Department of Internal Medicine, Division of Cardiology. University of Texas Southwestern Medical Center, Dallas (A.E.-G., S.D., S.S., B.S., A.G., M.P., A.R.).
Department of Pediatrics, Division of Infectious Disease, University of Colorado Anschutz Medical Campus, Aurora (M.I.).
Arterioscler Thromb Vasc Biol. 2021 Oct;41(10):2588-2597. doi: 10.1161/ATVBAHA.120.315648. Epub 2021 Aug 26.
Objective: Cholesterol efflux capacity (CEC), the ability of extracellular acceptors to pick-up cholesterol from macrophages, is a clinically relevant cardiovascular biomarker. CEC is inversely associated with incident atherosclerotic cardiovascular disease events. However, CEC is only modestly associated with HDL-C (high-density lipoprotein cholesterol) levels, which may explain the failure of HDL-C raising therapies to improve atherosclerotic cardiovascular disease outcomes. Determinants of variation in CEC are not well understood. Thus, we sought to establish whether extreme high and low CEC is a robust persistent phenotype and to characterize associations with cholesterol, protein, and phospholipids across the particle size distribution. Approach and Results: CEC was previously measured in 2924 participants enrolled in the Dallas Heart Study, a multi-ethnic population-based study from 2000 to 2002. We prospectively recruited those who were below the 10th and above 90th percentile of CEC. Our study revealed that extreme low and high CEC are persistent, robust phenotypes after 15 years of follow-up. Using size exclusion chromatography, CEC to fractionated plasma depleted of apolipoprotein B (fraction-specific CEC) demonstrated significant differences in CEC patterns between persistent high and low efflux groups. Fraction-specific CEC was correlated with fraction-specific total phospholipid but not apolipoprotein A-I, cholesterol, or total protein. These correlations varied across the size distribution and differed among persistent high versus low efflux groups. Conclusions: Extreme high and low CEC are persistent and robust phenotypes. CEC patterns in fractionated plasma reveal marked variation across the size distribution. Future studies are warranted to determine specific molecular species linked to CEC in a size-specific manner.
胆固醇外排能力（CEC），即细胞外受体从巨噬细胞中摄取胆固醇的能力，是一种具有临床相关性的心血管生物标志物。CEC 与动脉粥样硬化性心血管疾病事件的发生呈负相关。然而，CEC 与高密度脂蛋白胆固醇（HDL-C）水平的相关性仅适中，这可能解释了 HDL-C 升高疗法未能改善动脉粥样硬化性心血管疾病结局的原因。CEC 变异的决定因素尚不清楚。因此，我们试图确定极高和极低的 CEC 是否是一种稳健的持续表型，并描述其与胆固醇、蛋白质和磷脂在粒子大小分布上的关联。
CEC 先前在 2000 年至 2002 年进行的达拉斯心脏研究（一项多民族人群为基础的研究）中招募的 2924 名参与者中进行了测量。我们前瞻性地招募了 CEC 在第 10 百分位数以下和第 90 百分位数以上的参与者。我们的研究表明，极低和极高的 CEC 在 15 年的随访后仍然是持续的、稳健的表型。使用排阻色谱法，对载脂蛋白 B 耗尽的血浆进行了分馏（分馏特异性 CEC），结果表明在持续高和低外排组之间，CEC 模式存在显著差异。分馏特异性 CEC 与分馏特异性总磷脂相关，但与载脂蛋白 A-I、胆固醇或总蛋白无关。这些相关性在大小分布上存在差异，并且在持续高和低外排组之间存在差异。
极高和极低的 CEC 是持续的、稳健的表型。分馏血浆中的 CEC 模式在大小分布上存在显著差异。未来的研究需要确定以特定大小特异性方式与 CEC 相关的特定分子种类。
