Subclinical Hypothyroidism and the Risk of Cardiovascular Disease and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies

Thyroid. 2018 Sep;28(9):1101-1110. doi: 10.1089/thy.2017.0414. Epub 2018 Aug 17.


Objectives: To determine the impact of subclinical hypothyroidism (SCH) on the risk of cardiovascular disease (CVD) and all-cause mortality, a comprehensive meta-analysis was performed according to the age or coexisting CVD risk status of the participants.

Methods: Studies regarding the association of SCH with all-cause mortality from PubMed and Embase databases were included. The pooled relative risk (RR) of CVD and all-cause mortality was calculated using the Mantel-Haenszel method. A subgroup analysis of participants with high CVD risk was conducted, including history of coronary, cerebral, or peripheral artery disease; dilated cardiomyopathy; heart failure; atrial fibrillation; venous thromboembolism; diabetes mellitus; or chronic kidney disease.

Results: In total, 35 eligible articles incorporating 555,530 participants were included. SCH was modestly associated with CVD and all-cause mortality (RR for CVD = 1.33 [confidence interval (CI) 1.14-1.54]; RR for all-cause mortality = 1.20 [CI 1.07-1.34]). However, the association was not observed in participants aged ≥65 years. Subgroup analysis showed that participants with SCH and high CVD risk showed a significantly higher risk of all-cause mortality (RR for CVD = 2.20 [CI 1.28-3.77]; RR for all-cause mortality = 1.66 [CI 1.41-1.94]), whereas those with SCH and low CVD risk did not. Additional subgroup analysis of six studies with a mean participant age of ≥65 years and high CVD risk showed a significant high risk of all-cause mortality in the SCH group (RR = 1.41 [CI 1.08-1.85]; I2 = 0%).

Conclusions: SCH is associated with an increased CVD risk and all-cause mortality, particularly in participants with high CVD risk.

Keywords: cardiovascular disease; mortality; prognosis; subclinical hypothyroidism.

Publication types

  • Meta-Analysis

MeSH terms

  • Aged
  • Cardiovascular Diseases / epidemiology*
  • Female
  • Humans
  • Hypothyroidism / diagnosis
  • Hypothyroidism / epidemiology*
  • Hypothyroidism / mortality
  • Incidence
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Risk
  • Seveso Accidental Release
  • Survival Rate