| Title: | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| Journal: | Journal of the American Heart Association |
| Published: | 22 Nov 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39575717/ |
| DOI: | https://doi.org/10.1161/jaha.124.037490 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681563 |
Publication 14343
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: While atrial fibrillation (AF) is a key risk factor for stroke, recent studies have suggested that atrial cardiomyopathy may also increase stroke risk in the absence of AF. This study aimed to evaluate genetic determinants for left atrial (LA) function and volumes and risk of stroke.</p>
METHODS AND RESULTS: Polygenic scores (PGSs) for LA measures were constructed and used in 380 017 individuals in the UK Biobank, without history of ischemic stroke, systemic arterial embolism, or AF at enrollment. Risk of ischemic stroke was estimated using time-to-event models, considering all-cause death and incident AF as competing events. Systemic arterial embolism was investigated as a secondary end point. The PGS for LA passive emptying fraction was associated with risk of ischemic stroke. Individuals with a PGS for LA passive emptying fraction in the lowest quartile had a hazard ratio (HR) of 1.12 for ischemic stroke compared with those in the top quartile (P=0.004). These associations were robust in a subgroup free of prevalent cardiovascular disease at baseline (HR for lowest quartile versus top quartile, 1.22; P<0.001). No associations were found for 4 other PGSs for LA measures or for risk of systemic arterial embolism. Two-sample Mendelian randomization was conducted between LA measures and cardioembolic stroke and indicated a protective effect of higher LA functional measurements.</p>
CONCLUSIONS: The PGS for LA passive emptying fraction was significantly associated with incident ischemic stroke when considering AF as a competing risk. Consistent results were found in Mendelian randomization analyses. These findings suggest that atrial dysfunction may influence stroke risk independently of AF.</p>
16 Keywords
- Aged
- Atrial Fibrillation
- Atrial Function, Left
- Female
- Genetic Predisposition to Disease
- Heart Atria
- Humans
- Ischemic Stroke
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Multifactorial Inheritance
- Risk Assessment
- Risk Factors
- Stroke
- United Kingdom
10 Authors
- Oliver B. Vad
- Christian Paludan-Müller
- Søren Z. Diederichsen
- Emily A. McKaige
- Laia M. Monfort
- Pia R. Lundegaard
- Litten Bertelsen
- Laura Andreasen
- Jesper H. Svendsen
- Morten S. Olesen
1 Application
| Application ID | Title |
|---|---|
| 43247 | Genetics of complex human traits with a main focus on cardiac disease. |
Enabling scientific discoveries that improve human health