Author + information
- Received August 24, 2018
- Revision received September 21, 2018
- Accepted September 21, 2018
- Published online January 7, 2019.
- David Adlam, DPhila,∗∗∗ (, )@LeicesterBRC,
- Timothy M. Olson, MDb,∗,
- Nicolas Combaret, MDc,
- Jason C. Kovacic, MD, PhDd,
- Siiri E. Iismaa, PhDe,f,
- Abtehale Al-Hussaini, MB, BSa,
- Megan M. O'Byrne, MAg,
- Sara Bouajila, MD, MSc,
- Adrien Georges, PhDh,i,
- Ketan Mishra, MBTeche,f,
- Peter S. Braund, PhDa,
- Valentina d’Escamard, PhDd,
- Siying Huang, PhDh,i,
- Marios Margaritis, MD, DPhila,
- Christopher P. Nelson, PhDa,
- Mariza de Andrade, PhDg,
- Daniella Kadian-Dodov, MDd,
- Catherine A. Welch, PhDa,
- Stephani Mazurkiewicz, MSch,i,
- Xavier Jeunemaitre, MD, PhDh,i,j,
- DISCO Consortium,
- Claire Mei Yi Wong, MGCe,f,
- Eleni Giannoulatou, DPhile,f,
- Michael Sweeting, PhDa,
- David Muller, MDe,f,
- Alice Wood, BSc, MB, BSa,
- Lucy McGrath-Cadell, MB, BS, MPHf,
- Diane Fatkin, MD, PhDe,f,
- Sally L. Dunwoodie, PhDe,f,
- Richard Harvey, PhDe,f,
- Cameron Holloway, MDe,f,
- Jean-Philippe Empana, MD, PhDh,i,
- Xavier Jouven, MD, PhDh,i,
- CARDIoGRAMPlusC4D Study Group,
- Jeffrey W. Olin, MDd,
- Rajiv Gulati, MD, PhDb,
- Marysia S. Tweet, MDb,
- Sharonne N. Hayes, MDb,
- Nilesh J. Samani, MDa,
- Robert M. Graham, MDe,f,
- Pascal Motreff, MD, PhDc and
- Nabila Bouatia-Naji, PhDh,i,∗ (, )@n_bouatianaji@Inserm@parcc_inserm
- aDepartment of Cardiovascular Sciences, Glenfield Hospital, Leicester, and National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
- bDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
- cDepartment of Cardiology, University Hospital of Clermont-Ferrand, Auvergne University, Clermont-Ferrand, France
- dThe 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
- eMolecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia
- fSt. Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia
- gDepartment of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
- hINSERM, Paris Cardiovascular Research Center, Paris, France
- iFaculty of Medicine, Paris-Descartes University, Sorbonne Paris Cité, Paris, France
- jDepartment of Genetics, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France
- ↵∗Addresses for correspondence:
Dr. Nabila Bouatia-Naji, Paris Cardiovascular Research Center, INSERM UMR970, 56 Rue Leblanc, F-75015, Paris, France.
- ↵∗∗Dr. David Adlam, Department of Cardiovascular Sciences, NIHR Leicester Biomedical Research Unit, Glenfield Hospital, Groby Road, Leicester, LE3 9QP, United Kingdom.
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.
↵∗ Drs. Adlam and Olson are co-first authors.
The French SCAD study was supported by the French Society of Cardiology foundation, Coeur et recherche, the French Coronary Atheroma and Interventional Cardiology Group, and European Research Council grant ERC-Stg-ROSALIND-716628 to Dr. Bouatia-Naji. The U.K. SCAD study was supported by the British Heart Foundation and National Institute for Health Research rare disease translational collaboration, the Leicester NIHR Biomedical Research Centre, and BeatSCAD. The Mount Sinai DEFINE-FMD study was supported by a philanthropic gift. The Australian study was supported by National Health and Medical Research Council of Australia grant 1074386, the Cardiac Society of Australia and New Zealand, St. Vincent’s Clinic Foundation, the Catholic Archdiocese of Sydney, and SCAD Research Inc., Australia. The Mayo Clinic SCAD study was supported by SCAD Research, Inc., the Department of Cardiovascular Medicine, Mayo Clinic, and the National Institutes of Health “Building Interdisciplinary Research Careers in Women's Health” program grant NH HD 65987 to Dr. Tweet. Dr. Adlam has received research funding from Abbott Vascular Inc. and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received August 24, 2018.
- Revision received September 21, 2018.
- Accepted September 21, 2018.
- 2019 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.