{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T02:28:41Z","timestamp":1793845721420,"version":"4.6.1"},"reference-count":40,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"\n Importance<\/jats:title>\n Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg\/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75).<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2023.5597","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T11:01:44Z","timestamp":1707908504000},"page":"313","source":"Crossref","is-referenced-by-count":35,"title":["Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia"],"prefix":"10.1001","volume":"9","author":[{"given":"Janneke W. C. M.","family":"Mulder","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Erasmus Medical Center Cardiovascular Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tycho R.","family":"Tromp","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutaz","family":"Al-Khnifsawi","sequence":"additional","affiliation":[{"name":"University of Al-Qadisiyah, College of Pharmacy, Diwaniya City, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Lipidology and Cape Heart Institute, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krysztof","family":"Chlebus","sequence":"additional","affiliation":[{"name":"1st Department of Cardiology, Medical University of Gda\u0144sk, Gda\u0144sk, Poland"},{"name":"National Centre of Familial Hypercholesterolaemia, Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Cuchel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"D\u2019Erasmo","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Gallo","sequence":"additional","affiliation":[{"name":"Lipidology and Cardiovascular Prevention Unit, Department of Nutrition, Sorbonne Universit\u00e9, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale UMR 1166, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9-Salp\u00e8tri\u00eare, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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