Lipoprotein-associated Phospholipase A2 Activity Research Articles

Effect of Statin Treatment on Lipoprotein-Associated Phospholipase A2 Mass and Activity: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

The goal of this meta-analysis was to establish whether statin treatment reduces Lp-PLA2 mass concentration and/or activity. PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases were searched using MESH terms and keywords. Randomized controlled trials (RCT) with either parallel or cross-over design examining the effect of statins on Lp-PLA2 mass and/or activity were included in meta-analysis. Out of 256 articles, 10 RCT were selected for meta-analysis. Statin therapy significantly reduced both Lp-PLA2 mass (WMD -44.46 ng/mL; 95%CI -59.01, -29.90; p < 0.001; I2 = 93%) and activity (WMD -39.37 nmol/min/mL; 95%CI -69.99, -8.75; p = 0.01; I2 = 100%). The sensitivity analysis was robust for Lp-PLA2 mass and was also positive for two studies concerning Lp-PLA2 activity. Statin therapy significantly reduced both Lp-PLA2 mass and activity.

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

BackgroundLipoprotein-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). MethodsThe 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. ResultsCompared 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. ConclusionsThis 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.

Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant associations across 6 traits-E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin-that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Novel Plasma Biomarkers Associated with Future Peripheral Atherosclerotic Disease and Abdominal Aortic Aneurysm-Insights from Contemporary Prospective Studies from the Malmö Diet and Cancer Study.

The potential utility of inflammatory and hemodynamic plasma biomarkers for the prediction of incident lower extremity arterial disease (LEAD), carotid artery stenosis (CAS), isolated atherosclerotic disease without concomitant abdominal aortic aneurysm (AAA), and isolated AAA without concomitant atherosclerotic disease has not yet been integrated in clinical practice. The main objective of this prospective study was to find predictive plasma biomarkers for cardiovascular disease and to evaluate differences in plasma biomarker profiles between asymptomatic and symptomatic CAS, as well as between isolated atherosclerotic disease and isolated AAA. Blood samples collected at baseline from participants in the prospective Malmö Diet and Cancer study (MDCS) cardiovascular cohort (n = 5550 middle-aged individuals; baseline 1991-1994) were used for plasma biomarker analysis. Validation of each incident cardiovascular diagnosis was performed by random sampling. Cox regression analysis was used to calculate hazard ratios (HRs) per one standard deviation increment of each respective log-transformed plasma biomarker with 95% confidence intervals (CI). Adjusted lipoprotein-associated phospholipase A2 (Lp-PLA2) activity (HR 1.33; CI 1.17-1.52) and mass (HR 1.20; CI 1.05-1.37), C-reactive protein (CRP) (HR 1.55; CI 1.36-1.76), copeptin (HR 1.46; CI 1.19-1.80), N-terminal pro-B-type natriuretic peptide (N-BNP) (HR 1.28; 1.11-1.48), and cystatin C (HR 1.19; 95% 1.10-1.29) were associated with incident symptomatic LEAD. Adjusted N-BNP (HR 1.59; CI 1.20-2.11), mid-regional proadrenomedullin (HR 1.40; CI 1.13-1.73), cystatin C (HR 1.21; CI 1.02-1.43), and CRP (HR 1.53; CI 1.13-1.73) were associated with incident symptomatic but not asymptomatic CAS. Adjusted HR was higher for Lp-PLA2 (mass) for incident isolated AAA compared to for isolated atherosclerotic disease. Plasma biomarker profile data support that subclinical vascular inflammation and cardiovascular stress seem to be relevant for the development of atherosclerotic disease and AAA.

The Food Compass Score is Negatively Related to the Activity of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in Healthy Adults.

The Food Compass Score is Negatively Related to the Activity of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in Healthy Adults.

Higher serum Lp-PLA2 is associated with cognitive impairment in Parkinson's disease patients.

To explore the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cognitive impairment in Parkinson's disease (PD-CI). A case-control study involving 100 hospitalized PD patients and 60 healthy controls was carried out. Serum Lp-PLA2 level was detected by automatic biochemical analyzer. Based on whether Parkinson's patients have cognitive impairment, PD patients were subdivided to analyze the clinical value of Lp-PLA2. Relationship between Lp-PLA2 and PD-CI risk was analyzed by logistic regression. Diagnostic value of Lp-PLA2 in PD-CI patients was investigated using receiver's operator characteristic curves. The levels of serum Lp-PLA2 activity in Parkinson's disease with normal cognition (PD-NC) and PD-CI patients were significantly higher than those in healthy controls (HCs), respectively. Furthermore, compared to the PD-NC group, the serum Lp-PLA2 activity level was significantly higher in PD-CI patients. Multivariable logistic regression analysis indicated that higher Lp-PLA2 level was an independent risk factor for PD patients with cognitive impairment. Moreover, the area under the efficacy curve of Lp-PLA2 for predicting PD-CI is 0.659. Our study shows that higher levels of Lp-PLA2 activity in PD patients are associated with the risk of developing cognitive impairment. Therefore, given the wide availability, safety, and convenience of monitoring serum Lp-PLA2 activity, it may serve as an early biomarker for cognitive impairment in PD patients.

Abstract WMP108: Association of Circulating Markers of Inflammation to Baseline and Progression of Carotid Artery Intima-Media Thickness

Introduction: There is strong evidence of an association between systemic inflammation and ischemic stroke. While the exact mechanism underpinning that association is unclear, there is evidence that systemic inflammation contributes to atherosclerosis progression. One measure of subclinical atherosclerosis, carotid artery intima-media thickness (CIMT), is independently associated with ischemic stroke. Because of mixed data on the association between systemic inflammation and CIMT progression, we sought to evaluate this relationship in a prospective cohort study. Hypothesis: Baseline elevation in circulating markers of inflammation are associated with CIMT progression in the Framingham Heart Study cohort. Methods: Among participants with two carotid ultrasounds (n=2350) about 10 years apart, 2,269 had data available on circulating markers of inflammation. Multivariable linear regression was used to assess the association between circulating markers of inflammation with internal carotid artery (ICA) CIMT. Analyses were adjusted for age, sex, hypertension, diabetes, APOE4, and body mass index (BMI), and baseline IMT. Results: Participants with higher baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6), intracellular adhesion molecule, p-selectin, lipoprotein-associated phospholipase A2 (LPa) activity, homocysteine, isoprostanes (ISO), and CD40 ligand had significantly higher rates of ICA IMT progression adjusting for age, sex, hypertension, diabetes, APOE4, BMI, and baseline ICA IMT (Table). Participants with higher levels of CRP, IL-6, OPG, p-selectin, LPa activity, and ISO had greater follow-up ICA IMT adjusting for age, sex, hypertension, diabetes, APOE4, and BMI. Conclusion: Specific markers of inflammation are associated with increased later life carotid intima media thickening and carotid atherosclerosis progression, supporting a link between systemic inflammation and cerebrovascular disease.

Lipoprotein-associated phospholipase A2 predicts cardiovascular death in patients on maintenance hemodialysis: a 7-year prospective cohort study

BackgroundCardiovascular diseases (CVD) is the leading cause of death among maintenance hemodialysis patients, with dyslipidemia being a prevalent complication. The paradoxical relationship between cardiovascular outcomes and established lipid risk markers, such as low-density lipoprotein cholesterol (LDL-C), complicates lipid management in this population. This study investigated Lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging biomarker known for its proinflammatory and proatherogenic properties, as a potential cardiovascular prognostic marker in this cohort. In this context, the association between Lp-PLA2 levels and cardiovascular outcomes was evaluated, with the aim to facilitate more accurate stratification and identification of high-risk individuals.MethodsFrom August 2013 to January 2014, 361 hemodialysis patients were prospectively enrolled. Lp-PLA2 activity and laboratory measures at baseline were quantified. Comorbidities and medications were recorded. All patients were followed until the end of April, 2022. The individual and combined effects of Lp-PLA2 activity and LDL-C on patient outcomes were examined. The association between Lp-PLA2 activity and all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACEs) was analyzed.ResultsThe median Lp-PLA2 activity was 481.2 U/L. In subjects with Lp-PLA2 activity over 481.2 U/L, significantly higher total cholesterol (4.89 vs. 3.98 mmol/L; P < 0.001), LDL-C (3.06 vs. 2.22 mmol/L; P < 0.001), and apolipoprotein B (0.95 vs. 0.75 mmol/L; P < 0.001) were observed. Over a median follow-up of 78.1 months, 182 patients died, with 77 cases identified as cardiovascular death, 88 MACEs happened. Cardiovascular mortality and MACEs, but not all-cause mortality, were significantly increased in the high Lp-PLA2 group. Cox regression analyses showed that high Lp-PLA2 activity was associated with cardiovascular mortality and MACE occurrence. After comprehensive adjustment, high Lp-PLA2 activity was independently associated with cardiovascular mortality(as a dichotomous variable: HR:2.57, 95%CI:1.58,4.18, P < 0.001; as a continuous variable: HR:1.25, 95%CI:1.10,1.41, P = 0.001) and MACEs(as a dichotomous variable: HR:2.17, 95%CI:1.39,3.40, P = 0.001; as a continuous variable: HR:1.20, 95%CI:1.07,1.36, P = 0.002). When participants were grouped by median Lp-PLA2 activity and LDL-C values, those with high Lp-PLA2 and low LDL-C had the highest CV mortality. The addition of Lp-PLA2 significantly improved reclassification (as a dichotomous variable NRI = 42.51%, 95%CI: 5.0%,61.33%; as a continuous variable, NRI = 33.32%, 95% CI: 7.47%,56.21%).ConclusionsHigh Lp-PLA2 activity is an independent risk factor for cardiovascular mortality and MACEs occurrence in patients on hemodialysis. The combined measures of Lp-PLA2 and LDL-C help to identify individuals with a higher risk of cardiovascular death.

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.

Associations between healthy food groups and platelet-activating factor, lipoprotein-associated phospholipase A2 and C-reactive protein: a cross-sectional study.

To investigate the association between pro-inflammatory markers platelet-activating factor (PAF), lipoprotein-associated phospholipase A2 (Lp-PLA2), hsCRP, and intake of core food groups including fruit, cruciferous and other vegetables, grains, meat and poultry, fish and seafood, nuts and legumes, and dairy. A cross-sectional study was conducted. 100 adults (49 ± 13 years, 31% male) with variable cardiovascular disease risk were recruited. Data were collected in 2021 and 2022. Fasting PAF, Lp-PLA2 activity, hsCRP and usual dietary intake (via a validated food frequency questionnaire) were measured. Intake of foods were converted into serves and classified into food groups. Correlations and multiple regressions were performed with adjustment for confounders. A one-serve increase in cruciferous vegetables per day was associated with 20-24% lowerPAFlevels. An increase of one serve per day of nuts and legumes was associated with 40% lowerhsCRPlevels. There were small correlations with PAF and Lp-PLA2 and cheese, however, these were not significant at the Bonferroni-adjusted P < 0.005 level. The lack of associations between PAF and Lp-PLA2 and other healthy foods may be due to confounding by COVID-19 infection and vaccination programs which prevents any firm conclusion on the relationship between PAF, Lp-PLA2 and food groups. Future research should aim to examine the relationship with these novel markers and healthy food groups in a non-pandemic setting.

Excessive daytime sleepiness, morning tiredness, loud snoring, and prognostic biomarkers in patients with chronic coronary syndrome

Abstract Background Sleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established. Methods Associations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-relatedsymptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring [LS]; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac Troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A2 activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models with never/rarely as reference. Results EDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03-1.10], always 1.15 [1.10-1.21]), GDF-15 (often 1.03 [1.01-1.06], always 1.07 [1.03-1.11]), NT-proBNP (always 1.22 [1.12-1.33]), and hs-cTnT (always 1.07 [1.01-1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01-1.09], always 1.09 [1.04-1.15]), and GDF-15 (always 1.06 [1.03-1.10]). LS was associated with decreased levels of NT-proBNP (sometimes 0.94 [0.90-0.98], often 0.92 [0.87-0.97], always 0.87 [0.81-0.92]), and hs-cTnT (always 0.94 [0.91-0.98]). Conclusions In patients with CCS, gradually increased frequency of SRBD-related symptoms, such as EDS, MT, and LS, were independently and consistently associated with varying levels of IL-6, GDF-15, and NT-proBNP, each reflecting distinct pathophysiological pathways or underlying pathology of cardiovascular disease. Figure 1. Adjusted analysis of associations between sleep-related breathing disorder-related questions and geometric mean ratios of prognostic biomarkersFigure 1A.Excessive Daytime SleepinessFigure 1B.Loud Snoring

Normolipidic diet containing deep-fried saturated and unsaturated fatty acids rich edible oils promotes metabolic dysregulation and inflammatory microenvironment in Wistar rats.

Deleterious health impacts of high dietary intake of deep-fried edible oils have been reported however, their health impacts at normal dietary levels are yet to be evaluated. This study investigated the influence of prolonged consumption of thermally oxidised long-chain saturated and unsaturated edible oils on metabolic dysregulation and inflammation. The thermally oxidised oils used in the study possess higher p-anisidine values and free fatty acid contents compared to unoxidised oils. Fourier transform infrared spectroscopy and fatty acid methyl ester analysis confirmed the presence of free fatty acids, hydroperoxides, and aldehydes, formed during thermal oxidation. The study analysed the effects of dietary intake of 5% sunflower oil, palm oil, and their thermally-oxidised forms in male Wistar rats for six months. Unoxidised and thermally oxidised palm oil-fed animals experienced metabolic syndrome with obesity-associated inflammatory changes. However, sunflower oil-fed animals exhibited increased inflammation, as evidenced by enhanced C-reactive protein, IL-6, and lipoprotein-associated phospholipase A2 activity and hepatosteatosis condition. This study indicates that prolonged consumption of thermally oxidised oil leads to the dysregulation of carbohydrate and lipid metabolism andpromotes inflammatory microenvironment in Wistar rats that may contribute to metabolic syndrome associated with obesity and hepatic steatosis.

Excessive daytime sleepiness, morning tiredness, and prognostic biomarkers in patients with chronic coronary syndrome

BackgroundSleep-related breathing disorders (SRBD) are related to cardiovascular outcomes in patients with chronic coronary syndrome (CCS). Whether SRBD-related symptoms are associated with prognostic biomarkers in patients with CCS is not established. MethodsAssociations between frequency (never/rarely, sometimes, often, always) of self-reported SRBD-related symptoms (excessive daytime sleepiness [EDS]; morning tiredness [MT]; loud snoring; multiple awakenings/night; gasping, choking, or apnea when asleep) and levels of biomarkers related to cardiovascular prognosis (high-sensitivity C-reactive protein [hs-CRP], interleukin 6 [IL-6], high-sensitivity cardiac troponin T [hs-cTnT], N-terminal pro B-type natriuretic peptide [NT-proBNP], cystatin C, growth differentiation factor 15 [GDF-15] and lipoprotein-associated phospholipase A2 activity) were assessed at baseline in 15,640 patients with CCS on optimal secondary preventive therapy in the STABILITY trial. Cross-sectional associations were assessed by adjusted linear regression models testing for trends with the never/rarely category serving as reference. ResultsEDS was associated (geometric mean ratio, 95% confidence interval) with increased levels of IL-6 (often 1.07 [1.03–1.10], always 1.15 [1.10–1.21]), GDF-15 (often 1.03 [1.01–1.06], always 1.07 [1.03–1.11]), NT-proBNP (always 1.22 [1.12–1.33]), and hs-cTnT (always 1.07 [1.01–1.12]). MT was associated with increased levels of IL-6 (often 1.05 [1.01–1.09], always 1.09 [1.04–1.15]), and GDF-15 (always 1.06 [1.03–1.10]). All symptoms were to some degree associated with higher levels of hs-CRP and loud snoring was also associated with decreased levels of NT-proBNP and hs-cTnT. ConclusionsIn patients with CCS, stepwise increased frequency of SRBD-related symptoms, such as EDS and MT, were associated with gradually higher levels of IL-6 and GDF-15, each reflecting distinct pathophysiological pathways.

Traditional and novel risk factors for incident aortic stenosis in community-dwelling older adults

ObjectivesCalcific aortic stenosis (AS) is the most common valvular disease in older adults, yet its risk factors remain insufficiently studied in this population. Such studies are necessary to enhance understanding...

Phenotypic changes in low-density lipoprotein particles as markers of adverse clinical outcomes in COVID-19.

Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes. Individuals hospitalized due to COVID-19 (n=40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured. In a consecutive series of cases (n=13), LDL was isolated by gradient ultracentrifugation from D0 and D6 and was quantified by lipidomic analysis. Association between clinical outcomes and LDL phenotypic changes was investigated. In the first 30days, 42.5% of participants died due to Covid-19. The serum ox-LDL increased from D0 to D6 (p<0.005) and decreased at D30. Moreover, individuals who had an ox-LDL increase from D0 to D6 to over the 90th percentile died. The plasma Lp-PLA2 activity also increased progressively from D0 to D30 (p<0.005), and the change from D0 to D6 in Lp-PLA2 and ox-LDL were positively correlated (r=0.65, p<0.0001). An exploratory untargeted lipidomic analysis uncovered 308 individual lipids in isolated LDL particles. Paired-test analysis from D0 and D6 revealed higher concentrations of 32 lipid species during disease progression, mainly represented by lysophosphatidyl choline and phosphatidylinositol. In addition, 69 lipid species were exclusively modulated in the LDL particles from non-survivors as compared to survivors. Phenotypic changes in LDL particles are associated with disease progression and adverse clinical outcomes in COVID-19 patients and could serve as a potential prognostic biomarker.

Lipoprotein-Associated Phospholipase A2 Activity as Potential Biomarker of Vascular Dementia.

A wealth of evidence suggests that Lipoprotein-associated phospholipase A2 (Lp-PLA2) plays a relevant role in atherogenesis and inflammation, which in turn are associated with the risk of developing dementia. The aim of this study was to evaluate whether serum Lp-PLA2 activity might be an early and/or late biomarker for different forms of dementia. Serum Lp-PLA2 activity was assessed in older patients with mild cognitive impairment (MCI, n = 166; median clinical follow-up = 29 months), Late-Onset Alzheimer's disease (LOAD, n = 176), vascular dementia (VAD, n = 43), dementia characterized by an overlap between LOAD and VAD (AD-VAD MIXED dementia) (n = 136), other dementia subtypes (n = 45), and cognitively normal controls (n = 151). We found a significant trend towards higher levels of Lp-PLA2 activity in VAD compared with the other groups (ANOVA, p = 0.028). Similarly, Lp-PLA2 activity was greater in MCI converting to VAD compared with those that did not or did convert to the other types of dementia (ANOVA, p = 0.011). After adjusting for potential confounders, high levels of Lp-PLA2 activity were associated with the diagnosis of VAD (O.R. = 2.38, 95% C.I. = 1.06-5.10), but not with other types of dementia. Our data suggest that increased serum Lp-PLA2 activity may represent a potential biomarker for the diagnosis of VAD.

Mediation of Systemic Inflammation on Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke.

Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation. Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset. Insulin resistance was determined by using the homeostasis model assessment for insulin resistance (HOMA-IR) method. hs-CRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) activity were measured at baseline. The primary outcome was stroke recurrence, and other outcomes included composite vascular events, mortality, and poor functional outcome (modified Rankin Scale score, 3-6). Multivariable Cox or logistic regression analyses were performed to estimate the association between HOMA-IR and the study outcomes. A mediation analysis was performed to examine the relationship between insulin resistance and the study outcomes mediated by systemic inflammation. Among a total of 3808 nondiabetic patients with ischemic stroke who were included in the study, the median HOMA-IR was 1.79 (interquartile range, 1.05-2.97). After adjustments for potential confounders, higher HOMA-IR quartiles were associated with higher risks of stroke recurrence, ischemic stroke, and composite vascular events, especially in the large artery atherosclerosis subtype. hs-CRP partially mediated the association between the HOMA-IR index and the prognosis of ischemic stroke (mediation proportion, 5.9% for stroke recurrence and 7.5% for composite vascular events). No evidence of Lp-PLA2 activity mediating the association of insulin resistance with stroke outcomes was observed. Our study found that insulin resistance was associated with poor clinical outcomes in nondiabetic patients with ischemic stroke, which was partially mediated by hs-CRP with a modest amount.

Changes in Lp-PLA 2 are associated with elevated alanine aminotransferase levels: A nested case-control study in a three-year prospective cohort

Background/Aim: Elevation in liver enzymes and hepatic fat may indicate a higher susceptibility to cardiovascular disease (CVD). This research sought to find anthropometric/biochemical variables significantly related to the alanine aminotransferase (ALT) increase in healthy populations. Methods: Nine hundred healthy subjects were included in a 3-year prospective cohort study. The initial screening revealed that 538 were found to be nondiabetic (fasting glucose &lt; 126 mg/dL) and had normal ALT levels. Among them, 79 individuals with slightly elevated ALT levels after three years were assigned to the elevated ALT group. Of the remaining 459 participants, 241 subjects matched to the increased ALT group were the control group. Results: After three years of follow-up, individuals with elevated ALT showed notably higher aspartate aminotransferase (AST), ALT, gamma-glutamyl-transferase (g-GT), high sensitivity C-reactive protein (hs-CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2 ) activity, oxidised low-density lipoprotein (ox-LDL), urinary 8-epi-prostaglandin F2a (8-epi-PGF2a) levels and brachial-ankle pulse wave velocity (ba-PWV) in comparison to the control group. Changes (D) in ALT showed a positive correlation with D AST, D gammaGT, D hs-CRP, D Lp-PLA2 activity, D ox-LDL, D urinary 8-epi-PGF2a and D ba-PWV. Furthermore, a direct positive link was observed between the D Lp-PLA2 activity and D AST, D ox-LDL and D ba-PWV. Conclusion: Increased Lp-PLA2 activity and other CVD risk indicators were observed to have a pronounced association with elevated ALT levels. This mild ALT elevation could potentially contribute to chronic low-grade inflammation.

Značaj određivanja fosfolipaze A2 udružene sa lipoproteinom kod pacijenata sa antifosfolipidnim sindromom

Introduction: Lipoprotein-associated Phospholipase A2 (Lp-PLA2) is an essential mediator of inflammation, which has a vital role in inflammatory diseases of the vascular system. It has a significant role in the occurrence of thrombosis, the main manifestation of antiphospholipid syndrome. Aim: To investigate the values of Lp-PLA2 in patients with antiphospholipid syndrome (APS) regarding the distribution of all data, age, gender, disease duration, and type of disease. Material and methods: This experimental work analyzed samples of 74 patients diagnosed with APS. Concentrations of Lp-PLA2 were determined by ELISA (Enzyme-Linked Immunosorbent Assay) method. Results: The activity of Lp-PLA2 was higher than the recommended referent values. There is no significant difference in the values of Lp-PLA2 concerning patients' age, gender, disease duration, and type of disease (p &gt; 0,05). There was a statistically significant correlation between the patients' age and the disease duration (rho = 0.359; p = 0.002). Conclusion: Elevated values of Lp-PLA2, so as the correlation between the years of age and duration of APS can be important information to doctors in the appropriate treatment of these patients. It is up to future prospective studies to confirm the significance of Lp-PLA2 determination in patients with APS.

101 LIPOPROTEIN ASSOCIATED PHOSPHOLIPASE A2 IN STEMI VS NSTE-ACS PATIENTS: A MARKER OF CARDIOVASCULAR ATHEROSCLEROTIC RISK RATHER THAN THROMBOSIS

Abstract Background The precise role of Lipoprotein associated phospholipase A2 (Lp-PlA2) in the pathogenesis of acute coronary syndromes (ACS) and in the prediction of future cardiovascular events is still debated. So far, few data exist on the variations of Lp-PlA2 activity in ACS and especially in NSTE-ACS vs STEMI patients, where thrombotic and atherosclerotic mechanisms could play a differential role. The aim of the present study was, then, to compare Lp-PlA2 activity according to the type of ACS presentation. Methods A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed on blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. Results We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p=0.05), displayed a lower rate of hypertension (p=0.002), previous MI (p=0.001) and PCI (p=0.01) and used less frequently statins (p=0.01) and clopidogrel (p=0.02). White blood cells and admission glycemia were increased in STEMI (p=0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p&amp;lt;0.001) and lower TIMI flow (p=0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132±41.1 vs 154.6 ±40.9 nmol/min/mL, p=0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs 57%, p=0.02, adjusted OR[95% CI]=0.20[0.06-0.68], p=0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r=0.47, p&amp;lt;0.001), but not with inflammatory biomarkers. Conclusion The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, and with recurrent cardiovascular events, therefore potentially representing a marker of a more aggressive atherosclerotic disease and higher cardiovascular burden and risk.