Metabolic and Cardiovascular Diseases Laboratory, Division of Nutrition, University of Alberta.
Division of Cardiology and Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Curr Opin Cardiol. 2024 Jul 1;39(4):300-307. doi: 10.1097/HCO.0000000000001140. Epub 2024 Mar 8.
Remnant cholesterol (RC) is the cholesterol carried in lipoproteins derived from the catabolism of chylomicrons and very low-density lipoproteins. Evidence supporting the causal relationship of RC with atherosclerotic cardiovascular disease (ASVD) is accumulating rapidly. The number of impactful contributions to this field are increasing and provide a pathophysiological insight into the current residual cardiovascular risk beyond low-density cholesterol (LDL)-cholesterol (LDL-C). They also raise the question of whether RC should be used in prediction models and become the target of new therapeutic interventions. The intent of this review is to highlight the recent advances on the role of RC in atherogenesis and the validation of RC as a predictor of ASVD.
Numerous prospective and retrospective cohorts helped validate a significant causal relationship of RC with various forms of ASVD, independent of LDL-C. A recent large Mendelian randomization study reinforced the existence of this relationship and showed that the risk of atherosclerotic events was driven nearly entirely by a direct effect of RC.
Both available and accumulating evidence suggest that a lifelong reduction in RC could translate into a substantial reduction in ASVD risk. The data support a revision of current guidelines to incorporate RC as an independent risk factor for ASVD. We propose that early screening of RC should be implemented and that RC lowering should become the target of future drug developments.
残胆固醇(RC)是指从乳糜微粒和极低密度脂蛋白的代谢产物中携带的胆固醇。支持 RC 与动脉粥样硬化性心血管疾病(ASVD)之间因果关系的证据正在迅速积累。越来越多的研究对这一领域做出了重要贡献,为目前 LDL-胆固醇(LDL-C)以外的剩余心血管风险提供了病理生理学见解。它们还提出了这样一个问题,即 RC 是否应该用于预测模型,并成为新的治疗干预的目标。本综述的目的是强调 RC 在动脉粥样形成中的作用的最新进展,以及 RC 作为 ASVD 预测因子的验证。
许多前瞻性和回顾性队列研究有助于验证 RC 与各种形式的 ASVD 之间存在显著的因果关系,而与 LDL-C 无关。最近的一项大型孟德尔随机研究强化了这种关系的存在,并表明动脉粥样硬化事件的风险几乎完全是由 RC 的直接作用驱动的。
现有和不断积累的证据表明,终生降低 RC 可显著降低 ASVD 风险。这些数据支持修订现行指南,将 RC 作为 ASVD 的一个独立危险因素纳入其中。我们建议应早期筛查 RC,并将 RC 降低作为未来药物开发的目标。