Department of Obstetrics and Gynecology (A.R., J.H., S.B., M.S., A.D.), Division of Reproductive Endocrinology, University of Pennsylvania, Philadelphia, Pennsylvania 19104; Division of Translational Medicine and Human Genetics (D.R.), 11-125 Translational Research Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104; and Section of Inflammation and Cardiometabolic Disease (M.P., N.N.M.), National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
J Clin Endocrinol Metab. 2014 May;99(5):E841-7. doi: 10.1210/jc.2013-3918. Epub 2014 Feb 10.
Women with polycystic ovary syndrome (PCOS) have a high prevalence of cardiovascular disease (CVD) risk factors including dyslipidemia. Lipoproteins are heterogeneous, and measurement of serum lipids provides only the size of the pool and does not predict their function or composition. Recently, high-density lipoprotein cholesterol (HDL-C) function, as determined by cholesterol efflux capacity from macrophages, has been shown to be an independent predictor of subclinical CVD.
The aim of the study was to comprehensively evaluate lipoprotein profile including lipid particle size and number and cholesterol efflux capacity in PCOS to better define CVD risk.
A case control study was performed at an academic PCOS center.
Women with PCOS (n = 124) and geographically matched controls (n = 67) were included in the study.
The primary outcome was to measure HDL-C efflux capacity by an ex vivo system involving the incubation of macrophages with apolipoprotein (Apo) B-depleted serum from subjects, and the secondary outcome was to measure lipid particle size and number using nuclear magnetic resonance spectroscopy.
Women with PCOS had significantly higher body mass index and blood pressure but similar HDL-C and low-density lipoprotein cholesterol levels compared to controls. The mean ApoA1 levels were lower, and the ApoB/ApoA1 ratio was higher in PCOS subjects compared to controls (P < .01). There were no differences in ApoB levels. Women with PCOS had an 7% decrease in normalized cholesterol efflux capacity compared to controls (P < .003). Cholesterol efflux capacity in PCOS correlated with body mass index, ApoA1, HDL-C, and the presence of metabolic syndrome. In a multivariable regression model, PCOS was significantly associated with diminished cholesterol efflux. PCOS was also associated with an atherogenic profile including an increase in large very low-density lipoprotein particles, very low-density lipoprotein (VLDL) size, and small low-density lipoprotein cholesterol particles (P < .01).
Our novel findings of decreased cholesterol efflux and an atherogenic lipid particle number and size pattern in women with PCOS, independent of obesity, further substantiate the increased risk of CVD in this population.
多囊卵巢综合征（PCOS）患者存在多种心血管疾病（CVD）危险因素，包括血脂异常。脂蛋白是异质的，血清脂质的测量仅提供了脂质池的大小，而不能预测其功能或组成。最近，通过巨噬细胞胆固醇流出能力来测定高密度脂蛋白胆固醇（HDL-C）的功能已被证明是亚临床 CVD 的独立预测因子。
本研究旨在全面评估 PCOS 患者的脂蛋白谱，包括脂质颗粒大小和数量以及胆固醇流出能力，以更好地定义 CVD 风险。
在学术 PCOS 中心进行了病例对照研究。
纳入了 124 名 PCOS 患者（病例组）和在地理位置上相匹配的 67 名对照者（对照组）。
主要结局是通过涉及用载脂蛋白（Apo）B 耗尽的血清孵育巨噬细胞的体外系统测量 HDL-C 流出能力，次要结局是使用磁共振波谱测量脂质颗粒大小和数量。
与对照组相比，PCOS 患者的体重指数和血压明显更高，但 HDL-C 和低密度脂蛋白胆固醇水平相似。PCOS 患者的 ApoA1 水平较低，ApoB/ApoA1 比值较高（P<.01）。ApoB 水平无差异。与对照组相比，PCOS 患者的标准化胆固醇流出能力降低了 7%（P<.003）。PCOS 患者的胆固醇流出能力与体重指数、ApoA1、HDL-C 和代谢综合征的存在相关。在多变量回归模型中，PCOS 与胆固醇流出减少显著相关。PCOS 还与致动脉粥样硬化的脂质颗粒数量和大小模式相关，包括大的极低密度脂蛋白颗粒、极低密度脂蛋白（VLDL）大小和小的低密度脂蛋白胆固醇颗粒增加（P<.01）。
我们的新发现表明，PCOS 女性胆固醇流出减少以及致动脉粥样硬化的脂质颗粒数量和大小模式，独立于肥胖，进一步证实了该人群 CVD 风险增加。
