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Prospective data suggests similar mortality, to the general population, in Denmark\u2019s 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\u2009=\u20091286). 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      59 deaths occurred over average follow-up time of 3.4\u00a0years (max 8.6\u00a0years). A history of anemia was associated with increased mortality (HR\u2009=\u20092.93, 95% CI 1.37\u20136.26,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), as were gastro-intestinal (GI) bleeding (HR\u2009=\u20092.63, 95% CI 1.46\u20134.74,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), and symptomatic liver VMs (HR\u2009=\u20092.10, 95% CI 1.15\u20133.84,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015). Brain VMs and pulmonary arteriovenous malformations (AVMs) were not associated with mortality (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). Patients with\n                      <jats:italic>SMAD4<\/jats:italic>\n                      mutation had significantly higher mortality (HR\u2009=\u200918.36, 95% CI 5.60\u201360.20,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) compared to patients with\n                      <jats:italic>ACVRL1<\/jats:italic>\n                      or\n                      <jats:italic>ENG<\/jats:italic>\n                      mutation, but this estimate is imprecise given the rarity of\n                      <jats:italic>SMAD4<\/jats:italic>\n                      patients (n\u2009=\u200933, 4 deaths).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-020-01579-2","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T14:04:06Z","timestamp":1609941846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Predictors of mortality in patients with hereditary hemorrhagic telangiectasia"],"prefix":"10.1186","volume":"16","author":[{"name":"the Brain Vascular Malformation Consortium HHT Investigator Group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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