Subclinical hypothyroidism and the risk of coronary heart disease and mortality

Nicolas Rodondi, Wendy P J Den Elzen, Douglas C. Bauer, Anne R. Cappola, Salman Razvi, John P. Walsh, Bjørn O. Åsvold, Giorgio Iervasi, Misa Imaizumi, Tinh Hai Collet, Alexandra Bremner, Patrick Maisonneuve, José A. Sgarbi, Kay Tee Khaw, Mark P J Vanderpump, Anne B. Newman, Jacques Cornuz, Jayne A. Franklyn, Rudi G J Westendorp, Eric Vittinghoff & 1 others Jacobijn Gussekloo

Research output: Contribution to journalArticle

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Abstract

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

Original languageEnglish
Pages (from-to)1365-1374
Number of pages10
JournalJournal of the American Medical Association
Volume304
Issue number12
DOIs
Publication statusPublished - Sep 22 2010

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Hypothyroidism
Coronary Disease
Thyrotropin
Mortality
Confidence Intervals
Cohort Studies
Cardiovascular Diseases
Prospective Studies
Preexisting Condition Coverage
Information Storage and Retrieval
Thyroxine
MEDLINE
Brazil
Japan
Thyroid Gland
Language
Databases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Rodondi, N., Den Elzen, W. P. J., Bauer, D. C., Cappola, A. R., Razvi, S., Walsh, J. P., ... Gussekloo, J. (2010). Subclinical hypothyroidism and the risk of coronary heart disease and mortality. Journal of the American Medical Association, 304(12), 1365-1374. https://doi.org/10.1001/jama.2010.1361

Subclinical hypothyroidism and the risk of coronary heart disease and mortality. / Rodondi, Nicolas; Den Elzen, Wendy P J; Bauer, Douglas C.; Cappola, Anne R.; Razvi, Salman; Walsh, John P.; Åsvold, Bjørn O.; Iervasi, Giorgio; Imaizumi, Misa; Collet, Tinh Hai; Bremner, Alexandra; Maisonneuve, Patrick; Sgarbi, José A.; Khaw, Kay Tee; Vanderpump, Mark P J; Newman, Anne B.; Cornuz, Jacques; Franklyn, Jayne A.; Westendorp, Rudi G J; Vittinghoff, Eric; Gussekloo, Jacobijn.

In: Journal of the American Medical Association, Vol. 304, No. 12, 22.09.2010, p. 1365-1374.

Research output: Contribution to journalArticle

Rodondi, N, Den Elzen, WPJ, Bauer, DC, Cappola, AR, Razvi, S, Walsh, JP, Åsvold, BO, Iervasi, G, Imaizumi, M, Collet, TH, Bremner, A, Maisonneuve, P, Sgarbi, JA, Khaw, KT, Vanderpump, MPJ, Newman, AB, Cornuz, J, Franklyn, JA, Westendorp, RGJ, Vittinghoff, E & Gussekloo, J 2010, 'Subclinical hypothyroidism and the risk of coronary heart disease and mortality', Journal of the American Medical Association, vol. 304, no. 12, pp. 1365-1374. https://doi.org/10.1001/jama.2010.1361
Rodondi N, Den Elzen WPJ, Bauer DC, Cappola AR, Razvi S, Walsh JP et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. Journal of the American Medical Association. 2010 Sep 22;304(12):1365-1374. https://doi.org/10.1001/jama.2010.1361
Rodondi, Nicolas ; Den Elzen, Wendy P J ; Bauer, Douglas C. ; Cappola, Anne R. ; Razvi, Salman ; Walsh, John P. ; Åsvold, Bjørn O. ; Iervasi, Giorgio ; Imaizumi, Misa ; Collet, Tinh Hai ; Bremner, Alexandra ; Maisonneuve, Patrick ; Sgarbi, José A. ; Khaw, Kay Tee ; Vanderpump, Mark P J ; Newman, Anne B. ; Cornuz, Jacques ; Franklyn, Jayne A. ; Westendorp, Rudi G J ; Vittinghoff, Eric ; Gussekloo, Jacobijn. / Subclinical hypothyroidism and the risk of coronary heart disease and mortality. In: Journal of the American Medical Association. 2010 ; Vol. 304, No. 12. pp. 1365-1374.
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AU - Rodondi, Nicolas

AU - Den Elzen, Wendy P J

AU - Bauer, Douglas C.

AU - Cappola, Anne R.

AU - Razvi, Salman

AU - Walsh, John P.

AU - Åsvold, Bjørn O.

AU - Iervasi, Giorgio

AU - Imaizumi, Misa

AU - Collet, Tinh Hai

AU - Bremner, Alexandra

AU - Maisonneuve, Patrick

AU - Sgarbi, José A.

AU - Khaw, Kay Tee

AU - Vanderpump, Mark P J

AU - Newman, Anne B.

AU - Cornuz, Jacques

AU - Franklyn, Jayne A.

AU - Westendorp, Rudi G J

AU - Vittinghoff, Eric

AU - Gussekloo, Jacobijn

PY - 2010/9/22

Y1 - 2010/9/22

N2 - 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

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