Diagnosis And Evaluation Of Coronary Heart Disease By Lipoprotein Associated Phospholipase A2 In Chiese Han Population

Objectives:Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of calcium-independent phospholipase that catalyzes the hydrolysis of ester bond at the sn-2 position of phospholipid substrates. Results from recent basic, clinical and epidemiological studies have provided evidence indicating that this enzyme can promote the atherosclerotic lesion invasion, increase arterial plaque instability, and could be serving as biomarker for the prediction of future cardiovascular events. In addition, pharmacological agents that inhibiting increased plasma mass or activity of Lp-PLA2 could be a promising target for the treatment of coronary heart disease (CHD) and related clinical complications. To our knowledge, the diagnostic threshold of Lp-PLA2 plasma mass for CHD in Chinese population and, the relationship between Lp-PLA2 plasma mass and coronary plaque stability in Chinese population have not been investigated.Materials and Methods:We applied a case-control study, based on consecutively admitted CHD or suspected CHD patients from Department of Cardiology, Pingjin Hospital, Medical College of Chinese People's Armed Police Forces. All enrolled patients are Han population, and have finished selective coronary angiography (CAG). A total of 180 controls without CAG and clinical manifestation of CHD were enrolled. The case group consisted of 932 CHD patients, among which 288 had single vessel disease with stenosis less than 50%(low risk group), and 644 had single vessel disease (stenosis no less than 50%) or multi-vessel disease (high risk group). Receiver operating characteristic curve (ROC curve) analysis was used to evaluate the diagnostic value of plasma Lp-PLA2 mass in CHD. Multivariate Logistic regression analysis was used to investigate the relative contribution of plasma Lp-PLA2 mass in association with CHD, acute coronary syndrome (ACS) and CAG-confirmed coronary stenosis. We also performed intravascular ultrasound-virtual histology (IVUS-VH) technique to investigate the association between plasma Lp-PLA2 mass and coronary plaque stability. Results:We calculated one-tailed 95%reference value of plasma Lp-PLA2 mass in non-CHD controls (174.12 ng/mL, derived from mean plus standard deviation multiplied by 1.64). By using this threshold value, the diagnostic sensitivity, specificity and accuracy for CHD in our population is 93.4%,92.8%and 97.0%, respectively. The ROC curve analysis showed that the diagnostic value of plasma Lp-PLA2 mass for CHD is of excellent discrimination [referred as with an area under curve (AUC) value between 0.8-0.9], with an AUC value of 0.8561 (95%CI: 0.8326-0.8796, P<0.0001). The diagnostic value of plasma Lp-PLA2 mass for CAG confirmed coronary stenosis (single vessel less than 50%stenosis and, single vessel no less than 50%or multi-vessel disease) is of outstanding discrimination (referred as with an AUC value between 0.9-1.0), with an AUC value of 0.9275 (95%CI: 0.9039-0.9511, P<0.0001). By multivariate Logistic regression, after adjusting for age, blood pressure, cholesterol, triglyceride, HDL, LDL, and C reactive peptide, Lp-PLA2 (every ng/mL) is an independent risk factor CHD (OR 1.029,95%CI: 1.024-1.034, P<0.0001), ACS (OR 1.005,95%CI:1.003-1.007, P<0.0001) and CAG confirmed coronary stenosis (OR 1.044,95%CI:1.038～1.050, P<0.0001). The IVUS-VH analysis showed that for CHD patients with upper quartile of plasma Lp-PLA2 mass (more than 256 ng/mL), the prevalence of unstable coronary plaques, and thrombosis was significantly higher than patients with lower level of plasma Lp-PLA2 mass, whose plaques were mainly composed of fibro-fatty tissue and necrotic core compared with low risk patients whose plaques consisted of fibrous tissue and dense calcium.Conclusions:(1) For the first time, we established a cut off point of plasma Lp-PLA2 mass for CHD diagnosis in a Chinese population. (2) Our results confirmed that plasma Lp-PLA2 mass is an independent risk factor for CHD, ACS and severity of CAG confirmed coronary stenosis. (3) Plasma Lp-PLA2 mass is an efficient biomarker for CHD diagnosis. (4) The high plasma Lp-PLA2 mass level is associated with more prevalence of unstable coronary plaques in CHD patients.