Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33923
Title: Genetic Insights on the Relation of Vascular Risk Factors and Cervical Artery Dissection.
Austin Authors: Le Grand, Quentin;Ecker Ferreira, Leslie;Metso, Tiina M;Schilling, Sabrina;Tatlisumak, Turgut;Grond-Ginsbach, Caspar;Engelter, Stefan T;Lyrer, Philippe;Majersik, Jennifer J;Worrall, Bradford B;Southerland, Andrew M;Markus, Hugh S;Lathrop, Mark;Thijs, Vincent N ;Leys, Didier;Amouyel, Philippe;Dallongeville, Jean;Dichgans, Martin;Pezzini, Alessandro;Bersano, Anna;Sargurupremraj, Muralidharan;Debette, Stéphanie
Affiliation: University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Center (BPH), Unité Mixte de Recherche (U) 1219, Bordeaux, France.
Department of Medicine and Joinville Stroke Biobank, University of Region of Joinville, Joinville, Brazil.
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Center (BPH), Unité Mixte de Recherche (U) 1219, Bordeaux, France.
Department of Clinical Neurosciences/Neurology, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Vascular and Endovascular Surgery, University of Heidelberg, Heidelberg, Germany.
Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland; Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Neurology and Stroke Center, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
Department of Neurology, University of Virginia, Charlottesville, Virginia, USA; Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia, USA.
Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Quebec, Canada.
Stroke Division, Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Neurology, Austin Health, Melbourne, Victoria, Australia.
INSERM U1172, Lille Neuroscience and Cognition, University of Lille, Lille, France.
Laboratory of Excellence Development of Innovative Strategies for a Transdisciplinary Approach to Alzheimer's Disease (LabEx DISTALZ), University of Lille, Lille, France; INSERM U1167 (Risk Factors and Molecular Determinants of Aging-Related Diseases - RID-AGE), Lille, France; Centre Hospitalier Universitaire Lille, Lille, France; Institut Pasteur de Lille, Lille, France.
Institute for Stroke and Dementia Research, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany; Munich Cluster for Systems Neurology, Munich, Germany; German Center for Neurodegenerative Diseases, Munich, Germany.
Department of Clinical and Experimental Sciences, Neurology Unit, University of Brescia, Brescia, Italy.
Cerebrovascular Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Neurologico Carlo Besta, Milan, Italy.
Neurology
University of Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Center (BPH), Unité Mixte de Recherche (U) 1219, Bordeaux, France; Department of Neurology, Institute of Neurodegenerative Diseases, Bordeaux University Hospital, Bordeaux, France.
Issue Date: 3-Oct-2023
Publication information: Journal of the American College of Cardiology 2023-10-03; 82(14)
Abstract: The association between vascular risk factors and cervical artery dissections (CeADs), a leading cause of ischemic stroke (IS) in the young, remains controversial. 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. 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. 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. 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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33923
DOI: 10.1016/j.jacc.2023.07.021
ORCID: 
Journal: Journal of the American College of Cardiology
Start page: 1411
End page: 1423
PubMed URL: 37758436
ISSN: 1558-3597
Type: Journal Article
Subjects: Mendelian randomization
blood pressure
cervical artery dissection
drug effect
ischemic stroke
young adults
Appears in Collections:Journal articles

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