Thyroid-Stimulating Hormone and Risk of Sudden Cardiac Death, Total Mortality and Cardiovascular Morbidity

Ville L. Langén; Teemu J. Niiranen; Pauli Puukka; Arttu O. Lehtonen; Jussi A. Hernesniemi; Jouko Sundvall; Veikko Salomaa; Antti M. Jula


Clin Endocrinol. 2018;88(1):105-113. 

In This Article

Abstract and Introduction


Background Previous data on the association of thyroid function with total mortality, cardiovascular disease (CVD) outcomes and sudden cardiac death (SCD) are conflicting or limited. We investigated associations of thyroid-stimulating hormone (TSH) with these outcomes in a nationwide population-based prospective cohort study.

Methods We examined 5211 participants representative of the Finnish population aged ≥30 years in 2000–2001 and followed them for a median of 13.2 years. Using Cox proportional hazards regression models adjusted for baseline age, gender, smoking, diabetes, systolic blood pressure and total and high-density lipoprotein cholesterol, we assessed the associations of continuous baseline TSH and TSH categories (low [<0.4 mU/L], reference range [0.4–3.4 mU/L] and high [>3.4 mU/L]) with incident total mortality, SCD, coronary heart disease events, stroke, CVD, major adverse cardiac events and atrial fibrillation.

Results High TSH at baseline was related to a greater risk of total mortality (HR 1.34, 95% CI 1.02–1.76) and SCD (HR 2.28, 95% CI 1.13–4.60) compared with TSH within the reference range. High TSH was not associated with the other outcomes (P ≥ .51), whereas low TSH was not associated with any of the outcomes (P ≥ .09). TSH at baseline over the full range did not have a linear relation with any of the outcomes (P ≥ .17). TSH showed a U-shaped association with total mortality after a restricted cubic spline transformation (P = .01).

Conclusions Thyroid function abnormalities could be linked with higher risks of total mortality and SCD. Large-scale randomized studies are needed for evidence-based recommendations regarding treatment of mild thyroid failure.


Cardiovascular disease is the leading cause of mortality in the world.[1] Given the enormous disease burden and toll on health budgets inflicted by it, identification of its predictors is imperative. The many ways thyroid function potentially affects the cardiovascular system have been delineated in previous review articles in detail.[2,3] Overt and even subclinical hypothyroidism are possibly associated with several cardiovascular risk factors, such as an impaired lipid profile, arterial stiffness and endothelial dysfunction.[2,3] There has been a long-simmering controversy about whether an excess cardiovascular risk related to even mild thyroid dysfunction exists, and whether that putative risk could be ameliorated with thyroid medication. Previous cohort studies[4–15] and meta-analyses[16–19] on thyroid dysfunction and cardiovascular outcomes have provided conflicting results. Furthermore, there has been paucity of published data on the association of thyroid function and sudden cardiac death (SCD). To our knowledge, only Chaker et al have previously studied this association in the general population, illustrating a direct relationship between free thyroxine levels and an increased risk of SCD.[20] To fill this gap in the literature, we studied in a prospective setting the association of thyroid function with total mortality, SCD and incident major coronary heart disease (CHD) events, stroke, cardiovascular disease (CVD), major adverse cardiac events (MACE) and atrial fibrillation (AF) in a randomly sampled population cohort. Our hypothesis was that thyroid dysfunction could predispose to greater risks of mortality and cardiovascular disease through higher incidence of AF in hyperthyroid states and accelerated atherosclerosis in hypothyroid conditions.[3]