Genetic Determinants of Left Atrial Function Are Associated With Stroke

Area of Science:

• Cardiology
• Genetics
• Neurology

Background:

• Atrial fibrillation (AF) is a known stroke risk factor.
• Emerging evidence suggests atrial cardiomyopathy may increase stroke risk independently of AF.

Purpose of the Study:

• To investigate genetic determinants of left atrial (LA) function and volumes.
• To evaluate the association between genetic factors for LA function and stroke risk.

Main Methods:

• Constructed polygenic scores (PGSs) for LA measures in 380,017 UK Biobank participants without prior stroke or AF.
• Assessed ischemic stroke risk using time-to-event models with competing risks.
• Employed two-sample Mendelian randomization to explore causal relationships between LA measures and cardioembolic stroke.

Main Results:

• A PGS for LA passive emptying fraction was associated with increased ischemic stroke risk.
• Individuals in the lowest quartile of this PGS had a 12% higher risk of ischemic stroke (HR 1.12).
• Mendelian randomization indicated a protective effect of higher LA functional measurements on cardioembolic stroke.

Conclusions:

• A genetic predisposition for impaired LA passive emptying fraction is linked to incident ischemic stroke, independent of AF.
• These findings highlight atrial dysfunction as a potential independent risk factor for stroke.
• Genetic insights into LA function can inform stroke risk prediction.