renin ratio are significantly associated with an increased long-term risk of developing cardiovascular disease, though not all-cause mortality.
Introduction Primary aldosteronism (PA) is a state of autonomous, renin-independent aldosterone production. It is linked with harmful metabolic and cardiovascular effects, however limited research has explored its impact on long term clinical outcomes. Purpose To evaluate the impact of subclinical primary aldosteronism in the risk of developing cardiovascular disease. Methods We assessed participants from the Generation 3 cohort of the Framingham Heart Study, where plasma renin activity (PRA) and aldosterone to renin ratio (ARR) were measured. We excluded patients without a diagnosis of hypertension. Cardiovascular disease was defined by the history of coronary heart disease, intermittent claudication, congestive heart failure, stroke or transient ischemic attack, or atrial fibrillation. Linear and Cox regression analyses were performed adjusted for relevant baseline variables. Results A total of 1308 patients were included (mean age 43.9±8.1, 34.9% female, 98.0% white, 49.2% with dyslipidemia, 8.7% with diabetes, 6.1% with coronary artery disease, 1.6% with heart failure, 1.4% with atrial fibrillation, 15.7% smokers). A total of 94 (7.2%) had a positive screening for primary hyperaldosteronism. Over a mean follow-up period of 13.8 years, there were 101 first cardiovascular events corresponding to 8.3% of the participants. PRA had a significant negative correlation with incident cardiovascular disease (Hazard Ratio [HR]= 0.76, 95% Confidence Interval [CI] 0.64 to 0.90, p=0.001). ARR had a positive correlation with incident cardiovascular disease (HR= 1.24, 95% CI 1.07 to 1.44, p=0.004). Neither PRA (HR=0.94, 95% CI 0.74 to 1.20, p=0.62), nor ARR (HR= 1.06, 95% CI 0.85 to 1.31, p=0.62) had a significant correlation with all cause death. Conclusions Lower renin levels and increased aldosterone were significantly associated with increased risk for developing cardiovascular disease. Renin and aldosterone measurements may help to stratify cardiovascular risk. Early mineralocorticoid receptor antagonists initiation may provide cardiovascular benefits to the subset of hypertensive patients with suppressed renin and increased aldosterone.
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Angélico‐Gonçalves et al. (2026) conducted a cohort in Hypertension and subclinical primary aldosteronism (n=1,308). Aldosterone-to-renin ratio (ARR) and plasma renin activity (PRA) was evaluated on Incident cardiovascular disease (coronary heart disease, intermittent claudication, congestive heart failure, stroke or transient ischemic attack, or atrial fibrillation) (HR 1.24, 95% CI 1.07-1.44, p=0.004). Higher aldosterone-to-renin ratio (HR 1.24; 95% CI 1.07-1.44; p=0.004) and lower plasma renin activity (HR 0.76; 95% CI 0.64-0.90; p=0.001) were associated with incident cardiovascular disease.
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