Cardiac Structure and Function Across the Spectrum of Aldosteronism: the Atherosclerosis Risk in Communities Study

Abstract

Background: Aldosterone production and mineralocorticoid receptor activation are implicated in myocardial fibrosis and cardiovascular events.

Methods: Cardiac structure and function were assessed in 4547 participants without prevalent heart failure (HF) in the ARIC study (Atherosclerosis Risk in Communities), with echocardiography, aldosterone, and plasma renin activity measurement (2011-2013). Subjects were characterized by plasma renin activity as suppressed (≤0.5 ng/mL per hour) or unsuppressed (>0.5 ng/mL per hour). Cross-sectional relationships with cardiac structure and function, and longitudinal relationships with outcomes (HF hospitalization; HF and all-cause death; HF, death, myocardial infarction, and stroke; and incident atrial fibrillation) were assessed. Models were adjusted for demographic and anthropometric characteristics and additively, for blood pressure and antihypertensives.

Results: Evidence of primary aldosteronism physiology was prevalent (11.6% with positive screen) and associated with echocardiographic parameters. Renin suppression was associated with greater left ventricular mass, left ventricular volumes, and left atrial volume index, and a lower E/A ratio (adjusted P<0.001 for all). Higher aldosterone was associated with greater left ventricular mass and lower global longitudinal strain and lateral E'. The highest tertile of aldosterone was associated with a hazard ratio of 1.37 (95% CI, 1.06-1.77; 5.5-year follow-up) for incident atrial fibrillation relative to the lowest. Renin suppression was associated with HF (hazard ratio, 1.34 [95% CI, 1.05-1.72]; 7.3-year follow-up), although these relationships did not remain statistically significant after additional adjustment for hypertension.

Conclusions: Renin suppression and aldosterone excess, consistent with primary aldosteronism pathophysiology, were associated with cardiac structural and functional alterations and may represent an early target for mitigation of fibrosis with mineralocorticoid receptor antagonists.

Keywords: aldosterone; echocardiography; heart failure; mineralocorticoids; renin.

Figure 1.. Association of Aldosterone with Cardiac Structure and Function by Renin Suppression.

Continuous relationships of log-transformed aldosterone with left ventricular mass index (A), left atrial volume index (B), global longitudinal strain (C), and lateral E’ (D), categorized by renin suppression and adjusted for age, sex, race-center, diabetes, BMI, eGFR, low density lipoprotein cholesterol, smoking, systolic and diastolic blood pressure, and antihypertensive classes. Black = renin suppressed (≤0.5 ng/ml/h). Blue = renin non-suppressed (>0.5 ng/ml/h). Dashed lines: 95% confidence interval.

Figure 2.. Association between Aldosterone-to-Renin Ratio and Cardiac Structure and Function.

Continuous relationships of the log-transformed aldosterone-to-renin ratio with left ventricular mass index (A), left atrial volume index (B), global longitudinal strain (C), and lateral E’ (D), categorized by renin suppression, and adjusted for age, sex, race-center, diabetes, BMI, eGFR, low density lipoprotein cholesterol, smoking, systolic and diastolic blood pressure, and antihypertensive classes. Dashed lines: 95% confidence interval.