Remnant cholesterol and early prognosis after Acute ischaemic stroke: The potential mediating role of maximum carotid plaque thickness

Background Remnant cholesterol (RC) is now widely regarded as a contributor to residual cardiovascular risk; however, its relationship with early prognosis following acute ischaemic stroke (AIS) remains uncertain, and whether carotid plaque burden may act as a mediator remains unclear. Therefore, the present study examined the association between RC and two early outcomes after AIS (early neurological deterioration [END] and 3-month poor functional outcome [3 M-PFO]) and evaluated whether maximum carotid plaque thickness (cPTmax) could serve as a potential mediator of these relationships. Methods This retrospective cohort study included 623 consecutive patients with AIS. Analyses included (1) restricted cubic splines and multivariable logistic regression for assessing the associations of RC with END and 3 M-PFO; (2) subgroup analyses for assessing 3 M-PFO according to age, diabetes status, stroke severity, and Trial of Org 10172 in Acute Stroke Treatment (TOAST) subtype; and (3) mediation analyses of cPTmax as a potential mediator. Results Restricted cubic spline analysis revealed that RC was linearly associated with both END and 3 M-PFO ( P < 0.001; nonlinearity test not significant). Each 0.1 mmol/L increase in RC was associated with an odds ratio (OR) of 1.182 for END (95% confidence interval [CI]: 1.114–1.255) and an OR of 1.188 for 3 M-PFO (95% CI: 1.119–1.260). Using Q1 as the reference, the ORs for the two aforementioned outcomes in Q4 were 3.467 (95% CI: 1.980–6.071) and 2.846 (95% CI: 1.681–4.817), respectively. Subgroup analyses revealed consistent associations across age, diabetes status, stroke severity, and TOAST subtype, with no significant interactions being observed (interaction P > 0.05). In the mediation analyses, cPTmax was observed to be consistent with a potential partial mediation of the association between RC and END (indirect effect = 0.144, 95% CI: 0.033–0.256); a similar potential mediating pathway was observed for 3 M-PFO (indirect effect = 0.146, 95% CI: 0.030–0.262). Conclusions A higher RC was linked to both END and 3 M-PFO after AIS, and cPTmax was observed to be consistent with a potential mediating pathway. The monitoring of RC and cPT may help identify high-risk patients at early points in time. However, based on the observational design of this study, whether the targeting of RC can improve the secondary prevention of stroke remains to be investigated in future randomised controlled trials.