Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers‐Danlos Syndrome-Reference-Cited by-同舟云学术

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers‐Danlos Syndrome

Published:2023-10-03 Issue:19 Volume:12 Page:
ISSN:2047-9980
Container-title:Journal of the American Heart Association
language:en
Short-container-title:JAHA

Author:

Stephens Sara B.¹²^ORCID,Shalhub Sherene³^ORCID,Dodd Nicholas⁴,Li Jesse⁵,Huang Michael⁵,Oda Seitaro⁶⁷^ORCID,Kancherla Kalyan⁷⁸⁹,Doan Tam T.¹^ORCID,Prakash Siddharth K.⁵^ORCID,Weigand Justin D.¹^ORCID,Asch Federico M.⁷⁸^ORCID,Beecroft Taylor¹,Cecchi Alana⁵^ORCID,Shittu Teniola¹,Preiss Liliana¹⁰,LeMaire Scott A.¹¹^ORCID,Devereux Richard B.¹²,Pyeritz Reed E.¹³^ORCID,Holmes Kathryn W.¹⁴^ORCID,Roman Mary J.¹²^ORCID,Lacro Ronald V.¹⁵^ORCID,Shohet Ralph V.¹⁶^ORCID,Krishnamurthy Rajesh¹⁷^ORCID,Eagle Kim⁷¹⁸,Byers Peter¹⁹^ORCID,Milewicz Dianna M.⁵^ORCID,Morris Shaine A.¹^ORCID

Affiliation:

1. Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children’s Hospital Houston TX USA

2. Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston Houston TX USA

3. Division of Vascular and Endovascular Surgery, Department of Surgery Oregon Health & Science University Portland OR USA

4. Memorial Health University Medical Center Savannah GA USA

5. Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA

6. Department of Diagnostic Radiology, Faculty of Life Sciences Kumamoto University Kumamoto Japan

7. National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)

8. MedStar Heart and Vascular Institute Washington DC USA

9. CHI St. Vincent Little Rock AR USA

10. RTI International, Research Triangle Park NC USA

11. Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston TX USA

12. Department of Medicine Weill Cornell Medicine New York NY

13. Division of Translational Medicine and Human Genetics Perelman School of Medicine at the University of Pennsylvania PA USA

14. Section of Cardiology, Department of Pediatrics Oregon Health & Science University and OHSU Doernbecher Children’s Hospital Portland OR USA

15. Department of Cardiology Boston Children’s Hospital Boston MA USA

16. John A. Burns School of Medicine Honolulu HI USA

17. Department of Radiology Nationwide Children’s Hospital Columbus OH USA

18. Division of Cardiovascular Medicine, Frankel Cardiovascular Center, Department of Internal Medicine, Michigan Medicine University of Michigan Ann Arbor MI USA

19. Department of Laboratory Medicine and Pathology, Department of Medicine (Medical Genetics) University of Washington Seattle WA USA

Abstract

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys‐Dietz syndromes but remains understudied in Vascular Ehlers‐Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height‐adjusted vertebral artery tortuosity index (VTI‐h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI‐h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed‐effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI‐h was 12 (interquartile range, 8–16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty‐two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI‐h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22–0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI‐h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76–4.24], P =0.185). However, VTI‐h ≥15.5 was associated with events among those with high‐risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13–15.10], P =0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers‐Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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