Faculty of Biology, Medicine and Health, University of Manchester.
Department of Endocrinology, Diabetes and Metabolism, Peter Mount Building, Manchester University NHS Foundation Trust.
Curr Opin Lipidol. 2024 Aug 1;35(4):208-218. doi: 10.1097/MOL.0000000000000939. Epub 2024 Jun 6.
This review endeavours to explore the aetiopathogenesis and impact of severe hypertriglyceridemia (SHTG) and chylomicronaemia on cardiovascular, and pancreatic complications and summarizes the novel pharmacological options for management.
SHTG, although rare, presents significant diagnostic and therapeutic challenges. Familial chylomicronaemia syndrome (FCS), is the rare monogenic form of SHTG, associated with increased acute pancreatitis (AP) risk, whereas relatively common multifactorial chylomicronaemia syndrome (MCS) leans more towards cardiovascular complications. Despite the introduction and validation of the FCS Score, FCS continues to be underdiagnosed and diagnosis is often delayed. Longitudinal data on disease progression remains scant. SHTG-induced AP remains a life-threatening concern, with conservative treatment as the cornerstone while blood purification techniques offer limited additional benefit. Conventional lipid-lowering medications exhibit minimal efficacy, underscoring the growing interest in novel therapeutic avenues, that is, antisense oligonucleotides (ASO) and short interfering RNA (siRNA) targeting apolipoprotein C3 (ApoC3) and angiopoietin-like protein 3 and/or 8 (ANGPTL3/8).
Despite advancements in understanding the genetic basis and pathogenesis of SHTG, diagnostic and therapeutic challenges persist. The rarity of FCS and the heterogenous phenotype of MCS underscore the need for the development of predictive models for complications and tailored personalized treatment strategies. The establishment of national and international registries is advocated to augment disease comprehension and identify high-risk individuals.
本综述旨在探讨严重高甘油三酯血症（SHTG）和乳糜微粒血症对心血管和胰腺并发症的病因和发病机制，并总结新型药理学治疗选择。
尽管 SHTG 罕见，但它在诊断和治疗方面存在重大挑战。家族性乳糜微粒血症综合征（FCS）是 SHTG 的罕见单基因形式，与急性胰腺炎（AP）风险增加相关，而相对常见的多因素乳糜微粒血症综合征（MCS）则更倾向于心血管并发症。尽管 FCS 评分已被引入和验证，但 FCS 仍被漏诊，诊断往往被延迟。关于疾病进展的纵向数据仍然很少。SHTG 诱导的 AP 仍然是危及生命的问题，保守治疗是基石，而血液净化技术的益处有限。常规降脂药物疗效有限，突显了对新型治疗途径的日益关注，即针对载脂蛋白 C3（ApoC3）和血管生成素样蛋白 3 和/或 8（ANGPTL3/8）的反义寡核苷酸（ASO）和短发夹 RNA（siRNA）。
尽管对 SHTG 的遗传基础和发病机制的理解取得了进展，但诊断和治疗方面仍存在挑战。FCS 的罕见性和 MCS 的异质性表型突出表明需要开发预测并发症的预测模型和量身定制的个体化治疗策略。提倡建立国家和国际登记处，以增强对疾病的理解并识别高危个体。
