Genetic Determinants of Left Atrial Function Are Associated With Stroke
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. Meth...
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Wiley
2024-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.037490 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Oliver B. Vad |
| collection | DOAJ |
| description | 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. 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. 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. |
| format | Article |
| id | doaj-art-3d7bd92057ad4d4fbc4861165e541d9b |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-3d7bd92057ad4d4fbc4861165e541d9b2024-12-03T10:06:25ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-12-01132310.1161/JAHA.124.037490Genetic Determinants of Left Atrial Function Are Associated With StrokeOliver B. Vad0Christian Paludan‐Müller1Søren Z. Diederichsen2Emily A. McKaige3Laia M. Monfort4Pia R. Lundegaard5Litten Bertelsen6Laura Andreasen7Jesper H. Svendsen8Morten S. Olesen9Department of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Science University of Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Science University of Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Cardiology, The Heart Centre Copenhagen University Hospital – Rigshospitalet Copenhagen DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Science University of Copenhagen DenmarkBackground 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. 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. 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.037490atrial myopathygeneticsischemic strokeMendelian randomizationpolygenic risk |
| spellingShingle | 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 Genetic Determinants of Left Atrial Function Are Associated With Stroke Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atrial myopathy genetics ischemic stroke Mendelian randomization polygenic risk |
| title | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| title_full | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| title_fullStr | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| title_full_unstemmed | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| title_short | Genetic Determinants of Left Atrial Function Are Associated With Stroke |
| title_sort | genetic determinants of left atrial function are associated with stroke |
| topic | atrial myopathy genetics ischemic stroke Mendelian randomization polygenic risk |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.037490 |
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