Subclinical Hyperthyroidism and the Risk of Coronary Heart Disease and Mortality | Atrial Fibrillation | JAMA Internal Medicine | JAMA Network
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Original Investigation
May 28, 2012

Subclinical Hyperthyroidism 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 Collet, Gencer, and Cornuz and Mr Balmer); Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands (Drs Gussekloo and den Elzen); Departments of Medicine (Dr Bauer) and Epidemiology and Biostatistics (Drs Bauer and Vittinghoff), University of California, San Francisco; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia (Dr Cappola); National Council Research Institute of Clinical Physiology/Tuscany Region G. Monasterio Foundation, Pisa, Italy (Drs Iervasi and Molinaro); Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway (Dr Åsvold); Division of Endocrinology, Department of Medicine, Federal University of São Paulo, Brazil (Drs Sgarbi and Maciel); Division of Endocrinology, Faculdade de Medicina de Marília, Marília, Brazil (Dr Sgarbi); Institute for Community Medicine, Clinical-Epidemiological Research, University of Greifswald, Greifswald, Germany (Dr Völzke); Schools of Population Health (Dr Bremner) and Medicine and Pharmacology (Dr Walsh), The University of Western Australia, Crawley, Australia; Department of Public Health and Primary Care, University of Cambridge, Cambridge, England (Drs Luben and Khaw); Division of Epidemiology and Biostatistics, European Institute of Oncology, Milano, Italy (Dr Maisonneuve); Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Newman); Department of Gerontology and Geriatrics, Leiden University Medical Center, and Netherlands Consortium for Healthy Ageing, Leiden (Dr Westendorp); School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England (Dr Franklyn); Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia (Dr Walsh); and Department of General Internal Medicine, Inselspital, University of Bern, Bern, Switzerland (Dr Rodondi).

Arch Intern Med. 2012;172(10):799-809. doi:10.1001/archinternmed.2012.402

Background Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.

Methods Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.

Results Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age- and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06-1.46), CHD mortality (HR, 1.29; 95% CI, 1.02-1.62), CHD events (HR, 1.21; 95% CI, 0.99-1.46), and AF (HR, 1.68; 95% CI, 1.16-2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03).

Conclusion Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.