Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Department of Interventional Radiology, Gelderse Vallei Hospital, Ede, The Netherlands; Department of Interventional Radiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Int J Cardiol. 2017 Oct 15;245:114-118. doi: 10.1016/j.ijcard.2017.06.059.
Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls.
Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area.
In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (β-coefficient 3.5, p<0.001) and ascending aorta diameter (β-coefficient 1.6, p=0.04).
SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls.
转化生长因子-β信号通路中的 ENG、ACVRL1 和 SMAD4 基因突变导致遗传性出血性毛细血管扩张症（HHT）。该通路中的非 HHT 基因中的突变已被发现与主动脉扩张相关。因此，我们研究了与非 HHT 对照相比，大量 HHT 患者是否存在主动脉扩张。
回顾连续的 HHT 患者（ENG、ACVRL1 和 SMAD4 基因突变携带者）和非 HHT 对照者的胸部计算机断层扫描。主动脉根部扩张定义为 z 分数>1.96。升主动脉和降主动脉的尺寸根据年龄、性别和体表面积进行校正。
共纳入 178 名受试者（57.3%为女性，平均年龄 43.9±14.9 岁）（32 名 SMAD4、47 名 ENG、50 名 ACVRL1 基因突变携带者和 49 名非 HHT 对照者）。共有 42 名受试者存在主动脉病变（占总数的 24%）。SMAD4 组中有 31%的患者出现主动脉根部扩张，ENG 组中有 2%的患者，ACVRL1 基因突变携带者中有 6%的患者，非 HHT 对照组中有 4%的患者（p<0.001）。SMAD4 组的主动脉根部直径为 36.3±5.2mm，非-SMAD4 组为 32.7±3.9mm（p=0.001）。SMAD4 是主动脉根部（β 系数 3.5，p<0.001）和升主动脉直径（β 系数 1.6，p=0.04）增大的独立预测因子。
与其他 HHT 患者和非 HHT 对照组相比，HHT 患者中的 SMAD4 基因突变与主动脉根部和升主动脉扩张的风险增加独立相关。
