Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Elucida Research LLC, Beverly, MA, 01915, USA.
Curr Atheroscler Rep. 2019 Jan 12;21(1):2. doi: 10.1007/s11883-019-0762-1.
Treatment of hypercholesterolemia with statins results in significant reductions in cardiovascular risk; however, individuals with well-controlled low-density lipoprotein cholesterol (LDL-C) levels, but persistent high triglycerides (TG), remain at increased risk. Genetic and epidemiologic studies have shown that elevated fasting TG levels are associated with incident cardiovascular events. At effective doses, omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels but may have additional atheroprotective properties compared to other TG-lowering therapies such as niacin and fibrates. The purpose of this review is to evaluate mechanisms related to the potential benefits of omega-3 fatty acids in atherothrombotic disease.
Large randomized clinical trials are currently under way to test the cardiovascular benefits of omega-3 fatty acids at a pharmacologic dosage (4 g/day). A large randomized trial with a prescription EPA-only formulation was shown to reduce a composite of cardiovascular events by 25% in statin-treated patients with established cardiovascular disease or diabetes and other CV risk factors. EPA and DHA have distinct tissue distributions as well as disparate effects on membrane structure and lipid dynamics, rates of lipid oxidation, and signal transduction pathways. Compared to other TG-lowering therapies, EPA has been found to inhibit cholesterol crystal formation, inflammation, and oxidative modification of atherogenic lipoprotein particles. The anti-inflammatory and endothelial benefits of EPA are enhanced in combination with a statin. Omega-3 fatty acids like EPA only at a pharmacologic dose reduce fasting TG and interfere with mechanisms of atherosclerosis that results in reduced cardiovascular events. Additional mechanistic trials will provide further insights into their role in reducing cardiovascular risk in subjects with well-managed LDL-C but elevated TG levels.
他汀类药物治疗高胆固醇血症可显著降低心血管风险；然而，尽管低密度脂蛋白胆固醇（LDL-C）水平得到良好控制，但甘油三酯（TG）持续升高的个体仍存在较高的风险。遗传和流行病学研究表明，空腹 TG 水平升高与心血管事件的发生有关。在有效剂量下，ω-3 脂肪酸，如二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），可降低 TG 水平，但与其他降低 TG 的治疗方法（如烟酸和贝特类药物）相比，可能具有额外的抗动脉粥样硬化作用。本综述的目的是评估与 ω-3 脂肪酸在动脉粥样血栓形成性疾病中潜在益处相关的机制。
目前正在进行大型随机临床试验，以测试 ω-3 脂肪酸在药理学剂量（4 g/天）下的心血管益处。一项大型随机试验表明，在他汀类药物治疗的已患有心血管疾病或糖尿病和其他心血管危险因素的患者中，仅用处方 EPA 制剂可使心血管事件复合减少 25%。EPA 和 DHA 具有不同的组织分布，对膜结构和脂质动力学、脂质氧化率以及信号转导途径有不同的影响。与其他降低 TG 的治疗方法相比，EPA 已被发现可抑制胆固醇晶体形成、炎症和致动脉粥样硬化脂蛋白颗粒的氧化修饰。EPA 与他汀类药物联合使用可增强其抗炎和内皮益处。只有在药理学剂量下的 EPA 等 ω-3 脂肪酸可降低空腹 TG，并干扰导致心血管事件减少的动脉粥样硬化机制。进一步的机制试验将提供更多关于其在降低 LDL-C 控制良好但 TG 水平升高的个体心血管风险中的作用的见解。
