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

Although remnant cholesterol (RC) and residual inflammation are established risk factors for stroke, their joint prognostic value for ischemic stroke remains unclear.

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.

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.

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.

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.