Joint Exposure to Estimated Small Dense LDL-C and Long-Term PM 2.5 and Risk of Incident Stroke: A Chinese...

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.