Joint Exposure to Estimated Small Dense LDL ‐C and Long‐Term PM 2.5 and Risk of Incident Stroke: A Chinese Longitudinal Cohort Study

The joint effects of small dense low‐density lipoprotein cholesterol (sd‐LDL‐C) and ambient PM 2.5 exposure on stroke risk remain unclear. This longitudinal cohort study included 6457 stroke‐free participants from the China Health and Retirement Longitudinal Study (2011–2020). PM 2.5 exposure was estimated from the ChinaHighPM 2.5 dataset. Cox regression models assessed hazard ratios (HR) with 95% confidence intervals (CI). K‐means trajectory analysis identified sd‐LDL‐C risk groups. The restricted cubic spline examined the dose–response relationship. During a median 9‐year follow‐up, 710 stroke cases occurred. Both sd‐LDL‐C (HR per 1‐SD: 1.116, 95% CI: 1.018–1.224) and PM 2.5 (HR per 1‐SD: 1.321, 95% CI: 1.222–1.428) independently predicted stroke risk. Significant multiplicative interaction was detected ( p = 0.037). Combined high sd‐LDL‐C and high PM 2.5 exposure conferred the greatest risk (HR: 1.713, 95% CI: 1.335–2.198) versus double‐low exposure. Sustained high sd‐LDL‐C trajectory increased stroke risk by 36% (HR: 1.361, 95% CI: 1.086–1.706). Cumulative sd‐LDL‐C (cu‐sd‐LDL‐C) exposure showed dose‐dependent associations (Q4 vs. Q1: HR = 1.580, 95% CI: 1.115–2.239). Baseline sd‐LDL‐C ( p = 0.009), annual average PM 2.5 ( p < 0.001), and cu‐sd‐LDL‐C exposure ( p = 0.037) all showed significant nonlinear relationship with incident stroke. sd‐LDL‐C demonstrated superior predictive ability over conventional LDL‐C (AUC: 0.578 vs. 0.534, p < 0.001). Long‐term elevated sd‐LDL‐C and PM 2.5 exposure were independently associated with incident stroke risk, and participants with dual‐high exposure showed the highest risk. sd‐LDL‐C outperforms LDL‐C in stroke prediction, supporting its integration into risk assessment strategies and the importance of simultaneous lipid and pollution control.