title: Clinical and genetic correlates of aldosterone-to-renin ratio and relations to blood pressure in a community sample.
abstract: Aldosterone:renin ratio (ARR) is used to screen for hyperaldosteronism. Data regarding correlates of ambulatory ARR in the community and its relation to hypertension incidence are limited. We defined clinical correlates of ARR, determined its heritability, tested for association and linkage, and related ARR to blood pressure (BP) progression in nonhypertensive individuals among 3326 individuals from the Framingham Heart Study (53% women; mean age: 59 years). Ambulatory morning ARR (serum aldosterone and plasma renin concentrations) were related to clinical covariates, genetic variation across the REN locus, a 10-cM linkage map, and among nonhypertensive participants (n=1773) to progression of >or=1 Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure BP category (optimal: <120/80 mm Hg, normal: 120 to 129/80 to 84 mm Hg, high normal: 130 to 139/85 to 89 mm Hg, hypertension: >or=140/90 mm Hg), or incident hypertension (systolic BP: >or=140 mm Hg, diastolic BP: >or=90 mm Hg, or use of antihypertensive treatment). ARR was positively associated with age, female sex, untreated hypertension, total/high-density lipoprotein cholesterol ratio, hormone replacement therapy, and beta-blocker use, but negatively associated with angiotensin-converting enzyme inhibitor and diuretic use. ARR was heritable (h(2)=0.40), had modest linkage to chromosome 11p (logarithm of the odds: 1.89), but was not associated with 17 common variants in REN (n=1729). On follow-up (mean: 3 years), 607 nonhypertensive individuals (34.2%) developed BP progression, and 283 (16.0%) developed hypertension. Higher baseline logARR was associated with increased risk of BP progression (odds ratio per SD increment: 1.23; 95% CI: 1.11 to 1.37) and hypertension incidence (odds ratio per SD increment: 1.16; 95% CI: 1.00 to 1.33). ARR is a heritable trait influenced by clinical and genetic factors. There is a continuous gradient of increasing risk of BP progression across ARR levels in nonhypertensive individuals.
authors.affiliation: Framingham Heart Study of the National Heart Lung and Blood Institute and Boston University School of Medicine, Framingham, MA 01702-5827, USA. cnewtoncheh@partners.org
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Chao-Yu
authors.initials: CY
authors.lastname: Guo
authors.forename: Philimon
authors.initials: P
authors.lastname: Gona
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Stacy L
authors.initials: SL
authors.lastname: Musone
authors.forename: Amy L
authors.initials: AL
authors.lastname: Camargo
authors.forename: Jared A
authors.initials: JA
authors.lastname: Drake
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood*; D001794:Blood Pressure; D002880:Chromosomes, Human, Pair 11; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012083:Renin / Q000097:blood* / Q000235:genetics*; D012307:Risk Factors
chemical_list: D000450:Aldosterone; D012083:Renin