Subclinical Primary Aldosteronism and Cardiovascular Health: A Population-Based Cohort Study

Abstract

Background: Primary aldosteronism, characterized by overt renin-independent aldosterone production, is a common but underrecognized form of hypertension and cardiovascular disease. Growing evidence suggests that milder and subclinical forms of primary aldosteronism are highly prevalent, yet their contribution to cardiovascular disease is not well characterized.

Methods: This prospective study included 1284 participants between the ages of 40 and 69 years from the randomly sampled population-based CARTaGENE cohort (Québec, Canada). Regression models were used to analyze associations of aldosterone, renin, and the aldosterone-to-renin ratio with the following measures of cardiovascular health: arterial stiffness, assessed by central blood pressure (BP) and pulse wave velocity; adverse cardiac remodeling, captured by cardiac magnetic resonance imaging, including indexed maximum left atrial volume, left ventricular mass index, left ventricular remodeling index, and left ventricular hypertrophy; and incident hypertension.

Results: The mean (SD) age of participants was 54 (8) years and 51% were men. The mean (SD) systolic and diastolic BP were 123 (15) and 72 (10) mm Hg, respectively. At baseline, 736 participants (57%) had normal BP and 548 (43%) had hypertension. Higher aldosterone-to-renin ratio, indicative of renin-independent aldosteronism (ie, subclinical primary aldosteronism), was associated with increased arterial stiffness, including increased central BP and pulse wave velocity, along with adverse cardiac remodeling, including increased indexed maximum left atrial volume, left ventricular mass index, and left ventricular remodeling index (all P<0.05). Higher aldosterone-to-renin ratio was also associated with higher odds of left ventricular hypertrophy (odds ratio, 1.32 [95% CI, 1.002-1.73]) and higher odds of developing incident hypertension (odds ratio, 1.29 [95% CI, 1.03-1.62]). All the associations were consistent when assessing participants with normal BP in isolation and were independent of brachial BP.

Conclusions: Independent of brachial BP, a biochemical phenotype of subclinical primary aldosteronism is negatively associated with cardiovascular health, including greater arterial stiffness, adverse cardiac remodeling, and incident hypertension.

Keywords: aldosterone; cardiovascular diseases; hyperaldosteronism; hypertension; renin; vascular stiffness.

Figure 1.. Flow diagram for study cohort.

Abbreviations: BP, blood pressure; CAHHM, Canadian Alliance for Healthy Hearts and Minds; MRI, magnetic resonance imaging.

Figure 2.. Associations of aldosterone, renin, and ARR with arterial stiffness assessed by central systolic blood pressure and pulse wave velocity.

Cross-sectional studies of arterial stiffness in: A) all participants [N = 1,284] and B) participants with normal BP only [n = 736]. Studies performed at CARTaGENE study entry (i.e., at the time of aldosterone and renin measurements). Models adjusted for brachial systolic BP, age, sex, smoking status, height, weight, estimated glomerular filtration rate, serum sodium, serum potassium, total cholesterol, HDL cholesterol, LDL cholesterol, statin use, diabetes mellitus, history of cardiovascular disease, and antihypertensive medication use. * Log-transformed variable. ^† Normal BP defined as blood pressure <130/80 mmHg and no use of antihypertensive medication. Abbreviations: ARR, aldosterone-to-renin ratio; BP, blood pressure.

Figure 3.. Associations of aldosterone, renin, and ARR with cardiac remodeling assessed via cardiac MRI.

A) All participants [N = 1,284] and B) participants with normal BP only [n = 736]. Outcomes based on cardiac MRI 5–7 years post-CARTaGENE enrollment (i.e., 5–7 years after initial aldosterone and renin measurements). Models adjusted for brachial systolic BP, age, sex, smoking status, height, weight, estimated glomerular filtration rate, serum sodium, serum potassium, total cholesterol, HDL cholesterol, LDL cholesterol, statin use, diabetes mellitus, history of cardiovascular disease, and antihypertensive medication use. * Log-transformed variable. ^† Normal BP defined as blood pressure <130/80 mmHg and no use of antihypertensive medication. ^‡ Left ventricular hypertrophy defined as top 5% of left ventricular mass index among males and females in the overall study cohort. Abbreviations: ARR, aldosterone-to-renin ratio; BP, blood pressure; CI, confidence interval; MRI, magnetic resonance imaging.

Figure 4.. Associations of aldosterone, renin, and ARR with incident hypertension.

Assessed prospectively via brachial BP measurement 5–7 years post-CARTaGENE enrollment (i.e., 5–7 years after initial aldosterone and renin measurements). Models adjusted for brachial systolic BP, age, sex, smoking status, height, weight, estimated glomerular filtration rate, serum sodium, serum potassium, total cholesterol, HDL cholesterol, LDL cholesterol, statin use, diabetes mellitus, and history of cardiovascular disease. * Log-transformed variable. ^† Hypertension defined as blood pressure ≥130/80 mmHg and/or use of antihypertensive medication. Abbreviations: ARR, aldosterone-to-renin ratio; BP, blood pressure.