Relationship between renin, aldosterone, aldosterone-to-renin ratio and left ventricular mass index in young adults

Abstract Background Primary aldosteronism (PA), characterised by excessive aldosterone production and mineralocorticoid receptor activation, is associated with adverse cardiovascular outcomes including left ventricular hypertrophy and failure. Elevated cardiovascular risk is observed even in milder and subclinical forms of PA, especially in middle-aged and elderly populations. It is unclear if early changes in PA biomarkers can affect left ventricular mass index (LVMI), which is a strong predictor of cardiovascular diseases. Aim To evaluate the relationship between PA biomarkers, namely renin concentration, aldosterone concentration and aldosterone-to-renin ratio (ARR), and LVMI in young adults. Methods The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analysed the data from the offspring of these women at age 27. Participants with PA biomarkers and LVMI measured by cardiac magnetic resonance imaging were included. Females who were on oral contraception were excluded due to its confounding effect on the ARR. We examined the relationship between LVMI and plasma renin, aldosterone, and ARR using multivariate-adjusted linear regression and used mediation analysis to test whether these relationships were dependent on systolic blood pressure (SBP). Results Of 758 participants, 252 (33.2%) were females and the mean (SD) age was 26.7 (0.4) years. Females had lower median plasma renin concentration (12.0 vs 15.4mU/L; p<0.001) and higher median ARR (21.0 vs 15.6; p<0.001) than males. There was no sex-difference in median plasma aldosterone concentration (257 vs 237pmol/L in males; p=0.143). Females had lower LVMI (52.2 vs 70.2 g/m²; p<0.001) than males. A significant association between LVMI and aldosterone was detected in males (β-coefficient 0.009; 95% CI 0.001 to 0.017; p=0.027), and between LVMI and ARR in females (β-coefficient 0.098; 95% CI 0.001 to 0.196; p=0.050) after adjusting for confounders. This relationship was not mediated by brachial SBP. Conclusion An elevated aldosterone concentration or ARR was associated with higher LVMI in young adults, independent of brachial SBP. Long-term follow-up is required to determine if the relationship persists over time and leads to reduced cardiac function. One may speculate that an intervention trial in young adults with subclinical PA is warranted to determine the role of aldosterone blockade in preventing future cardiovascular diseases.