Abstract
<title>Abstract</title> <p> <bold>Background</bold> Stroke remains a leading cause of disability and mortality worldwide, yet optimal markers reflecting long-term integrated cardiometabolic burden remain limited. The hemoglobin A1c–systolic blood pressure index (HSI) may capture combined glycemic and hemodynamic stress, but its longitudinal association with stroke is not fully established. <bold>Methods</bold> Data were from the China Health and Retirement Longitudinal Study (CHARLS). Baseline HSI was calculated using measurements from the 2011–2012 baseline survey. Cumulative HSI was derived from repeated measurements in 2011 and 2015 using a time-weighted average. Participants were also categorized into four transition patterns based on wave-specific median cutoffs: low-low (LL), high-low (HL), low-high (LH), and high-high (HH). Incident stroke was identified through follow-up surveys. Cox proportional hazards models, restricted cubic splines, competing risk models, and sensitivity analyses were applied. <bold>Results</bold> A total of 9,342 participants were included in the baseline analysis, and 6,071 in the cumulative HSI landmark cohort. Higher baseline HSI was independently associated with increased stroke risk (per 1-SD HR = 1.26, 95% CI: 1.19–1.33). Cumulative HSI showed a similar association (HR = 1.24, 95% CI: 1.15–1.34). Both baseline and cumulative HSI exhibited nonlinear dose-response relationships ( <italic>P</italic> for nonlinearity = 0.031 and 0.013, respectively). Compared with the LL pattern, the HH pattern had the highest risk (HR = 1.99, 95% CI: 1.55–2.55), followed by LH (HR = 1.93, 95% CI: 1.43–2.61) and HL (HR = 1.54, 95% CI: 1.12–2.12). All findings remained robust in competing risk and sensitivity analyses. <bold>Conclusions</bold> Higher HSI is independently associated with increased risk of incident stroke in a dose-dependent manner. Long-term cumulative exposure and persistent elevation of HSI provide additional risk stratification beyond baseline measurement, highlighting the importance of longitudinal cardiometabolic burden in stroke prevention. </p>