The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study

Abstract

Background: Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease.

Objective: To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure.

Design: Cross-sectional study.

Setting: 4 U.S. academic medical centers.

Participants: Participants with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408).

Measurements: Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 μg/24 h.

Results: Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower serum potassium levels. Mean adjusted levels of urinary aldosterone were 6.5 μg/24 h (95% CI, 5.2 to 7.7 μg/24 h) in normotension, 7.3 μg/24 h (CI, 5.6 to 8.9 μg/24 h) in stage 1 hypertension, 9.5 μg/24 h (CI, 8.2 to 10.8 μg/24 h) in stage 2 hypertension, and 14.6 μg/24 h (CI, 12.9 to 16.2 μg/24 h) in resistant hypertension; corresponding adjusted prevalence estimates for biochemically overt primary aldosteronism were 11.3% (CI, 5.9% to 16.8%), 15.7% (CI, 8.6% to 22.9%), 21.6% (CI, 16.1% to 27.0%), and 22.0% (CI, 17.2% to 26.8%). The aldosterone-renin ratio had poor sensitivity and negative predictive value for detecting biochemically overt primary aldosteronism.

Limitation: Prevalence estimates rely on arbitrary and conventional thresholds, and the study population may not represent nationwide demographics.

Conclusion: The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of "essential" hypertension.

Primary funding source: National Institutes of Health.

Keywords: Aldosterone; Blood pressure; Cardiovascular diseases; Excretion; Hypertension; Potassium; Resistant hypertension; Salts; Sensitivity; Sodium.

Conflict of interest statement

Disclosures: Dr. Brown reports grants from the National Heart, Lung, and Blood Institute. Dr. Williams reports grants from the National Institutes of Health. Dr. Vaidya reports consultancy for Catalys Pacific, Corcept Therapeutics, HRA Pharma, Orphagen, and Selenity Therapeutics and grants from the National Institutes of Health and Ventus Charitable Foundation. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-0065.

Figures

Figure 1.

Overall pooled study population. The eligible study population consisted of all participants in high sodium balance. Renin-independent aldosterone production could be assessed only in the subset in whom renin was suppressed. * Adequate oral sodium suppression with a high sodium balance is defined as 24-h urinary sodium excretion ≥190 mmol. † Suppressed renin activity is defined as seated plasma renin activity

Figure 2.

Distribution of renin-independent aldosterone production, by blood pressure category. A. The unadjusted urinary aldosterone excretion rate in the context of high sodium balance and renin suppression. Vertical bars represent the unadjusted renin-independent aldosterone excretion rate (y-axis) for each individual participant, ordered from lowest to highest (x-axes). The dashed horizontal line represents the conventional 12 μg/24 h threshold for the diagnosis of biochemically overt primary aldosteronism. B. Unadjusted overlaid density plots depicting the distribution of renin-independent aldosterone production, by blood pressure category (truncated at 45 μg/24 h). The x-axis shows the 24-h urinary aldosterone excretion rate. The y-axis shows the probability density function (smoothed using a kernel density estimation) per unit on the x-axis. C. Mean (95% CI) urinary aldosterone excretion rates for each blood pressure category, unadjusted (solid lines with circles) and adjusted (dotted lines with squares) for age, body mass index, race, sex, history of diabetes, and 24-h urinary sodium excretion.