Circulating Lipoprotein Lipids, Apolipoproteins and Ischemic Stroke

Area of Science:

• Cardiovascular Genetics
• Neurology
• Metabolic Disorders

Background:

• Lipids and apolipoproteins are crucial in cardiovascular health.
• Their specific roles in ischemic stroke etiology require clarification.
• Mendelian randomization (MR) offers a powerful tool to assess causality.

Purpose of the Study:

• To investigate the causal relationships between lipids, apolipoproteins, and ischemic stroke.
• To disentangle the comparative effects of various lipoproteins on stroke risk.
• To identify the predominant etiological factor among apoB, LDL cholesterol, and triglycerides.

Main Methods:

• Utilized genome-wide significant single-nucleotide polymorphisms from UK Biobank as instrumental variables.
• Employed summary-level data for ischemic stroke and subtypes from the MEGASTROKE consortium.
• Conducted univariable and multivariable Mendelian randomization analyses.

Main Results:

• Elevated apolipoprotein B (apoB), LDL cholesterol, and triglycerides were linked to increased risk of ischemic stroke subtypes.
• In multivariable analysis, apoB remained a significant risk factor, while LDL and triglyceride effects were attenuated or reversed.
• Lower apoA-I and HDL cholesterol levels were associated with higher stroke risk, but apoA-I's effect diminished upon adjustment.

Conclusions:

• Apolipoprotein B (apoB) is the predominant etiological factor for ischemic stroke among the studied lipids and apolipoproteins.
• The causal effect of apoB on large artery and small vessel stroke is robust.
• Further research is needed to confirm the independent protective role of HDL cholesterol against ischemic stroke.