Subclinical thyroid dysfunction is associated with adverse prognosis in heart failure patients with reduced ejection fraction

Background: Subclinical thyroid dysfunction whose typical patterns include subclinical hypothyroidism and subclinical hyperthyroidism, has been indicated to be associated with an increased risk of heart failure (HF). However, the relationship between subclinical thyroid dysfunction and the clinical outcomes of HF patients is uncertain. This meta-analysis was conducted to assess the association between subclinical thyroid dysfunction and the clinical outcomes of HF patients. Methods: Pubmed, Embase, Web of Science and Cochrane Central Register of Clinical Trials were searched for eligible studies published up to August 1, 2018 which reported the association between subclinical thyroid dysfunction and the clinical outcomes of HF patients. The pooled hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used to assess the association. Results: Fourteen studies met the eligibility criteria and a total of 21,221 patients with heart failure were included in the meta-analysis. Compared with HF patients with euthyroidism, the pooled HR of subclinical hypothyroidism for all-cause mortality was 1.45 (95% CI 1.26-1.67) in a randomized effects model with mild heterogeneity (I-2=40.1, P=0.073). The pooled HR of subclinical hypothyroidism for cardiac death and/or hospitalization was 1.33 (1.17-1.50) in a randomized effects model with moderate heterogeneity (I-2=69.4, P<0.001). Subclinical hyperthyroid can increase the risk of all-cause mortality without heterogeneity (HR 1.31, 95% CI 1.10-1.55, I-2=25.5%, P=0.225) but have no influence on the risk of cardiac death and/or hospitalization (HR 1.03, 95% CI 0.87-1.23, I-2=0.0%, P=0.958). These significant adverse associations were also retained in subgroup analysis. Sensitivity analysis demonstrated the stability of the results of our meta-analysis. Conclusions: Both subclinical hypothyroidism and subclinical hyperthyroidism are associated with adverse prognosis in patients with HF. Subclinical thyroid dysfunction may be a useful and promising predictor for the long-term prognosis in HF patients.