Associations of the C-reactive protein–triglyceride–glucose index and the cholesterol–HDL–glucose index with cardiovascular disease among adults below prespecified eligibility thresholds for hypertension, diabetes, and hypercholesterolemia: a longitudinal CHARLS cohort with exploratory angiographic analyses

Adults below the prespecified eligibility thresholds for hypertension, diabetes, or hypercholesterolemia experience cardiovascular disease (CVD). The C-reactive protein–triglyceride–glucose index (CTI) and the cholesterol–HDL–glucose index (CHG) integrate inflammatory, lipid, and glycemic markers and may characterize cardiometabolic burden in such adults. We prospectively followed 2,676 participants from the China Health and Retirement Longitudinal Study (CHARLS; 2011–2020) without documented diagnoses, relevant medication use, or measured values above prespecified eligibility cutoffs for the three conditions and free of baseline cardiovascular disease (CVD); associations of baseline CTI and CHG (per 1-standard-deviation increase) with incident self-reported CVD were estimated by Cox regression. Exploratorily, 715 hospitalized patients below the same eligibility cutoffs underwent coronary angiography, and associations with angiographic coronary heart disease (CHD) and disease extent were assessed by logistic regression. Over 9 years (22,586 person-years), 477 participants (17.8%) had a first reported CVD diagnosis. Per 1-SD increase, CTI hazard ratios were 1.179 (95% CI, 1.081–1.287) unadjusted and 1.098 (95% CI, 0.996–1.210, P = 0.061) after full adjustment; for CHG, 1.135 (95% CI, 1.038–1.241) and 1.067 (95% CI, 0.963–1.182). The association was not uniformly maintained across sensitivity analyses: in a sensitivity analysis comparing participants in the highest CTI quartile (Q4) with those in Q1–Q3 using truncated inverse-probability weighting, the association remained directionally consistent (HR 1.225, 95% CI, 0.994–1.510). CTI was associated with prevalent CVD (odds ratio 1.130, 95% CI 1.008–1.267, P = 0.036) and with angiographic CHD (odds ratio 1.271, 95% CI 1.056–1.533, P = 0.012); no clear association was observed for CHG. Incremental discrimination was small (ΔAUC 0.008). In adults below prespecified eligibility thresholds, neither index effectively predicted incident CVD after conventional adjustment, whereas CTI was more consistently associated with prevalent cardiovascular and coronary disease. CTI and CHG may therefore be more closely associated with concurrent metabolic-inflammatory burden than with subsequent clinically recognized CVD in this population; studies with adjudicated outcomes across a wider cardiometabolic range are warranted.