Normal Thyroid-stimulating Hormone Levels, Autoimmune Activation, and Coronary Heart Disease Risk

Whether euthyroid status affects cardiovascular disease risk is unclear. We aimed to investigate whether serum thyroid-stimulating hormone (TSH) levels within the normal range are related to the risk of coronary heart disease (CHD). In participants of the Turkish Adult Risk Factor Study (mean age 52.7±11.5), in whom TSH was measured in the 2004/05 survey, cross-sectional and longitudinal analyses were performed. Subjects with TSH concentrations<0.3 and >4.2 mIU/L were excluded to ensure euthyroid status leaving 956 individuals as the study sample. Mean follow-up was 4.81±1.3 years. Men had 18% lower (p<0.001) geometric mean TSH levels (1.10 mIU/L) than women (1.35 mIU/L). Correlations of TSH with risk variables were notably virtually absent except weakly positive ones in men with age and systolic blood pressure (SBP). The age-adjusted TSH mid-tertile in men was associated with lowest lipoprotein [Lp](a), apoB, and total cholesterol values. Incident CHD was predicted in Cox regression analyses in men [HR of 2.45 (95 %CI 1.05; 5.74] and in combined sexes by the lowest compared with the highest TSH tertile, after adjustment for age, smoking status, SBP, and LDL-cholesterol. Analysis for combined prevalent and incident CHD stratified by metabolic syndrome (MetS) confirmed the independent association with the lowest TSH tertile in men, specifically in men without MetS. TSH levels within normal range, low due to partial assay failure, may manifest as independent predictors of incident CHD, particularly in middle-aged men. Autoimmune responses involving serum Lp(a) under oxidative stress might be implicated mechanistically.