The Incidence of Ischemic Heart Disease and Mortality in People with Subclinical Hypothyroidism: Reanalysis of the Whickham Survey Cohort

Context: The Whickham Survey evaluated vascular events over 20 yr in community-dwelling subjects stratified by thyroid function and thyroid autoantibody status. No association between ischemic heart disease (IHD) and a composite autoimmune thyroid disease group, comprising individuals with subclinical hypothyroidism (SCH), with positive thyroid antibodies or those using levothyroxine, was found. This result appears to be at odds with the findings of other cohort studies. Objective: The objective of the study was to evaluate incident IHD and mortality in participants in relation to their thyroid status. Outcomes, Design, and Participants: Data were reanalyzed assessing incident IHD events and mortality during 20 yr of follow-up in individuals with endogenous SCH (n = 97; TSH 6.0-15 mIU/liter) vs. the euthyroid group (n = 2279), who were IHD free at baseline. Results: Incident IHD was significantly higher in the SCH group [adjusted hazard ratio 1.76 (95% confidence interval 1.15-2.71); P = 0.01]. IHD mortality was also increased in the SCH group [hazard ratio of 1.79 (1.02-3.56); P = 0.05]. These findings lost their significance when subsequent treatment with levothyroxine was excluded from the regression model. There was no difference in all-cause mortality between the groups. Conclusion: In the Whickham Survey, there is an association between incident IHD events and IHD-related mortality with SCH over the 20 yr of follow-up. Furthermore, subsequent treatment of SCH with levothyroxine appears to attenuate IHD-related morbidity and mortality, and this may explain why some other longitudinal studies of SCH have not shown such an association; properly designed controlled trials of treatment of SCH are required to answer this question definitively. (J Clin Endocrinol Metab 95: 1734-1740, 2010)