Relation of Plasma Renin Activity to Subclinical Peripheral and Coronary Artery Disease (from the Multiethnic Study of Atherosclerosis)

Abstract

Experimental studies support a link between activation of the renin-angiotensin-aldosterone system and cardiovascular disease (CVD). The relationship with subclinical atherosclerosis is uncertain. Among 1,699 individuals without prevalent CVD from the Multiethnic Study of Atherosclerosis, we measured plasma renin activity (PRA) and aldosterone. Using multivariable logistic regression with restricted cubic splines, we assessed continuous log-transformed PRA and aldosterone associations with the ankle-brachial index (ABI) and coronary artery calcium (CAC) scores (Agatston) with adjustment for cardiovascular disease (CVD) risk factors, kidney function, and inflammatory biomarkers. In fully adjusted models mutually adjusting for PRA and aldosterone, higher PRA was associated with an ABI <1.0 (p overall <0.001, p nonlinear = 0.02) and CAC Agatston score >300 (p overall = 0.02, p nonlinear = 0.22), while aldosterone was not associated with either outcome. For example, compared to the 10th percentile (0.16 ng/ml/hr) of PRA, the 90th percentile (2.68 ng/ml/hr) had 3.6 times (OR 3.62; 95% CI: 2.13 to 6.13) and 1.7 times higher odds (odds ratio 1.67; 95% confidence interval: 1.13 to 2.48) of ABI <1.0 and CAC >300, respectively. These associations persisted after adjustment for levels of C-reactive protein, Interleukin-6, and Tumor Necrosis Factor-alpha. There were no significant differences in these associations by race/ethnicity or antihypertensive medication status. In conclusion, in a multiethnic cohort of community-living adults without prevalent clinical CVD, PRA was associated with greater burden of subclinical peripheral artery and coronary artery disease. These findings provide additional evidence that PRA may have deleterious effects on cardiovascular health through an atherosclerotic pathway.