全球EAS家族性高胆固醇血症研究协作组（FHSC）研究了全球家族性高胆固醇血症的特征与管理现状。2021年9月7日出版的《柳叶刀》杂志发表了这项成果。

欧洲动脉粥样硬化协会家族性高胆固醇血症研究合作（FHSC）全球注册中心通过协调和汇集跨国数据，为全球监测家族性高胆固醇血症提供了一个平台。该研究旨在描述成年人群杂合子家族性高胆固醇血症的特征，并提出如何在全球范围内对其进行监测和管理。

利用FHSC全球注册数据，研究组对登记时临床或遗传诊断为可能或明确杂合子家族性高胆固醇血症的成人（年龄18岁及以上）进行了一项横断面评估。研究组对数据进行了全面评估，并按世卫组织区域、性别、指数与非指数病例进行了评估。

该研究共有61612人登记，其中42167名成年人被纳入研究，53.6%为女性。其中31798例（75.4%）符合荷兰脂质临床网络诊断标准，35490例（84.2%）符合世卫组织欧洲地区诊断标准。登记时参与者的中位年龄为46.2岁；家族性高胆固醇血症的确诊年龄中位数为44.4岁，40.2%的受试者在确诊时年龄小于40岁。心血管危险因素的患病率随着年龄的增长而逐渐增加，并因世卫组织区域而异。

冠心病的患病率为17.4%（中风为2.1%，外周动脉疾病为5.2%），且随未经治疗的低密度脂蛋白胆固醇浓度的增加而增加，女性的患病率约为男性的两倍。在接受降脂药物治疗的患者中，16803名（81.1%）接受他汀类药物治疗，3691名（21.2%）接受联合治疗，男性比女性使用更多、更有效的降脂药物。

未服用降脂药物患者的LDL胆固醇中位数为5.43 mmol/L，服用降脂药物的患者为4.23 mmol/L。在服用降脂药物的患者中，2.7%的患者LDL胆固醇低于1.8 mmol/L；联合治疗，特别是使用三种药物和蛋白转化酶枯草杆菌素-可欣9型抑制剂，与低密度脂蛋白胆固醇低于1.8 mmol/L的比例和几率较高相关。与指数病例相比，非指数病例患者更年轻，低密度脂蛋白胆固醇更低，心血管危险因素和心血管疾病患病率更低。

研究结果表明，家族性高胆固醇血症诊断较晚。指南推荐的低密度脂蛋白胆固醇浓度很少能通过单一药物治疗达到。在早期诊断的非指数患者中，心血管危险因素和冠心病发病率较低。为了减少家族性高胆固醇血症的全球负担，需要及早发现和更多地使用联合疗法。

附：英文原文

Title: Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

Author: Antonio J. Vallejo-Vaz, Christophe A.T. Stevens, Alexander R.M. Lyons, Kanika I. Dharmayat, Tomas Freiberger, G. Kees Hovingh, Pedro Mata, Frederick J. Raal, Raul D. Santos, Handrean Soran, Gerald F. Watts, Marianne Abifadel, Carlos A. Aguilar-Salinas, Khalid F. Alhabib, Mutaz Alkhnifsawi, Wael Almahmeed, Fahad Alnouri, Rodrigo Alonso, Khalid Al-Rasadi, Ahmad Al-Sarraf, Nasreen Al-Sayed, Francisco Araujo, Tester F. Ashavaid, Maciej Banach, Sophie Béliard, Marianne Benn, Christoph J. Binder, Martin P. Bogsrud, Mafalda Bourbon, Krzysztof Chlebus, Pablo Corral, Kairat Davletov, Olivier S. Descamps, Ronen Durst, Marat Ezhov, Dan Gaita, Jacques Genest, Urh Groselj, Mariko Harada-Shiba, Kirsten B. Holven, Meral Kayikcioglu, Weerapan Khovidhunkit, Katarina Lalic, Gustavs Latkovskis, Ulrich Laufs, Evangelos Liberopoulos, Marcos M. Lima-Martinez, Jie Lin, Vincent Maher, A. David Marais, Winfried Mrz, Erkin Mirrakhimov, André R. Miserez, Olena Mitchenko, Hapizah Nawawi, Brge G. Nordestgaard, Andrie G. Panayiotou, Gyrgy Paragh, Zaneta Petrulioniene, Belma Pojskic, Arman Postadzhiyan, Katarina Raslova, Ashraf Reda, eljko Reiner, Fouzia Sadiq, Wilson Ehidiamen Sadoh, Heribert Schunkert, Aleksandr B. Shek, Mario Stoll, Erik Stroes, Ta-Chen Su, Tavintharan Subramaniam, Andrey V. Susekov, Myra Tilney, Brian Tomlinson, Thanh Huong Truong, Alexandros D. Tselepis, Anne Tybjg-Hansen, Alejandra Vázquez Cárdenas, Margus Viigimaa, Luya Wang, Shizuya Yamashita, Lale Tokgozoglu, Alberico L. Catapano, Kausik K. Ray, John J.P. Kastelein, Eric Bruckert, Branislav Vohnout, Laura Schreier, Jing Pang, Christoph Ebenbichler, Hans Dieplinger, Reinhold Innerhofer, Yvonne Winhofer-Stckl, Susanne Greber-Platzer, Konstantin Krychtiuk, Walter Speidl, Hermann Toplak, Kurt Widhalm, Thomas Stulnig, Kurt Huber, Florian Hllerl, Gersina Rega-Kaun, Lucas Kleemann, Martin Mser, Sabine Scholl-Bürgi, Christoph Sly, Florian J. Mayer, Gaelle Sablon, Eric Tarantino, Charlotte Nzeyimana, Lamija Pojskic, Ibrahim Sisic, Azra D. Nalbantic, Cinthia E. Jannes, Alexandre C. Pereira, Jose E. Krieger, Ivo Petrov, Assen Goudev, Fedya Nikolov, Snejana Tisheva, Yoto Yotov, Ivajlo Tzvetkov, Alexis Baass, Jean Bergeron, Sophie Bernard, Diane Brisson, Liam R. Brunham, Lubomira Cermakova, Patrick Couture, Gordon A. Francis, Daniel Gaudet, Robert A. Hegele, Etienne Khoury, G.B. John Mancini, Brian W. McCrindle, Martine Paquette, Isabelle Ruel, Ada Cuevas, Sylvia Asenjo, Xumin Wang, Kang Meng, Xiantao Song, Qiang Yong, Tao Jiang, Ziyou Liu, Yanyu Duan, Jing Hong, Pucong Ye

Issue&Volume: 2021-09-07

Abstract:

Background

The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally.

Methods

Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Data were assessed overall and by WHO regions, sex, and index versus non-index cases.

Findings

Of the 61612 individuals in the registry, 42167 adults (21999 [53·6%] women) from 56 countries were included in the study. Of these, 31798 (75·4%) were diagnosed with the Dutch Lipid Clinic Network criteria, and 35490 (84·2%) were from the WHO region of Europe. Median age of participants at entry in the registry was 46·2 years (IQR 34·3–58·0); median age at diagnosis of familial hypercholesterolaemia was 44·4 years (32·5–56·5), with 40·2% of participants younger than 40 years when diagnosed. Prevalence of cardiovascular risk factors increased progressively with age and varied by WHO region. Prevalence of coronary disease was 17·4% (2·1% for stroke and 5·2% for peripheral artery disease), increasing with concentrations of untreated LDL cholesterol, and was about two times lower in women than in men. Among patients receiving lipid-lowering medications, 16803 (81·1%) were receiving statins and 3691 (21·2%) were on combination therapy, with greater use of more potent lipid-lowering medication in men than in women. Median LDL cholesterol was 5·43 mmol/L (IQR 4·32–6·72) among patients not taking lipid-lowering medications and 4·23 mmol/L (3·20–5·66) among those taking them. Among patients taking lipid-lowering medications, 2·7% had LDL cholesterol lower than 1·8 mmol/L; the use of combination therapy, particularly with three drugs and with proprotein convertase subtilisin–kexin type 9 inhibitors, was associated with a higher proportion and greater odds of having LDL cholesterol lower than 1·8 mmol/L. Compared with index cases, patients who were non-index cases were younger, with lower LDL cholesterol and lower prevalence of cardiovascular risk factors and cardiovascular diseases (all p<0·001).

Interpretation

Familial hypercholesterolaemia is diagnosed late. Guideline-recommended LDL cholesterol concentrations are infrequently achieved with single-drug therapy. Cardiovascular risk factors and presence of coronary disease were lower among non-index cases, who were diagnosed earlier. Earlier detection and greater use of combination therapies are required to reduce the global burden of familial hypercholesterolaemia.

DOI: 10.1016/S0140-6736(21)01122-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01122-3/fulltext