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

Area of Science:

• Cardiology
• Neurology
• Pharmacology

Background:

• Dyslipidemia, particularly high low-density lipoprotein (LDL) cholesterol, is a key risk factor for atherosclerosis and atherosclerotic cardiovascular disease (ASCVD).
• LDL cholesterol-lowering therapies, mainly statins, are proven to reduce coronary events and stroke, forming a cornerstone of cardiovascular prevention.
• Ischemic stroke encompasses diverse pathologies (atherothrombotic, cardioembolic, small-vessel disease), with varying roles of dyslipidemia and lipid-lowering therapy efficacy.

Purpose of the Study:

• To provide an overview of current dyslipidemia guidelines for ischemic stroke management.
• To summarize the relationship between dyslipidemia and ischemic stroke, integrating pathophysiology, pathology, imaging, and biomarkers.
• To discuss the latest clinical trial evidence, novel lipid-lowering therapies, and residual risk interventions for stroke prevention.

Main Methods:

• Review of domestic and international dyslipidemia guidelines.
• Analysis of pathophysiological, pathological, imaging, and biomarker data linking dyslipidemia to ischemic stroke subtypes.
• Synthesis of evidence from large-scale clinical trials on lipid-lowering therapies and residual risk interventions.

Main Results:

• The efficacy of lipid management in stroke prevention varies significantly across different ischemic stroke subtypes.
• Emerging therapies targeting hypertriglyceridemia, lipoprotein(a) [Lp(a)], and residual inflammatory risk show promise for stroke prevention.
• New agents like PCSK9 inhibitors and ATP citrate lyase inhibitors are advancing stroke prevention strategies.

Conclusions:

• Current evidence for coronary artery disease cannot be directly extrapolated to all stroke subtypes, necessitating subtype-specific lipid management.
• Developing tailored lipid management strategies for each ischemic stroke subtype is a critical challenge.
• Future stroke prevention relies on personalized lipid management, incorporating novel therapies and residual risk reduction.