Unidad de Investigación en Enfermedades Metabólicas.
Departamento de Endocrinología y Metabolismo. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City.
Curr Opin Lipidol. 2020 Jun;31(3):132-139. doi: 10.1097/MOL.0000000000000682.
To critically appraise new insights into the biology of remnant lipoproteins and their putative role in the pathophysiology of atherosclerotic cardiovascular disease, and to compare the atherogenicity of remnant particles with that of low-density lipoproteins (LDL).
New in-vivo stable isotope tracer studies of the kinetics of apoB48 and apoB100-containing lipoproteins in postprandial conditions have revealed that apoB48-containing very low-density lipoproteins (VLDL) accumulated markedly in hypertriglyceridemic patients. These intestinally-derived particles were cleared slowly, and represented up to 25% of circulating VLDL; as part of the remnant particle population, they may increase cardiovascular risk. Importantly, the PCSK9 inhibitor, evolocumab, was shown to reduce remnant levels (-29%) during the postprandial period in diabetic patients on statin therapy - an effect which may be additive to that of LDL-cholesterol reduction in conferring cardiovascular benefit. In recent Mendelian randomization studies, the effect of lowering triglyceride-rich lipoproteins or LDL-cholesterol translated to similar clinical benefit per unit of apoB. Finally, in randomized trials involving statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol levels were associated with coronary atheroma progression independently of LDL-cholesterol.
Overall, data from observational studies in large cohorts, Mendelian randomization studies, meta-regression analyses, and post-hoc analyses of randomized trials are consistent with the contention that remnants are highly atherogenic particles and contribute to the atherosclerotic burden in an equivalent manner to that of LDL.
目的：批判性地评价残粒脂蛋白生物学方面的新见解及其在动脉粥样硬化性心血管疾病病理生理学中的潜在作用，并比较残粒与低密度脂蛋白（LDL）的致动脉粥样硬化性。
发现：新的体内稳定同位素示踪研究表明，在餐后条件下，载apoB48 和 apoB100 的脂蛋白的动力学，在高甘油三酯血症患者中，apoB48 载脂蛋白 B 残粒 VLDL 明显积累。这些来源于肠道的颗粒清除缓慢，占循环 VLDL 的 25%；作为残粒群体的一部分，它们可能会增加心血管风险。重要的是，在他汀类药物治疗的糖尿病患者中，PCSK9 抑制剂依洛尤单抗在餐后期间显示出降低残粒水平（-29%）的作用 - 这种作用可能与 LDL-胆固醇降低对心血管获益的作用相加。最近的孟德尔随机化研究表明，降低富含甘油三酯的脂蛋白或 LDL-胆固醇的效果与 apoB 每单位的临床获益相当。最后，在涉及动脉粥样硬化性心血管疾病的他汀类药物治疗患者的随机试验中，残胆固醇水平与 LDL-胆固醇独立相关，与冠状动脉粥样斑块进展相关。
总结：总的来说，来自大型队列观察性研究、孟德尔随机化研究、荟萃回归分析和随机试验的事后分析的数据与残粒是高度致动脉粥样硬化性颗粒的观点一致，并以与 LDL 相同的方式对动脉粥样硬化负担做出贡献。
