aNHMRC Clinical Trials Centre, The University of Sydney bDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales cDepartment of Diabetes and Endocrinology, St. Vincents Health, Melbourne, Victoria, Australia.
Curr Opin Lipidol. 2017 Dec;28(6):477-487. doi: 10.1097/MOL.0000000000000465.
We provide an overview of current evidence about the independent role of high triglyceride levels for cardiovascular risk and for acute pancreatitis.
Natural experiments of Mendelian randomization have given us a deeper understanding about the molecular pathways involved in triglyceride metabolism. Individuals with low-triglyceride levels generally have lower rates of cardiovascular disease (CVD). There has been a significant growth in the development of new agents that modulate enzymes involved in a variety of aspects of triglyceride packaging into VLDL or chylomicron particles, and triglyceride catabolism. Antisense inhibitors of apolipoprotein CIII are being tested, as are a variety of agents designed to increase lipoprotein lipase activity. Large-scale trials are underway with purified fatty acid (FA) formulations in over 20 000 individuals in aggregate. A large study of a new fibrate is underway.
A focus on patients with elevated triglyceride levels is a new paradigm not previously the focus of large trials. Clinical outcome data on cardiovascular risk reductions remains sparse. Some drugs are already approved for use in rare inherited disorders predisposing to severe hypertriglyceridaemia and acute pancreatitis. Safety and costs issues are critical.
我们概述了目前关于高甘油三酯水平对心血管风险和急性胰腺炎的独立作用的证据。
孟德尔随机化的自然实验使我们对甘油三酯代谢中涉及的分子途径有了更深入的了解。甘油三酯水平低的人通常患心血管疾病（CVD）的风险较低。目前，开发了许多新的药物来调节参与将甘油三酯包装成 VLDL 或乳糜微粒颗粒以及甘油三酯分解的各种酶，这些药物的开发取得了显著进展。正在测试载脂蛋白 CIII 的反义抑制剂，以及各种旨在增加脂蛋白脂肪酶活性的药物。在超过 20000 人的综合研究中，正在使用纯化的脂肪酸（FA）制剂进行大规模试验。一项新的贝特类药物的大型研究正在进行中。
关注甘油三酯水平升高的患者是一个新的范式，以前不是大型试验的重点。关于降低心血管风险的临床结果数据仍然很少。一些药物已经被批准用于治疗罕见的遗传性疾病，这些疾病易导致严重的高甘油三酯血症和急性胰腺炎。安全性和成本问题至关重要。
