Department of Internal Medicine, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia.
Nat Rev Cardiol. 2017 Jul;14(7):401-411. doi: 10.1038/nrcardio.2017.31. Epub 2017 Mar 16.
An elevated serum level of LDL cholesterol is a well-known risk factor for cardiovascular disease (CVD), but the role of elevated triglyceride levels is debated. Controversies regarding hypertriglyceridaemia as an independent risk factor for CVD have occurred partly because elevated triglyceride levels are often a component of atherogenic dyslipidaemia - they are associated with decreased levels of HDL cholesterol and increased levels of small dense LDL particles, which are highly atherogenic. Findings from several large studies indicate that elevated levels of triglycerides (either fasting or nonfasting) or, more specifically, triglyceride-rich lipoproteins and their remnants, are independently associated with increased risk of CVD. Possible mechanisms for this association include excessive free fatty acid release, production of proinflammatory cytokines, coagulation factors, and impairment of fibrinolysis. Therapeutic targeting of hypertriglyceridaemia could, therefore, reduce CVD and cardiovascular events, beyond the reduction achieved by LDL-cholesterol lowering. Elevated triglyceride levels are reduced with lifestyle interventions and fibrates, which can be combined with omega-3 fatty acids. Some new drugs are on the horizon, such as volanesorsen (which targets apolipoprotein C-III), pemafibrate, and others. However, CVD outcome studies with triglyceride-lowering agents have produced inconsistent results, meaning that no convincing evidence is available that lowering triglycerides by any approach can reduce mortality.
血清中 LDL 胆固醇水平升高是心血管疾病(CVD)的已知危险因素,但甘油三酯水平升高的作用仍存在争议。关于高甘油三酯血症是否为 CVD 的独立危险因素存在争议,部分原因是升高的甘油三酯水平通常是动脉粥样硬化性血脂异常的一个组成部分——它们与 HDL 胆固醇水平降低和小而密 LDL 颗粒水平升高有关,而后者具有高度致动脉粥样硬化性。几项大型研究的结果表明,甘油三酯水平升高(无论是空腹还是非空腹),或者更具体地说,富含甘油三酯的脂蛋白及其残基与 CVD 风险增加独立相关。这种关联的可能机制包括游离脂肪酸释放过多、促炎细胞因子、凝血因子的产生以及纤溶功能受损。因此,通过降低甘油三酯来治疗高甘油三酯血症,除了降低 LDL 胆固醇之外,还可能降低 CVD 和心血管事件的风险。通过生活方式干预和贝特类药物可以降低升高的甘油三酯水平,也可以与 ω-3 脂肪酸联合使用。一些新药正在研发中,例如靶向载脂蛋白 C-III 的 volanesorsen、 pemafibrate 等。然而,降低甘油三酯的药物对 CVD 结局的研究结果不一致,这意味着没有令人信服的证据表明任何方法降低甘油三酯都可以降低死亡率。