{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:36:35Z","timestamp":1789878995920,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The clinical focus of haemophilia has expanded beyond bleeding outcomes to encompass long\u2010term comorbidities such as cardiovascular disease (CVD). However, it remains unclear when vascular changes begin in this population. Carotid intima\u2010media thickness (cIMT), a validated, non\u2010invasive marker of subclinical atherosclerosis, may help detect early vascular remodelling in youth with haemophilia, even in the absence of conventional CVD risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single\u2010centre, cross\u2010sectional study compared adolescent males (ages 10\u201321 years) with severe haemophilia (FVIII or IX &lt;1%) to age\u2010matched healthy controls. Bilateral carotid ultrasonography was performed, and right\u2010sided cIMT was the prespecified primary endpoint. Conventional CVD clinical risk factors were also collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010eight participants were enrolled, 22 with haemophilia and 16 controls. Median right cIMT was higher in the haemophilia group (0.40\u00a0mm, SD 0.08 range 0.35\u20130.47) versus the control group (0.38\u00a0mm, SD 0.06 range 0.32\u20130.39;\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      = 0.009). When referenced to age\u2010and\u2010height specific nomograms, cIMT percentiles were also elevated in the haemophilia group (6.5% vs. 1.6%;\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      = 0.026 and 12.9%\u00a0vs. 1.7%;\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0= 0.018; respectively). HDL\u2010cholesterol was significantly lower in the haemophilia group (48.9 SD 9.9 vs. 60.2 SD 14.9\u00a0mg\/dL;\u00a0\n                      <jats:italic>p<\/jats:italic>\n                      = 0.012). No correlations were found between cIMT and any CVD risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Adolescent males with severe haemophilia show early arterial thickening, suggesting that vascular remodelling in this population may begin in adolescence. Incorporating cIMT and CVD risk assessment into routine haemophilia care may support timely interventions and reduce long\u2010term cardiovascular complications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.70187","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T13:47:37Z","timestamp":1766756857000},"page":"418-424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Carotid Intima\u2010Media Thickness as a Marker of Subclinical Atherosclerosis in Adolescents With Severe Haemophilia"],"prefix":"10.1111","volume":"32","author":[{"given":"Alyson","family":"Trillo","sequence":"first","affiliation":[{"name":"Johns Hopkins All Children's Hospital, Cancer and Blood Disorders Institute  St. Petersburg Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanita","family":"Hunter","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics University of Miami \u2010 Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Ofir","sequence":"additional","affiliation":[{"name":"Division of General Pediatrics Department of Pediatrics University of Miami \u2010 Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Shoag","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Cleveland Clinic Lerner College of Medicine  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna A.","family":"Davis","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Department of Pediatrics University of Miami \u2010 Miller School of Medicine  Miami Florida USA"},{"name":"University of Miami\u2010Hemophilia and Thrombosis Comprehensive Treatment Center  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando F.","family":"Corrales\u2010Medina","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology\/Oncology Department of Pediatrics University of Miami \u2010 Miller School of Medicine  Miami Florida USA"},{"name":"University of Miami\u2010Hemophilia and Thrombosis Comprehensive Treatment Center  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-215665"},{"issue":"3","key":"e_1_2_9_3_1","first-page":"469","article-title":"Increased Prevalence of Hypertension in Hemophilia Patients","volume":"108","author":"Fransen van de Putte D. E.","year":"2012","journal-title":"Thrombosis Haemostasis"},{"issue":"2","key":"e_1_2_9_4_1","first-page":"437","article-title":"Mortality Among Males With Hemophilia: Relations With Source of Medical Care","volume":"96","author":"Soucie J. M.","year":"2000","journal-title":"Blood"},{"issue":"3","key":"e_1_2_9_5_1","first-page":"e199","article-title":"US Hemophilia Treatment Center Population Trends 1990\u20132010: Patient Diagnoses, Demographics, Health Services Utilization","volume":"22","author":"Baker J. R.","year":"2016","journal-title":"Haemophilia"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02074.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001036"},{"issue":"1","key":"e_1_2_9_8_1","first-page":"e12","article-title":"Obesity and Cardiovascular Risk Factors Among Children and Young Adults With Hemophilia","volume":"42","author":"Sharathkumar A. A.","year":"2020","journal-title":"Journal of Pediatric Hematology\/Oncology"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"496","article-title":"Atherosclerosis in Severe Hemophilia: Is There a Protective Effect of Low Factor VIII Levels?","volume":"120","author":"Zwiers A.","year":"2012","journal-title":"Blood"},{"issue":"23","key":"e_1_2_9_10_1","first-page":"2302","article-title":"Hemophilia as a Model for Bleeding Disorders","volume":"360","author":"Rosendaal F. R.","year":"2009","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000178834.26353.d5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.11.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.03.004"},{"issue":"5","key":"e_1_2_9_14_1","first-page":"879","article-title":"Cardiovascular Risk Assessment in Haemophilia Patients","volume":"109","author":"Biere\u2010Rafi S.","year":"2013","journal-title":"Thrombosis Haemostasis"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04514.x"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.628875"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199901073400103"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15467-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000081812"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/hae.13278"},{"issue":"5","key":"e_1_2_9_21_1","first-page":"S213","article-title":"Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report","volume":"128","author":"Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute","year":"2011","journal-title":"Pediatrics"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70187","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hae.70187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hae.70187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:35:17Z","timestamp":1773408917000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hae.70187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/hae.70187"],"URL":"https:\/\/doi.org\/10.1111\/hae.70187","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]},"assertion":[{"value":"2025-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}