Hypothyroidism and Risks of All-Cause and Cardiovascular Mortality: A Retrospective Cohort Study of 70,276 Chinese Adults

Background: The association between hypothyroidism and mortality remains inconsistent across studies. We evaluated the associations of overt and subclinical hypothyroidism with all-cause and cardiovascular mortality in a large Chinese cohort. Methods: This retrospective cohort study included 70,276 adults aged 25 to 84 years who underwent routine health examinations at a large medical center in northern China between January 1, 2017, and December 31, 2022. Thyroid function was categorized as euthyroidism, overt hypothyroidism, or subclinical hypothyroidism. Mortality data were obtained through linkage with national death registries. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality. Subgroup analyses were conducted by age and diabetes status. Results: Among 70,276 participants, 853 (1.2%) had overt hypothyroidism, and 2436 (3.5%) had subclinical hypothyroidism. During a median follow-up of 5.1 years (interquartile range, 3.6-6.0), 359 deaths occurred. Compared with individuals with euthyroidism, overt hypothyroidism was associated with increased all-cause (HR, 2.01; confidence interval [CI], 1.17-3.45) and cardiovascular mortality (HR, 2.70; CI, 1.18-6.19). Among individuals with diabetes, overt hypothyroidism showed a stronger association with all-cause mortality (HR, 5.45; CI, 2.46-12.07) than among those without diabetes (HR, 1.19; CI, 0.56-2.54) (p for interaction = 0.045). Subclinical hypothyroidism was associated with increased all-cause mortality among participants younger than 50 years (HR, 3.28; CI, 1.31-8.23), including those with thyrotropin (TSH) levels <10 mIU/L (HR, 3.36; CI, 1.34-8.43), but not among those aged 50 to 69 years (HR, 0.32; CI, 0.08-1.31) or 70 years or older (HR, 1.00; CI, 0.51-1.98) (p for interaction = 0.022). Conclusions: Overt hypothyroidism was associated with increased mortality, particularly in individuals with diabetes. Subclinical hypothyroidism was associated with increased mortality risk only in younger adults, even at modest TSH elevations.