Bimodal aldosterone distribution in low-renin hypertension

In low-renin hypertension (LRH), serum aldosterone levels are higher in those subjects with primary aldosteronism and may be lower in those with non-aldosterone mineralocorticoid excess or primary renal sodium retention. We investigated the hypothesis that the frequency distribution of aldosterone in LRH is bimodal.

Of the 3,532 attendees at the sixth examination cycle of the Framingham Offspring Study, 1,831 were included in this cross-sectional analysis after we excluded those with conditions or taking medications such as antihypertensive drugs that might affect renin or aldosterone.

Three hundred three subjects (17%) had untreated hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg). LRH, defined as plasma renin ≤5 mU/L, was present in 93 of those 303 hypertensive subjects (31%). Aldosterone values were adjusted statistically for age, sex, and the urinary sodium/creatinine ratio. In the subjects with LRH, the adjusted aldosterone distribution was bimodal (dip test for unimodality, P = 0.008). The adjusted aldosterone distribution was unimodal in the normal subjects (P = 0.98) and in the hypertensive subjects with normal plasma renin (P = 0.94).

In this community-based sample of white subjects, those with low-renin hypertension had a bimodal adjusted aldosterone distribution. Subjects with normal-renin hypertension and subjects with normal blood pressure had unimodal adjusted aldosterone distributions. These findings suggest 2 pathophysiological variants of LRH, one that is aldosterone-dependent and one that is non-aldosterone-dependent.