In persons with dyslipidemia, a high residual risk of cardiovascular disease remains despite lipid lowering therapy. Current cardiovascular risk prediction mainly focuses on low-density lipoprotein cholesterol (LDL-c) levels, neglecting other contributing risk factors. Moreover, the efficacy of LDL-c lowering by statins resulting in reduced cardiovascular risk is only partially effective. Secondly, from a metrological viewpoint LDL-c falls short as a reliable measurand. Both direct and calculated LDL-c tests produce inaccurate test results at the low end under aggressive lipid lowering therapy. As LDL-c tests underperform both clinically and metrologically, there is an urging need for molecularly defined biomarkers. Over the years, apolipoproteins have emerged as promising biomarkers in the context of cardiovascular disease as they are the functional workhorses in lipid metabolism. Among these, apolipoprotein B (ApoB), present on all atherogenic lipoprotein particles, has demonstrated to clinically outperform LDL-c. Other apolipoproteins, such as Apo(a) - the characteristic apolipoprotein of the emerging risk factor lipoprotein(a) -, and ApoC-III - an inhibitor of triglyceride-rich lipoprotein clearance -, have attracted attention as well. To support personalized medicine, we need to move to molecularly defined risk markers, like the apolipoproteins. Molecularly defined diagnosis and molecularly targeted therapy require molecularly measured biomarkers. This review provides a summary of the scientific validity and (patho)physiological role of nine serum apolipoproteins, Apo(a), ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE and its phenotypes, ApoA-I, ApoA-II, and ApoA-IV, in lipid metabolism, their association with cardiovascular disease, and their potential as cardiovascular risk markers when measured in a multiplex apolipoprotein panel.

中文翻译：

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缩小血脂异常患者管理的差距：通过载脂蛋白分析进入心血管精准诊断

对于血脂异常患者，尽管进行降脂治疗，心血管疾病的残余风险仍然很高。目前的心血管风险预测主要集中在低密度脂蛋白胆固醇（LDL-c）水平，忽略了其他危险因素。此外，他汀类药物降低 LDL-c 从而降低心血管风险的功效仅部分有效。其次，从计量学的角度来看，LDL-c 不足以作为可靠的测量对象。在积极的降脂治疗下，直接和计算的 LDL-c 测试都会在低端产生不准确的测试结果。由于 LDL-c 测试在临床和计量方面均表现不佳，因此迫切需要分子定义的生物标志物。多年来，载脂蛋白已成为心血管疾病领域有前途的生物标志物，因为它们是脂质代谢的功能主力。其中，载脂蛋白 B (ApoB) 存在于所有致动脉粥样硬化脂蛋白颗粒上，临床证明其表现优于 LDL-c。其他载脂蛋白，例如 Apo(a)（新兴危险因素脂蛋白（a）的特征性载脂蛋白）和 ApoC-III（富含甘油三酯的脂蛋白清除抑制剂）也引起了人们的关注。为了支持个性化医疗，我们需要转向分子定义的风险标记，例如载脂蛋白。分子定义的诊断和分子靶向治疗需要分子测量的生物标志物。本综述总结了九种血清载脂蛋白 Apo(a)、ApoB、ApoC-I、ApoC-II、ApoC-III、ApoE 及其表型、ApoA-I、ApoA- 的科学有效性和（病理）生理作用。 II 和 ApoA-IV 在脂质代谢中的作用、它们与心血管疾病的关联，以及在多重载脂蛋白组中测量时它们作为心血管风险标记物的潜力。