Bruggen Folkert H van, Diamond David M
Department of Primary and Long-Term Care, University Medical Centre Groningen, University of Groningen, P.O. Box 196, 9700 AD Groningen, The Netherlands.
Department of Psychology, University of South Florida, Tampa, FL 33620, USA.
J Clin Med. 2025 May 20;14(10):3569. doi: 10.3390/jcm14103569.
Over the past two decades, cardiovascular disease (CVD) prevention guidelines have progressively lowered LDL-C targets to <70 mg/dL for high-risk individuals based on the assumption of a linear relationship between LDL-C levels and CVD risk. However, the available evidence challenges this premise. Multiple studies demonstrate a weak or inconsistent association between LDL-C levels and atherosclerosis progression at the individual patient-level. Systematic reviews supporting the linearity assumption have notable limitations, including extrapolation beyond observed LDL-C ranges and potential ecological fallacy, as meta-regression analyses rely on study-level data, while patient-level data within the same trials often show no association between LDL-C reduction and CVD outcomes. Moreover, randomized controlled trials explicitly designed to assess LDL-C targets have yielded inconclusive and biased results. LDL-C itself is a heterogeneous marker, with particle size and composition influencing its atherogenicity. The cardiovascular benefits of lipid-lowering therapies may arise in part from pleiotropic effects unrelated to LDL-C lowering. Additionally, several studies indicate that higher LDL-C levels are paradoxically associated with longevity in elderly populations that is equal to or even greater than that of the general population. Collectively, this body of evidence raises questions about the validity of current LDL-C targets < 70 mg/dL in high-risk patients.
在过去二十年中，心血管疾病（CVD）预防指南已逐步将高危个体的低密度脂蛋白胆固醇（LDL-C）目标降至<70mg/dL，这是基于LDL-C水平与CVD风险之间存在线性关系的假设。然而，现有证据对这一前提提出了挑战。多项研究表明，在个体患者层面，LDL-C水平与动脉粥样硬化进展之间的关联较弱或不一致。支持线性假设的系统评价存在显著局限性，包括超出观察到的LDL-C范围进行外推以及潜在的生态学谬误，因为Meta回归分析依赖于研究层面的数据，而同一试验中的患者层面数据往往显示LDL-C降低与CVD结局之间无关联。此外，专门设计用于评估LDL-C目标的随机对照试验产生了不确定且有偏差的结果。LDL-C本身是一个异质性标志物，其颗粒大小和组成会影响其致动脉粥样硬化性。降脂治疗的心血管益处可能部分源于与降低LDL-C无关的多效性作用。此外，多项研究表明，在老年人群中，较高的LDL-C水平与长寿呈悖论性关联，这种关联等同于甚至大于普通人群。总体而言，这一系列证据对目前高危患者<70mg/dL的LDL-C目标的有效性提出了质疑。
