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John P. Walsh, MBBS, PhD; Alexandra P. Bremner, PhD; Max K. Bulsara, MSc; Peter O’Leary, PhD; Peter J. Leedman, MBBS, PhD; Peter Feddema, BSc; Valdo Michelangeli, PhD

Arch Intern Med. 2005;165:2467-2472.

Background  There have been few large epidemiological studies examining the association between thyroid dysfunction and cardiovascular disease. In particular, it is uncertain if subclinical hypothyroidism is a risk factor for cardiovascular disease.

Methods  Serum thyrotropin and free thyroxine concentrations were measured in 2108 archived serum samples from a 1981 community health survey in Busselton, Western Australia (Busselton Health Study). In a cross-sectional study, we examined the prevalence of coronary heart disease in subjects with and without subclinical thyroid dysfunction. In a longitudinal study, we examined the risk of cardiovascular mortality and coronary heart disease events (fatal and nonfatal combined) to the end of 2001 (excluding subjects who had coronary heart disease at baseline).

Results  In the cross-sectional analysis, subjects with subclinical hypothyroidism (n = 119) had a significantly higher prevalence of coronary heart disease than euthyroid subjects (n = 1906) (age- and sex-adjusted prevalence odds ratio, 1.8; 95% confidence interval, 1.0-3.1; P = .04). In the longitudinal analysis of subjects with subclinical hypothyroidism (n = 101), there were 21 cardiovascular deaths observed compared with 9.5 expected (age- and sex-adjusted hazard ratio, 1.5; 95% confidence interval, 1.0-2.4; P = .08) and 33 coronary heart disease events observed compared with 14.7 expected (age- and sex-adjusted hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P<.01). The increased risk of coronary heart disease events remained significant after further adjustment for standard cardiovascular risk factors. Subjects with subclinical hyperthyroidism (n = 39) had no adverse outcomes.

Conclusion  Subclinical hypothyroidism may be an independent risk factor for coronary heart disease.

Author Affiliations: Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital (Dr Walsh), Genomics Directorate, Department of Health (Dr O’Leary), and Department of Endocrinology and Diabetes, Royal Perth Hospital, and Laboratory for Cancer Medicine, UWA Centre for Medical Research, Faculty of Medicine and Dentistry of The University of Western Australia (Dr Leedman), Perth; School of Medicine and Pharmacology (Drs Walsh and Leedman), School of Population Health (Dr Bremner and Mr Bulsara), and School of Women’s and Infants’ Health (Dr O’Leary), The University of Western Australia, Crawley; and BioMediq DPC, Doncaster, Victoria (Mr Feddema and Dr Michelangeli); Australia.

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