Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
University of Colorado Anschutz Medical Campus, Aurora.
Am J Med. 2021 Sep;134(9):1085-1090. doi: 10.1016/j.amjmed.2021.03.014. Epub 2021 Apr 17.
Elevated triglyceride (TG) levels have been linked to residual atherosclerotic cardiovascular risk in patients with controlled low-density lipoprotein cholesterol. However, outcome trials testing TG-lowering agents have failed to demonstrate cardiovascular risk reduction in statin-treated subjects. One such example is the recent STRENGTH trial, which tested mixed omega fatty acids (n3-FAs, 4 g/d) in high-risk patients with elevated TGs. Similar to trials using fibrates and niacin, the STRENGTH trial failed despite effective TG lowering. Results from these studies have contributed to skepticism about the use of TG-lowering therapy for cardiovascular risk. However, new mechanistic insights are provided by the REDUCE-IT trial that used icosapent ethyl (IPE), a purified formulation of the n3-FA eicosapentaenoic acid. In high-risk patients, IPE reduced a composite of cardiovascular events (25%, P < .001) in a manner not predicted by TG lowering. Benefits with IPE appear linked to broad pleiotropic actions associated with on-treatment eicosapentaenoic acid levels. These studies indicate that although TGs are a potential biomarker of cardiovascular risk, there is no evidence that TG lowering itself is an effective strategy for reducing such risk.
甘油三酯（TG）水平升高与低密度脂蛋白胆固醇控制良好的患者中残留的动脉粥样硬化心血管风险相关。然而，降低 TG 的试验并未在他汀类药物治疗的患者中显示出心血管风险降低。一个这样的例子是最近的 STRENGTH 试验，该试验测试了高甘油三酯血症高危患者混合的欧米伽脂肪酸（n3-FA，每天 4 克）。与使用贝特类药物和烟酸的试验类似，尽管 TG 降低有效，但 STRENGTH 试验仍失败了。这些研究的结果导致人们对使用降低 TG 的治疗方法来降低心血管风险产生了怀疑。然而，使用纯化的二十碳五烯酸（IPE）即icosapent ethyl（IPE）的 REDUCE-IT 试验提供了新的机制见解。在高危患者中，IPE 以 TG 降低无法预测的方式降低了心血管事件的复合发生率（25%，P <.001）。IPE 的益处似乎与治疗过程中二十碳五烯酸水平相关的广泛多效性作用有关。这些研究表明，尽管 TG 是心血管风险的潜在生物标志物，但没有证据表明降低 TG 本身就是降低这种风险的有效策略。
