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Anne R. Cappola, MD, ScM; Linda P. Fried, MD, MPH; Alice M. Arnold, PhD; Mark D. Danese, PhD; Lewis H. Kuller, MD, DrPH; Gregory L. Burke, MD, MS; Russell P. Tracy, PhD; Paul W. Ladenson, MD

JAMA. 2006;295:1033-1041.

Context  Previous studies have suggested that subclinical abnormalities in thyroid-stimulating hormone levels are associated with detrimental effects on the cardiovascular system.

Objective  To determine the relationship between baseline thyroid status and incident atrial fibrillation, incident cardiovascular disease, and mortality in older men and women not taking thyroid medication.

Design, Setting, and Participants  A total of 3233 US community-dwelling individuals aged 65 years or older with baseline serum thyroid-stimulating hormone levels were enrolled in 1989-1990 in the Cardiovascular Health Study, a large, prospective cohort study.

Main Outcome Measures  Incident atrial fibrillation, coronary heart disease, cerebrovascular disease, cardiovascular death, and all-cause death assessed through June 2002. Analyses are reported for 4 groups defined according to thyroid function test results: subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism.

Results  Individuals with overt thyrotoxicosis (n = 4) were excluded because of small numbers. Eighty-two percent of participants (n = 2639) had normal thyroid function, 15% (n = 496) had subclinical hypothyroidism, 1.6% (n = 51) had overt hypothyroidism, and 1.5% (n = 47) had subclinical hyperthyroidism. After exclusion of those with prevalent atrial fibrillation, individuals with subclinical hyperthyroidism had a greater incidence of atrial fibrillation compared with those with normal thyroid function (67 events vs 31 events per 1000 person-years; adjusted hazard ratio, 1.98; 95% confidence interval, 1.29-3.03). No differences were seen between the subclinical hyperthyroidism group and euthyroidism group for incident coronary heart disease, cerebrovascular disease, cardiovascular death, or all-cause death. Likewise, there were no differences between the subclinical hypothyroidism or overt hypothyroidism groups and the euthyroidism group for cardiovascular outcomes or mortality. Specifically, individuals with subclinical hypothyroidism had an adjusted hazard ratio of 1.07 (95% confidence interval, 0.90-1.28) for incident coronary heart disease.

Conclusion  Our data show an association between subclinical hyperthyroidism and development of atrial fibrillation but do not support the hypothesis that unrecognized subclinical hyperthyroidism or subclinical hypothyroidism is associated with other cardiovascular disorders or mortality.

Author Affiliations: Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and Division of Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia (Dr Cappola); Division of Geriatric Medicine and Gerontology and Center on Aging and Health, Johns Hopkins Medical Institutions, Baltimore, Md (Dr Fried); Department of Biostatistics, University of Washington, Seattle (Dr Arnold); Outcomes Insights Inc, Newbury Park, Calif (Dr Danese); Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pa (Dr Kuller); Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (Dr Burke); Departments of Pathology and Biochemistry, University of Vermont, Burlington (Dr Tracy); and Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (Dr Ladenson).

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