Associations of physiological dysregulation with cardiometabolic disease accumulation and all-cause mortality in Chinese middle-aged and older adults: evidence from a nationwide cohort study

Cardiometabolic disease (CMD), a major global health burden, involves a multisystem homeostatic imbalance. This study assessed the association of physiological dysregulation (PD) with CMD accumulation and all-cause mortality in Chinese middle-aged and older adults. Using data from the China Health and Retirement Longitudinal Study (CHARLS), PD was quantified via Mahalanobis distance based on eight biomarkers. Multivariable-adjusted ordered logistic and logistic regression models were employed to evaluate the associations of PD with CMD accumulation and all-cause mortality, respectively. Subgroup analyses and restricted cubic splines were applied. Among 8,747 participants (median age 60 years, 46.2% male), each unit increase in log-PD was associated with a 19% higher risk of CMD accumulation (OR = 1.19, 95% CI: 1.14–1.25) and a 37% increased mortality risk (OR = 1.37, 95% CI: 1.23–1.53). Compared to the lowest tertile (T1), participants in the highest PD tertile (T3) had a 38% increased CMD risk and 88% higher mortality risk. Subgroup analyses revealed elevated CMD risk in older adults, males, and baseline CMD-free individuals, while mortality risk was higher in middle-aged adults, females, and overweight/obese participants. A nonlinear threshold effect for PD and mortality was identified at log-PD > 4.306. PD is significantly associated with CMD accumulation and all-cause mortality, supporting its potential as a practical prognostic indicator in primary care.