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Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality
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CONTEXT: Data regarding the association between subclinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospective cohort studies. This might reflect differences in participants' age, sex, thyroid-stimulating hormone (TSH) levels, or preexisting cardiovascular disease. OBJECTIVE: To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism. DATA SOURCES AND STUDY SELECTION: The databases of MEDLINE and EMBASE (1950 to May 31, 2010) were searched without language restrictions for prospective cohort studies with baseline thyroid function and subsequent CHD events, CHD mortality, and total mortality. The reference lists of retrieved articles also were searched. DATA EXTRACTION: Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan. The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data. Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Subclinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations. RESULTS: Among 55,287 adults, 3450 had subclinical hypothyroidism (6.2%) and 51,837 had euthyroidism. During follow-up, 9664 participants died (2168 of CHD), and 4470 participants had CHD events (among 7 studies). The risk of CHD events and CHD mortality increased with higher TSH concentrations. In age- and sex-adjusted analyses, the hazard ratio (HR) for CHD events was 1.00 (95% confidence interval [CI], 0.86-1.18) for a TSH level of 4.5 to 6.9 mIU/L (20.3 vs 20.3/1000 person-years for participants with euthyroidism), 1.17 (95% CI, 0.96-1.43) for a TSH level of 7.0 to 9.9 mIU/L (23.8/1000 person-years), and 1.89 (95% CI, 1.28-2.80) for a TSH level of 10 to 19.9 mIU/L (n = 70 events/235; 38.4/1000 person-years; P <.001 for trend). The corresponding HRs for CHD mortality were 1.09 (95% CI, 0.91-1.30; 5.3 vs 4.9/1000 person-years for participants with euthyroidism), 1.42 (95% CI, 1.03-1.95; 6.9/1000 person-years), and 1.58 (95% CI, 1.10-2.27, n = 28 deaths/333; 7.7/1000 person-years; P = .005 for trend). Total mortality was not increased among participants with subclinical hypothyroidism. Results were similar after further adjustment for traditional cardiovascular risk factors. Risks did not significantly differ by age, sex, or preexisting cardiovascular disease. CONCLUSIONS: Subclinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels, particularly in those with a TSH concentration of 10 mIU/L or greater.
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“Recent individual patient meta-analysis by the Thyroid Studies Collaboration8,9,10,11 did not find higher risk of CVD and all-cause mortality among adults with subclinical hypothyroidism compared with those with euthyroidism”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [8]
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In the citing paper
“a recent metaanalysis showed that significantly increased risk of cardiovascular mortality and morbidity was primarily observed in individuals with TSH levels > 10mIU/L, with potential effects of TSH values > 7mIU/L (52).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [52]
In the citing paper
“A previous meta-analysis8 reported that subclinical hypothyroidism is associated with higher CVD risk, and thus treatment with levothyroxine is recommended when serum TSH concentrations reach 10 mIU/L or greater.4,31”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [8]
In the citing paper
“Although epidemiological studies have shown an association between subclinical hypothyroidism and coronary heart disease in younger people (<65 years) 16 or those with high TSH (>10 mU/l), 17”
From Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee (2016) · cites this paper as [17]
In the citing paper
“Similarly, several studies have found an association of elevated serum TSH with adverse cardiac outcomes, including myocardial infarction (MI), heart failure, and mortality (8, 10, 21–24).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [24]
In the citing paper
“some studies suggest an adverse effect of this state (8, 10, 22, 24) whereas others show a neutral or even protective effect on outcome (2, 17, 25, 29, 36, 37).”
From Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study (2016) · cites this paper as [24]
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Self-citation
Metadata
- Authors
- Rodondi, N., den Elzen, W. P. J., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., Åsvold, B. O., Iervasi, G., Imaizumi, M., Collet, T.-H., Bremner, A., Maisonneuve, P., Sgarbi, J. A., Khaw, K.-T., Vanderpump, M. P. J., Newman, A. B., Cornuz, J., Franklyn, J. A., Westendorp, R. G. J., Vittinghoff, E., Gussekloo, J., & Thyroid Studies Collaboration, F. T.
- Affiliations
- University of Lausanne (CH)
- The University of Western Australia (AU)
- University of Pittsburgh (US)
- Leiden University (NL)
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2010-09-22
- Volume
- 304
- Issue
- 12
- Pages
- 1365
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3923470
- OpenAlex
- W2128219988
- Cited by
- 1,216
- References
- 55
- Citations by year
- 2026: 56 · 2025: 53 · 2024: 52 · 2023: 99 · 2022: 94 · 2021: 87 · 2020: 97 · 2019: 77 · 2018: 93 · 2017: 84 · 2016: 74 · 2015: 79 · 2014: 86 · 2013: 69 · 2012: 69
- FWCI
- 43.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- IRIS (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- U.S. Department of Energy
- American Heart Association (N01-HC-)
- University of Pittsburgh (P30-AG024827)
- Norges Teknisk-Naturvitenskapelige Universitet
- Cancer Research UK
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (911-03-016)
- National Institutes of Health (N01-AG-6-2103, n01hc085082-026, n01hc085081-021, n01ag062101-007, n01hc045133-001, n01hc085079-024, n01hc015103-009, n01hc085084-005, n01cn015103-001, n01ag062103-006, n01hc085085-011, n01hc085083-027, n01hc085080-026, N01‐AG‐6‐2106, n01ag062106-007, n01hc085086-022, N01-AG-6-2101, n01hc075150-004, n01hc035129-010, n01hc055222-001, N01HC85086, AG 20098, N01HC85079, AG-023629, N01-HC-75150, N01HC-35129, N01HC-15103, N01-HC-45133, HL080295)
- Medical Research Council
- Norwegian Institute of Public Health
- National Institute on Aging (N01‐AG‐6–2101, N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106, N01HC85079, N01 HC‐15103, AG 20098, R56AG023629, AG-15928, R01AG032317, N01HC55222, N01‐HC‐35129, N01-HC-75150, R01AG020098, AG023629, N01 AG062106, AG027058, N01AG62106, HL080295, 024827, N01‐HC‐45133, N01‐HC‐85086, R01AG023629, R01AG015928, N01-AG-62103, N01 AG062103, R01AG027058, AG-032317, P30AG024827, N01 AG062101)
- National Heart, Lung, and Blood Institute (N01-HC-85081, N01 HC085086, AG-023629, N01HC-85083, AG-027058, HC-85086, N01HC15103, N01 HC085079, HC85079, N01 HC085083, N01HC85082, N01HC‐75150, N01 HC85086, AG-20098, N01 HC085080, N01 HC035129, HL-075366, N01HC85080, N01-HC, HC-35129, N01AG62101, N01 HC015103, N01HC80007, N01 HC55222, R01HL075366, N01 HC085085, HC-45133, N01‐HC‐45133, N01AG62106, N01HC085082, U01HL080295, N01 HC055222, R01 HL, N01AG62103, AG-15928, N01 HC085081, N01-HC-85079 through N01-HC-85086, HL080295, N01 HC075150, HC-15103, N01 HC085084, N01 HC045133, N01-HC85079, N01HC35129)
- National Cancer Institute (N01 CN015103)
- National Institute of Neurological Disorders and Stroke (N01-AG-6-2106, N01-AG-6-2103, AG023629, AG‐15928, AG‐027058, AG‐20098, N01-HC-75150, HL080295, N01-HC-35129, N01-HC-45133, N01-AG-6-2101, N01-HC-85086, N01 HC-55222, N01HC85079, N01-HC-15103)
- 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 › Hormonal and reproductive studies
- Keywords
- subclinical hypothyroidism, coronary artery disease, cardiovascular mortality, thyroid-stimulating hormone, thyroid function, cardiovascular risk, euthyroidism, prospective cohort, cardiovascular outcomes, sex differences, age differences, cardiovascular risk factors, cardiovascular screening, cardiovascular disease prevention
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Coronary Disease, Female, Humans, Hypothyroidism, Male, Middle Aged, Mortality, Prospective Studies, Risk, Thyrotropin, Young Adult
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