Abstract Body: Background: Subclinical primary aldosteronism (PA), defined as renin-independent aldosterone production without overt PA, has recently been associated with adverse cardiac remodelling, unfavorable indices of arterial stiffness and incident hypertension. The objective of this study was to evaluate whether subclinical PA is linked to an increased risk of cardiovascular events.

Methods: This study used data from CARTaGENE, a populational cohort of randomly selected individuals aged 40-69 years, with prospective outcomes data obtained from linkage with governmental administrative databases. The outcome of interest was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, stroke and heart failure, assessed from enrollment (2009-2010) to March 2021. All individuals with available plasma renin and aldosterone measurements, outcomes data and nutritional assessment were included in this study. Cox regression models were used to test the associated between MACE and the log-transformed aldosterone-to-renin ratio (ARR), with adjustments for sex, age, height, weight, race, diabetes, prior cardiovascular disease, smoking status, systolic BP, heart rate, estimated glomerular filtration rate, sodium and potassium levels, LDL- and total-cholesterol, antihypertensive drugs (listed as individual classes), statin and aspirin use, and 24-hour nutritional intake of sodium and potassium. Multiple imputation was used for missing data.

Results: In 2,055 participants with available data (45.5% female, mean age 55.6 years, 6.6% diabetes, 2.9% prior cardiovascular disease, mean baseline systolic BP 128.5 mmHg), 58 MACEs occurred over a median follow-up of 10.8 years (IQR 10.6-11.0). In the Cox regression analysis, the log-transformed ARR was predictive of MACE with a hazard ratio (HR) of 2.86 (95% CI 1.34 to 6.10, p=0.007). Results were similar when participants taking any anti-hypertensive drug were excluded (HR 3.05, 95% CI 1.38 to 6.71, p=0.006).

Conclusion: In a representative sample of the general population, a higher ARR appears to be highly predictive of adverse cardiovascular events. This indicates that subclinical PA could be an important and yet unrecognized risk factor for cardiovascular diseases, and may warrant screening in a broader population.