Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.
Predictors of mortality in patients with hereditary hemorrhagic telangiectasia.
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DOI：
10.1186/s13023-020-01579-2
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发表时间：
2021-01-06
影响因子：
3.7
通讯作者：
Brain Vascular Malformation Consortium HHT Investigator Group
中科院分区：
文献类型：
--
作者：
Thompson KP;Nelson J;Kim H;Pawlikowska L;Marchuk DA;Lawton MT;Faughnan ME;Brain Vascular Malformation Consortium HHT Investigator Group
回顾性调查问卷和医疗保健管理数据表明，未经治疗的遗传性出血性毛细血管扩张症 (HHT) 的预期寿命会缩短。前瞻性数据表明，丹麦中心治疗的 HHT 患者的死亡率与普通人群相似。然而，HHT 的临床表型差异很大，可能会影响死亡率。我们的目的是测量中心治疗的 HHT 患者死亡率的预测因素。自 2010 年以来，脑血管畸形联盟 (BVMC) 的 14 个 HHT 中心招募了 HHT 患者，并每年进行随访。在基线和随访期间收集生命状态、器官血管畸形（VM）和临床症状数据（N = 1286）。我们使用 Cox 回归分析测试了器官 VM、HHT 症状和 HHT 基因是否与死亡率增加相关，并根据患者年龄、性别和吸烟状况进行了调整。 平均随访时间为 3.4 年（最长 8.6 年），共发生 59 例死亡。贫血病史与死亡率增加相关（HR = 2.93，95% CI 1.37–6.26，p = 0.006），胃肠道（GI）出血（HR = 2.63，95% CI 1.46–4.74，p = 0.001）和有症状的肝脏也与死亡率增加相关。 VM（HR = 2.10，95% CI 1.15–3.84，p = 0.015）。脑 VM 和肺动静脉畸形 (AVM) 与死亡率无关 (p>0.05)。与ACVRL1或ENG突变患者相比，SMAD4突变患者的死亡率显着较高（HR = 18.36，95% CI 5.60-60.20，p< 0.001），但鉴于SMAD4患者的稀有性（n = 33例，4例死亡），这一估计并不精确。慢性胃肠道出血、贫血和有症状的肝脏 VM 与 HHT 患者死亡率增加相关，与年龄无关，并且与 HHT 这些方面的有限治疗选择一致。相反，死亡率似乎与肺 AVM 或脑 VM 无关，HHT 中心会定期对患者进行筛查和预防性治疗。这表明需要开发新疗法来治疗慢性贫血、胃肠道出血和有症状的肝脏 VM，以降低 HHT 患者的死亡率。
Retrospective questionnaire and healthcare administrative data suggest reduced life expectancy in untreated hereditary hemorrhagic telangiectasia (HHT). Prospective data suggests similar mortality, to the general population, in Denmark’s centre-treated HHT patients. However, clinical phenotypes vary widely in HHT, likely affecting mortality. We aimed to measure predictors of mortality among centre-treated HHT patients. HHT patients were recruited at 14 HHT centres of the Brain Vascular Malformation Consortium (BVMC) since 2010 and followed annually. Vital status, organ vascular malformations (VMs) and clinical symptoms data were collected at baseline and during follow-up (N = 1286). We tested whether organ VMs, HHT symptoms and HHT genes were associated with increased mortality using Cox regression analysis, adjusting for patient age, sex, and smoking status. 59 deaths occurred over average follow-up time of 3.4 years (max 8.6 years). A history of anemia was associated with increased mortality (HR = 2.93, 95% CI 1.37–6.26, p = 0.006), as were gastro-intestinal (GI) bleeding (HR = 2.63, 95% CI 1.46–4.74, p = 0.001), and symptomatic liver VMs (HR = 2.10, 95% CI 1.15–3.84, p = 0.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (p > 0.05). Patients with SMAD4 mutation had significantly higher mortality (HR = 18.36, 95% CI 5.60–60.20, p < 0.001) compared to patients with ACVRL1 or ENG mutation, but this estimate is imprecise given the rarity of SMAD4 patients (n = 33, 4 deaths). Chronic GI bleeding, anemia and symptomatic liver VMs are associated with increased mortality in HHT patients, independent of age, and in keeping with the limited treatment options for these aspects of HHT. Conversely, mortality does not appear to be associated with pulmonary AVMs or brain VMs, for which patients are routinely screened and treated preventatively at HHT Centres. This demonstrates the need for development of new therapies to treat chronic anemia, GI bleeding, and symptomatic liver VMs in order to reduce mortality among HHT patients.
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影响因子：
3.9
作者：
Maria Mora-Lujan, Jose;Iriarte, Adriana;Riera-Mestre, Antoni
通讯作者：
Riera-Mestre, Antoni
影响因子：
13.3
作者：
Gallitelli, M;Pasculli, G;Sabbà, C
通讯作者：
Sabbà, C
影响因子：
8.8
作者：
Grosse, Scott D.;Boulet, Sheree L.;Faughnan, Marie E.
通讯作者：
Faughnan, Marie E.
影响因子：
3.7
作者：
Al-Samkari, Hanny;Albitar, Hasan A.;Iyer, Vivek N.
通讯作者：
Iyer, Vivek N.
影响因子：
168.9
作者：
Gallione, CJ;Repetto, GM;Marchuk, DA
通讯作者：
Marchuk, DA