Normal Is Actually Normal: Difference in Thyrotropin Levels Within Reference Range Not Associated With Heart Disease | Journal Scan

Study Questions:

Are individuals with thyrotropin levels in the upper part of the reference range at increased risk of coronary heart disease (CHD)?


This was a meta-analysis of individual patient data in 14 cohort studies included in the Thyroid Studies Collaboration consortium. The authors used a common thyrotropin reference range of 0.45-4.49 mIU/L for all cohorts except for the Whickham Survey (in which authors used a reference range of 0.5-5.9 mIU/L because the first-generation thyrotropin assay used in that study yields consistently higher levels than measurements of current assays). The authors determined hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status.


The analytic sample included 55,412 individuals. Of these, 1,813 people (3.3%) died of CHD during 643,183 person-years of follow-up. There was no association between thyrotropin levels and risk of CHD mortality or first-time CHD event. There was a U-shaped association between free thyroxine (FT4) levels at baseline with risk of CHD; participants with FT4 levels in the second quartile had lower risks of CHD mortality (HR, 0.76; 95% confidence interval [CI], 0.57-0.99) and CHD events (HR, 0.73; 95% CI, 0.58-0.94) compared with participants in the highest quartile of FT4 levels.


In a meta-analysis of individual patient level data, differences in thyrotropin levels within the reference range were not associated with risk of CHD mortality or CHD events.


The results from this meta-analysis provide convincing evidence that thyrotropin levels in the upper part of the reference range are not associated with an increased risk of CHD events or CHD mortality. Less is more. As the authors suggest, further study is necessary to understand the possible association of FT4 levels and CHD risk among individuals with clinically normal thyroid function. As the authors opine, the U-shaped association between FT4 levels and CHD risk may be due to chance or impacted by low albumin levels and cardiovascular medications (which may impact FT4 levels).

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention, Atherosclerotic Disease (CAD/PAD)

Keywords: Albumins, Cohort Studies, Coronary Artery Disease, Coronary Disease, Mortality, Reference Values, Risk, Risk Factors, Thyrotropin, Thyroxine, Secondary Prevention, Metabolic Syndrome X

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