Serum Aldosterone Concentration, Blood Pressure, and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis

Abstract

Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04-1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 μg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10-2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.

Keywords: aldosterone; atherosclerosis; blood pressure; hypertension; mortality; renin.

Figure 1.

Dose-response association between serum aldosterone concentrations and CAC Association between aldosterone and CAC using a restricted cubic spline regression model with three knots at 10^th, 50^th, and 90^th percentile of serum aldosterone concentrations. Negative binomial regression model was employed adjusting for age, sex, CAC at exam 2 or 3, race, education, insurance status, income, smoking status, alcohol intake, physical activity, statin prescription, BMI, LDL, serum sodium, serum potassium, urinary sodium, urinary potassium, plasma renin activity, and time from aldosterone measurement to CAC follow-up. The dashed lines represent the 95% CIs for the spline model (reference is 50 pg/ml). We restricted the range of aldosterone to below 300 pg/ml because predictions >300pg/ml are based on too few data points.

Figure 2.

Direct and Indirect effects of serum aldosterone concentrations on coronary artery calcium score via 10mmHg increase in blood pressure CAC, coronary artery calcium score; CI, confidence interval. Adjusted for age, sex, CAC at exam 2 or 3, race, education, insurance status, income, smoking status, alcohol intake, physical activity, statin prescription, BMI, LDL, serum sodium, serum potassium, urinary sodium, urinary potassium, plasma renin activity, and time from aldosterone measurement to CAC follow-up. Relative ratio of CAC at follow-up is calculated per 100 pg/ml increase in serum aldosterone concentrations. 200 iterations were performed for bootstrapping to estimate 95% CI.