Targeting Dyslipidemia in Ischemic Stroke: Pathophysiology, Clinical Evidence, and Future Perspectives

Dyslipidemia is a major risk factor for atherosclerosis, and high low-density lipoprotein (LDL) cholesterol is closely associated with the onset of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease. Numerous large-scale clinical trials have demonstrated that LDL cholesterol-lowering therapy, primarily involving statins, reduces not only coronary events, but also stroke, and has been established as a cornerstone of cardiovascular prevention. However, ischemic stroke is a group of diseases comprising different pathologies, such as atherothrombotic stroke, cardioembolic stroke, and small-vessel disease; the involvement of dyslipidemia and the efficacy of lipid-lowering therapy vary significantly depending on the subtype. Therefore, the evidence established for coronary artery disease cannot necessarily be applied directly to stroke management, and establishing lipid management strategies tailored to each subtype has become a critical challenge in stroke management. Furthermore, in recent years, in addition to LDL cholesterol-lowering therapy, treatments targeting hypertriglyceridemia, lipoprotein(a) [Lp(a)], and residual inflammatory risk have advanced, and the development of new therapeutic agents-such as PCSK9 inhibitors, selective PPARα modulators, and ATP citrate lyase inhibitors-is progressing, thus raising expectations for their application in stroke prevention. This article provides an overview of domestic and international guidelines for dyslipidemia and summarizes the association between dyslipidemia and ischemic stroke from the perspectives of pathophysiology, pathological findings, and imaging and blood biomarker. In addition, it outlines the latest evidence from large-scale clinical trials, new lipid-lowering therapies, acute-phase lipid management, and interventions targeting residual risk, and discusses the current status and future prospects of lipid management tailored to specific stroke subtypes.