Genetic insights on the relation of vascular risk factors and cervical artery dissection

Background - The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. - Objectives - This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and c...

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Hauptverfasser: Le Grand, Quentin (VerfasserIn) , Ecker Ferreira, Leslie (VerfasserIn) , Metso, Tiina M. (VerfasserIn) , Schilling, Sabrina (VerfasserIn) , Tatlisumak, Turgut (VerfasserIn) , Grond-Ginsbach, Caspar (VerfasserIn) , Engelter, Stefan T. (VerfasserIn) , Lyrer, Philippe (VerfasserIn) , Majersik, Jennifer J. (VerfasserIn) , Worrall, Bradford B. (VerfasserIn) , Southerland, Andrew M. (VerfasserIn) , Markus, Hugh S. (VerfasserIn) , Lathrop, Mark (VerfasserIn) , Thijs, Vincent (VerfasserIn) , Leys, Didier (VerfasserIn) , Amouyel, Philippe (VerfasserIn) , Dallongeville, Jean (VerfasserIn) , Dichgans, Martin (VerfasserIn) , Pezzini, Alessandro (VerfasserIn) , Bersano, Anna (VerfasserIn) , Sargurupremraj, Muralidharan (VerfasserIn) , Debette, Stéphanie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 3 October 2023
In: Journal of the American College of Cardiology
Year: 2023, Jahrgang: 82, Heft: 14, Pages: 1411-1423
ISSN:1558-3597
DOI:10.1016/j.jacc.2023.07.021
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.jacc.2023.07.021
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0735109723063775
Volltext
Verfasserangaben:Quentin Le Grand, PhD, Leslie Ecker Ferreira, PhD, Tiina M. Metso, MD, PhD, Sabrina Schilling, PhD, Turgut Tatlisumak, MD, PhD, Caspar Grond-Ginsbach, PhD, Stefan T. Engelter, MD, Philippe Lyrer, MD, Jennifer J. Majersik, MD, MS, Bradford B. Worrall, MD, Andrew M. Southerland, MD, MSC, Hugh S. Markus, PhD, Mark Lathrop, PhD, Vincent Thijs, MD, PhD, Didier Leys, MD, PhD, Philippe Amouyel, MD, PhD, Jean Dallongeville, MD, PhD, Martin Dichgans, MD, Alessandro Pezzini, MD, Anna Bersano, MD, PhD, Muralidharan Sargurupremraj, PhD, Stéphanie Debette, MD, PhD, on behalf of the CADISP Consortium

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520 |a Background - The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. - Objectives - This study aimed to explore the causal relation of vascular risk factors with CeAD risk and recurrence and compare it to their relation with non-CeAD IS. - Methods - This study used 2-sample Mendelian randomization analyses to explore the association of blood pressure (BP), lipid levels, type 2 diabetes, waist-to-hip ratio, smoking, and body mass index with CeAD and non-CeAD IS. To simulate effects of the most frequently used BP-lowering drugs, this study constructed genetic proxies and tested their association with CeAD and non-CeAD IS. In analyses among patients with CeAD, the investigators studied the association between weighted genetic risk scores of vascular risk factors and the risk of multiple or early recurrent dissections. - Results - Genetically determined higher systolic BP (OR: 1.51; 95% CI: 1.32-1.72) and diastolic BP (OR: 2.40; 95% CI: 1.92-3.00) increased the risk of CeAD (P < 0.0001). Genetically determined higher body mass index was inconsistently associated with a lower risk of CeAD. Genetic proxies for β-blocker effects were associated with a lower risk of CeAD (OR: 0.65; 95% CI: 0.50-0.85), whereas calcium-channel blockers were associated with a lower risk of non-CeAD IS (OR: 0.75; 95% CI: 0.63-0.90). Weighted genetic risk scores for systolic BP and diastolic BP were associated with an increased risk of multiple or early recurrent CeAD. - Conclusions - These results are supportive of a causal association between higher BP and increased CeAD risk and recurrence and provide genetic evidence for lower CeAD risk under β-blockers. This may inform secondary prevention strategies and trial design for CeAD. 
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