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

被引：3

作者：

Stephens, Sara B. ^{[1
,2
]}

Shalhub, Sherene ^{[3
]}

Dodd, Nicholas ^{[4
]}

Li, Jesse ^{[5
]}

Huang, Michael ^{[5
]}

Oda, Seitaro ^{[6
,7
]}

Kancherla, Kalyan ^{[7
,8
,9
]}

Doan, Tam T. ^{[1
]}

Prakash, Siddharth K. ^{[5
]}

Weigand, Justin D. ^{[1
]}

Asch, Federico M. ^{[7
,8
]}

Beecroft, Taylor ^{[1
]}

Cecchi, Alana ^{[5
]}

Shittu, Teniola ^{[1
]}

Preiss, Liliana ^{[10
]}

Lemaire, Scott A. ^{[11
]}

Devereux, Richard B. ^{[12
]}

Pyeritz, Reed E. ^{[13
]}

Holmes, Kathryn W. ^{[14
,15
]}

Roman, Mary J. ^{[12
]}

Lacro, Ronald V. ^{[16
]}

Shohet, Ralph V. ^{[17
]}

Krishnamurthy, Rajesh ^{[18
]}

Eagle, Kim ^{[7
,19
]}

Byers, Peter ^{[20
]}

Milewicz, Dianna M. ^{[5
]}

Morris, Shaine A. ^{[1
,21
]}

机构：

[1] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Div Cardiol, Houston, TX 77030 USA

[2] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX USA

[3] Oregon Hlth & Sci Univ, Dept Surg, Div Vasc & Endovasc Surg, Portland, OR USA

[4] Mem Hlth Univ, Med Ctr, Savannah, GA USA

[5] Univ Texas Hlth Sci Ctr, Dept Internal Med, Div Med Genet, Houston, TX USA

[6] Kumamoto Univ, Fac Life Sci, Dept Diagnost Radiol, Kumamoto, Japan

[7] Natl Registry Genet Triggered Thorac Aort Aneurysm, Washington, DC USA

[8] MedStar Heart & Vasc Inst, Washington, DC USA

[9] CHI St Vincent, Little Rock, AR USA

[10] RTI Int, Res Triangle Pk, NC USA

[11] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX USA

[12] Weill Cornell Med, Dept Med, New York, NY USA

[13] Univ Penn, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA USA

[14] Oregon Hlth & Sci Univ, Dept Pediat, Sect Cardiol, Portland, OR USA

[15] OHSU Doernbecher Childrens Hosp, Portland, OR USA

[16] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA

[17] John A Burns Sch Med, Honolulu, HI USA

[18] Nationwide Childrens Hosp, Dept Radiol, Columbus, OH USA

[19] Univ Michigan, Frankel Cardiovasc Ctr, Dept Internal Med, Div Cardiovasc Med,Michigan Med, Ann Arbor, MI USA

[20] Univ Washington, Dept Lab Med & Pathol, Dept Med Med Genet, Seattle, WA USA

[21] Texas Childrens Hosp, 6651 Main St E1920, Houston, TX 77030 USA

来源：

JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2023年 / 12卷 / 19期

关键词：

arterial rupture; cardiovascular; dissection; genetics; VEDS; SYNDROME TYPE-IV; PHENOTYPE; HAPLOINSUFFICIENCY; MUTATIONS; VARIANTS; ADULTS;

D O I：

10.1161/JAHA.123.029518

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页数：14

共 36 条

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