Prevalence of unrecognized primary aldosteronism in essential hypertension

Abstract

Few studies have assessed the prevalence of primary aldosteronism (PA) in population based samples representative of adults with previously diagnosed essential hypertension (EH), and none has documented the classic diagnostic criteria of (1) suppressed plasma renin activity (PRA), (2) inability to suppress aldosterone (aldo) production in response to sodium (Na+) loading, and (3) inability to stimulate PRA in response to volume (Na+) depletion. To estimate the prevalence of unrecognized PA, we considered 280 adults recruited through a diagnostic index of all residents of Olmsted County, MN with a previous diagnosis of EH. Of these, 140 individuals with stage I-II EH agreed to participate and 117 subjects (72 men, 45 women [age 52±7 years]) successfully completed both an aldo suppression test (positive for PA if PRA ≤1.0 ng/mL/hr and 24-hr urinary excretion of Na+ ≥200 mEq and aldo ≥12μg on high Na+ diet) and a PRA stimulation test (positive for PA if upright PRA ≤3.4 ng/mL/hr after oral furosemide [2 mg/kg body weight x 2]). In all 117 subjects, serum potassium values were in the normal range (4.0±0.4 mEq/L) and blood pressure averaged 139±14/92±7 mm Hg. Thirty subjects (26%) failied to suppress aldo production in response to Na+ loading (median urinary aldo excretion = 14.6 μg [range12-31]; median urinary Na+ excretion = 314 mEq [range 201-536]). Of these 30, 16 (14% of 117) also had suppressed PRA on high Na+ diet (median PRA = 0.4 ng/mL/hr [range 0.1-1.0]) and 14 (12% of 117) also failed to stimulate PRA in response to furosemide diuresis (median PRA = 1.4 ng/mL/hr [range 0.5-2.6]). Of the 14 with confirmed PA, 2 (14%) did not have suppressed PRA at initial screening. In addition, of 15 who had suppressed PRA at initial screening and who failed to suppress aldo on high Na+ diet, 3 (20%) did not have suppressed PRA on high Na+ diet or blunted stimulation of PRA with furosemide diuresis. Based on all three criteria, the prevalence of unsuspected PA in subjects with stage I-II EH is estimated to be 12±6%. Thus, the prevalence of PA among adults with previously diagnosed EH appears higher than previously estimated but lower than estimates based only upon inability to suppress aldo production in response to Na+ loading. Accurate diagnosis also depends on demonstration of suppressed PRA on high Na+ diet and inability to stimulate PRA with Na+ depletion.