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Subclinical hypothyroidism and the risk of coronary heart disease and mortality.

TitleSubclinical hypothyroidism and the risk of coronary heart disease and mortality.
Publication TypeJournal Article
Year of Publication2010
AuthorsRodondi, N, Elzen, WPJ den, Bauer, DC, Cappola, AR, Razvi, S, Walsh, JP, Asvold, BO, Iervasi, G, Imaizumi, M, Collet, T-H, Bremner, A, Maisonneuve, P, Sgarbi, JA, Khaw, K-T, Vanderpump, MPJ, Newman, AB, Cornuz, J, Franklyn, JA, Westendorp, RGJ, Vittinghoff, E, Gussekloo, J
Corporate/Institutional AuthorsThyroid Studies Collaboration,
JournalJAMA
Volume304
Issue12
Pagination1365-74
Date Published2010 Sep 22
ISSN1538-3598
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Coronary Disease, Female, Humans, Hypothyroidism, Male, Middle Aged, Mortality, Prospective Studies, Risk, Thyrotropin, Young Adult
Abstract<p><b>CONTEXT: </b>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.</p><p><b>OBJECTIVE: </b>To assess the risks of coronary heart disease (CHD) and total mortality for adults with subclinical hypothyroidism.</p><p><b>DATA SOURCES AND STUDY SELECTION: </b>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.</p><p><b>DATA EXTRACTION: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p>
DOI10.1001/jama.2010.1361
Alternate JournalJAMA
PubMed ID20858880
PubMed Central IDPMC3923470
Grant ListN01 HC085086 / HC / NHLBI NIH HHS / United States
P30 AG024827 / AG / NIA NIH HHS / United States
R01 AG-15928 / AG / NIA NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
N01-AG-6-2101 / AG / NIA NIH HHS / United States
N01-HC-80007 / HC / NHLBI NIH HHS / United States
N01 HC085081 / HC / NHLBI NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
N01 AG062101 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL-075366 / HL / NHLBI NIH HHS / United States
N01-AG-6-2103 / AG / NIA NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
N01 HC085083 / HC / NHLBI NIH HHS / United States
/ / Medical Research Council / United Kingdom
P30-AG-024827 / AG / NIA NIH HHS / United States
AG-032317 / AG / NIA NIH HHS / United States
N01 HC085085 / HC / NHLBI NIH HHS / United States
N01 AG062106 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
N01 HC085082 / HC / NHLBI NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC085080 / HC / NHLBI NIH HHS / United States
/ / Intramural NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
/ / Cancer Research UK / United Kingdom
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01 AG062103 / AG / NIA NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
N01-HC-85083 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85080 / HC / NHLBI NIH HHS / United States
R01 AG-20098 / AG / NIA NIH HHS / United States
N01-AG-6-2106 / AG / NIA NIH HHS / United States
N01 HC085084 / HC / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
R01 AG032317 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States