Stress-hyperglycemia ratio, its longitudinal trajectories, and stress-metabolism synergy in predicting cardiometabolic multimorbidity: A nationwide prospective cohort study.

摘要

ObjectiveCardiometabolic multimorbidity is a major driver of chronic disease burden in aging Chinese populations. Conventional single disease risk scores cannot reliably identify those at high cardiometabolic multimorbidity risk, which stems from interconnected metabolic and cardiovascular dysregulation. The stress-hyperglycemia ratio, a marker of acute glycemic dysregulation independent of glycosylated hemoglobin, predicts individual cardiometabolic events; however, to our knowledge, its longitudinal association with cardiometabolic multimorbidity and modification by insulin resistance remain uncharacterized.MethodsWe performed a 9-year prospective analysis of the data from 4019 cardiometabolic multimorbidity-free adults aged ≥45 years enrolled in the nationally representative China Health and Retirement Longitudinal Study. Incident cardiometabolic multimorbidity was defined as new-onset of ≥2 cardiometabolic disorders (hypertension, diabetes, coronary heart disease, and stroke). We assessed baseline stress-hyperglycemia ratio, identified stress-hyperglycemia ratio trajectories using latent class growth modeling, constructed stress-metabolism synergy indices, and evaluated associations with incident cardiometabolic multimorbidity using multivariable Cox regression, predictive performance testing, and mediation analysis.ResultsEach 1-SD increase in the baseline stress-hyperglycemia ratio was associated with 13% higher fully adjusted cardiometabolic multimorbidity risk (hazard ratio = 1.13, 95% confidence interval = 1.03-1.24, p = 0.013) in a linear dose-response pattern. The moderate-increasing stress-hyperglycemia ratio trajectory conferred an approximately twofold higher fully adjusted cardiometabolic multimorbidity risk versus the low-stable trajectory (hazard ratio = 2.04, 95% confidence interval = 1.01-4.15, p = 0.048). The stress-hyperglycemia ratio-estimated glucose disposal rate index showed the most pronounced association and improved discriminative performance (concordance index = 0.70), with potential mediators, including accelerated biological aging, glycemic dyscontrol, and atherogenic dyslipidemia.ConclusionBaseline stress-hyperglycemia ratio, its longitudinal trajectories, and the stress-hyperglycemia ratio-estimated glucose disposal rate index demonstrate a modest yet significant incremental predictive value for incident cardiometabolic multimorbidity among middle-aged and older Chinese adults, providing a potential, low-cost framework for cardiometabolic multimorbidity risk stratification in primary care that requires further external validation.