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Clinician's Corner
September 22/29, 2010

Subclinical Hypothyroidism and the Risk of Coronary Heart Disease and Mortality

Author Affiliations

Author Affiliations: Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland (Drs Rodondi, Collet, and Cornuz); Departments of Public Health and Primary Care (Ms den Elzen and Dr Gussekloo) and Gerontology and Geriatrics (Dr Westendorp), Leiden University Medical Center, Leiden, the Netherlands; Departments of Medicine, Epidemiology, and Biostatistics (Drs Bauer and Vittinghoff) and Medicine (Dr Bauer), University of California, San Francisco; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia (Dr Cappola); Department of Endocrinology, Gateshead Health Foundation NHS Trust, Gateshead, England (Dr Razvi); Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia (Dr Walsh); Schools of Medicine and Pharmacology (Dr Walsh) and Population Health (Dr Bremner), University of Western Australia, Crawley; Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway (Dr Åsvold); National Council Research Institute of Clinical Physiology, Pisa, Italy (Dr Iervasi); Department of Clinical Studies, Radiation Effects Research Foundation, Nagasaki, Japan (Dr Imaizumi); Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy (Mr Maisonneuve); Division of Endocrinology, Department of Medicine, Federal University of Sao Paulo, Brazil (Dr Sgarbi); Division of Endocrinology, Faculdade de Medicina de Marília, Marília, Brazil (Dr Sgarbi); Department of Public Health and Primary Care, University of Cambridge, Cambridge, England (Dr Khaw); Department of Endocrinology, Royal Free Hospital, London, England (Dr Vanderpump); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Newman); School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England (Dr Franklyn); and the Netherlands Consortium for Healthy Ageing, Leiden (Dr Westendorp).

JAMA. 2010;304(12):1365-1374. doi:10.1001/jama.2010.1361

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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