沙特阿拉伯纯合子家族性高胆固醇血症评估和生存单中心研究：HESSA登记

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis Pub Date : 2025-05-02 DOI:10.1016/j.atherosclerosis.2025.119214

Naji Kholaif , Lin Batha , Sumayah Aljenedil , Zuhier Ahmed Awan , Nadiah AlRuwaili , Abdulrahman Khalid Habib , Ahmed Awni Jouda , Maria Teresa Savo , Fadl Elmula M. Fadl Elmula , Tahir I. Mohamed , Abdullah Al-Ashwal , Valeria Pergola , Naser Elkum , Domenico Galzerano

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引用次数: 0

摘要

纯合子家族性高胆固醇血症（HoFH）是一种罕见的、危及生命的遗传性疾病，可导致极高的低密度脂蛋白胆固醇（LDL-C）水平，导致早期心血管疾病（CVD）和过早死亡。在血缘关系普遍的沙特阿拉伯，HoFH患病率较高，具有独特的遗传致病性家族性高胆固醇血症（FH）导致变异和治疗挑战。本研究旨在分析在费萨尔国王专科医院治疗的沙特儿童和成人HoFH患者的临床、遗传、治疗和心血管结局数据；研究中心（KFSHRC）超过23年。方法采用欧洲动脉粥样硬化协会2023标准，对2000-2023年KFSHRC所有患者（LDL-C≤8mmol /L）进行回顾性分析，确认HoFH。已证实的数据包括人口统计学、脂质谱、致病性fh变异、治疗、死亡率和心血管结局。结果514例重度高胆固醇血症患者中，有127例发生HoFH。平均诊断年龄14.3±9.7岁。死亡率为16%，随访丢失12%。31%的患者接受了心血管干预（28%的患者接受了冠状动脉干预，17%的患者接受了主动脉瓣置换术）。最常见的致病性fh变异（57%）是创始零突变c.2027del p.（Gly676Alafs * 33）。他汀类药物和依折麦布是主要的治疗方法（73%），但许多患者需要ldl -单采（36%）或肝移植（21%）。LTx的围手术期死亡率为7%，但平均随访6.2±3.6年，无长期死亡率，只有1例患者需要经皮冠状动脉介入治疗。成人更有可能接受他汀类药物/依折麦比(儿科94% / 91%对50% / 53%，p <；0.01)和ldl分离(64% vs. 8%, p <；0.001)，而肝移植在儿童中更为常见(38% vs. 7%, p <；0.001)。结论本研究强调了沙特HoFH患者LDL-R致病性无致fh变异的负担和频繁的侵入性治疗需求。肝移植是一种可行的选择，具有低围手术期死亡率和良好的长期无病生存。早期诊断、区域遗传筛查和获得先进疗法对于取得更好的结果至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Homozygous familial hypercholesterolemia evaluation and survival single center study in Saudi Arabia: The HESSA registry

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Homozygous familial hypercholesterolemia evaluation and survival single center study in Saudi Arabia: The HESSA registry

Background and aims background

Homozygous Familial Hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder causing extremely high low density lipoprotein cholesterol (LDL-C) levels, leading to early cardiovascular disease (CVD) and premature death. In Saudi Arabia, where consanguinity is common, HoFH prevalence is higher with unique genetic pathogenic familial hypercholesterolemia (FH) causing variants and treatment challenges. This study aims to analyze the clinical, genetic, treatment, and cardiovascular outcomes data of Saudi pediatric and adult HoFH patients treated at King Faisal Specialist Hospital & Research Centre (KFSHRC) over 23 years.

Methods

A retrospective review of all patients (LDL-C >8 mmol/L) at KFSHRC (2000–2023) using European Atherosclerosis Society 2023 criteria to confirm HoFH. Data from those confirmed included demographics, lipid profiles, pathogenic FH-causing variants, treatments, mortality, and cardiovascular outcomes.

Results

Among 514 severe hypercholesterolemia cases, 127 had HoFH. Diagnosis occurred at an average age of 14.3 ± 9.7 years. The mortality was 16 %, and 12 % were lost to follow-up. Cardiovascular interventions were performed in 31 % (coronary interventions in 28 % and aortic valve replacement in 17 %). The most common pathogenic FH-causing variants (57 %) was the founder null mutation c.2027del p.(Gly676Alafs∗33). Statins and ezetimibe were the primary treatments (73 %), but many required LDL-apheresis (36 %) or liver transplantation (LTx) (21 %). The peri-operative mortality for LTx was 7 %, but there was no long-term mortality on average follow-up of 6.2 ± 3.6 years, with only one patient requiring percutaneous coronary intervention. Adults were more likely to receive statins/ezetimibe (94 %/91 % vs. 50 %/53 % in pediatrics, p < 0.01) and LDL-apheresis (64 % vs. 8 %, p < 0.001), while liver transplantation was more common in children (38 % vs. 7 %, p < 0.001).

Conclusions

This study highlights the burden of null LDL-R pathogenic FH-causing variants and the frequent need for invasive treatments in Saudi HoFH patients. Liver transplantation is a viable option with low peri-operative mortality and favorable long-term disease-free survival. Early diagnosis, regional genetic screening, and access to advanced therapies are essential in achieving better outcomes.

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.