David Adlam1, Timothy M Olson2, Nicolas Combaret3, Jason C Kovacic4, Siiri E Iismaa5, Abtehale Al-Hussaini6, Megan M O'Byrne7, Sara Bouajila3, Adrien Georges8, Ketan Mishra5, Peter S Braund6, Valentina d'Escamard4, Siying Huang8, Marios Margaritis6, Christopher P Nelson6, Mariza de Andrade7, Daniella Kadian-Dodov4, Catherine A Welch6, Stephani Mazurkiewicz8, Xavier Jeunemaitre9, Claire Mei Yi Wong5, Eleni Giannoulatou5, Michael Sweeting6, David Muller5, Alice Wood6, Lucy McGrath-Cadell10, Diane Fatkin5, Sally L Dunwoodie5, Richard Harvey5, Cameron Holloway5, Jean-Philippe Empana8, Xavier Jouven8, Jeffrey W Olin4, Rajiv Gulati2, Marysia S Tweet2, Sharonne N Hayes2, Nilesh J Samani6, Robert M Graham5, Pascal Motreff3, Nabila Bouatia-Naji11. 1. Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom. Electronic address: da134@le.ac.uk. 2. Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. 3. Department of Cardiology, University Hospital of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France. 4. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine, Marie-Josée and Henry R. Kravis Cardiovascular Health Center at Mount Sinai, New York, New York. 5. Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia; St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia. 6. Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom. 7. Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. 8. INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France. 9. INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France; Department of Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France. 10. St. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia. 11. INSERM, Paris Cardiovascular Research Center, Paris, France; Faculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France. Electronic address: nabila.bouatia-naji@inserm.fr.
Abstract
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
Authors: Vanessa L Kronzer; Alex D Tarabochia; Angie S Lobo Romero; Nicholas Y Tan; Thomas J O'Byrne; Cynthia S Crowson; Tamiel N Turley; Elena Myasoedova; John M Davis; Claire E Raphael; Rajiv Gulati; Sharonne N Hayes; Marysia S Tweet Journal: J Am Coll Cardiol Date: 2020-11-10 Impact factor: 24.094
Authors: Fernando Macaya; Manuel Moreu; Virginia Ruiz-Pizarro; Carlos H Salazar; Eduardo Pozo; Andrés Aldazábal; Reddy Guerra; Santiago Rosati; Pablo Salinas; Nieves Gonzalo; María J Pérez-Vizcayno; Leopoldo Pérez de Isla; Antonio Fernández-Ortiz; Carlos Macaya; David Adlam; Juan Arrazola; Javier Escaned Journal: Cardiovasc Diagn Ther Date: 2019-06
Authors: Alexandre Persu; Piotr Dobrowolski; Heather L Gornik; Jeffrey W Olin; David Adlam; Michel Azizi; Pierre Boutouyrie; Rosa Maria Bruno; Marion Boulanger; Jean-Baptiste Demoulin; Santhi K Ganesh; Tomasz J Guzik; Magdalena Januszewicz; Jason C Kovacic; Mariusz Kruk; Peter de Leeuw; Bart L Loeys; Marco Pappaccogli; Melanie H A M Perik; Emmanuel Touzé; Patricia Van der Niepen; Daan J L Van Twist; Ewa Warchoł-Celińska; Aleksander Prejbisz; Andrzej Januszewicz Journal: Cardiovasc Res Date: 2022-01-07 Impact factor: 10.787
Authors: Clint L Miller; Amy R Kontorovich; Ke Hao; Lijiang Ma; Conrad Iyegbe; Johan L M Björkegren; Jason C Kovacic Journal: J Am Coll Cardiol Date: 2021-05-25 Impact factor: 24.094
Authors: Lijiang Ma; Nirupama Chandel; Raili Ermel; Katyayani Sukhavasi; Ke Hao; Arno Ruusalepp; Johan L M Björkegren; Jason C Kovacic Journal: Atherosclerosis Date: 2020-08-29 Impact factor: 5.162
Authors: Siiri E Iismaa; Stephanie Hesselson; Lucy McGrath-Cadell; David W Muller; Diane Fatkin; Eleni Giannoulatou; Jason Kovacic; Robert M Graham Journal: Heart Lung Circ Date: 2020-07-06 Impact factor: 2.975
Authors: Adrien Georges; Juliette Albuisson; Takiy Berrandou; Délia Dupré; Aurélien Lorthioir; Valentina D'Escamard; Antonio F Di Narzo; Daniella Kadian-Dodov; Jeffrey W Olin; Ewa Warchol-Celinska; Aleksander Prejbisz; Andrzej Januszewicz; Patrick Bruneval; Anna A Baranowska; Tom R Webb; Stephen E Hamby; Nilesh J Samani; David Adlam; Natalia Fendrikova-Mahlay; Stanley Hazen; Yu Wang; Min-Lee Yang; Kristina Hunker; Nicolas Combaret; Pascal Motreff; Antoine Chédid; Béatrice Fiquet; Pierre-François Plouin; Elie Mousseaux; Arshid Azarine; Laurence Amar; Michel Azizi; Heather L Gornik; Santhi K Ganesh; Jason C Kovacic; Xavier Jeunemaitre; Nabila Bouatia-Naji Journal: Cardiovasc Res Date: 2021-03-21 Impact factor: 10.787