The etiology of ischemic stroke is heterogeneous and can be categorized into five subtypes based on potential mechanisms: large artery atherosclerosis (LAA), cardioembolism (CE), small vessel occlusion (SVO), other determined etiology, and undetermined etiology.1 Understanding these subtypes is essential for tailoring stroke treatment and prevention strategies to address the specific underlying causes.

An elevated low-density lipoprotein-cholesterol (LDL-C) level is associated with an increased risk of atherosclerotic cardiovascular disease.2 However, the associations between LDL-C levels and ischemic stroke subtypes, as well as their impact on vascular outcomes, are not well understood. Previous studies found that proportions of patients with higher cholesterol levels differed among stroke subtypes.3

Moreover, the role of LDL-C levels after ischemic stroke seems to be controversial. Several studies based primarily on hospital cohorts of stroke or coronary artery disease patients have reported a paradoxical association of low cholesterol levels with an increased risk of mortality or cardiovascular events,4 while high cholesterol levels, typically considered as risk factors for cardiovascular disease, have been associated with better outcomes in patients with ischemic stroke.5 The mechanism involved in this lipid paradox is unclear, but frailty or serious illness appears to be related to the lipid paradox phenomenon.6,7 Also, in a recent study, lipid paradox was only observed in acute ischemic stroke (AIS) patients with no statin pretreatment.8

Because ischemic stroke is heterogeneous, which is different from coronary artery disease, understanding whether the stroke subtype might differentially influence outcomes after ischemic stroke will help in decision making regarding the optimal strategy of lipid-lowering treatment among patients with different stroke subtypes. Current dyslipidemia guidelines mainly focus on atherosclerotic diseases;9 therefore, further study related to non-LAA stroke subtypes is warranted.

In this study, we investigated whether the associations between LDL-C levels and early vascular outcomes might be different according to the stroke subtype in AIS patients without statin pretreatment.