作者
Janneke W. C. M. Mulder,Tycho R. Tromp,Mutaz Al‐Khnifsawi,Dirk Blom,Krzysztof Chlebus,Marina Cuchel,Laura D’Erasmo,Antonio Gallo,G. Kees Hovingh,Ngoc‐Thanh Kim,Long Jiang,Frederick J. Raal,Willemijn A. M. Schonck,Handrean Soran,Thanh‐Huong Truong,Eric Boersma,Jeanine E. Roeters van Lennep,Mohammed Alareedh,Rano Alieva,Massimiliano Allevi,Bülent B. Altunkeser,Khalid Al-Waili,Ali Fawzi Abdalsahib Al-Zamili,Marcello Arca,Luigi Atzori,Maurizio Averna,Mahmoud H. Ayesh,Sami T. Azar,Giuseppe Banderali,Francesco Baratta,Andrea Bartuli,Sophie Béliard,Vanessa Bianconi,Simone Bini,Khalid Bin Thani,Fadi Bitar,V. Bláha,Katia Bonomo,Mafalda Bourbon,Adriana Branchi,Julie A. Brothers,Éric Bruckert,Liam R. Brunham,Patrizia Bruzzi,Marco Bucci,Paola Sabrina Buonuomo,Paolo Calabrò,Sebastiano Calandra,Francesca Carubbi,David Cassiman,Manuela Casula,Alberico L. Catapano,Franco Cavalot,Angelo Baldassare Cefalù,Arturo Cesaro,Richard Češka,Min‐Ji Charng,Francesco Cipollone,Hofit Cohen,Sergio D’Addato,Beatrice Dal Pino,Eldad J. Dann,Joep C. Defesche,Maria Del Ben,Si̇nan Demi̇rci̇oğlu,Olivier Descamps,Alessia Di Costanzo,Maria Donata Di Taranto,Doan‐Loi Do,Ronen Durst,Jana Dvořáková,Christoph Ebenbichler,Avishay Elis,Sameh Emil,M. Ezhov,Akl C. Fahed,Tommaso Fasano,Claudio Ferri,Federica Fogacci,Elena Formisano,Giuliana Fortunato,Gordon A. Francis,Tomáš Freiberger,Federica Galimberti,Isabel Gaspar,Jacques Genest,Marco Gentile,Antonina Giammanco,Cumali Gökçe,Susanne Greber‐Platzer,Liliana Grigore,Urh Grošelj,Mariko Harada‐Shiba,Merel L. Hartgers,Robert A. Hegele,Pavel Horák,Mika Hori,Lisa C. Hudgins,Osama Hussein,Gabriella Iannuzzo,Osman İlhan,Lorenzo Iughetti,Meral Kayıkçıoğlu,Leylagül Kaynar,Brooke A. Kennedy,Weerapan Khovidhunkit,Genovefa Kolovou,Melis Köse,İrfan Kuku,Erdal Kurtoğlu,Katarina Lalić,Hong‐An Le,Thanh‐Tung Le,Eran Leitersdorf,Evangelos Liberopoulos,Alexander R.M. Lyons,Ramón Madriz,Giuseppe Mandraffino,Martin Mäser,Roopa Mehta,Olena Mitchenko,Giuliana Mombelli,Tiziana Montalcini,Carmela Morace,Elie Moubarak,Sandro Muntoni,Tarek Naguib,Fabio Nascimbeni,Hapizah Md Nawawi,Georges Nemer,Mai‐Ngoc Thi Nguyen,Serena Notargiacomo,Harika Okutan,Osman Özcebe,Jing Pang,Angelina Passaro,Chiara Pavanello,Lorenzo Pecchioli,Valerio Pecchioli,Cristina Pederiva,Zafer Pekkolay,Fabio Pellegatta,Salvatore Piro,Matteo Pirro,Livia Pisciotta,Arturo Pujia,Kausik K. Ray,Ashraf Reda,M. Reijman,Željko Reiner,Sabah H. Rhadi,Luigi Rizzi,Alessandra Romandini,Isabelle L. Ruel,Daisy Rymen,Fouzia Sadiq,Saim Sağ,Osman Z. Salcioglu,Raul D. Santos,Juana María Sanz,Riccardo Sarzani,Francesco Sbrana,Daniel Schurr,Francesco Purrello,Nitika Setia,Foaad Shaghee,Aleksandr B. Shek,Mark Sherman,Vladimír Soška,C. Stevens,Erik S.G. Stroes,Thomas Stulnig,Patrizia Suppressa,А. В. Сусеков,Patrizia Tarugi,Ahmet Temizhan,Lukáš Tichý,Chiara Trenti,Tycho R. Tromp,R Urbánek,Antonio J. Vallejo‐Vaz,H Vaverková,Ishwar C. Verma,Michal Vráblík,Luya Wang,Gerald F. Watts,José Pablo Werba,Albert Wiegman,Peter Witters,Mustafa Yenerçağ,Mehmet Birhan Yılmaz,Hamiyet Yılmaz Yaşar,Alberto Zambón,Sabina Zambon,Stanislav Zemek,Maria Grazia Zenti,Lukáš Zlatohlávek,Linda Zuurbier
摘要
Importance 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. Objective To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. Design, Setting, and Participants 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. Main Outcomes and Measures 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. Results 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). Conclusions and Relevance 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.