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Nicolas Rodondi, MD, MAS; Anne B. Newman, MD, MPH; Eric Vittinghoff, PhD; Nathalie de Rekeneire, MD; Suzanne Satterfield, MD; Tamara B. Harris, MS, MD; Douglas C. Bauer, MD

Arch Intern Med. 2005;165:2460-2466.

Background  Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited.

Methods  We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and 10.0 mIU/L).

Results  Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P = .006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P = .03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality.

Conclusions  Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure.

Author Affiliations: Department of Epidemiology and Biostatistics (Drs Rodondi, Vittinghoff, and Bauer) and Division of General Internal Medicine, Department of Medicine (Dr Bauer), University of California, San Francisco; Department of Community Medicine and Public Health, University of Lausanne, Lausanne, Switzerland (Dr Rodondi); Department of Medicine, University of Pittsburgh, Pittsburgh, Pa (Dr Newman); Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Md (Drs de Rekeneire and Harris); and Department of Preventive Medicine, University of Tennessee College of Medicine, Memphis (Dr Satterfield).

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