The Incidence of Cardiovascular Disease Events in Women with Hypothyroidism: The Study of Women's Health Across the Nation.

BACKGROUND

Patients treated for hypothyroidism with levothyroxine (LT4) monotherapy may be exposed to periods of excess and/or inadequate circulating thyroid hormone levels, which may increase the risk of cardiovascular disease (CVD). We hypothesized that the risk of CVD events in women treated with LT4 may be higher than in women without thyroid disease in the period from midlife to early old age.

METHODS

The Study of Women's Health Across the Nation is a multisite longitudinal study of a diverse cohort of midlife women from seven geographic sites across the United States. Women were screened for a history of thyroid disease and the use of LT4. Each participant completed up to 17 follow-up visits during which the occurrence of CVD events was ascertained. The composite CVD outcome was defined as any of the following fatal or nonfatal events myocardial infarction, stroke, heart failure, percutaneous coronary intervention, and coronary artery bypass graft surgery. A multivariable Cox proportional hazards model with time-varying exposure was used to determine the relationship of LT4 treatment to the incidence of the first CVD event. A sensitivity analysis was conducted, stratifying the group with LT4 treatment by thyrotropin (TSH) level.

RESULTS

Of the 2647 women who were included in the study, 421 (15.9%) received LT4 treatment during the study period. A total of 33 (7.8%) CVD events occurred in the group with LT4 treatment compared with 191 (8.6%) in the group without thyroid disease (p = 0.616). In the adjusted Cox proportional hazards model, there was no statistically significant relation of LT4 treatment to risk of CVD events (hazard ratio 0.85, confidence interval [0.55-1.31]; p = 0.463). No significant relation was identified after stratification by TSH level at baseline in the LT4 group.

CONCLUSIONS

In a diverse sample of women with long-term follow-up through the menopause transition, we observed no difference in the risk of CVD events between women receiving LT4 treatment for hypothyroidism compared with women without thyroid disease.