Nanba K; Vaidya A; Williams GH; Zheng I; Else T; Rainey WE
Circulation 2017[Jul]; 136 (4): 347-55 PMID28566337show ga
Background: Both aging and inappropriate secretion of aldosterone increase the risk for developing cardiovascular disease; however, the influence of aging on aldosterone secretion and physiology is not well understood. Methods: The relationship between age and adrenal aldosterone synthase (CYP11B2) expression was evaluated in 127 normal adrenals from deceased kidney donors (age 9mo-68y). Following immunohistochemistry, CYP11B2 expressing area and areas of abnormal foci of CYP11B2 expressing cells, called aldosterone-producing cell clusters (APCCs), were analyzed. In a separate ancillary clinical study of 677 participants without primary aldosteronism, who were studied on both high and restricted sodium diets (age 18-71y), we used multivariable linear regression to assess the independent associations between age and renin-angiotensin-aldosterone system physiology. Results: In adrenal tissue, the total CYP11B2 expressing area was negatively correlated with age (r=?0.431, P <0.0001), whereas the total APCC area was positively correlated with age (r=0.390, P<0.0001). The integrated ratio of APCC to CYP11B2 expressing area was most strongly and positively correlated with age (r=0.587, P < 0.0001). When participants in the clinical study were maintained on a high sodium balance, renin activity progressively declined with older age, whereas serum and urinary aldosterone did not significantly decline. Correspondingly, the aldosterone-to-renin ratio (ARR) was positively and independently associated with older age (adjusted ?=+5.54 ng/dL per ng/mL/h per 10 years, P<0.001). In contrast, when participants were assessed under sodium restricted conditions, physiologic stimulation of aldosterone was blunted with older age (?=?4.6 ng/dL per 10 years, P<0.0001). Conclusion: Aging is associated with a pattern of decreased normal zona glomerulosa CYP11B2 expression and increased APCC expression. This histopathologic finding parallels an age-related autonomous aldosteronism and abnormal aldosterone physiology that provides one potential explanation for age-related cardiovascular risk.
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Circulation 2017 ; 136 (4): 347-55
