{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:06:33Z","timestamp":1791194793022,"version":"4.1.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Arterial tortuosity is associated with adverse events in Marfan and Loeys\u2010Dietz syndromes but remains understudied in Vascular Ehlers\u2010Danlos syndrome.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Subjects with a pathogenic\n              <jats:italic>COL3A1<\/jats:italic>\n              variant diagnosed at age &lt;50\u2009years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height\u2010adjusted vertebral artery tortuosity index (VTI\u2010h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI\u2010h and outcomes of (1) cardiovascular events (arterial dissection\/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse\/rupture at age &lt;50\u2009years were evaluated using receiver operator curve analysis (using outcome by age 30\u2009years) and mixed\u2010effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI\u2010h was 12 (interquartile range, 8\u201316). Variants were missense in 46%, splice site in 31%, and null\/gene deletion in 14%. Thirty\u2010two 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\u2010h \u226515.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22\u20130.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI\u2010h \u226515.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76\u20134.24],\n              <jats:italic>P<\/jats:italic>\n              =0.185). However, VTI\u2010h \u226515.5 was associated with events among those with high\u2010risk variants &lt;40\u2009years (incidence rate ratios, 4.14 [95% CI, 1.13\u201315.10],\n              <jats:italic>P<\/jats:italic>\n              =0.032), suggesting effect modification by genotype and age.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers\u2010Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.029518","type":"journal-article","created":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T10:44:05Z","timestamp":1696070645000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers\u2010Danlos Syndrome"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-2198","authenticated-orcid":false,"given":"Sara B.","family":"Stephens","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"},{"name":"Department of Epidemiology, Human Genetics &amp; Environmental Sciences, School of Public Health The University of Texas Health Science Center at Houston Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-2750","authenticated-orcid":false,"given":"Sherene","family":"Shalhub","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Surgery Oregon Health &amp; Science University Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Dodd","sequence":"additional","affiliation":[{"name":"Memorial Health University Medical Center Savannah GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4101-5113","authenticated-orcid":false,"given":"Seitaro","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Faculty of Life Sciences Kumamoto University Kumamoto Japan"},{"name":"National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyan","family":"Kancherla","sequence":"additional","affiliation":[{"name":"National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)"},{"name":"MedStar Heart and Vascular Institute Washington DC USA"},{"name":"CHI St. Vincent Little Rock AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8256-1535","authenticated-orcid":false,"given":"Tam T.","family":"Doan","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6341-9624","authenticated-orcid":false,"given":"Siddharth K.","family":"Prakash","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0016-8140","authenticated-orcid":false,"given":"Justin D.","family":"Weigand","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-5271","authenticated-orcid":false,"given":"Federico M.","family":"Asch","sequence":"additional","affiliation":[{"name":"National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)"},{"name":"MedStar Heart and Vascular Institute Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Beecroft","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-8705","authenticated-orcid":false,"given":"Alana","family":"Cecchi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teniola","family":"Shittu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Preiss","sequence":"additional","affiliation":[{"name":"RTI International, Research Triangle Park NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8736-4266","authenticated-orcid":false,"given":"Scott A.","family":"LeMaire","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Devereux","sequence":"additional","affiliation":[{"name":"Department of Medicine Weill Cornell Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-1442","authenticated-orcid":false,"given":"Reed E.","family":"Pyeritz","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics Perelman School of Medicine at the University of Pennsylvania PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-089X","authenticated-orcid":false,"given":"Kathryn W.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Section of Cardiology, Department of Pediatrics Oregon Health &amp; Science University and OHSU Doernbecher Children\u2019s Hospital Portland OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0183-6769","authenticated-orcid":false,"given":"Mary J.","family":"Roman","sequence":"additional","affiliation":[{"name":"Department of Medicine Weill Cornell Medicine New York NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6261-6239","authenticated-orcid":false,"given":"Ronald V.","family":"Lacro","sequence":"additional","affiliation":[{"name":"Department of Cardiology Boston Children\u2019s Hospital Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5966-6470","authenticated-orcid":false,"given":"Ralph V.","family":"Shohet","sequence":"additional","affiliation":[{"name":"John A. Burns School of Medicine Honolulu HI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-642X","authenticated-orcid":false,"given":"Rajesh","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Radiology Nationwide Children\u2019s Hospital Columbus OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Eagle","sequence":"additional","affiliation":[{"name":"National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)"},{"name":"Division of Cardiovascular Medicine, Frankel Cardiovascular Center, Department of Internal Medicine, Michigan Medicine University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7786-7030","authenticated-orcid":false,"given":"Peter","family":"Byers","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Department of Medicine (Medical Genetics) University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-0068","authenticated-orcid":false,"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Internal Medicine The University of Texas Health Science Center Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-0934","authenticated-orcid":false,"given":"Shaine A.","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics, Baylor College of Medicine Texas Children\u2019s Hospital Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","volume-title":"GeneReviews\u00ae","author":"Byers PH","year":"1999","unstructured":"Byers PH. Vascular Ehlers\u2010Danlos syndrome. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Lora JHB, Gripp KW, Amemiya A, eds. GeneReviews\u00ae. Seattle (WA): University of Washington, Seattle; 1993\u20102023. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1494\/; 1999."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000507"},{"key":"e_1_3_2_5_2","unstructured":"Dietz H. FBN1\u2010Related Marfan Syndrome. Accessed December 31 2022. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1335\/."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.72"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.32"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-008-0884-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.181"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.990549"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.a6218"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.05.072"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/RCT.0000000000000764"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013736"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2008.10.005"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2011.07.002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2021.03.080"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2015.06.023"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-17-S1-P403"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2010.03.019"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10225290"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/9781444306309.ch5"},{"key":"e_1_3_2_23_2","unstructured":"Z\u2010Score Calculator . Accessed May 21 2022. https:\/\/zscore.chboston.org\/"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-10-56"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2014.06.024"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcct.2008.08.002"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182180c89"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/324123"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31553"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31829c7a59"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000218"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2006.10.011"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2349"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiomech.2008.11.011"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000161277.46464.11"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.134.suppl_1.14983"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001647"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.123.029518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:54:59Z","timestamp":1715604899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.123.029518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,3]]},"references-count":36,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2023,10,3]]}},"alternative-id":["10.1161\/JAHA.123.029518"],"URL":"https:\/\/doi.org\/10.1161\/jaha.123.029518","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,3]]},"assertion":[{"value":"2023-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e029518"}}