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J Clin Endocrinol Metab. 2014 Sep;99(9):3353-62. doi: 10.1210/jc.2014-1250. Epub 2014 Jun 10.

Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.

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Service of Endocrinology, Diabetes, and Metabolism (T.-H.C.), University Hospital of 1011 Lausanne, Switzerland; Department of Ambulatory Care and Community Medicine (T.-H.C., J.C.), University of Lausanne, 1011 Lausanne, Switzerland; Departments of Epidemiology and Biostatistics (D.C.B., E.V.) and Medicine (D.C.B.), University of California, San Francisco, San Francisco, California 94143; Division of Endocrinology, Diabetes, and Metabolism (A.R.C.), Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; Department of Public Health (B.O.Å.), Norwegian University of Science and Technology, N-7491 Trondheim, Norway; Department of Endocrinology (B.O.Å.), St Olavs Hospital, Trondheim University Hospital, N-7006 Trondheim, Norway; Department of General Internal Medicine (S.W., D.A., N.R.), Inselspital, University of Bern, 3000 Bern, Switzerland; Department of Clinical Pharmacology and Toxicology (S.W.), University Hospital of Zürich, 8091 Zürich, Switzerland; Department of Public Health and Primary Care (J.G., W.P.J.d.E.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; School of Population Health (A.B.) and School of Medicine and Pharmacology (J.P.W.), The University of Western Australia, Crawley, and Department of Endocrinology and Diabetes (J.P.W.), Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia; Division of Endocrinology (R.M.B.M., J.A.S.), Department of Medicine, Federal University of Sao Paulo, 04023-900 São Paulo, Brazil; Department of Endocrinology (M.P.J.V.), Royal Free Hospital, London NW3 2PF, United Kingdom; Clinic for Internal Medicine B (M.D.) and Institute of Clinical Chemistry and Laboratory Medicine (H.W.), University Medicine Greifswald, and Institute for Community Medicine (H.V.), Study of Health in Pomerania/Clinical-Epidemiological Research, University of Greifswald, D-17487 Greifswald, Germany; DZHK (German Centre for Cardiovascular Research) (M.D.,



Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk.


The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs).


A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes.


Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events.


Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status.


CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

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