The Unrecognized Prevalence of Primary Aldosteronism

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.