Nathalie Timmerman1, Dominique P V de Kleijn1, Gert J de Borst1, Hester M den Ruijter2, Folkert W Asselbergs3, Gerard Pasterkamp4, Saskia Haitjema4, Sander W van der Laan5. 1. Department of Vascular Surgery, Division of Surgical Specialties, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. 2. Laboratory of Experimental Cardiology, Division Heart & Lungs, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. 3. Department of Cardiology, Division Heart & Lungs, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK. 4. Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. 5. Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: s.w.vanderlaan-2@umcutrecht.nl.
Abstract
BACKGROUND AND AIMS: Family history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA). METHODS: We included 1788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years of follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition. RESULTS: Positive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p = 0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p = 0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p = 0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p = 0.006). CONCLUSIONS: In CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.
BACKGROUND AND AIMS: Family history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA). METHODS: We included 1788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years of follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition. RESULTS: Positive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p = 0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p = 0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p = 0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p = 0.006). CONCLUSIONS: In CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.
Authors: Atlas Khan; Michael C Turchin; Amit Patki; Vinodh Srinivasasainagendra; Ning Shang; Rajiv Nadukuru; Alana C Jones; Edyta Malolepsza; Ozan Dikilitas; Iftikhar J Kullo; Daniel J Schaid; Elizabeth Karlson; Tian Ge; James B Meigs; Jordan W Smoller; Christoph Lange; David R Crosslin; Gail P Jarvik; Pavan K Bhatraju; Jacklyn N Hellwege; Paulette Chandler; Laura Rasmussen Torvik; Alex Fedotov; Cong Liu; Christopher Kachulis; Niall Lennon; Noura S Abul-Husn; Judy H Cho; Iuliana Ionita-Laza; Ali G Gharavi; Wendy K Chung; George Hripcsak; Chunhua Weng; Girish Nadkarni; Marguerite R Irvin; Hemant K Tiwari; Eimear E Kenny; Nita A Limdi; Krzysztof Kiryluk Journal: Nat Med Date: 2022-06-16 Impact factor: 87.241
Authors: Johannes T Neumann; Moeen Riaz; Andrew Bakshi; Galina Polekhina; Le T P Thao; Mark R Nelson; Robyn L Woods; Gad Abraham; Michael Inouye; Christopher M Reid; Andrew M Tonkin; John McNeil; Paul Lacaze Journal: Circ Genom Precis Med Date: 2021-12-24