Long-Term Impact of Subclinical Hypothyroidism on Cardiovascular Outcomes in Adults: A Meta-Analysis of Cohort and Observational Studies

Background: Subclinical hypothyroidism (SCH), defined by elevated thyroid-stimulating hormone (TSH) levels with normal free thyroxine (FT4), has been increasingly linked to cardiovascular disease. However, evidence remains mixed regarding its long-term impact on coronary outcomes. Objective: To evaluate the association between subclinical hypothyroidism and the risk of coronary heart disease (CHD) events, cardiovascular mortality, and all-cause mortality in adults using data from cohort and observational studies. Methods: A systematic search was conducted across PubMed, Scopus, Embase, and Web of Science from 2015 to 2024. Eligible studies included prospective cohorts reporting cardiovascular outcomes in adults with SCH versus euthyroid controls. Pooled hazard ratios (HRs) and relative risks (RRs) were calculated using a random-effects model. Subgroup analysis was conducted based on TSH levels (<10 mIU/L vs. ≥10 mIU/L). Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: Three high-quality cohort studies involving 60,047 participants were included. SCH was significantly associated with an increased risk of CHD events (HR/RR = 1.20; 95% CI: 1.02–1.41; p = 0.03). The association with CHD mortality (HR/RR = 1.18; 95% CI: 0.97–1.43) and total mortality (HR/RR = 1.12; 95% CI: 0.99–1.26) was not statistically significant. Subgroup analysis revealed that individuals with TSH ≥10 mIU/L had a markedly increased CHD risk (HR/RR = 1.89; 95% CI: 1.28–2.80; p = 0.002). Conclusion: Subclinical hypothyroidism, particularly at higher TSH levels (≥10 mIU/L), is associated with an increased risk of coronary heart disease events. While associations with mortality were non-significant, the observed trends highlight the need for closer monitoring and targeted intervention strategies in patients with elevated TSH. Further large-scale studies are warranted to establish causality and optimize clinical management.