Research Advance of Chinese Medicine in Treating Atherosclerosis: Focus on Lipoprotein-Associated Phospholipase A2 / 中国结合医学杂志

As a serious cardiovascular disease, atherosclerosis (AS) causes chronic inflammation and oxidative stress in the body and poses a threat to human health. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a member of the phospholipase A2 (PLA2) family, and its elevated levels have been shown to contribute to AS. Lp-PLA2 is closely related to a variety of lipoproteins, and its role in promoting inflammatory responses and oxidative stress in AS is mainly achieved by hydrolyzing oxidized phosphatidylcholine (oxPC) to produce lysophosphatidylcholine (lysoPC). Moreover, macrophage apoptosis within plaque is promoted by localized Lp-PLA2 which also promotes plaque instability. This paper reviews those researches of Chinese medicine in treating AS via reducing Lp-PLA2 levels to guide future experimental studies and clinical applications related to AS.

Evaluation of 256 slice spiral CTA of coronary and serum indicators on the severity of coronary artery stenosis of patients with coronary heart disease / 中国医学装备

Objective:To explore the evaluation of 256 slice spiral computed tomography angiography(CTA)of coronary,serum lipoprotein associated phospholipase A2(Lp-PLA2)and angiopoietin like protein 3(ANGPTL3)on the severity of coronary artery stenosis of patients with coronary heart disease.Methods:A total of 102 patients with coronary heart disease who were diagnosed and treated at Hebei Chest Hospital from July 2022 to March 2023 were selected as the study subjects.According to the Gensini score about the severity of coronary artery stenosis,they were divided into mild stenosis group(0 score≤Gensini score≤20 scores),moderate stenosis group(20 scores<Gensini score≤60 scores)and severe stenosis group(Gensini score>60 scores),with 34 cases in each group.The minimum lumen diameter(MLD),percentage of area of stenosis(%AS),percentage of diameter of stenosis(%DS),minimum lumen area(MLA),Lp-PLA2 and ANGPTL3 among three groups were compared.The diagnostic efficiency of the severity of coronary artery stenosis was predicted according to receiver operating characteristic(ROC)curve.Results:The MLA and MLD values in severe stenosis group were significantly lower than those in moderate and mild stenosis groups,while%AS and%DS were significantly higher than those in moderate and mild stenosis groups(t=6.905,4.083,5.871,6.976,3.387,2.198,2.668,3.505,P<0.05),respectively.The Lp-PLA2 and ANGPTL3 values in severe stenosis group were significantly higher than those in moderate and mild stenosis groups(t=4.164,8.220,2.575,3.050,P<0.05),respectively.ROC curve analysis showed that the area under curve(AUC)values of MLA,MLD,%AS,%DS,CCTA comprehensive parameter,LpPLA2 and ANGPTL3 were respectively were 0.838,0.690,0.742,0.801,0.904,0.808 and 0.807 in predicting the severity of coronary artery stenosis.The sensitivities of them were respectively 91.20%,91.20%,64.70%,94.10%,97.10%,70.60%and 88.20%.The specificities of them were respectively 76.50%,57.40%,75.00%,50.00%,70.60%,97.10%and 70.60%.The AUC value of CCTA comprehensive parameter was respectively higher than that of LpPLA2 and ANGPTL3,but the difference was not statistically significant(P>0.05).Conclusion:256 slice spiral CCTA,serum Lp-PLA2 and ANGPTL3 have a certain efficiency in assessing the severity of coronary artery stenosis of coronary heart disease,and 256 slice spiral CCTA has higher predictive efficiency.

Diagnostic and prognostic value of combined detection of serum Lp-PLA2,NSE and S-100β in patients with carbon monoxide poisoning complicated with acute cerebral infarction / 国际检验医学杂志

Objective To explore the value of combined detection of lipoprotein-associated phospholipase A2(Lp-PLA2),neuron specific enolase(NSE)and S-100 calcium binding protein β(S-100β)in the diagnosis and prognosis evaluation of acute cerebral infarction(ACI)in patients with carbon monoxide poisoning(CMP).Methods A total of 102 patients with CMP complicated with ACI admitted to the hospital from Jan-uary 2020 to November 2021 were selected as the study group,meanwhile,102 patients with simple CMP were enrolled as the control group.Patients in the study group were followed up for 6 months after discharge,ac-cording to the follow-up results,they were grouped into good prognosis group(60 cases)and poor prognosis group(42 cases).The serum levels of Lp-PLA2,NSE and S-100β were detected by enzyme-linked immunosor-bent assay(ELISA).The receiver operating characteristic(ROC)curve was applied to analyze the value of the combination of serum Lp-PLA2,NSE and S-100β in the early diagnosis and prognosis evaluation of patients with CMP and ACI.Results Compared with the control group,the levels of Lp-PLA2,NSE and S-100β in the study group were obviously higher(P<0.05).The ROC curve analysis results showed that the area under the curve(AUC)of the combined detection of serum Lp-PLA2、NSE、S-100β for the diagnosis of CMP complicat-ed with ACI was greater than the AUC of single detection of each indicator(P<0.001).Compared with the good prognosis group,the levels of Lp-PLA2,NSE and S-100β in the poor prognosis group were obviously higher(P<0.05).The results of ROC curve analysis showed that the AUC of the combined detection of ser-um Lp-PLA2、NSE、S-100β for the prognosis of patients with CMP complicated with ACI was greater than the AUC of single detection of each indicator(P<0.05).Conclusion The expression of Lp-PLA2,NSE and S-100β in serum of patients with CMP complicated with ACI is high,and the combined detection of the three has certain value in the diagnosis and prognosis evaluation for patients with CMP complicated with ACI.

Research progress on the role of lipoprotein-associated phospholipase A2 in acute coronary syndrome / 基础医学与临床

Lipoprotein-associated phospholipase A2(Lp-PLA2)is a protein composed of 441 amino acids,which can promote the aggregation of inflammatory cells to the inflammatory response site and the release of inflammatory factors.It can promote the synthesis of matrix metalloproteinases,increase the number of foam cells and extra cel-lular matrix in atherosclerotic plaque,attenuate plaque fiber cap and prone to rupture,thus promote the onset of acute coronary syndrome(ACS).Therefore,the determination and regulation of Lp-PLA2 levels in patients with ACS are clinically significant.

Relationship between serum indexes,pathogenetic condition and prognosis in patients with acute ischemic stroke / 天津医药

Objective To discuss the relationship between serum lipoprotein-associated phospholipase A2(Lp-PLA2),low-density lipoprotein(LDL),amyloid beta 1-42(Aβ1-42)and soluble intercellular adhesion molecule-1(sICAM-1)levels,the National Institutes of Health Stroke Scale(NIHSS)score and prognosis in patients with acute ischemic stroke(AIS).Methods A total of 106 patients with AIS who underwent intravenous thrombolysis(the thrombolysis group),30 AIS patients without thrombolysis(the non-thrombolysis group)and 95 healthy individuals(the control group)were included in the study.The thrombolysis group was divided into the recanalization group(n=41)and the non-recanalization group(n=65)according to whether the vein was recanalized after thrombolysis.Patients were divided into the mild group(n=45),the moderate group(n=36)and the severe group(n=25)based on the NIHSS score.They were divided into the good prognosis group(n=65)and the poor prognosis group(n=41)based on the modified Rankin Scale(mRS)score.Serum levels of four indexes in different groups were compared.Their relationship with the NIHSS score and the prognosis was analyzed.Results The vein recanalization rate in 106 patients with thrombolysis was 38.68%(41/106).Serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 levels were lower in the recanalization group than those in the non-canalization group(P＜0.05).Serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 levels increased successively in the control group,the thrombolysis group and the non-thrombolysis group(P＜0.05).The 4 serum indexes increased with the aggravation of disease condition,and were positively correlated with NIHSS score(P＜0.05).High serum levels of Lp-PLA2,LDL,Aβ1-42 and sICAM-1 were risk factors for poor prognosis of patients with thrombolysis(P＜0.05).The area under the curve(AUC)and specificity of the combination of 4 serum indexes for predicting poor prognosis of patients with thrombolysis were higher than those of prediction with single index(P＜0.05).Conclusion The expression levels of serum Lp-PLA2,LDL,Aβ1-42 and sICAM-1 in patients with AIS are high.They can be used as important reference indexes for disease condition monitoring and prognosis evaluation.

Correlation between smoking and serum lipoprotein-associated phospholipase A2 level in overweight and obese men / 中南大学学报(医学版)

OBJECTIVES@#Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a vaso-specific inflammatory marker that exacerbates atherosclerotic through inflammatory responses. It can be used to predict the occurrence of adverse cardiovascular events and to assess the residual risk of cardiovascular diseases. This study aims to investigate the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men, and to provide evidence for preventing the cardiovascular diseases.@*METHODS@#Male subjects, who participated in health examination at the Health Management Center, Third Xiangya Hospital, Central South University from May 1, 2020 to April 30, 2021, were selected. The smoking status and other information were collected by the Self-test Scale of Physical Examination. According to the smoking status, they were divided into a never-smoking group, a current smoking group, a quit smoking group and a passive smoking group. According to the daily smoking amount, the current smoking subjects were divided into a <10 cigarettes group, a 10 to 20 cigarettes group, a 21 to 30 cigarettes group, and a >30 cigarettes group. According to the smoking years, the current smoking subjects were divided into a <5 years group, a 5 to 10 years group, a 11 to 20 years group, and a >20 years group.Serum Lp-PLA2 levels and other clinical indexes in different smoking groups were measured and compared, the correlation between smoking and serum Lp-PLA2 levels in overweight and obese men was analyzed by logistic regression analysis.@*RESULTS@#Serum Lp-PLA2 levels were significantly different between the never-smoking group and the current smoking group (P<0.05). Logistic regression analysis showed that, before adjusting other influencing factors and in terms of smoking status, the current smoking group (OR=1.81, 95% CI 1.27 to 2.58, P<0.01) and the quit smoking group (OR=2.09, 95% CI 1.12 to 3.90, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the passive smoking group had no correlation with serum Lp-PLA2 levels (OR=1.27, 95% CI 0.59 to 2.73, P>0.05). In terms of daily smoking amount, the 10 to 20 cigarettes group (OR=2.09, 95% CI 1.40 to 3.12, P<0.001) and the 21 to 30 cigarettes group (OR=1.98, 95% CI 1.22 to 3.20, P<0.01) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <10 cigarettes group (OR=1.45, 95% CI 0.81 to 2.60, P>0.05) and the >30 cigarettes group (OR=1.17, 95% CI 0.60 to 2.28, P>0.05) had no correlation with serum Lp-PLA2 levels. In terms of smoking years, the 5 to 10 years group (OR=1.94, 95% CI 1.07 to 3.53, P<0.05), the 11 to 20 years group (OR=2.06, 95% CI 1.33 to 3.18, P<0.01), and the >20 years group (OR=1.66, 95% CI 1.11 to 2.47, P<0.05) were positively correlated with serum Lp-PLA2 levels compared with the never-smoking group, while the <5 years group had no correlation with serum Lp-PLA2 levels (OR=1.12, 95% CI 0.38 to 3.33, P>0.05). After adjusting for age and other indicators, the correlation between smoking years and serum Lp-PLA2 levels was the same as before adjustment among the above smoking groups, except that the correlation between the smoking 5 to 10 years group and serum Lp-PLA2 levels was not significant (OR=1.77, 95% CI 0.95 to 3.29, P>0.05).@*CONCLUSIONS@#Smoking is correlated with serum Lp-PLA2 levels in overweight and obese men.

Serum lipoprotein-associated phospholipase A2 level is positively correlated with the recurrence risk of acute ischemic cerebral infarction in hypertensive patients / 南方医科大学学报

OBJECTIVE@#To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients.@*METHODS@#This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis.@*RESULTS@#Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737.@*CONCLUSION@#Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.

Lipoprotein-associated phospholipase A2 combined with D-dimer to fibrinogen ratio to construct a prognostic nomogram model for patients with acute myocardial infarction after percutaneous coronary intervention / 中国医师进修杂志

Objective:To construct acute ST-segment elevation myocardial infarction (STEMI) percutaneous coronary intervention (PCI) by using lipoprotein-associated phospholipase A2 (Lp-PLA2) and D-dimer to fibrinogen ratio (D/F) and other indicators postoperative patient prognosis nomogram model and evaluation of its predictive value.Methods:A total of 291 acute STEMI patients admitted to the BenQ Hospital Affiliated to Nanjing Medical University from January 2017 to January 2020 were retrospectively selected, including but not limited to Lp-PLA2 and D/F, were collected. Receiver operating characteristic (ROC) curve and multivariate Logistic regression were used to analyze the risk factors of death within 90 d after PCI in STEMI patients, and Kaplan-Meier survival curves were drawn to compare the survival of patients in different Lp-PLA2 and D/F groups. The R language software was used to build nomogram model and decision curve.Results:The AUCs of LpPLA2 and D/F for predicting the risk of death from cardiac causes at 90 s after PCI in patients with acute STEMI were 0.896 (95% CI 0.850 to 0.932) and 0.884 (95% CI 0.837 to 0.922), respectively. The values were 59.50 μg/L and 0.46 respectively ( P<0.05); the mortality rates of acute STEMI patients in LpPLA2>59.50 μg/L and D/F>0.46 groups after PCI were higher than those in LpPLA2≤59.50 μg/L group and D/F≤0.46 group ( P<0.05); age (>66 years), left ventricular ejection fraction (LVEF) (≤45%), LpPLA2 (>59.50 μg/L), D/F (>0.46), N-terminal brain natriuretic peptide precursor (>1.55 μg/L) and fasting blood glucose (>7.00 mmol/L) were the risk of death from cardiac causes at 90 d after PCI in patients with acute STEMI ( P<0.05); when the risk thresholds were >0.24, the nomogram model could provide significant additional net clinical benefit. Conclusions:Lp-PLA2 and D/F are closely related to the prognosis of patients with acute STEMI after PCI, and the nomogram model constructed in combination with other clinical indicators can effectively predict the risk of death within 90 d after PCI.

Correlation between lipoprotein-associated phospholipase A2 and albuminuria in patients with type 2 diabetes mellitus / 安徽医科大学学报

Objective@#To explore the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2) level and albuminuria in patients with type 2 diabetes mellitus (T2DM) ．@*Methods @#200 T2DM patients were chosen to collect general data and relevant laboratory indicators． According to the urinary albumin / creatinine ratio ( UACR) ，they were divided into normal group (UACR＜30 mg / g，n = 66) ，microalbuminuria group (30 mg / g≤ UACR＜300 mg / g，n = 64) and macroalbuminuria group (UACR≥300 mg / g，n = 70) ．On the basis of Lp-PLA2 tertile，they were divided into low Lp-PLA2 group (Lp-PLA2 ＜104 ng / ml，n = 66) ，medium Lp-PLA2 group ( 104 ng / ml≤Lp-PLA2 ＜161 ng / ml，n = 67) and high Lp-PLA2 group (Lp-PLA2 ≥161 ng / ml，n = 67) ．Group differences were compared by analysis of variance and nonparametric test．Associations between Lp-PLA2 and other indicators were performed by Pearson correlation and Spearman correlation. Related factors of albuminuria in T2DM patients were explored by multivariate Logistic regression analysis． In addition ，receiver operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of Lp-PLA2 for albuminuria in T2DM patients. @*Results@#Lp-PLA2 was significantly higher in the macroalbuminuria group than that in both the normal group and the microalbuminuria group，and the differences were statistically significant (P＜0. 05) ．Compared with the normal group，Lp-PLA2 in the microalbuminuria group increased(P＜0. 05) ．With the increase in Lp-PLA2 tertile， there was gradual increase in UACR , and the difference was statistically significant (P＜0. 05) ．Correlation analysis showed that Lp-PLA2 was positively correlated with duration of DM，systolic blood pressure (SBP) ，glycosylated hemoglobin (HbA1c) ，fasting blood glucose (FBG) ，blood urea nitrogen (BUN) ，serum creatinine (Scr) ，UACR and negatively correlated with estimated glomerular filtration rate ( eGFR) (P ＜0. 05 ) ． Multivariate Logistic regression analysis showed that Lp-PLA2 ［OR = 1. 046，95% CI( 1. 031，1. 060) ］was an independent risk factor for albuminuria (P＜0. 05) ．The AUC of Lp-PLA2 for predicting albuminuria was 0. 902 ［95% CI(0. 862，0. 942) ］. The cut-off value of Lp-PLA2was 148 ng / ml，the sensitivity was 65. 7% and specificity was 98. 5%．@*Conclusion@#Lp-PLA2 is closely related to the albuminuria in T2DM patients，which provides a new method for the diagnosis and treatment of diabetic kidney disease (DKD) .

Predictive value of lipoprotein-associated phospholipase A2 combine with systemic immune-inflammation index for coronary heart disease risk in patients with type 2 diabetes mellitus / 中国医师进修杂志

Objective:To explore the predictive value of lipoprotein-associated phospholipase A2 (Lp-PLA2) combined with systemic immune-inflammation index (SII) for coronary heart disease risk in patients with type 2 diabetes mellitus.Methods:A prospective study was performed, 130 patients with type 2 diabetes mellitus from May 2018 to May 2021 in the People′s Hospital of Pengzhou were selected. All patients underwent coronary angiography examination, and 49 cases were complicated with coronary heart disease (coronary heart disease group), 81 cases were not complicated with coronary heart disease (non-coronary heart disease group). The clinical data were recorded; the white blood cell, monocyte, platelet, neutrophils, lymphocyte, hemoglobin, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose, C-reactive protein (CRP), glycated hemoglobin and Lp-PLA2 were detected; and the SII was calculated. Multivariate Logistic regression analysis was used to analyze the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus; the efficacy of Lp-PLA2 and SII in predicting the coronary heart disease in patients with type 2 diabetes mellitus was evaluated using the receiver operating characteristics (ROC) curve.Results:There were no statistical differences in white blood cell, hemoglobin, TC, TG, LDL-C, fasting blood glucose, glycated hemoglobin and CRP between two groups ( P>0.05); the monocyte, platelet, neutrophils, Lp-PLA2 and SII in coronary heart disease group were significantly higher than those in the non-coronary heart disease group: (0.55 ± 0.22) × 10 9/L vs. (0.40 ± 0.11) × 10 9/L, (227.84 ± 40.76) × 10 9/L vs. (205.81 ± 39.04) × 10 9/L, (6.78 ± 1.45) × 10 9/L vs. (6.30 ± 1.18) × 10 9/L, (240.67 ± 41.48) μg/L vs. (214.83 ± 36.35) μg/L and 1 245.76 ± 383.08 vs. 929.84 ± 260.27, the lymphocyte and HDL-C were significantly lower than those in the non-coronary heart disease group: (1.26 ± 0.17) × 10 9/L vs. (1.41 ± 0.19) × 10 9/L and (1.15 ± 0.14) mmol/L vs. (1.23 ± 0.21) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Multivariate Logistic regression analysis result showed that monocyte, HDL-C, Lp-PLA2 and SII were the independent risk factors of coronary heart disease in patients with type 2 diabetes mellitus ( OR = 1.812, 1.013, 1.013 and 2.004; 95% CI 4.430 to 6.801, 0.992 to 1.013, 1.001 to 1.026 and 0.004 to 0.855; P<0.01 ore <0.05). ROC curve analysis result showed that the area under the curve of Lp-PLA2 combined with SII to predict the coronary heart disease in patients with type 2 diabetes mellitus was significantly larger than Lp-PLA2 and SII alone: 0.783 (95% CI 0.702 to 0.851) vs. 0.681 (95% CI 0.593 to 0.760) and 0.744 (95% CI 0.660 to 0.816), and there was statistical difference ( P<0.05). Conclusions:Lp-PLA2 and SII are independent risk factors for coronary heart disease in patients with type 2 diabetes mellitus, and their combined detection can improve the predictive value of coronary heart disease.

The correlation of serum lipoprotein-associated phospholipase A2 with intra-stent restenosis after drug-eluting stent implantation / 中国医师杂志

Objectives:To investigate the correlation of serum lipoprotein-associated phospholipase A2 (Lp-PLA2) with intra-stent restenosis (ISR) after drug-eluting stent (DES) implantation.Methods:A total of 227 patients with coronary artery disease, who were diagnosed with severe epicardial coronary stenosis by coronary angiography (CAG) and treated by percutaneous coronary intervention (PCI) and DES implantation were enrolled in our study. After follow-up for 1-1.5 years, the CAG was performed and the patients were divided into ISR group and non-ISR (nISR) group according to the consequence of CAG. Biochemical data and multiple serum inflammatory factors such as Lp-PLA2, hypersensitive C-reactive protein (hs-CRP), interleukin 2 (IL-2), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were analyzed before the CAG. Multivariate logistic regression and multiple linear regression were used to analyze the influencing factors of stent restenosis after DES implantation.Results:The level of serum Lp-PLA2 and the proportion of hypertension in ISR group were significantly higher than those in nISR group, and the level of high density lipoprotein cholesterol (HDL-C) was significantly lower than that in nISR group (all P<0.05), but there was no significant difference in other biochemical indexes and inflammatory factors between the two groups (all P>0.05). The minimum lumen diameter of stent segment in ISR group was significantly lower than that in nISR group ( t=14.975, P<0.01), and the stenosis degree of stent segment diameter was significantly higher than that in nISR group ( P<0.01). Multivariate logistic regression analysis showed that Lp-PLA2 remained an independent predictor for ISR (1.011, 95% CI: 1.005-1.017). Only the serum levels of Lp-PLA2 had linear relationship with the degree of ISR by multivariate linear regression analysis ( β=0.790, P<0.01). Conclusions:Serum Lp-PLA2 level is independently associated with an increased risk of ISR in patients with coronary heart disease.

The Use of Lipoprotein-Associated Phospholipase A2 in a Chinese Population to Predict Cardiovascular Events / 生物医学与环境科学（英文）

Objective@#To explore associations between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular events in a Chinese population, with a long-term follow-up.@*Methods@#A random sample of 2,031 participants (73.6% males, mean age = 60.4 years) was derived from the Asymptomatic Polyvascular Abnormalities Community study (APAC) from 2010 to 2011. Serum Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). The composite endpoint was a combination of first-ever stroke, myocardial infarction (MI) or all-cause death. Lp-PLA2 associations with outcomes were assessed using Cox models.@*Results@#The median Lp-PLA2 level was 141.0 ng/mL. Over a median follow-up of 9.1 years, we identified 389 events (19.2%), including 137 stroke incidents, 43 MIs, and 244 all-cause deaths. Using multivariate Cox regression, when compared with the lowest Lp-PLA2 quartile, the hazard ratios with 95% confidence intervals for developing composite endpoints, stroke, major adverse cardiovascular events, and all-cause death were 1.77 (1.24-2.54), 1.92 (1.03-3.60), 1.69 (1.003-2.84), and 1.94 (1.18-3.18) in the highest quartile, respectively. Composite endpoints in 145 (28.6%) patients occurred in the highest quartile where Lp-PLA2 (159.0 ng/mL) was much lower than the American Association of Clinical Endocrinologists recommended cut-off point, 200 ng/mL.@*Conclusion@#Higher Lp-PLA2 levels were associated with an increased risk of cardiovascular event/death in a middle-aged Chinese population. The Lp-PLA2 cut-off point may be lower in the Chinese population when predicting cardiovascular events.

Early prediction of prognosis of acute type A aortic dissection by lipoprotein-associated phospholipase A2: A prospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To investigate the relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2) level and in-hospital prognosis in patients with acute type A aortic dissection within 24 hours of admission. Methods    Fortysix patients diagnosed with type A aortic dissection were included in our hospital and their Lp-PLA2 levels within 24 hours of admission were measured between January 2017 and June 2019. According to their Lp-PLA2 levels within 24 hours of admission, 23 patients were classified into a high Lp-PLA2 group (Lp-PLA2 > 200 μg/L, 16 males and 7 females at age of 52.0±14.0 years) and 23 patients were into a low Lp-PLA2 group (Lp-PLA2 ≤200 μg/L, 15 males and 8 females at age of 53.0±11.0 years). The relationship between Lp-PLA2 level and clinical outcome was analyzed. Results    The incidences of bleeding, hospital infection, multiple organ dysfunction and mortality in the high Lp-PLA2 group were higher than those in the low Lp-PLA2 group (P<0.05). Seven (15.2%) patients died during 3 months of follow-up. The 3-month survival rate of patients with an increase of Lp-PLA2 was significantly lower than that of the patients with normal Lp-PLA2 (P<0.01), which was an independent predictor of adverse outcomes at 3 months of onset (P<0.01). Conclusion    Lp-PLA2 may be a predictor of disease progression in the patients with acute type A aortic dissection, and the patients with significantly elevated Lp-PLA2 have a higher 3-month mortality than the patients with normal Lp-PLA2.

The relationship between the level of serum lipoprotein associated phospholipase A2 and the condition and prognosis of patients with acute ischemic stroke / 中风与神经疾病杂志

@#Objective　To investigate the relationship between the level of Lp-PLA2 and the condition as well as prognosis of patients with acute ischemic stroke.Methods　The general data of 120 patients with acute ischemic stroke and 92 healthy persons were collected.The serum Lp-PLA2 levels were detected by ELISA.NIHSS scale was used to assess the severity of the disease at admission.mRS was used to evaluate the prognosis 3 months after discharge.The correlation between serum Lp-PLA2 level and the severity of the disease was analyzed.The risk factors of prognosis were analyzed.Results　The proportion of hypertension and the level of serum Lp-PLA2 in patients with acute ischemic stroke were significantly higher than those in control group (P<0.05).Among 120 patients with acute ischemic stroke,47 cases were mild,38 cases were moderate,and 35 cases were severe.There was significant difference in serum Lp-PLA2 level among the three groups (P<0.05).Pearson correlation analysis showed that serum Lp-PLA2 levels were positively correlated with NIHSS score (P<0.05).Among 120 patients with acute ischemic stroke,81 cases had good prognosis and 39 cases had poor prognosis.The age of patients in poor prognosis group was significantly longer than that in good prognosis group (P<0.05),the time from onset to admission was significantly longer than that in good prognosis group (P<0.05),and serum Lp-PLA2 levels were significantly higher than that in good prognosis group (P<0.05).Multivariate logistic regression analysis showed that age and Lp-PLA2 were risk factors for prognosis of patients with acute ischemic stroke(P<0.05).Conclusion　The higher the level of Lp-PLA2,the more serious the disease is.Lp-PLA2 is a risk factor of prognosis in patients with acute ischemic stroke.

Correlation analysis between HCY,LP-PLA2,RDW,and UA in ischemic stroke patients with H-type hypertension / 中风与神经疾病杂志

@#Objective　To explore the changes of HCY and LP-PLA2,RDW,and UA in patients with H-type hypertension with acute cerebral infarction.Methods　A total of 408 patients with acute cerebral infarction treated in the Department of Neurology,First Hospital of Lanzhou University from January 2017 to June 2019 were selected and divided into H type hypertension group (248 cases),HCY alone group (107 cases).The non-H hypertension group (31 cases),the simple acute cerebral infarction group (22 cases),and the healthy physical examination patients in the same period were selected as the control group (63 cases).Results　(1)The levels of male,LP-PLA2,HCY,and RDW were significantly higher in the H-type hypertension group than in the simple acute cerebral infarction group and the normal control group(P<0.05);(2)HCY levels were significantly higher in men with H-type hypertension than women(P<0.05);(3)HCY was positively correlated with RDW and UA in the H-type hypertension group (r=0.389,P<0.001;r=0.171,P<0.001);(4)In the H-type hypertension group,HCY,LP-PLA2,RDW,and UA all have certain diagnostic efficacy (AUC=0.724,0.916,0.731),respectively,0.677 were less than the joint detection AUC=0.947.Conclusion　HCY,LP-PLA2,RDW,and UA can prompt the inflammation status of H-type hypertension with acute cerebral infarction;H-type hypertension and LP-PLA2 levels have certain synergistic effect in acute cerebral infarction.

The predictive value of TOAST and Lp-PLA2 for early recurrence of ischemic cerebrovascular disease after transient ischemic attack and minor ischemic stroke of anterior circulation / 中风与神经疾病杂志

@#Objective　To investigate the predictive value of TOAST（Trial of Org 10172 in Acute Stroke Treatment） and lipoprotein-associated phospholipase A2（Lp-PLA2） for early recurrence of ischemic cerebrovascular disease after transient ischemic attack（TIA）and minor ischemic stroke of anterior circulation. Methods　A total of 190 patients with TIA and minor ischemic stroke of anterior circulation were selected and the general information and supplementary examinations were recorded. The patients were classified etiologically into large-artery atherosclerotic stroke（LAA） group and non-LAA group according to TOAST. According to the recurrence of ischemic cerebrovascular disease within 30 days，the patients were divided into positive event group and negative event group，and the differences between the two groups were compared. ROC curve was used to determine the best cutoff value of Lp-PLA2 for predicting positive event. Multivariate analysis was performed to identify potential predictors of recurrence. Finally，ROC curve was used to analyze the predictive value of Lp-PLA2 and LAA alone or in combination for recurrent ischemic cerebrovascular disease in the early stage of TIA and minor ischemic stroke of anterior circulation. Results　For positive event group，the age，proportion of TIA or cerebral infarction history，proportion of LAA and the level of Lp-PLA2 were higher than those of negative event group（P<0.05）.The best cutoff value of Lp-PLA2 was 304.50 ng/ml（sensitivity and specificity were 0.645 and 0.711 respectively）. LAA and Lp-PLA2 ≥ 304.50 ng/ml were independent risk factors for recurrent ischemic cerebrovascular disease within 30 days after TIA and minor ischemic stroke of anterior circulation. The area under ROC curve of LAA，Lp-PLA2≥ 304.50 ng/ml and combination of both were 0.671，0.678 and 0.729 respectively. The area under ROC curve of combined prediction of LAA and Lp-PLA2 was the largest. Conclusion　LAA combined with Lp-PLA2≥304.50 ng/ml could predict the risk of early recurrence of ischemic cerebrovascular disease in TIA and minor ischemic stroke of anterior circulation.

Development and application of monoclonal antibodies anti-human lipoprotein-associated phospholipase A2 / 生物工程学报

The aim of this study is to prepare monoclonal anti-human Lp-PLA2 antibodies, and establish a rapid and accurate immunochromatographic Lp-PLA2 assay used in community medical institution. The gene sequence of human Lp-PLA2 was obtained from NCBI to construct the expression plasmid. Lp-PLA2 protein expressed in CHO-K1 cells was used to immune BALB/c mice. The monoclonal antibodies were produced in mouse ascites after hybridoma cells screening. Antibodies were evaluated by SDS-PAGE, ELISA and other methods. The Lp-PLA2 test strip was prepared based on sandwich method and evaluated with the portable detection instrument. The affinity of the paired antibodies, PLA1 and PLA5, both reached 1×10⁻⁸. The antibody subclass was IgG1. Both antibodies recognized the Lp-PLA2 protein in the blood specifically. The Lp-PLA2 test strip was prepared based on sandwich method, with linear range of 20-2000 ng/mL. The Lp-PLA2 test strip correlated well with the diaDexus ELISA test kit. In conclusion, the paired antibodies were successfully prepared with high affinity and specificity. The immunochromatographic test of Lp-PLA2 provided a fast and accurate method to detect the concentration of Lp-PLA2 in blood sample for clinical use in the community medical institution and could contribute to the management of cardiovascular diseases.

Lipoprotein-associated phospholipase A2 predicts early neurological deterioration in patients with lacunar infarction / 中国脑血管病杂志

Objective To study the predictive value of lipoprotein-associated phospholipase A2 ( Lp-PLA2)for early neurological deterioration (END) in patients with lacunar infarction. Methods Between January 2016 and July 2018,281 consecutive patients with first-ever acute lacunar infarction admitted to the Department of Neurology, the Second People's Hospital of Lianyungang were enrolled retrospectively. They were divided into END group (n = 75 ) and non-END group ( n = 206) depending on whether END occurred or not. The general data ( age, sex, body mass index,past medical history) ,clinical data (National Institute of Health stroke scale [ NIHSS score] ) , onset to admission time,imaging data (white matter lesion score,cerebral microhemorrhage score and branch atherosclerosis) , treatment methods and laboratory findings such as neutrophil to lymphocyte ratio, total cholesterol,low- density lipoprotein cholesterol, fasting blood glucose, hypersensitive C-reactive protein, homocysteine, and Lp-PLA2 were compared in patients between the two groups. Immunoturbidimetry was used to determine the level of Lp-PLA2 in blood. SPSS 22. 0 software was used to analyze and process the data. Multivariate logistic regression was used to analyze the risk factors for affecting the occurrence of END in patients with lacunar cerebral infarction. Receiver operating characteristic (ROC) curve was used to analyze the value of Lp-PLA2 in predicting the occurrence of END in lacunar infarction. Results Univariate analysis showed that NLR (2. 5 ± 0. 5 vs. 2. 3 ± 0. 5, t = 2. 996) , low-density lipoprotein cholesterol (2. 6 ± 0. 8 mmol/L vs. 2. 3 ± 0. 7 mmol/L, t = 3. 056), NIHSS score on admission ( 3.4 ± 1.5 vs. 3.0 ± 1.4, l = 2. 080), and the proportion of patients with branch atherosclerosis (21. 3% [ 16/75] vs. 7. 3% [ 15/206] #=1 1-061) in the END group were higher than those in the non-END group (240 ± 26 jxg/L vs. 180 ±23 p,g/L, I = 9. 032) ,and the difference was statistically significant (all P <0. 05). Multivariate logistic regression analysis showed that the increased level of NLR (0/,3.927,95% CI 2.918 -5.016,P = 0.020),Lp-PLA2 (OR, 1.026,95% 67 1.019-1.034, P <0.01), low-density lipoprotein cholesterol (OR, 2.715,95% CI 2.193 -3.273, P =0.025) , NIHSS score on admission (OR,2. 831 ,95% CI 2.412 -3. 197, P = 0.028) , and branch atherosclerosis ( OR,4. 552 ,95% CI 2. 934 -7. 017 , P = 0. 002) were the independent risk factors for lacunar infarction occurring END. Receiver operating characteristic ( ROC) curve analysis showed that the area under the curve of Lp-PLA2 predicting END was 0. 799 (95% CI 0. 728 -0. 833 ,P< 0. 01 ) ;the optimal cut-off value was 189 jtg/L, the sensitivity for predicting END was 92. 3% ,and the specificity was 55. 4%. Conclusion The increased level of serum I.p-PLA2 is an independent risk factor for lacunar infarction occurring END,and it has certain predictive value for END.

Correlations of serum level of thyroid-stimulating hormone with tumor necrosis factor-α, lipoprotein associated phospholipase A2 and interleukine-6 levels in ischemic stroke patients with subclinical hypothyroidism / 中华神经医学杂志

Objective To evaluate the correlations of serum level of thyroid-stimulating hormone (TSH) with levels of inflammatory factors lipoprotein associated phospholipase A2 (Lp-PLA2), tumor necrosis factor-α(TNF-α) and interleukine (IL)-6 in ischemic stroke (IS) patients with subclinical hypothyroidism (SCH) and its clinical significance.MethodsTwenty SCH patients, 30 IS patients and 30 IS+SCH patients, admitted to our hospital from October 2017 to October 2018, were enrolled in our study; 27 subjects underwent physical examination in our hospital at the same period were selected as the control group. The serum levels of TSH, Lp-PLA2, TNF-αand IL-6 were measured by up-converting phoshor assay and enzyme - linked immunosorbent assay with double antibody sandwich. The common carotid artery, internal carotid artery and vertebral artery were examined by Doppler ultrasonography to analyze the morphology, location, and echo characteristics of the plaques and stenosis rates. Pearson correlation analysis was used to analyze the correlations of TSH with inflammatory factors, carotid artery stenosis rate.ResultsThe levels of Lp-PLA2, TNF-αand IL-6 in IS+SCH group were significantly higher than those in SCH group, IS group and control group (P<0.05); those in the SCH group and IS group were significantly higher than those in the control group (P<0.05). The serum TSH levels in IS+SCH group and SCH group were positively correlated with Lp-PLA2 level (r=0.739,P=0.000;r= 0.697,P=0.000), TNF-αlevel (r=0.981,P=0.000;r=0.723,P=0.000) and IL-6 level (r=0.859,P=0.000;r=0.583,P=0.000); but the serum TSH levels in IS group and NC group were not correlated with Lp-PLA2 level (r=0.223,P=0.236;r=0.249,P=0.210), TNF-αlevel (r=0.304,P=0.103;r=0.056,P=0.780) and IL-6 level (r=0.027,P=0.887;r=0.138,P=0.491). The number of unstable plaques and degree of stenosis in IS+SCH group were larger/higher than those in IS group, SCH group and control group (P< 0.05); there was a positive correlation between serum TSH level and artery stenosis rate (r=0.739,P= 0.000).ConclusionSCH may lead to occurrence and development of atherosclerosis by increasing the serum levels of TNF-α, Lp-PLA2 and IL-6 caused by low-level chronic inflammation, which in turn increases the risk of ischemic stroke.

Change of Inflammatory Factors in Patients with Acute Coronary Syndrome / 中华医学杂志(英文版)

<p><b>Background</b>Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance.</p><p><b>Methods</b>A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed.</p><p><b>Results</b>The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively).</p><p><b>Conclusions</b>The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.</p>