Age-related changes in HPT axis sensitivity and their associations with metabolic and cardiovascular health: a cross-sectional, Chinese nationwide study

Abstract

The regulation and secretion of hormones in the endocrine system change with aging. While these changes may influence age-related disease risks, the role of hypothalamic-pituitary-thyroid (HPT) axis sensitivity in metabolic and cardiovascular health remains unclear. This study enrolled 13,646 participants (6,221 males, 7,425 females). Metabolic (BMI, SUA, FPG, lipoproteins) and cardiovascular (ECG, CK-MB, NT-proBNP) indices were measured. Multivariable logistic regression adjusted for age (per 10-year increment), sex, and outcome-specific confounders. Nonlinear relationships between age and TFQI were analyzed using restricted cubic splines (RCS). RCS analysis revealed a significant age-dependent decline in TFQI-fT3 values, with an inflection point at 48 years (p<0.001); TFQI-fT4 showed a similar but attenuated trend. For metabolic outcomes, increased fT3 sensitivity (TFQI-fT3 Q1) was associated with lower MetS risk in older adults (>48 years) (OR 0.79, 95% CI 0.65-0.97, p=0.023), whereas no significant association was observed in younger adults (≤48 years) (all p>0.05). For cardiovascular outcomes, higher fT3 sensitivity was associated with reduced risk of abnormal ST segments in both age groups (younger: OR 0.57, 95% CI 0.32-0.97, p=0.046; older: OR 0.68, 95% CI 0.48-0.95, p=0.027). Conversely, decreased fT4 sensitivity (TFQI-fT4 Q4) specifically increased abnormal ST-segment risk in older adults (OR 1.43, 95% CI 1.04-1.96, p=0.025), with no significant effect in younger adults (OR 1.11, 95% CI 0.65-1.82, p=0.693). Enhanced HPT axis sensitivity to fT3 increased with age (inflection point at 48 years in this study) and was associated with a lower prevalence of metabolic syndrome (in >48-year-olds) and ST-segment abnormalities (all adults).