Roles for circulating polyunsaturated fatty acids in ischemic stroke and modifiable factors: a Mendelian...

Area of Science:

• Nutritional Epidemiology
• Genetics
• Cardiovascular Disease Research

Background:

• Limited and conflicting data exist on the impact of circulating polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS) and its risk factors.
• Mendelian randomization (MR) is a valuable tool for investigating causal relationships between exposures and outcomes, minimizing confounding factors.

Purpose of the Study:

• To investigate the causal effect of genetically predicted polyunsaturated fatty acids (PUFAs) on ischemic stroke (IS).
• To assess the association between PUFAs and key risk factors for IS, including lipids and blood pressure (BP).

Main Methods:

• Utilized large-scale genome-wide association study (GWAS) data for IS, lipids, and BP.
• Employed Mendelian randomization (MR) with inverse-variance weighted (IVW) as the primary analysis method.
• Conducted sensitivity analyses including MR-Egger, weighted median, and weighted mode to ensure robustness of findings.

Main Results:

• Increased serum alpha-linolenic acid (ALA) was associated with a reduced risk of ischemic stroke (IS) (OR: 0.867).
• Elevated arachidonic acid (AA) levels were linked to a higher risk of IS (OR: 1.053).
• ALA showed inverse associations with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC), while AA demonstrated positive associations with these lipid profiles.

Conclusions:

• Higher plasma ALA concentrations appear protective against IS, whereas higher AA levels may increase IS risk.
• Linoleic acid (LA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) did not show significant associations with IS risk.
• Findings suggest differential roles of specific PUFAs in the pathogenesis of ischemic stroke.