Impacts of Remnant Cholesterol and Residual Inflammation on Clinical Outcomes After Ischemic Stroke

BACKGROUND: Although remnant cholesterol (RC) and residual inflammation are established risk factors for stroke, their joint prognostic value for ischemic stroke remains unclear. OBJECTIVES: The authors aimed to evaluate the combined effects of RC and high-sensitivity C-reactive protein (hs-CRP), as well as a novel index-the remnant cholesterol-inflammation index (RCII)-for long-term clinical outcomes after ischemic stroke. METHODS: We measured RC and hs-CRP levels in 3,008 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Participants were categorized into 4 groups according to dichotomized RC (≥median, 28.62 mg/dL) and hs-CRP (≥threshold, 2.00 mg/L). RCII was calculated as (RC mg/dL×hs-CRP mg/L)/10 to quantify their joint effects. The study outcomes included all-cause mortality, cardiovascular events, and unfavorable functional outcome at 24 months. RESULTS: Compared with patients with no residual risk, HRs or ORs for those with residual cholesterol and inflammation risk were 2.33 (95% CI: 1.57-3.44) for all-cause mortality, 2.28 (95% CI: 1.49-3.49) for stroke-specific mortality, and 1.91 (95% CI: 1.44-2.53) for unfavorable functional outcome. In addition, the highest quartile of RCII exhibited increased risks of all-cause mortality, cardiovascular events, and unfavorable functional outcome. Both combined RC/hs-CRP and RCII offered substantial risk discrimination and reclassification improvement for study outcomes beyond traditional risk factors, as evidenced by an increase in C-statistics, net reclassification index, and integrated discrimination improvement. CONCLUSIONS: Elevated RC and hs-CRP were synergistically associated with increased risks of long-term all-cause mortality and unfavorable functional outcome, and RCII manifested dose-dependent associations with adverse clinical outcomes and superior predictive capacity.