Bashir Bilal, Schofield Jonathan, Downie Paul, France Michael, Ashcroft Darren M, Wright Alison K, Romeo Stefano, Gouni-Berthold Ioanna, Maan Akhlaq, Durrington Paul N, Soran Handrean
Faculty of Biology Medicine and Health, University of Manchester, Manchester, United Kingdom.
Department of Endocrinology, Diabetes & Metabolism, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Front Cardiovasc Med. 2024 Aug 7;11:1389106. doi: 10.3389/fcvm.2024.1389106. eCollection 2024.
AIMS: Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors. FINDINGS: Hypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors. IMPLICATIONS: Hypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.
目的:从历史上看,减轻动脉粥样硬化性心血管疾病(ASCVD)风险主要集中在低密度脂蛋白胆固醇(LDL-C)上。在这篇叙述性综述中,我们探讨了LDL-C之外的残余ASCVD风险,重点关注高甘油三酯血症、针对高甘油三酯血症的治疗药物近期临床试验以及解决其他残余ASCVD风险因素的新方法。 研究结果:在接受他汀类药物或前蛋白转化酶枯草溶菌素/kexin 9型抑制剂治疗的患者中,尽管LDL-C水平较低,但高甘油三酯血症仍是一个显著的ASCVD风险因素。基于大量人群的观察性研究一直表明高甘油三酯血症与ASCVD之间存在关联。这种关系因高密度脂蛋白胆固醇水平低的共存而变得复杂。尽管显著改善了致动脉粥样硬化性血脂异常,但最近的临床试验结果对使用贝特类药物降低甘油三酯浓度的效用提出了质疑。另一方面,纯化的二十碳五烯酸(EPA),但不与二十二碳六烯酸(DHA)联合使用,已产生了有利的ASCVD结果。这些试验的结果表明在ASCVD风险调节中涉及其他途径。还提出了其他几种药物疗法来解决针对炎症、血栓形成和代谢因素的其他ASCVD风险因素。 启示:在已经接受降低LDL-C治疗的患者中,高甘油三酯血症构成了显著的残余ASCVD风险。药物降低甘油三酯的结果相互矛盾。贝特类药物以及EPA和DHA联合使用的作用存在疑问,但现在有令人信服的证据表明,在高甘油三酯血症患者亚组中,纯EPA可降低ASCVD风险。临床指南应根据最近的临床试验证据进行更新。针对非传统ASCVD风险的新型药物需要进一步评估。
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