title: Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: the multi-ethnic study of atherosclerosis.
abstract: BACKGROUND
  Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed.
  
  
  OBJECTIVE
  We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort.
  
  
  METHODS
  We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements.
  
  
  RESULTS
  Serum PTH concentration.
  
  
  RESULTS
  Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = -2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication.
  
  
  CONCLUSIONS
  Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration. These results extend prior evidence from observational and intervention studies suggesting a potentially important and modifiable relationship between the RAAS and PTH in humans.
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension (J.B., A.V.), Center for Adrenal Disorders (A.V.), Brigham and Women's Hospital and Harvard Medical School (J.B., A.V.), Boston, Massachusetts 02115; Department of Medicine, Kidney Research Institute (I.H.d.B., C.R.-C., B.K.), University of Washington, Seattle, Washington 98104; Department of Medicine, Division of Nephrology (I.H.d.B., B.K.), University of Washington, Seattle, Washington 98104; The New York Academy of Medicine (D.S.S.), New York, New York 10029; Veterans' Affairs Hospital (M.A.), San Diego, California 92161; and Division of Preventive Medicine (M.A.), Department of Family and Preventive Medicine, University of California San Diego, San Diego, California 92093.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Brown
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.forename: Cassianne
authors.initials: C
authors.lastname: Robinson-Cohen
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
mesh_terms: D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001213:Asian; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy* / Q000208:ethnology; D003430:Cross-Sectional Studies; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D044465:White People
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D010281:Parathyroid Hormone; D000450:Aldosterone