From the Department of Pediatrics (S.E., U.J.F.T.), University of Groningen, University Medical Center Groningen, the Netherlands.
Department of Endocrinology (E.G.G., R.P.F.D.), University of Groningen, University Medical Center Groningen, the Netherlands.
Arterioscler Thromb Vasc Biol. 2019 Sep;39(9):1874-1883. doi: 10.1161/ATVBAHA.119.312645. Epub 2019 Jul 18.
Focus is shifting from HDL-C (high-density lipoprotein cholesterol) as predictive biomarker for cardiovascular disease (CVD) towards antiatherogenic HDL functionalities. Still, limited data exist on the prospective association of HDL function metrics with CVD events. The current work aimed to determine, if baseline HDL-C efflux capacity (CEC) is associated with future CVD events in the general population. Approach and Results: We performed a prospective study among participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort (follow-up, 12 years). From the overall n=8592 subjects 325 with previous CVD events were excluded; of the remaining 8267 eligible participants all subjects with new CVD events during follow-up were selected and individually matched to controls for age, sex, smoking status, and HDL-C levels. CEC at baseline was quantified using human THP-1-derived macrophage foam cells and apolipoprotein B-depleted plasma. Despite identical HDL-C and apoA (apolipoprotein)-I levels between cases (n=351) and controls (n=354) CEC was significantly lower in cases (0.93±0.29 versus 1.01±0.24 arbitrary units; P<0.001). In all subjects combined, CEC correlated positively with HDL-C and apoA-I and negatively with body mass index, hsCRP (high-sensitivity C-reactive protein), and urinary albumin excretion. CEC was inversely associated with incident CVD events, both expressed per quartile and per 1 SD change (odds ratio, 0.73; 95% CI, 0.62-0.86; P<0.001); this association remained significant after adjustments for HDL-C, hsCRP, kidney function, and several other clinical covariates.
Combined these data demonstrate that in the general population baseline CEC is significantly associated with the future development of CVD events independent of HDL-C and apoA-I plasma levels.
人们对心血管疾病（CVD）的预测生物标志物高密度脂蛋白胆固醇（HDL-C）的关注正逐渐转移到抗动脉粥样硬化的 HDL 功能上。然而，关于 HDL 功能指标与 CVD 事件之间的前瞻性关联的数据仍然有限。本研究旨在确定基线 HDL-C 外排能力（CEC）是否与普通人群未来的 CVD 事件相关。
我们在 PREVEND（预防肾脏和血管终末期疾病）队列的参与者中进行了一项前瞻性研究（随访 12 年）。在总共 8592 名受试者中，排除了 325 名有既往 CVD 事件的患者；在其余 8267 名合格的参与者中，选择了随访期间发生新 CVD 事件的所有患者，并按年龄、性别、吸烟状况和 HDL-C 水平与对照个体匹配。使用人 THP-1 衍生的巨噬细胞泡沫细胞和载脂蛋白 B 耗尽的血浆来定量 CEC。尽管病例组（n=351）和对照组（n=354）的 HDL-C 和载脂蛋白 A-I（apoA-I）水平相同，但病例组的 CEC 明显较低（0.93±0.29 与 1.01±0.24 任意单位；P<0.001）。在所有受试者中，CEC 与 HDL-C 和 apoA-I 呈正相关，与体重指数、高敏 C 反应蛋白（hsCRP）和尿白蛋白排泄量呈负相关。CEC 与 CVD 事件的发生率呈负相关，按四分位数和 1 SD 变化表示（比值比，0.73；95%CI，0.62-0.86；P<0.001）；在调整了 HDL-C、hsCRP、肾功能和其他几个临床协变量后，这种相关性仍然显著。
综合这些数据表明，在普通人群中，基线 CEC 与 CVD 事件的未来发展显著相关，与 HDL-C 和 apoA-I 血浆水平无关。
