Abstract
BACKGROUND: Pre-diabetes, pre-hypertension, and pre-dyslipidemia are early metabolic abnormalities associated with cardiovascular disease (CVD), but their joint effects on CVD and metabolic disease progression remain unclear. This study examines their joint associations and interactions on CVD and progression to diabetes, hypertension, and dyslipidemia in Chinese adults aged ≥ 45 years. METHODS: A prospective cohort of 3405 adults (mean age 57.07 years, 49.9% women) from the China Health and Retirement Longitudinal Study (CHARLS) was analyzed. Pre-diabetes, pre-hypertension, and pre-dyslipidemia were defined as elevated but subclinical thresholds for blood pressure, glucose, and lipids. Cox model was used to assess associations between the number of pre-disease risk factors (0-3) and incident CVD or progression to diabetes, hypertension, and dyslipidemia. Additive/multiplicative interactions were conducted. RESULTS: At baseline, 24.8%, 38.7%, 28.3%, and 8.2% had 0, 1, 2, and 3 pre-disease factors, respectively. Over 7.1 years, 527 CVD cases occurred. Cumulative pre-disease factors were associated with higher CVD risk: HRs for 1, 2, and 3 factors were 1.33 (95% CI 1.04-1.69), 1.37 (1.14-1.89), and 1.55 (1.11-2.16), respectively. Each additional factor was associated with a 16% higher CVD risk (HR = 1.16, 95% CI 1.06-1.27). Significant additive and multiplicative interactions were observed between pairs of pre-disease factors, with combined risks for CVD exceeding those expected from individual effects (all P < 0.05). Each additional factor was also associated with 44%, 48%, and 18% higher risks of diabetes (HR = 1.44, 95% CI, 1.29-1.62), hypertension (HR = 1.48, 95% CI 1.38-1.58), and dyslipidemia (HR = 1.18, 95% CI 1.11-1.27). CONCLUSIONS: Coexisting pre-diabetes, pre-hypertension, and pre-dyslipidemia jointly increase CVD risk and accelerate metabolic disease progression among Chinese adults aged ≥ 45 years. These findings support early, integrated interventions to mitigate CVD risk in individuals with subclinical metabolic abnormalities.