Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis
Open accessAbstract
Context: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. Objective: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). Data Sources and Study Selection: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Data Extraction: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Data Synthesis: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. Conclusions: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.
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Recent evidence suggests that mild hyperthyroidism or hypothyroidism may increase overall and cardiovascular-specific mortality and morbidity.
“However, recent evidence suggests that mild hyperthyroidism or hypothyroidism may increase overall and cardiovascular-specific mortality and morbidity (213)(214)(215)(216)(217)(218).”
From Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [215]
The introduction (p. 2) reports an association between subclinical hypothyroidism and coronary heart disease mortality and events, and the Results (p. 4) examine those outcomes. The paper does not establish the broader claim about mild hyperthyroidism or overall mortality; its reported outcomes here are coronary heart disease-specific. (LLM, conf=0.88)
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- Authors
- Collet, T.-H., Bauer, D. C., Cappola, A. R., Åsvold, B. O., Weiler, S., Vittinghoff, E., Gussekloo, J., Bremner, A., den Elzen, W. P. J., Maciel, R. M. B., Vanderpump, M. P. J., Cornuz, J., Dörr, M., Wallaschofski, H., Newman, A. B., Sgarbi, J. A., Razvi, S., Völzke, H., Walsh, J. P., Aujesky, D., & Rodondi, N.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- University of California, San Francisco (US)
- University of Pennsylvania (US)
- Norwegian University of Science and Technology (NO)
- University of Bern (CH)
- Departments of Epidemiology and Biostatistics (D.C.B., E.V.), San Francisco, San Francisco, California 94143
- Leiden University Medical Center (NL)
- The University of Western Australia (AU)
- Department of Public Health and Primary Care (J.G., W.P.J.d.E.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands
- Universidade Federal de São Paulo (BR)
- The Royal Free Hospital (GB)
- University of Lausanne (CH)
- Universitätsmedizin Greifswald (DE)
- University of Pittsburgh (US)
- Faculdade de Medicina de Marília (BR)
- National Health Service (GB)
- Corresponding author
- Rodondi, Nicolas
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-09-01
- Volume
- 99
- Issue
- 9
- Pages
- 3353-3362
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4154087
- OpenAlex
- W2095948051
- Semantic Scholar
- 6f9046b1a8155463d364f2028cdf11ecf4444ce8
- Cited by
- 71
- References
- 43
- Citations by year
- 2026: 3 · 2025: 4 · 2023: 5 · 2022: 7 · 2021: 7 · 2020: 12 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 2 · 2014: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- BORIS (University Library Bern) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (150025, 138267, 320030)
- National Institutes of Health (n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085086-022, n01hc55222-0-0-0, n01hc075150-004, n01hc035129-010)
- University of California, San Francisco
- National Institute on Aging (R56AG023629, R01AG032317, R01AG020098, R01-AG-15928, R01 AG20098, AG027058, R01AG023629, R01AG015928, R01AG027058, AG-032317, P30AG024827)
- National Heart, Lung, and Blood Institute (N01 HC085086, N01 HC085079, N01HC‐75150, N01 HC85086, N01 HC035129, N01 HC015103, N01HC80007, N01 HC55222, R01HL075366, U01HL080295, N01 HC055222, N01 HC075150, N01 HC045133, N01-HC85079)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K24AR051895)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- subclinical hypothyroidism, thyroid peroxidase antibodies, thyroid autoimmunity, coronary artery disease, coronary heart disease mortality, thyroid-stimulating hormone, prognostic factors, individual patient data meta-analysis, prospective cohort, cardiovascular risk stratification
- MeSH terms
- Adult, Aged, Aged, 80 and over, Autoantibodies, Coronary Disease, Female, Humans, Hypothyroidism, Male, Middle Aged, Prognosis, Risk Factors, Severity of Illness Index, Incidence, Prevalence, Seroepidemiologic Studies, Young Adult
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