title: Thyroid function within the normal range and risk of coronary heart disease: an individual participant data analysis of 14 cohorts.
abstract: OBJECTIVE
  Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD).
  
  
  OBJECTIVE
  To assess the association between differences in thyroid function within the reference range and CHD risk.
  
  
  METHODS
  Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55,412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline.
  
  
  METHODS
  Thyroid function as expressed by serum thyrotropin levels at baseline.
  
  
  METHODS
  Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.
  
  
  RESULTS
  Among 55,412 individuals, 1813 people (3.3%) died of CHD during 643,183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48,875 individuals (9.5%) experienced a first-time CHD event during 533,408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results.
  
  
  CONCLUSIONS
  Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim2Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim3Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, Massachusetts.
authors.forename: Lars J
authors.initials: LJ
authors.lastname: Vatten
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway5Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Bjøro
authors.affiliation: Department of Medicine, University of California, San Francisco7Department of Epidemiology and Biostatistics, University of California, San Francisco.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.affiliation: School of Population Health, The University of Western Australia, Crawley.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bremner
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.affiliation: Department of Clinical and Experimental Medicine, Geriatric Endocrine Unit, University Hospital of Parma, Parma, Italy.
authors.forename: Graziano
authors.initials: G
authors.lastname: Ceresini
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Wendy P J
authors.initials: WP
authors.lastname: den Elzen
authors.affiliation: National Institute on Aging, Baltimore, Maryland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England.
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Franklyn
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jacobijn
authors.initials: J
authors.lastname: Gussekloo
authors.affiliation: National Council Research Institute of Clinical Physiology/Tuscany Region G. Monasterio Foundation, Pisa, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Iervasi
authors.affiliation: Department of Clinical Studies, Radiation Effects Research Foundation, Nagasaki, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Imaizumi
authors.affiliation: Department of Epidemiology and Public Health, University College Cork, Cork, Ireland.
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Kearney
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, England.
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: Division of Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Newman
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands21Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
authors.affiliation: Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle23Group Health Research Institute, Group Health Cooperative, Seattle, Washington.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.affiliation: Department of Endocrinology, Gateshead Health Foundation National Health Service Trust, Gateshead, England.
authors.forename: Salman
authors.initials: S
authors.lastname: Razvi
authors.affiliation: Division of Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil25Division of Endocrinology, Faculdade de Medicina de Marília, Marília, Brazil.
authors.forename: José A
authors.initials: JA
authors.lastname: Sgarbi
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands28Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: Department of Endocrinology, Royal Free Hospital, London, England.
authors.forename: Mark P J
authors.initials: MP
authors.lastname: Vanderpump
authors.affiliation: Institute for Community Medicine, Study of Health in Pomerania/Clinical-Epidemiological Research and German Centre of Cardiovascular Research, University of Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia32School of Medicine and Pharmacology, The University of Western Australia, Crawley.
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
authors.affiliation: Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands33Netherlands Consortium for Healthy Aging, Leiden, the Netherlands34Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of General Internal Medicine, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
mesh_terms: D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood / Q000209:etiology*; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D013972:Thyrotropin / Q000097:blood*
chemical_list: D013972:Thyrotropin