Causal Effect of Lipoprotein-Associated Phospholipase A2 Activity on Ischemic Stroke: A Mendelian Randomization Study.

BACKGROUND: The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization (MR) was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes. METHODS: Based on information from a meta-analysis of genome-wide association studies, which included 13,664 European people, five single nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables. Summary statistics information about the MEGESTROKE consortium with the European group (40,585 cases and 406,111 controls) include any IS (AIS; n = 34,217), large-artery stroke (LAS; n = 4,373), cardioembolic stroke (CES; n = 7,193), and small-vessel stroke (SVS; n = 5,386). In order to determine the causal relationships between Lp-PLA2 activity and IS as well as its subtypes, the inverse-variance-weighted (IVW) approach was chosen as the primary analysis. Significant estimates were then tested by sensitivity analysis to rule out heterogeneity and pleiotropy. RESULTS: IVW showed that Lp-PLA2 activity was causally associated with LAS (odds ratio = 3.25, 95% confidence interval = 1.65-6.41, p = 0.0007) but not with other subtypes of stroke. Sensitivity analysis for causal estimates between Lp-PLA2 activity and LAS showed no significant heterogeneity or pleiotropy. CONCLUSIONS: These MR analyses support a causal effect of Lp-PLA2 activity on LAS but not on AIS, CES, or SVS, which suggests that serum Lp-PLA2 activity might be a biomarker for prediction of LAS.

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Analysis of the Relationship Between the Changes of Serum SAA, LP-PLA2, sCD40L and Carotid Atherosclerosis Plaque in Patients with Acute Cerebral Infarction.

Objective: To explore the relationship between Serum amyloid protein A(SAA), lipoprotein-associated Phospholipase A2 (Lp-PLA2) and soluble CD40 ligand (sCD40L) in detecting the stability of carotid Atherosclerosis plaque. Methods: We examined 90 patients admitted to our hospital with acute cerebral infarction from July 2020 to December 2022. Carotid artery ultrasounds were performed for all of them. These patients were then divided into two groups: the stable plaque group (45 cases) and the unstable plaque group (45 cases), based on the ultrasound results. Additionally, we included a control group of 30 healthy individuals from our hospital. We collected fasting blood samples from the patients upon admission and used enzyme-linked immunosorbent assays to measure the mass concentrations of sCD40L, Lp-PLA2, and SAA in their serum. The results of these biomarkers were compared and analyzed to assess potential associations with plaque stability in patients with cerebral infarction. Results: Comparison of general clinical data and laboratory data: except for High-density lipoprotein, there was a statistical difference between the control group and the cerebral infarction group (P < .05), there was no statistical difference in gender, smoking history, drinking history and age (P > .05). Compared with the control group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in patients with stable and unstable plaques increased significantly (P < .05); Compared with the stable plaque group, the mass concentrations of sCD40L, Lp-PLA2, and SAA in unstable plaque patients increased with statistical significance (P < .05). Correlation analysis shows that the mass concentrations of sCD40L, Lp-PLA2, and SAA are positively correlated with the stability of carotid artery plaques. SCD40L, Lp-PLA2 and SAA have certain diagnostic significance in the subject's working characteristic curve (Receiver operating characteristic) as a marker molecule for the diagnosis of unstable plaque. sCD40L (AUC=0.883) has more diagnostic value than SAA (AUC=0.756) and Lp-PLA2 (AUC=0.826). A binary logistic regression analysis was conducted using the stability of carotid artery plaques as the dependent variable and sCD40L, Lp-PLA2, and SAA as independent variables. The results showed that elevated serum sCD40L, Lp-PLA2, and SAA were independent risk factors for unstable carotid artery plaques (P < .05). Conclusion: The concentrations of sCD40L, Lp-PLA2 and SAA are closely related to the formation and type of carotid Atherosclerosis plaque in patients with acute cerebral infarction. This has potentially important clinical implications for the management and prevention of cardiovascular disease.

Lipoprotein-associated phospholipase A2 activity levels is associated with artery to artery embolism in symptomatic intracranial atherosclerotic disease.

BACKGROUND: Lipoprotein-associated phospholipase A2 activity (Lp-PLA2-A) is a pivotal enzyme involved in the inflammatory process and atherosclerotic plaque vulnerability. This study aimed to investigate the potential of Lp-PLA2-A as a biomarker for reflecting artery-to-artery embolism (AAE), a critical mechanism with high risk of stroke recurrence in symptomatic intracranial atherosclerotic disease (sICAD). METHODS: The current analysis included a cohort of 1,908 patients with sICAD and baseline levels of Lp-PLA2-A from the Third China National Stroke Registry (CNSR-III). The baseline Lp-PLA2-A levels were quantified centrally using an automatic enzyme assay system. Diagnosis of sICAD was made by experienced stroke neurologists based on the presence of a cerebral infarction within the territory of a stenotic (>50 %) or occluded artery, or when clinical symptoms were consistent with the diagnosis. Infarct lesions affecting the cortex serve as imaging biomarkers for stroke mechanism involving AAE.The relationship between baseline Lp-PLA2-A quartile levels and the presence of cortical infarction was analyzed using multivariate logistic regression. RESULTS: Compared to patients in the first Lp-PLA2-A quartile, those in the second, third and fourth quartiles demonstrated a significantly higher proportion of AAE. The proportion of patients with cortical infarction increased with rising Lp-PLA2-A quartiles, observed at 39.3 %, 47.1 %, 47.4 %, and 50.7 % for the first, second, third and fourth quartiles respectively (P for trend=0.004). Compared with the first quartile, the odds ratios (ORs) were 1.38 (95 % CI = 1.06-1.79) for the second, 1.33 (95 % CI = 1.02-1.72) for the third quartile and 1.48 (95 % CI = 1.14-1.92) for the fourth quartile. The association between higher Lp-PLA2-A and increased proportion of cortical infarction was also present in the subgroups defined by age <65 years, male, and high-sensitivity C-reactive protein ≥2 mg/L. In sensitivity analyses, the positive correlation between Lp-PLA2-A levels and proportion of cortical infarction remained consistent. CONCLUSIONS: This research highlights the significance of Lp-PLA2-A as a biomarker for reflecting stroke mechanism in sICAD. Additional studies are warranted to explore the potential of targeting Lp-PLA2-associated inflammatory pathways as a pivotal approach in arresting the advancement of intracranial atherosclerotic stenosis and reducing the incidence of embolic strokes.

Time-resolved Fluorescence Immunoassay (TRFIA) for the Simultaneous Detection of MMP-9 and Lp-PLA2 in Serum.

Currently, atherosclerosis accounts for the majority of cardiovascular morbidity and mortality worldwide, and predicting the stability of atherosclerotic plaque is the main method to prevent atherosclerotic death. This study aims to establish a dual-label time-resolved fluorescence immunoassay (TRFIA) of matrix metalloprotein-9 (MMP-9) and lipoprotein-associated phospholipaseA2 (Lp-PLA2) to predict atherosclerotic plaque stability. A dual-label TRFIA was introduced for the simultaneous quantification of MMP-9 and Lp-PLA2 using fluorescent lanthanide (Eu3+ and Sm3+) chelates. The performance (sensitivity, specificity, accuracy, precision and reference intervals in different subjects) of this TRFIA was evaluated and compared with commercial kit. The sensitivity of the TRFIA for MMP-9 was 0.85 ng/mL and for Lp-PLA2 was 0.68 ng/mL with high affinity and specificity. The average recoveries were 94.58% to 109.82%, and 104.32% to 109.26%, respectively. All intra- and inter-assay CVs ranged from 3.10% to 5.46%. For the normal subjects, the cutoff value was 160.70 ng/mL for MMP-9 and 183.73 ng/mL for LP-PLA2; for the subjects with stable plaque, the cutoff value was 181.98~309.22 ng/mL for MMP-9 and 194.73~337.89 ng/mL for LP-PLA2; for the subjects with unstable plaque, the cutoff value was 330.43 ng/mL for MMP-9 and 343.23 ng/mL for LP-PLA2. This TRFIA detection results agreed well with the results of commercial kit (R2=0.9567 and R2=0.9771, respectively) in clinical serum samples. The TRFIA developed has a wide detection range and good sensitivity for the high-throughput simultaneous detection of MMP-9 and Lp-PLA2 in serum, which provides a new method for predicting the stability of atherosclerotic plaque.

A novel prognosis prediction model, including cytotoxic T lymphocyte-associated antigen-4, ischemia-modified albumin, lipoprotein-associated phospholipase A2, glial fibrillary acidic protein, and homocysteine, for ischemic stroke in the Chinese hypertensive population.

BACKGROUND: There is still a lack of tools to assess the prognosis of ischemic stroke patients induced by hypertension. In this study, we built a novel prognostic assessment model for ischemic stroke in the Chinese hypertensive population. METHODS: Mass spectrometry technique was used to analyze the changes in serum protein profiles of hypertensive patients with ischemic stroke. A total of 314 hypertensive patients were divided into the testing group (206 patients) and the validation group (108 patients). RESULTS: Compared with hypertensive patients without ischemic stroke, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), ischemia-modified albumin (IMA), lipoprotein-associated phospholipase A2 (Lp-PLA2), glial fibrillary acidic protein (GFAP), and homocysteine (HCY) levels were significantly increased among hypertensive patients with ischemic stroke (p < 0.05). Then, we built a novel prognostic assessment model for hypertensive patients with ischemic stroke [Logit(P) = 29.172-1.088*CTLA-4-0.952*IMA-0.537*Lp-PLA2 -0.066*GFAP -0.149*HCY]. It showed higher efficiency (AUC = 0.981, sensitivity = 95.5%, specificity = 93.8%) than any single marker. The estimated probability was 0.739, which means if higher than 0.739, it was classified into poor prognosis. Compared with the estimated probability ≤0.739 group, the survival rate of hypertensive patients with ischemic stroke in the estimated probability >0.739 group was significantly decreased (χ2  = 40.001, p < 0.001). In the validation group, our novel prognostic assessment model still showed good efficiency (AUC = 0.969, sensitivity = 89.4%, specificity = 92.5%; χ2  = 47.551, p < 0.001). CONCLUSION: Current novel prognostic assessment model we have built is of great value in the prognostic evaluation for ischemic stroke in the Chinese hypertensive population.

Lp-PLA2 evaluates the severity of carotid artery stenosis and predicts the occurrence of cerebrovascular events in high stroke-risk populations.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent risk factor for cardiovascular disease. However, relationship between carotid artery stenosis and cerebrovascular events in high stroke-risk populations is still unclear. METHODS: A total of 835 people at a high risk of stroke were screened from 15,933 people aged >40 years in April 2013 and followed at 3, 6, 12, and 24 months. Finally, 823 participants met the screening criteria, and the clinical data and biochemical parameters were investigated. RESULTS: Among the 823 participants, 286 had varying degrees of carotid artery stenosis and 18 had cerebrovascular events. The level of Lp-PLA2 in the carotid artery stenosis group was higher than that in the no stenosis group, and the level in the event group was higher than that in the no event group (p < 0.05). Spearman correlation analysis showed that Lp-PLA2 was positively correlated with the degree of carotid artery stenosis (r = 0.093, p = 0.07) and stenosis involvement (r = 0.094, p = 0.07). The correlation coefficient between Lp-PLA2 and lipoprotein was the highest on the levels of sdLDL (r = 0.555, p < 0.001), followed by non-HDL, LDL, TC, and TG. Cox multivariate regression analysis revealed that, compared with the first quantile of Lp-PLA2 level (Q1, low level), the risk of cerebrovascular events in the fourth quantile of Lp-PLA2 was 10.170 times that of the first quantile (OR = 10.170, 95% CI 1.302-79.448, p = 0.027). CONCLUSIONS: Lp-PLA2 levels can evaluate carotid artery stenosis and predict the occurrence of cerebrovascular events in high stroke-risk populations and provide scientific guidance for risk stratification management.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) - possible diagnostic and risk biomarker in chronic ischaemic heart disease.

In a group of 208 patients with chronic ischaemic heart disease, the variation of A2-associated-LDL phosphatase (Lp-PLA2) serum concentration values was analysed in dynamics at a two-week interval. The conclusion of the study is that the values of serum concentration of Lp-PLA2 can be accepted as a biomarker with diagnostic specificity for chronic ischaemic heart disease, a parameter of real utility in medical practice, both in situations where the patient, although clinically reporting the existence of angina pectoris, does not show specific changes on an EKG, and for the assessment of the response to personalised therapy.

Serum Lp-PLA2 Level Predicting Coronary Artery Lesions in Children with Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is an inflammatory disease associated with coronary vasculitis in children. In this study, we explored the correlation between Lipoprotein associated phospholipase A2 (Lp-PLA2) and coronary artery lesions (CAL) in children with KD. METHODS: Ninety-three children with KD were divided into a normal coronary artery (NCA, 54 cases) group and coronary artery lesions (CAL, 39 cases) group, according to the results of echocardiography. Another 42 healthy children were selected as the control group. The serumal levels of Lp-PLA2, Interferon-γ(IFN-γ) and Interleukin-6 (IL-6) were determined by using an enzyme-linked immunosorbent assay. In addition, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level were analyzed. The left main coronary artery (LMCA), diameters of left anterior descending coronary artery (LADC), right proximal coronary artery (PRCA), and carotid intima-media thickness (IMT) were obtained by color Doppler ultrasound. The correlation between the above indexes and KD was analyzed. RESULTS: The levels of white blood cell counts (WBC), ESR, CRP, IFN-γ, IL-6 and Lp-PLA2 as well as IMT were significantly increased in KD children (P < 0.05), and the levels of CRP, IFN-γ, IL-6 and Lp-PLA2 as well as IMT in the CAL group increased more significantly (P < 0.05). An increasing trend also has been described in the diameters of LMCA, LADC and PRCA for KD children with CAL compared with with NCA. The results of logistic regression analysis showed that the elevated levels of CRP, IFN-γ, IL-6 and Lp-PLA2 were independent risk factors for KD with CAL. Correlation analysis showed that Lp-PLA2 level was positively correlated with the levels of IFN-γ, IL-6 and CRP in CAL group and NCA group (respectively, all P < 0.01). In addition, a similar correlation was also described between Lp-PLA2 level and the diameters of LMCA, LADC and PRCA in CAL group (respectively, all P < 0.01). CONCLUSION: Lp-PLA2 may participate in the pathological mechanism of KD. Detection of the serum Lp-PLA2 level can be used in the diagnosis of KD disease and the assessment of coronary artery lesions in KD children.

Combined Assessment of Elevated Plasma Lipoprotein-Associated Phospholipase A2 and Plaque Enhancement Improved Accuracy in the Risk of Acute Ischemic Stroke in Patients with Intracranial Artery Stenosis.

PURPOSE: We evaluated the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and plaque characteristics in patients with intracranial artery stenosis and their clinical relevance in acute ischemic stroke. METHODS: Eighty-seven patients with intracranial atherosclerotic stenosis (66 males, 21 females) were retrospectively enrolled. Plasma Lp-PLA2 concentration was measured, and vessel wall magnetic resonance imaging (VW-MRI) was used to determine intracranial vascular stenosis and plaque characteristics, including plaque enhancement, surface morphology, and T1 hyperintensity. Binary logistic regression was used to evaluate the relationship between Lp-PLA2 concentration and plaque characteristics of intracranial artery after adjusting for demographic and confounding factors and to assess their diagnostic efficacy for the risk of acute ischemic stroke. RESULTS: After adjustment for demographic, medication and related lipid factors, Lp-PLA2 elevation was associated with plaque enhancement (odds ratio [OR]=12.7, 95% confidence interval [CI] 2.51-64.82, P=0.002) and surface irregularity (OR=2.9, 95% CI 1.06-7.98, P=0.038). Both Lp-PLA2 elevation (OR=8.8, 95% CI 1.64-47.72, P=0.011) and plaque enhancement (OR=34.3, 95% CI 5.88-200.4, P=0.001) were associated with acute ischemic stroke. Receiver operating characteristic curve analysis showed that the area under the curve for Lp-PLA2 concentration and plaque enhancement combined in the diagnosis of acute ischemic stroke was 0.884, significantly higher than that for Lp-PLA2 concentration (0.724) and plaque enhancement (0.794) alone. CONCLUSION: Elevated Lp-PLA2 is associated with plaque enhancement and plaque surface irregularity. Combined assessment of Lp-PLA2 concentration and plaque enhancement is of greater diagnostic value for the risk of acute ischemic stroke in patients with intracranial artery stenosis.

Evaluation of maternal plasma platelet activating factor acetylhydrolase activity and mRNA expression in pre-eclampsia: a case control study.

Preeclampsia (PE) remains a leading cause of maternal morbidity and mortality all over the world. However, its aetiology and pathophysiology remain elusive. Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) inactivates PAF and is seen to decrease in normotensive women. The role of PAF-AH in preeclampsia has been in investigational literature, so far. The few studies done have shown a positive association of elevated levels of PAF-AH with preeclampsia. However, this marker has not been studied in the Indian population to-date and such studies are needed to elucidate the pathogenesis of this condition. Our study aimed to determine the PAF-AH activity by spectrophotometric assay in maternal plasma of 73 PE patients versus 73 normotensive controls and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the genetic level. Relative mRNA expression was calculated by Δ DCT method and a fold change was calculated by 2-ΔDCT. We found that the mean plasma PAF-AH activity levels among cases was significantly higher than the normotensive controls. However, the mRNA expression of the PAF-AH gene was similar between the cases and controls, as well as between severe and non-severe preeclampsia (true fold change =1). To conclude, PAF-AH appears to be increased in women with preeclampsia and hence may contribute to pathophysiology and severity. However, a larger sample size will be required to reiterate this association. Recently, PAF-AH inhibitors such as Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.IMPACT STATEMENTWhat is already known on this subject? Platelet activating factor (PAF) is produced in response to oxidative stress and is a potent hypotensive agent. PAF acetylhydrolase (PAF-AH) hydrolyses and inactivates PAF and is seen to decrease in normotensive women. The role of platelet activating factor-acetylhydrolase (PAF-AH) in preeclampsia has been investigational so far. Few studies done have shown a positive association of elevated levels of PAF-AH in preeclamptic women.What do the results of this study add? Our study aimed to determine the activity of PAF-AH in maternal plasma of PE patients versus normal pregnancy and plasma PAF-AH mRNA expression to know the aberration of PAF-AH activity at the level of the gene. We found that plasma PAF-AH activity among preeclamptics was significantly higher than in the controls with a possible role in early-onset preeclampsia (<32 weeks), in the Indian population. This marker has never been studied in this population earlier. The results of our study re-emphasised its role in the pathogenesis of preeclampsia.What are the implications of these findings for clinical practice and/or further research? Such studies are important to not only give us a greater understanding of the various pathways involved in this multifactorial dreaded condition, but can also offer us a marker for early identification of women at risk. Recently, PAF-AH inhibitors like Darapladib has been tested as a therapeutic option in atherosclerosis. After studying the role of PAF-AH in the pathogenesis of PE, PAF-AH inhibitors may be used as a therapeutic tool in the future in PE.

Calcific Aortic Valve Stenosis and Atherosclerotic Calcification.

PURPOSE OF REVIEW: This review summarizes the pathophysiology of calcific aortic valve stenosis (CAVS) and surveys relevant clinical data and basic research that explain how CAVS arises. RECENT FINDINGS: Lipoprotein(a) [Lp(a)], lipoprotein-associated phospholipase A2 (Lp-PLA2), oxidized phospholipids (OxPL), autotaxin, and genetic driving forces such as mutations in LPA gene and NOTCH gene seem to play a major role in the development of CAVS. These factors might well become targets of medical therapy in the coming years. CVAS seems to be a multifactorial disease that has much in common with coronary artery disease, mainly regarding lipidic accumulation and calcium deposition. No clinical trials conducted to date have managed to answer the key question of whether Lp(a) lowering and anti-calcific therapies confer a benefit in terms of reducing incidence or progression of CAVS, although additional outcome trials are ongoing.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

Increased plasma lipoprotein-associated phospholipase A2 levels are associated with coronary slow flow.

OBJECTIVE: Coronary slow flow (CSF) is characterized by delayed opacification of distal epicardial coronary arteries without significant coronary stenosis. In addition, The changes of lipoprotein-associated phospholipase A2 (Lp-PLA2) as a significant predictive factor for CSF remain controversial. The study aims to investigate the association between plasma Lp-PLA2 and CSF. METHODS: In this retrospective study, 170 consecutive patients who underwent coronary angiography were enrolled in Beijing Anzhen Hospital from January 2017 to September 2019, and were divided into CSF group and normal control groups. According to coronary blood flow rate measured by the thrombolysis in myocardial infarction frame count (TFC) method, CSF was defined as TFC > 27. Serum Lp-PLA2 levels were measured in an enzyme-linked immunosorbent assay. RESULTS: Lp-PLA2 levels were higher in the CSF group than in the control group (288.6 ± 50.3 versus 141.9 ± 49.7, P < 0.001) and were significantly correlated with the mean coronary artery thrombolysis in myocardial infarction (TIMI) frame count (r = 0.790, P<0.001). Logistic regression analysis showed that high Lp-PLA2 was independently associated with CSF after adjustment for conventional risk factors (OR = 1.040, CI = 1.022-1.059, P<0.001). Male sex (OR = 2.192, CI = 1.161-4.140, P = 0.016) and hypertension (OR = 1.965, CI = 1.034-3.736, P = 0.039) were also CSF risk factors. Receiver-operating characteristic curve (ROC) analysis showed that Lp-PLA2 levels can predict CSF severity; the predictive power was higher than the other risk factors. CONCLUSION: Our study demonstrated that patients with CSF had higher circulating levels of Lp-PLA2 than normal controls. After adjustment for potential confounders, increased Lp-PLA2 was independently associated with presence of CSF.

The relationship of lipoprotein-associated phospholipase A2 activity with the seriousness of coronary artery disease.

BACKGROUND: The level of lipoprotein-associated phospholipase A2 (LP-PLA2) in serum is independently correlated to coronary artery diseases (CAD). The aim of the study was to determine whether LP-PLA2 activity is positively associated with the seriousness of CAD. METHODS: Amount to 1056 patients suspected of having CAD underwent coronary angiography (CAG) to determine the seriousness of CAD. According to the amount of diseased coronary branches, the 1056 patients were split into three groups: single-vessel stenosis group, multiple-vessels stenosis group (> or = 2 diseased coronary branches),and control group (no diseased coronary branches). According to CAG results, electrocardiography, cardiac biomarker, and clinical presentation, all patients were split into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina (SA), and control groups (excluding CAD). The activity of LP-PLA2 was compared statistically among the subgroups. Receiver operating characteristic analysis was applied to investigate the role of LP-PLA2 in evaluating the presence and seriousness of CAD. RESULTS: The level of LP-PLA2 increased in line with the number of diseased coronary branches. The levels of LP-PLA2 in the AMI and UA groups were observably higher when compared with the control and SA groups. LP-PLA2 had 75.6% sensitivity and 67.3% specificity for recognizing CAD, and 53.0% sensitivity and 80.3% specificity for recognizing severe coronary artery lesions. CONCLUSION: The activity of LP-PLA2 is positively correlated to the seriousness of CAD.

Oxidized LDL induces procoagulant profiles by increasing lysophosphatidylcholine levels, lysophosphatidylethanolamine levels, and Lp-PLA2 activity in borderline hypercholesterolemia.

BACKGROUND AND AIMS: The increased risk of cardiovascular disease under hypercholesterolemia is due to associations between oxidized low-density lipoprotein (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and between ox-LDL and coagulant profiles. We investigated the impact of different ox-LDL levels on coagulation time and plasma metabolomes in subjects with borderline hypercholesterolemia. METHODS AND RESULTS: One hundred thirty-one subjects with borderline hypercholesterolemia (serum cholesterol ≥200 mg/dL) were divided into low ox-LDL (n = 66) and high ox-LDL (n = 65) groups. After adjusting for confounding factors, the high ox-LDL group exhibited a significantly decreased activated partial thromboplastin time (aPTT) and prothrombin time (PT) and increased Lp-PLA2 activity. Compared to the low ox-LDL group, the high ox-LDL group exhibited significantly increased intensities of 17 lysophosphatidylcholines (lysoPCs) and 7 lysophosphatidylethanolamines (lysoPEs). Ox-LDL was inversely correlated with aPTT and PT and positively correlated with Lp-PLA2 activity. Positive correlations were also found among ox-LDL, Lp-PLA2 activity, lysoPCs, and lysoPEs. LysoPCs and lysoPEs were inversely correlated with PT and aPTT. The identified plasma metabolites, including amino acids, fatty acid amides, acylcarnitines, and lysophospholipids, were significantly upregulated in the high ox-LDL group. CONCLUSION: High ox-LDL levels may be involved in the development of a procoagulant state in subjects with borderline hypercholesterolemia by increasing Lp-PLA2 activity and lysoPC and lysoPE levels.

Lipoprotein-Associated Phospholipase A2 in Cardiac Disease: a Potential Early Biomarker of Unstable Coronary Artery Disease.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a serine lipase that deteriorates the stability of atherosclerotic plaques. This study aims to investigate Lp-PLA2 activity and its diagnostic potential in the early period of acute coronary syndromes (ACS). METHODS: Two hundred sixty-two patients referred for acute chest pain within 6 hours of symptom onset were included. Among the candidates, 67 were diagnosed with ST-elevation myocardial infarction (STEMI) and 167 unstable angina (UA). The STEMI patients were divided into cardiac troponin I (cTnI) negative and cTnI positive groups according to the cTnI values at admission. As control, 184 stable coronary artery disease (CAD) patients were also enrolled. Blood samples were collected immediately after admission. The levels of Lp-PLA2 activity and lipids were measured. The diagnostic value of Lp-PLA2 was determined based on receiver operating characteristic curves. RESULTS: Lp-PLA2 activity levels of STEMI and UA groups were dramatically higher than that in CAD group. However, Lp-PLA2 values showed no marked difference between STEMI and UA groups. Similar results were obtained between cTnI negative and positive groups among STEMI patients. In the three groups combined, there was a significant correlation between LDL-C concentration and Lp-PLA2 activity. In the ACS group, the area under the curve was 0.719 (95% CI: 0.671 - 0.768), and the optimal Lp-PLA2 cutoff value was 306.4 U/L, with a sensitivity of 67% and specificity of 69%. CONCLUSIONS: Lp-PLA2 activity was significantly elevated in the early stage of ACS. The obtained statistical data suggest that Lp-PLA2 activity may represent a novel early marker of unstable coronary disease.

Association of Carotid Plaque and Serum Lipoprotein-Associated Phospholipase A2 (LP-PLA2) with Postoperative Delirium in Geriatric Patients Undergoing Hip Replacement: A Prospective Cohort Study.

BACKGROUND The aim of this study was to investigate the relationships among carotid plaque (CP), serum lipoprotein-associated phospholipase (LP-PLA2), and POD in elderly patients. MATERIAL AND METHODS Sixty-two elderly patients undergoing hip replacement with spinal-epidural anesthesia were divided into CP and non-CP groups based on the preoperative presence or absence of carotid atherosclerotic plaques, as assessed by ultrasound. POD was diagnosed by means of the Confusion Assessment Method (CAM). Blood samples were collected (preoperatively, postoperatively, and postoperative day 2) for the assessment of serum LP-PLA2 by enzyme-linked immunosorbent assay. The CP group was further divided into POD and no-POD subgroups based on the occurrence of POD. RESULTS The incidence of POD was higher in the CP group than in the non-CP group (P0.05), it was higher in the CP group than in the non-CP group postoperatively and on postoperative day 2 (P0.05), but was significantly higher in the POD subgroup than in the no-POD subgroup on postoperative day 2 (P<0.05). Furthermore, the LP-PLA2 level on postoperative day 2 was an independent risk factor for POD (odds ratio: 1.03, 95% confidence interval: 1.00-1.07). CONCLUSIONS The preoperative presence of carotid plaque is closely associated with a higher incidence of POD. The potential mechanism may involve the increased expression of LP-PLA2 in the serum, which can lead to plaque destabilization and subsequent inflammatory cascades.

Effects of canola or olive oil on plasma lipids, lipoprotein-associated phospholipase A2 and inflammatory cytokines in patients referred for coronary angiography.

BACKGROUND: The potential cardioprotective benefits of olive oil (OO) and canola oil (CO) consumption have been shown in some studies. The present study compared the effects of CO and OO on plasma lipids, some inflammatory cytokines, and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity in patients undergoing coronary angiography. METHODS: The current randomized, controlled, parallel-arm, clinical trial involved 48 patients (44 men and 4 women, aged 57.63 ± 6.34 years) with at least one classic cardiovascular risk factor (hypertension, dyslipidemia, or diabetes) who referred for coronary angiography. Patients were randomly divided into two groups and received 25 mL/day refined olive oil (n = 24) or canola oil (n = 24) for 6 weeks. Plasma lipids, some selected inflammatory markers, and Lp-PLA2 levels were measured at baseline and after the intervention. RESULTS: CO consumption produced a significant reduction in plasma Lp-PLA2 mass (- 0.97 ± 1.84 vs. 0.34 ± 1.57 ng/mL, p = 0.008 for CO and OO, respectively), whereas the mean changes in interleukine-6 concentration were significantly lower after OO consumption compared with CO (- 9.46 ± 9.46 vs. -0.90 ± 6.80 pg/mL, p = 0.008 for OO and CO, respectively). After 6 weeks of intervention, no significant changes were observed in plasma Lp-PLA2 activity, complement C3, C4, or lipid profiles in the two intervention groups. CONCLUSIONS: Comparing the two vegetable oils in subjects with cardiovascular risk factors showed that the consumption of olive oil is more effective in reducing the level of inflammatory cytokine interleukine-6, whereas canola oil was more effective in lowering Lp-PLA2 levels; however, this finding should be interpreted with caution, because Lp-PLA2 activity did not change significantly. TRIAL REGISTRATION: IRCT20160702028742N5 at www.irct.ir (04/19/2019).

Comparison of serum Lp-PLA2 levels in ischemic stroke patients with H-type hypertension or non-H-type hypertension.

BACKGROUND: Increased serum Lp-PLA2 levels have been reported in patients who experienced an ischemic stroke; however, the relationship between Lp-PLA2 and H-type hypertension in patients with ischemic stroke remains unclear. METHODS: In the present study, we investigated the correlation between serum Lp-PLA2 and H-type hypertension in patients with ischemic stroke. A total of 135 patients who experienced acute ischemic stroke were enrolled in Tianjin Huanhu Hospital during October 2015 to May 2016. The demographic characteristics of the patients were collected, and biochemical parameters were detected. RESULTS: Among the 135 patients, 111 patients had essential hypertension, including 41 patients with H-type hypertension and 70 with non-H-type hypertension. There were higher proportions of males and patients with diabetes mellitus in the H-type hypertension group compared with the non-H-type hypertension group (P < .05). Lp-PLA2, glucose, and LDL-C levels were higher in the H-type hypertension group than in the non-H-type hypertension group (P < .05). Multivariate logistic regression showed that Lp-PLA2 levels >208.46 mg/L were independently associated with H-type hypertension in patients with ischemic stroke (OR: 2.560, 95% CI: 1.085-6.040, P = .032). The area under the ROC curve of Lp-PAL2 levels in the H-type hypertension group was 0.665 (95% CI: 0.561-0.768, P = .004). CONCLUSION: Synergetic effects of H-type hypertension and Lp-PLA2 levels were noted in the pathogenesis of ischemic stroke.