Ischemic or brain stroke is caused by blockage of blood supply. Fats, cholesterol, and lipoproteins can aggravate this situation. High levels of such proteins can lead to different types of severe strokes. Understanding their role in ischemic stroke is crucial for risk assessment. This study compares and separates the effects of lipids and apolipoprotein on stroke-related cases.

The objective of the study is to understand the association between lipids and stroke. A Mendelian randomization study was done on 514791 subjects. The MEGASTROKE consortium provided summary-level data of 60341 ischemic and 454450 non-cases, and the UK Biobank provided significant, genome-wide, single-nucleotide polymorphisms(SNPs). The instrumental variables were LDL and HDL cholesterol, apoA-I, triglycerides, and apoB lipoproteins.

Main and sensitivity univariable MR analyses signified risk. High levels of apoB, LDL, and triglycerides led to the ischemic, large artery, and small-vessel strokes. In multivariable MR analyses, apoB had a robust effect. The LDL effects were reversed, while triglycerides’ effects got largely weakened. In univariable MR analyses, low apoA-I and HDL levels increased the risks for all three types of strokes. But apoA-I effects weakened to null after mutual adjustments.

The study reveals apoB as the predominant trait for three types of stroke. But HDL effect on ischemic stroke independent of apoA-I requires further research.