title: Subclinical hyperthyroidism and the risk of coronary heart disease and mortality.
abstract: BACKGROUND
  Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting.We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.
  
  
  METHODS
  Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.
  
  
  RESULTS
  Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio[HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR,1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95%CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43).Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% forAF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L(for both, P value for trend, .03).
  
  
  CONCLUSIONS
  Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.
authors.affiliation: Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Tinh-Hai
authors.initials: TH
authors.lastname: Collet
authors.forename: Jacobijn
authors.initials: J
authors.lastname: Gussekloo
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.forename: Wendy P J
authors.initials: WP
authors.lastname: den Elzen
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.forename: Philippe
authors.initials: P
authors.lastname: Balmer
authors.forename: Giorgio
authors.initials: G
authors.lastname: Iervasi
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
authors.forename: José A
authors.initials: JA
authors.lastname: Sgarbi
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Bariş
authors.initials: B
authors.lastname: Gencer
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.forename: Sabrina
authors.initials: S
authors.lastname: Molinaro
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bremner
authors.forename: Robert N
authors.initials: RN
authors.lastname: Luben
authors.forename: Patrick
authors.initials: P
authors.lastname: Maisonneuve
authors.forename: Jacques
authors.initials: J
authors.lastname: Cornuz
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D002423:Cause of Death; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000175:diagnosis / Q000401:mortality*; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000150:complications / Q000175:diagnosis* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D013557:Switzerland; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*; D055815:Young Adult
chemical_list: D013972:Thyrotropin