Circulating aldosterone levels positively correlate with incident, resistant, obesity-, and obstructive sleep apnea-related hypertension.22–25 The relationship between aldosterone and incident hypertension was shown in the Framingham Offspring Study where over 4-years there was a 17% increased risk for developing hypertension per quartile increase in plasma aldosterone levels.23 Among patients with resistant hypertension (i.e., hypertension requiring ≥3 different antihypertensive medications at pharmacologically effective doses), the prevalence of primary hyperaldosteronism is between 17–23%.24, 25 Interestingly, the majority of patients with primary hyperaldosteronism and hypertension had a normal serum potassium at the time of diagnosis indicating that hypokalemia is a late manifestation of aldosterone excess.26 Furthermore, patients with hypertension and primary hyperaldosteronism had higher rates of atrial fibrillation, myocardial infarction, and stroke compared to hypertensive patients matched for elevations in blood pressure.27
Individual studies have shown that spironolactone and eplerenone are each efficacious in reducing blood pressure; however, there have been a limited number of head-to-head comparison studies designed to establish drug superiority.28 In one small study of patients with resistant hypertension, 6 months of spironolactone added to diuretic and ACE-I therapy reduced systolic and diastolic blood pressure by 25 and 12 mmHg, respectively, and the magnitude of the response was not predicted by the plasma aldosterone level.29 Similar conclusions from a substudy of 1,411 patients with resistant hypertension participating in ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) support the use of spironolactone as add-on therapy to conventional regimens requiring at least two anti-hypertensive medications (e.g., amlodipine plus perindopril or atenolol plus bendroflumethiazide).30 In mildly hypertensive self-described black patients, another group at increased risk for hypertension-associated cardiovascular complications, eplerenone is superior to ARB monotherapy, but has not been sufficiently compared to other anti-hypertensive drugs in this population.31