冠心病患者高敏感性C反应蛋白可能是高密度脂蛋白功能异常和结构重塑的标志物  

High-sensitivity C-reactive protein may be a biomarker of high-density lipoprotein dysfunction and structural remodeling in patients with coronary atherosclerotic heart disease

作　　者：唐晓禹 蒋泽楠 毛玲 陈瑾[1,2] 张天铧 翁书炜[1,2] 刘人可 刘立明 彭道泉 于碧莲[1,2] Tang Xiaoyu;Jiang Zenan;Mao Ling;Chen Jin;Zhang Tianhua;Weng Shuwei;Liu Renke;Liu Liming;Peng Daoquan;Yu Bilian(Department of Cardiovascular Medicine,the Second Xiangya Hospital of Central South University,Changsha 410011,China;Research Institute of Blood Lipids and Atherosclerosis,Central South University,Changsha 410011,China;Department of Cardiovascular Surgery,the Second Xiangya Hospital of Central South University,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院心血管内科,长沙410011 [2]中南大学血脂与动脉粥样硬化研究所,长沙410011 [3]中南大学湘雅二医院心血管外科,长沙410011

出　　处：《中华心血管病杂志（网络版）》2022年第1期218-228,共11页Chinese Video Journal of Cardiology

基　　金：国家自然科学基金(81670420,81670426,82170483)。

摘　　要：目的探寻冠心病(coronary atherosclerotic heart disease,CHD)患者中能反映高密度脂蛋白(high‑density lipoprotein,HDL)介导的胆固醇流出能力(cholesterol efflux capacity,CEC)的指标。研究对象连续纳入2018年6月至7月在中南大学湘雅二医院心血管内科住院且经冠状动脉造影确诊的冠心病患者(CHD组)36例和同期非冠心病患者(非CHD组)61例。干预措施采集患者入院次日晨起空腹血,离心全血后获得血浆样本。将血浆样本分装后冻存于-80℃冰箱用于CEC和HDL结构的检测。CEC的检测主要有以下5个步骤:以肝素锰沉淀法获得HDL、巨噬细胞荷脂、上调胆固醇流出通道蛋白的表达、胆固醇流出及检测同位素含量。使用核磁共振波谱技术(nuclear magnetic resonance spectroscopy,NMRS)检测HDL的结构。观测指标及测量方法收集研究对象的基线特征、常规生化指标,并检测CEC和HDL的结构参数。应用Pearson相关分析寻找与CEC相关的变量,并以多重线性回归分析进一步评价变量与CEC的关系。结果CHD组的CEC低于非CHD组,为(11.9%±2.3%)vs.(13.0%±2.2%)(t=-2.32,P=0.022)。非CHD组中,CEC与酶法测得的HDL胆固醇(high‑density lipoprotein cholesterol,HDL‑C,r=0.358,P=0.006)或NMRS测得的HDL‑C_(NMRS)(r=0.416,P=0.001)呈正相关。但在CHD组中,此相关性消失(HDL‑C:r=0.216,P=0.206;HDL‑C_(NMRS):r=0.065,P=0.708)。CAD组中,血清高敏感性C反应蛋白(high‑sensitivity C‑reactive protein,hs‑CRP)与CEC呈负相关(r=-0.351,P=0.036)。多重线性回归分析调整心血管危险因素、HDL‑C后,hs‑CRP仍与CEC呈负相关,但该相关性在以Bonferroni检验校正P值后,差异无统计学意义。NMRS检查进一步发现,hs‑CRP高的冠心病患者,血浆中HDL颗粒的分布向大颗粒倾斜。结论CHD患者的HDL‑C不能反映CEC,但是hs‑CRP可以反映CEC。hs‑CRP水平越高,CEC越低,伴随HDL向大颗粒重塑。hs‑CRP可能是CHD患者HDL功能异常和结构重塑的标志�Objective To explore an easily acquired index for evaluating high‑density lipoprotein(HDL)‑mediated cholesterol efflux capacity(CEC)in patients with coronary atherosclerotic heart disease(CHD).Subjects Thirty‑six CHD(CHD group)and 61 non‑coronary heart disease(non‑CHD group)patients hospitalized in the Department of Cardiovascular Medicine,Second Xiangya Hospital of Central South University and confirmed by coronary angiography between June and July 2018 were included.Interventions Patients′fasting blood was collected the following day after admission.Plasma samples were obtained after whole blood centrifugation,aliquoted and stored at-80℃to detect CEC and HDL structure.CEC detection mainly consists of the following five steps:obtaining HDL by heparin manganese precipitation,macrophage lipid loading,cholesterol efflux‑channel protein expression up‑regulation,cholesterol efflux,and isotope content detection.The structure of HDL was examined using nuclear magnetic resonance spectroscopy(NMRS).Main Outcomes and Measurements The study participant′s baseline characteristics and routine biochemical indicators were collected,and the structural parameters of HDL and CEC were detected.Pearson correlation analysis was used to find variables related to CEC,and multiple linear regression analysis was used to evaluate the relationship between variables and CEC further.Results CEC was significantly reduced in CHD group than in non‑CHD group[(11.9%±2.3%)vs.(13.0%±2.2%),t=-2.32,P=0.022].In the no-CHD group,CEC was positively correlated with enzymatically measured HDL cholesterol(HDL‑C,r=0.358,P=0.006)or NMRS determined HDL‑C(HDL‑C_(NMRS),r=0.416,P=0.001).However,in the CHD group,there was no significant correlation(HDL‑C:r=0.216,P=0.206,HDL‑C_(NMRS):r=0.065,P=0.708).Instead,the level of high‑sensitivity C‑reactive protein(hs‑CRP)was inversely associated with CEC(r=-0.351,P=0.036).The negative correlation remained after adjusting for other cardiovascular risk factors and HDL‑C.by multiple

关 键 词：冠心病 C反应蛋白质 脂蛋白类 HDL 磁共振波谱学 胆固醇流出 

分 类 号：R541.4[医药卫生—心血管疾病]