Lipoprotein-Associated Phospholipase A2 and Risk of Carotid Atherosclerosis and Cardiovascular Events in Community-Based Older Adults in China.

Plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA(2) is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA(2) and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA(2) protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA(2) mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA(2) were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA(2) were negatively correlated (r = - 0.578). The ratio of Lp-PLA(2) to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA(2) existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA(2) epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA(2) and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

Lipoprotein-associated Phospholipase A2 during the Hyperacute Stage of Ischemic and Hemorrhagic Strokes

The aim of this study is to evaluate serum level biomarkers of atherosclerosis lipoprotein-associated phospholipase A2 and E-selectin in patients with atherosclerotic carotid stenosis with different clinical manifestation in associated with vascular risk factors. Materials and methods: A total 106 patients with atherosclerotic carotid stenosis (74 men and 32 women, aged from 31 to 74 years, mean 62.6±0.9) were included: with acute ipsilateral atherothrombotic stroke (35), history of stroke and carotid endarterectomy (41) and 30 patients with asymptomatic carotid stenosis. The control group consist of 20 health subjects without cardiovascular disease. All participants underwent duplex sonography. Lipoprotein-associated phospholipase A2 and E-selectin was measured using commercially available (ELISA) kit. Results: The level of lipoprotein-associated phospholipase A2 was in general 55.664±3.537 ng/ml, which was significantly higher (M-W U=10, p=1.023136´10-11 <0.05) than in the control group (9.296±0.935 ng/ml). Level was significantly higher in groups of symptomatic patients who underwent carotid endarterectomy (p=0.04893), and proportion patients with high degree stenosis >70 % was greater in this group. The level of E-selectin in the study patients was significantly higher (7.653±0.246 pg/ml) than in the control group (3.101±0.503 pg/ml) p<0.05. No association the serum level of lipoprotein-associated phospholipase A2 and E-selectin with common stroke risk factor such as hypercholesterinemia, smoking and body mass index were found, but positive correlation of lipoprotein-associated phospholipase A2 with E-selectin was significant (p=0.00085). Conclusions: Increasing plasma level lipoprotein-associated phospholipase A2 and E-selectin in patients with the carotid atherosclerotic stenosis were observe. Statistically significant correlation between the level of lipoprotein-associated phospholipase A2 and E-selectin were found in symptomatic carotid atherosclerotic stenosis

The relationships between lipoprotein-associated phospholipase A2 (Lp-PLA2) level, vasospasm, and clinical outcome of patients with aneurysmal subarachnoid hemorrhage (aSAH) are still unclear. To identify the associations between admission Lp-PLA2 and vasospasm following subarachnoid hemorrhage and the clinical outcome of aSAH. A total of 103 aSAH patients who had Lp-PLA2 level obtained within 24 h postbleeding were included. The relationships between Lp-PLA2 level, vasospasm, and clinical outcome were analyzed. Vasospasm was observed in 52 patients (50.49%). Patients with vasospasm had significantly higher Lp-PLA2 level than those without (P<.001). Both modified Fisher grade (P=.014) and Lp-PLA2 level (P<.001) were significant predictors associated with vasospasm. The Z test revealed that power of Lp-PLA2 was significantly higher than that of modified Fisher grade in predicting vasospasm (Z=2.499, P=.012). At 6-mo follow-up, 44 patients (42.72%) had unfavorable outcome and 36 patients (34.95%) died. The World Federation of Neurosurgical Societies (WFNS) grade and Lp-PLA2 level were both significant predictors associated with 6-mo unfavorable outcome and mortality (all P<.001). The predictive values of Lp-PLA2 for unfavorable outcome and mortality at 6-mo tended to be lower than those of the WFNS grade, but the differences were not statistically significant (P=.366 and 0.115, respectively). Poor-grade patients having Lp-PLA2>200 μg/L had significantly worse 6-mo survival rate than poor-grade patients having Lp-PLA2≤200 μg/L (P=.001). The Lp-PLA2 might be useful as a novel predictor in aSAH patients. A total of 30 poor-grade patients; those with elevated Lp-PLA2 level have higher risk of 6-mo mortality compared to those without.

The diagnostic and prognostic performance of Lp-PLA2 in acute ischemic stroke

The diagnostic and prognostic performance of Lp-PLA2 in acute ischemic stroke

20 % of ischemic stroke appear to originate from carotid artery atherosclerotic disease. Serum biomarkers reflecting the activity of atherosclerotic process and may help for estimate risk of acute cerebrovascular events. Several serum inflammatory markers have been proposed for risk assessment, but their prognostic role less known. The aim of this study is to clarify the prognostic value of biomarkers of atherosclerosis lipoprotein-associated phospholipase A2 (Lp-PLA2) and E-selectin in patients with symptomatic and asymptomatic carotid stenosis. Materials and methods. The study involved 106 patients with atherosclerotic carotid stenosis &gt;50 % (74 men and 32 women, mean age 62.6±0.9) from which 76 symptomatic (35 with acute ipsilateral atherothrombotic stroke and 41 after carotid endarterectomy) and 30 asymptomatic patients. The control group consisted of age- and sex-matched 20 healthy subjects. The level of serum Lp-PLA2 and E-selectin was determined using a commercially available enzyme-linked immunosorbent assay kit. Results. The level of Lp-PLA 2 was in general significantly higher (p&lt;0.05) in patients groups than in the control group and most high Lp-PLA2 concentration was in groups of symptomatic patients who underwent carotid endarterectomy. The level of E-selectin in the study patients was significantly higher than in the control group (p&lt;0.05). The correlation of Lp-PLA 2 with E-selectin was significant for total patients (R=0.365664, p=0.00085) and group after carotid endarterectomy (R=0.429143, p=0.01796), but not for asymptomatic group (p&gt;0.05). Receiver Operating Characteristics curves of logistic regression models which takes into joint both indicators was specificity and sensitive for predicting the occurrence of ischemic stroke. Conclusion. Conducted study show that the levels of Lp-PLA 2 and E-selectin have a significant impact on the development of stroke in patients with atherosclerotic carotid stenosis and can be used to predict it. A multidimensional model of the dependence of the probability of stroke on a linear combination of Lp-PLA 2 and E-selectin allows to obtaining significantly higher characteristics of the accuracy of stroke prediction than models with each factor alone.

There are no effective therapies to prevent the occurrence and progression of vertebrobasilar dolichoectasia (VBD). In this study, we investigated the relationship between serum levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the occurrence and progression of VBD. Sixty (60) cases without VBD and ischemia stroke were considered as Group A, 100 cases with VBD were further divided into Group B (VBD without ischemic stroke, n= 54) and Group C (VBD with first ever acute posterior circulation ischemic stroke, n= 46). Demographic data (such as gender and age) and past medical history (such as hypertension, diabetes, and smoking history) were collected. The levels of serum low-density lipoprotein cholesterol (LDL-C), hypersensitivity C reactive protein (hs-CRP), glycosylated hemoglobin (HbAlc), homocysteine (HCY), uric acid (UA), fibrinogen (Fib), and Lp-PLA2, etc. were measured. Logistic regression analysis was used to assess the related factors of VBD and ischemic stroke secondary to VBD. Logistic multivariate regression analysis showed that only age and the level of serum Lp-PLA2 were significantly higher in group B than those in group A (P < 0.012, P < 0.001, respectively), however, only the level of serum Lp-PLA2 was significantly higher in group C than those in group B (P < 0.001). The serum marker Lp-PLA2 is an independent risk factor for the occurrence of VBD and the progression of VBD to posterior circulation ischemic stroke. Whether intervening on atherosclerosis could prevent the occurrence and development of VBD needs to be further studied.

Objective To investigate the associations of plasma homocysteine (Hcy) and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels with dementia. Methods The patients with dementia admitted to hospital were enrolled retrospectively. They were divided into a vascular dementia (VaD) group, a mixed dementia (MD) group, and an Alzheimer's disease (AD) group according to the Hachinski Ischemic Score, and the dementia severity was further divided into a mild group, a moderate group and a severe group according to the Mini-Mental State Examination. The non-demented patients hospitalized during the same period were selected as controls. The demographics, vascular risk factors, and plasma Hcy and Lp-PLA2 levels in each group were compared. Logistic regression analysis was used to determine the independent associations of the plasma Hcy and Lp-PLA2 levels with the risk of dementia and severity. Results A total of 125 patients with dementia were enrolled, including 52 (41.6%) in the VaD group, 21 (16.8%) in the MD group, and 53 (41.6%) in the AD group. There were 49 patients (39.2%) in the mild group, 51 (40.8%) in the moderate group, and 25 (20%) in the severe group. A total of 40 non-demented patients were enrolled as control group. The plasma Hcy and Lp-PLA2 levels in VaD, MD and AD groups were significantly higher than those in the control group (all P<0.001). Multivariable logistic regression analysis showed that the advanced age (odds ratio[OR] 1.12, 95% confidence interval [CI] 1.03-1.21; P=0.010), high plasma Hcy level (OR 1.44, 95% CI 1.21-1.71; P<0.001), high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.02; P=0.006 ), and previous stroke (OR 4.29, 95% CI 1.50-12.36; P=0.007) were the independent risk factors for dementia; high Hcy level (OR 1.48, 95% CI 1.21-1.82; P<0.001, high Lp-PLA2 level (OR 1.01, 95% CI 1.00-1.03; P=0.002), and previous stroke (OR 152.78, 95% CI 20.41- 999.97; P<0.001) were the independent risk factors for VaD; advanced age (OR 1.10, 95% CI 1.02-1.17; P=0.008) and high Hcy level (OR 1.41, 95% CI 1.25-1.58; P<0.001) were the independent risk factor for severe dementia. Conclusions The increased plasma Hcy and Lp-PLA2 levels are associated with dementia. Reducing the plasma Hcy and Lp-PLA2 levels may be beneficial to the treatment and prevention of dementia. Key words: Dementia; Dementia, Vascular; Alzheimer Disease; Homocysteine; 1-Alkyl-2-acetylglycerophosphocholine Esterase; Biomarkers

Background: Cigarette smoking is a behavioural lifestyle in which a substance is burned and the resulting smoke breathed into the body system. Thus, cigarette smoking is a known public health challenge given the number of tobacco-related diseases like hypertension, lung cancer, cardiovascular diseases (CVD) etc. leading to increased mortality in developed and developing countries. Notwithstanding that the effects of smoking are well documented, individuals who practice cigarette smoking are still on the increase most especially in the developing countries. Study Design/Aim: This was a cross-sectional study designed to evaluate the serum levels of Cancer Antigen-242 (CA-242) and Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in adult male smokers in Nnewi Metropolis, as emerging inflammatory biomarkers. Materials and methods: A total of 135 subjects aged between 16-65 years were selected for this study. They were classified into 2 major groups (test and control); comprising of 85 cigarette smokers (55 and 30 as test subjects for the evaluation of CA-242 and Lp-PLA2) respectively and 50 non-cigarette smokers (35 and 15 as control subjects for CA-242 and Lp-PLA2 evaluations) respectively. A well-structured questionnaire was used for the collation of information from the participants. Results: the mean serum level of Lp-PLA2 was significantly elevated (P&lt;0.05) in cigarette smokers (67.52±27.29) compared with the non-smokers (63.63±20.81). While the serum level of CA-242 among smokers (1.77±0.70) was of no significant difference (P=0.711) when compared with the non-smokers (1.81±0.20). More so, the mean serum levels of Lp-PLA2 correlated positively with the duration of smoking (r=0.297) and age (r=0.085) in male cigarette smokers. However, there were negative relationships when CA-242 were correlated with duration of smoking (r = -0.156) and age of smokers (r=-0.155). Conclusion: The increased level of Lp-PLA2 along with its positive correlation with other traditional markers like age and smoking duration suggests that Lp-PLA2 is a suitable biomarker to predict cardiac related diseases among cigarette smokers. This is because, Lp-PLA2 is a more specific cardiac predictor compared to the non-specific conventional biomarkers. We therefore suggest that Lp-PLA2 as an independent advanced predictor of cardiovascular disease be further evaluated using follow-up studies with better sample size in CVDs related cases

Association Between Lipoprotein-Associated Phospholipase A2 and Cardiovascular Disease: A Systematic Review

Objective To explore the influence of Helicobacter pylori (Hp) infection in serum lipoprotein associated phospholipase A2 (Lp-PLA2), carotid intima-media thickness and stability of atherosclerotic plaques in atherosclerosis patients. Methods A total of 393 cases of patients with carotid artery arteriosclerosis confirmed by carotid color ultrasonography, who are informed consent, was selected as objects. The14C urea breath test was used to determine the infection situation of selected objects of helicobacter pylori. Meanwhile, enzyme-linked immunosorbent assay (ELISA) was used to determine the level of serum lipoprotein associated phospholipase A2 (Lp-PLA2). Results Serum Lp-PLA2 levels and carotid intima-media thickness (IMT) of patients with carotid artery atherosclerosis in Hp infection group were higher than that of Hp non-infection group, and with the degree of Hp infection aggravating in the patients of carotid artery atherosclerosis, their serum Lp-PLA2 levels and carotid IMT were also increased accordingly. F test showed that the differences of serum Lp-PLA2 levels and carotid IMT in different degree of carotid artery atherosclerosis group were statistically significant (P<0.01). The incidence of unstable plaque of Hp infection group was obviously higher than that of the Hp non-infection group in the carotid atherosclerosis with plaques with statistical significance (chi square value=4.744, P=0.029). Multivariate linear regression analysis showed that the possibility of complication of unstable plaques in Hp infection group of carotid artery atherosclerosis was 1.82 times than that of non-infection group. With serum Lp-PLA2 every increasing 1 μg/L, the possibility of instability plaque increased by 2%. Conclusions Hp infection may promote the occurrence and development of carotid artery atherosclerosis by increasing serum level of Lp-PLA2 and changing the stability of atherosclerotic plaques. Key words: Helicobacter infections; Helicobacter pylori; Carotid artery diseases/ME; Atherosclerosis/ME; Phospholipases A2/ME; Carotid arteries/PP

Lipoprotein-associated phospholipase A2 (Lp-PLA2), a novel marker of vulnerable plaque to prone rupture, is a predictor of both cardiovascular event and cerebrovascular event, and highly sensitive-C-reactive protein (hs-CRP) is an acute-phase response protein implicated in a broad range of cardiovascular diseases. We aimed to examine the association between periodic limb movements in sleep (PLMs) with circulating Lp-PLA2 and hs-CRP levels in patients with PLMs. Seventy patients with newly diagnosed PLM with polysomnography were enrolled this study. Patients were divided into two groups according to PLM index (normal PLM index, <15; elevated PLM index, ≥15). Lp-PLA2 and hs-CRP concentrations were measured in serum samples by turbidimetric and nephelometric methods, respectively. The concentrations of these parameters were compared between two groups and correlation analysis was performed between PLMs and Lp-PLA2 and hs-CRP levels. Lp-PLA2 levels and hs-CRP were significantly increased in elevated PLM index group compared with the control group (206.8 ± 78.1 vs 157.8 ± 56.7, p = 0.003, and 4.2 ± 3.5 vs 2.4 ± 2.1, p = 0.02, respectively). PLM index was positively correlated with Lp-PLA2 levels (r = 0.40, p = 0.001) and hs-CRP (r = 0.24, p = 0.05). In the linear regression model, Lp-PLA2 was an independent predictor of PLM index (R(2) = 0.36, p = 0.005). This study demonstrated an independent linear relation between PLM index and Lp-PLA2. In addition, it was seen increased Lp-PLA2 and hs-CRP levels in patients with elevated PLM index. Based on these results, we can suggest that risk of vascular events may be increased in patients with PLMs and with increased PLM index.

Although lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) levels are associated with cardiovascular events, Lp-PLA(2) is physically linked to LDL cholesterol (LDL-C). Whether measures of Lp-PLA(2) mass or activity continue to predict risk after LDL-C reduction by statin therapy is uncertain. Lp-PLA(2) mass concentration and activity were evaluated at baseline and after treatment in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial comparing rosuvastatin 20 mg to placebo among 17 802 men and women without cardiovascular disease or diabetes at study entry. The relationships of Lp-PLA(2) mass and activity with risk of future vascular events were evaluated in the placebo and rosuvastatin groups. Before randomization, levels of Lp-PLA(2) mass and activity correlated moderately with each other and with LDL-C. The magnitude of these correlations increased after statin therapy. Rosuvastatin reduced Lp-PLA(2) mass by 33.8%, Lp-PLA(2) activity by 33.2%, and LDL-C by 48.7% (all P < 0.0001). Among those study participants allocated to placebo, increasing quartiles of Lp-PLA(2) activity (P(trend) = 0.04) but not Lp-PLA(2) mass (P(trend) = 0.92) were associated with incident cardiovascular events after adjustment for LDL-C and conventional risk factors. Comparable analyses conducted among those allocated to rosuvastatin revealed no significant relationship between Lp-PLA(2) levels and subsequent vascular events. The ability of rosuvastatin to reduce vascular events was not significantly modified by baseline Lp-PLA(2) level. Among JUPITER trial participants allocated to placebo, levels of Lp-PLA(2) activity, but not mass, were associated with cardiovascular risk. However, Lp-PLA(2) no longer predicted risk or modified clinical outcomes when participants were treated with rosuvastatin.

Objective The study was to determine plasma myeloperoxidase (MPO), oxidized low density lipoprotein (OX-LDL) and lipoprotein-associated phospholipase A2 (LP-PLA2) levels in Beijing healthy adults and investigate the correlation among these three biomarkers and risk factors of cardiovascular disease. Methods One thousand one hundred and fifty-five healthy subjects, including 567 male and 588 female, were selected from Center of Health Examination of Armed Police General Hospital during the period of February to October 2015, who range in age from 18 to 87. Plasma MPO, OX-LDL and LP-PLA2 levels were determined by enzyme linked immunosorbent assay (ELISA). Groups were set by gender and age according to C28-A2 standard of Clinical and Laboratory Standards Institute (CLSI) and series of guiding principles of performance evaluation in vitro diagnostic reagent. Male and female subjects were classified into four subgroups by age respectively as those who were from 18 to 29,≥30 to 39,≥40 to 49,≥50. The correlation among levels of MPO, OX-LDL and LP-PLA2 was achieved by regression analysis method. Results One thousand one hundred and fifty-five healthy subjects of MPO reference value was 94.1 μg/L, while OX-LDL and LP-PLA2 reference range were 14.08-127.58 mg/L and 47.30-218.96 μg/L respectively. Experimental results showed that these three biomarkers in plasma of healthy subjects increased with the growing age. Male and female did not need to set up independent subgroups of reference range, but there was significant difference in plasma OX-LDL and LP-PLA2 between male and female (t value were 2.134, 2.381; P 0.05); Meanwhile, there was significant correlation among MPO, OX-LDL and LP-PLA2 (r value were 0.181, 0.174, 0.470; P<0.01). Conclusion Reference ranges of plasma MPO, LP-PLA2 and Ox-LDL have been set up for Beijing healthy adults, which can be used clinically as biomarkers of cardiovascular disease. Key words: Myeloperoxidase; Oxidized low density lipoprotein; Lipoprotein-associated phospholipase A2