Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
Pharmacology Department, School of Medicine, FASTA University, Mar del Plata.
Curr Opin Endocrinol Diabetes Obes. 2020 Apr;27(2):95-103. doi: 10.1097/MED.0000000000000530.
To review the recent evidence from observational/genetic/interventional studies addressing triglycerides and residual cardiovascular risk (CVRisk).
Large population-based and secondary prevention studies consistently show an association of higher triglycerides with increased CVRisk. This is compounded by genetic studies demonstrating an independent relationship between triglyceride raising or lowering genetic variants affecting triglyceride-rich lipoproteins (TRL) metabolism and CVRisk. Mendelian randomization analysis suggests the benefit of genetic lowering of triglycerides and LDL-cholesterol is similar per unit change in apolipoprotein-B. Among cholesterol-lowering trials, more intensive statin therapy produced greater CVRisk reductions in patients with higher TRL-cholesterol or triglycerides; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition led to similar triglycerides reduction but greater non-HDL-C or apolipoprotein-B reductions than fibrates or fish oils. Regarding n-3 fatty acids, A Study of Cardiovascular Events in Diabetes (ASCEND) and Vitamin D and Omega-3 Trial (VITAL) primary prevention trials with eicosapentaenoic acid (EPA) and docosahexaenoic acid failed to demonstrate cardiovascular benefits, Conversely, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) using high-dose icosapent-ethyl (purified EPA) in primary (diabetes) and secondary prevention with hypertriglyceridemia showed significant cardiovascular events reductions (greater than expected by the observed triglycerides or apolipoprotein-B reductions, suggesting potential benefits through non-lipid pathways).
Evidence suggests higher triglycerides are a marker of CVRisk and may help identify patients who benefit from intensification of therapy. Moreover, genetic studies support a causal link between TRL/triglycerides and cardiovascular disease. Treatment with high-dose EPA may be of benefit in high-risk patients with hypertriglyceridemia to reduce CVRisk.
观察性/遗传/干预研究中有关甘油三酯和残余心血管风险（CVRisk）的最新证据。
基于人群的大型研究和二级预防研究一致表明，较高的甘油三酯与增加的 CVRisk 相关。遗传研究进一步证明，影响富含甘油三酯脂蛋白（TRL）代谢的甘油三酯升高或降低的遗传变异与 CVRisk 之间存在独立关系，这使情况更加复杂。孟德尔随机分析表明，降低甘油三酯和 LDL 胆固醇的遗传获益与载脂蛋白-B 每单位变化相似。在降脂试验中，在 TRL 胆固醇或甘油三酯较高的患者中，更强化的他汀类药物治疗可降低更大的 CVRisk；与贝特类药物或鱼油相比，前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）抑制剂可导致相似的甘油三酯降低，但可降低非 HDL-C 或载脂蛋白-B。关于 n-3 脂肪酸，心血管疾病中的一项研究（ASCEND）和维生素 D 和 ω-3 试验（VITAL）的初级预防试验使用二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）未能显示出心血管益处，相反，使用高剂量二十碳五烯酸乙酯（纯化的 EPA）的心血管事件减少与icosapent 乙基干预试验（REDUCE-IT）在原发性（糖尿病）和二级预防伴高甘油三酯血症中显示出显著的心血管事件减少（大于观察到的甘油三酯或载脂蛋白-B 减少的预期，表明通过非脂类途径可能有潜在益处）。
证据表明，较高的甘油三酯是 CVRisk 的标志物，可能有助于识别从强化治疗中获益的患者。此外，遗传研究支持 TRL/甘油三酯与心血管疾病之间存在因果关系。在高甘油三酯血症的高危患者中，用高剂量 EPA 治疗可能有助于降低 CVRisk。
