Relationship Between Renin, Aldosterone, Aldosterone-to-Renin Ratio and Arterial Stiffness and Left Ventricular Mass Index in Young Adults

BACKGROUND: Primary aldosteronism, characterized by renin-independent aldosterone production, is associated with adverse cardiovascular remodeling and outcomes. Elevated cardiovascular risk is observed even in subclinical forms of primary aldosteronism according to studies conducted primarily in middle-aged and elderly populations. This study aimed to assess whether early changes in primary aldosteronism biomarkers during young adulthood are associated with arterial stiffness and left ventricular mass index (LVMI) before the onset of overt disease. METHODS: The Raine Study is a longitudinal, population-based cohort study in Western Australia that enrolled women during pregnancy. We analyzed the data from the offspring of these women at 17 (2006–2009) and 27 (2016–2018) years of age. Participants with elevated high-sensitivity C-reactive protein (>10 mg/L) and female participants who were on oral contraception were excluded. Pulse wave velocity and aortic augmentation index were measured by SphygmoCor Pulse Wave System at both ages, and aortic distensibility and LVMI were measured by cardiac magnetic resonance imaging at 27 years. Multivariable linear regression was used to examine the relationship between plasma renin, aldosterone, or aldosterone-to-renin ratio and arterial stiffness and LVMI. Mediation analysis was used to test the role of systolic blood pressure. RESULTS: This study included 859 participants at 17 (38.0% female) and 758 participants at 27 (33.2% female) years of age. Females had lower renin concentration at both 17 (20.7 mU/L versus 25.7 mU/L; P <0.001) and 27 (12.0 mU/L versus 15.4 mU/L; P <0.001) years of age; hence, the aldosterone-to-renin ratio was significantly higher at both 17 (18.2 versus 13.5; P <0.001) and 27 (21.0 versus 15.6; P <0.001) years of age in females compared with males. At 27 years of age, a significant association was detected between aldosterone and LVMI in males (β=0.009 95% CI, 0.001–0.017; P =0.027) and between aldosterone-to-renin ratio and LVMI in females (β=0.098 95% CI, 0.001–0.196; P =0.050) independently of systolic blood pressure and other confounders. No association was found between primary aldosteronism biomarkers and measures of arterial stiffness (pulse wave velocity, aortic augmentation index, and aortic distensibility) at either age. CONCLUSIONS: Aldosterone concentration and aldosterone-to-renin ratio were positively associated with the LVMI in young males and females, respectively, independently of systolic blood pressure. Long-term follow-up is required to determine whether the relationship persists over time, and clinical trials are needed to assess the cardiovascular benefits of early interventions to block aldosterone.