中国汉族人群高密度脂蛋白水平和功能与冠心病发生和预后的关系研究

Low HDL-C Level and Antioxidant Function Predict Risk and Post-PCI Outcomes of Coronary Heart Disease in Han Chinese

目的研究中国汉族人群高密度脂蛋白(HDL-C)水平和抗氧化功能与冠心病(CHD)发生和预后,尤其是PCI术后的预后的关系。方法本研究由病例对照研究和队列研究2个临床研究组成:①收集2013年5月至2014年7月西安交通大学医学院第一附属医院心内科CHD住院患者375例,以及健康对照者348例。清晨抽取空腹静脉血,检测总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白AI(apoAI)、载脂蛋白B(apoB)和对氧磷酶(PON)。通过logistic回归分析和ROC分析各血脂指标对CHD的关系和诊断价值。②选取2013年7月至2014年7月在西安交通大学医学院第一附属医院因CHD行PCI的患者468例,按照入院时HDL-C含量将患者分为2组(HDL-C≥1.04 mmol/L为HDL-C较高组,HDL-C<1.04 mmol/L为HDL-C较低组)。前瞻性随访观察两组患者心血管不良事件的发生情况,采用Kaplan-Meier生存曲线分析两组患者生存时间,采用Cox回归模型分析影响心血管不良事件的因素。结果在病例对照研究中,与对照组相比,CHD组患者TG水平明显增高,而HDL-C、apoA-I和lg(PON)明显降低。采用两种模型logistic回归分析各血脂指标与CHD之间的关系,模型1以是否发生CHD为因变量,分别以TC、TG、HDL-C、LDL-C、apoA-I、apoB和lg(PON)为自变量,经全变量logistic回归模型分析(α入选=0.10,α剔除=0.15),发现TG、HDL-C、apoA-I和lg(PON)进入回归模型,而LDL-C、apoB并未进入回归模型。模型2在校正年龄、性别、吸烟史、高血压病史和糖尿病史后,以是否发生CHD为因变量,分别以TC、TG、HDL-C、LDL-C、apoA-I、apoB和lg(PON)为自变量,经多变量logistic回归分析(α入选=0.10,α剔除=0.15),发现TG、HDL-C和lg(PON)进入回归模型,回归系数分别为:0.222、-1.878和-0.779。ROC曲线分析TG、HDL-C和lg(PON)对CHD诊断价值,经ROC曲线统计发现,上述各指标的曲线下面积分别为0.612(P<0.001)、0.283(P<0.001)和0.211(P<0.001),提示HDL-C水平和抗氧化功能降低对CHD具有显著诊断价值。在队列研究中,经过120周随访,468患者均完成随访,HDL-C较低组中62例出现终点事件,HDL-C较高组中15例出现终点事件。经Kaplan-Meier生存分析发现,两组患者生存时间和不良事件发生率均有明显差异,在HDL-C较高组中位生存时间明显长于HDL-C较低组,而不良事件发生率则明显低于HDL-C较低组。Cox回归分析发现HDL-C水平可以预测PCI术后不良事件的发生。结论HDL-C水平和抗氧化功能可以预测中国汉族人群CHD的发生风险和CHD患者PCI术后的预后。

Objective To investigate the predictive value of high density lipoprotein cholesterol(HDL-C)level and antioxidant function on the risk and clinical outcomes of coronary heart disease(CHD)in the Han Chinese population.Methods Two studies were conducted.In Study 1,we recruited 375 CHD patients and 328 healthy controls.Plasma levels of total cholesterol,triacylglyceride(TG),low-density lipoprotein cholesterol(LDL-C),HDL-C,apolipoprotein A-I(apoA-I),apolipoprotein B(apoB)and serum paraoxonase(PON)were measured.Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were applied to analyze the diagnosis value of these lipid parameters on CHD.In Study 2,a total of 468 CHD patients underwent percutaneous coronary intervention(PCI)were followed for a period of 120 weeks.Patients were divided into HDL-C high or low subgroups,using the cut-off level of 1.04 mmol/L.Kaplan-Meier and Cox regression analyses were applied to determine the predictive value of HDL-C on development of major cardiovascular events in this cohort of CHD patients.Results In Study 1,TG was significantly higher,while HDL-C,apoA-I and lg(PON)were significantly lower in the patients with CHD compared with the controls(all P<0.05).Two logistic regression models were applied to analyze the association between the lipid variables and CHD.In Model 1 with the occurrence of CHD as the binary dependent variable,total cholesterol,TG,HDL-C,LDL-C,apoA-I,apoB,and lg(PON)were independent variables,respectively.Notably,CHD was significantly and positively associated with TG,and negatively with HDL-C,apoA-I and lg(PON).Interestingly,LDL-C and total cholesterol did not enter the regression model.In Model 2,with adjustment for age,sex,smoking history,hypertension history,and diabetes history,it was found that TG,HDL-C,and lg(PON)entered the regression model with regression coefficients of 0.222,-1.878 and-0.779 respectively.The ROC method showed that the AUC of TG,HDL-C,and lg(PON)were 0.612,0.283 and 0.211(P<0.001).We did not find LDL-C and total cholesterol to be good diagnostic indicators of CHD in our cohort.In Study 2,in the low HDL-C subgroup of CHD patients(n=249)who underwent PCI,62(24.9%)patients had major adverse cardiovascular events during the follow-up period.In contrast,only 15(6.8%)patients had major cardiovascular events in the high HDL-C subgroup(n=219;P<0.05).Kaplan-Meier analysis revealed that the rate for major cardiovascular events was significantly higher in the low HDL-C subgroup than that of their counterparts with high HDL-C(P<0.05).Cox regression analysis showed that HDL-C was an independent predictor for low risk of major adverse cardiovascular events during follow-up.Conclusion In the Han Chinese cohort studied,low HDL-C level and antioxidant function is the most powerful lipid parameter for predicting the risk as well as the clinical outcome of CHD.