Cumulative and persistent glycemic–renal burden and incident cardiovascular disease in the Health and Retirement Study

Sustained glycemic and renal abnormalities may contribute to cardiovascular disease (CVD), but evidence from repeated joint assessment remains limited. We analyzed 2,867 Health and Retirement Study participants with three measurements of glycated hemoglobin and cystatin C who were free of heart disease and stroke at the third assessment. Standardized glycated hemoglobin and log-transformed cystatin C were averaged to construct a joint glycemic–renal burden score, with high burden defined by the pooled first-assessment median. Incident CVD was analyzed using interval-censored proportional hazards models. During follow-up, 411 incident CVD events occurred. In the prespecified primary Model 3, each 1-standard-deviation increase in time-averaged cumulative burden was associated with higher CVD risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.02–1.26), as was each additional high-burden assessment (HR 1.18, 95% CI 1.07–1.31). Participants with high burden at all three assessments had higher risk than those with none (HR 1.66, 95% CI 1.17–2.37). Cumulative burden was strongly correlated with third-assessment burden and provided no clear independent information beyond it. Persistent glycemic–renal burden was associated with subsequent CVD, while repeated measurements may primarily characterize longitudinal exposure rather than distinct incremental risk information.