Abstract
BACKGROUND: Insulin resistance (IR) is a well-established risk factor for cardiovascular disease (CVD). The metabolic score for insulin resistance (METS-IR) is a novel surrogate marker for IR, yet the association between its long-term cumulative burden and incident CVD remains unexplored, particularly in the Chinese population. METHODS: This prospective study included 5,264 participants (mean age 58.50 years; 46.6% male) from the China Health and Retirement Longitudinal Study (CHARLS). Cumulative average METS-IR was calculated as the mean of measurements from 2011 (baseline) and 2015 (wave 3). Incident CVD events were ascertained via standardized questionnaires. Multivariable logistic regression and restricted cubic spline models were employed to assess associations. RESULTS: During a 4-year follow-up, 554 (10.5%) incident CVD cases occurred. After full adjustment, each SD increase in cumulative average METS-IR was associated with a 16.1% higher risk of total CVD (OR = 1.161, 95% CI: 1.050-1.282). A significant dose-response relationship was observed (P for trend = 0.003). Crucially, we found a striking organ-specific disparity: the highest quartile of cumulative METS-IR was strongly associated with a 19.8% increased risk of heart disease (OR = 1.509, 95% CI: 1.118-2.046) but not with stroke (OR = 0.902, 95% CI: 0.440-1.865). Subgroup analyses revealed that this association was particularly pronounced among males, normotensive individuals, and current smokers or drinkers. CONCLUSIONS: Cumulative exposure to insulin resistance, quantified by METS-IR, is an independent predictor of CVD, especially heart disease, in middle-aged and older Chinese adults. Our findings highlight the clinical utility of longitudinal METS-IR assessment for early risk stratification and pinpoint specific high-risk populations for targeted preventive strategies.