title: Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.
abstract: Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; P<0.0001) and higher SASSI (β=-58.63; P=0.001) predicted lower RPF and a blunted RPF response to sodium loading and angiotensin II infusion. We observed a continuous, independent, multivariate-adjusted interaction between age and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (P<0.05). Higher SASSI and lower RPF independently predicted higher Framingham Risk Score (P<0.0001) and together displayed an additive effect. Aldosterone regulation and age may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.
authors.affiliation: MMSc, Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, RFB, Boston, MA 02115. avaidya1@partners.org.
authors.forename: Jenifer M
authors.initials: JM
authors.lastname: Brown
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Underwood
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferri
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Williams
authors.forename: Gail K
authors.initials: GK
authors.lastname: Adler
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
mesh_terms: D000367:Age Factors; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D004039:Diet, Sodium-Restricted; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D017595:Renal Plasma Flow / Q000187:drug effects / Q000502:physiology*; D012307:Risk Factors; D012982:Sodium, Dietary / Q000008:administration & dosage; D010130:p-Aminohippuric Acid / Q000494:pharmacology
chemical_list: D012982:Sodium, Dietary; D000804:Angiotensin II; D000450:Aldosterone; D010130:p-Aminohippuric Acid
keywords: aging; aldosterone; renal plasma flow; renin-angiotensin system