Baseline Myeloperoxidase Levels Research Articles

Myeloperoxidase: A Circulating Marker of Inflammation and Tooth Infection

BackgroundAtherosclerotic cardiovascular disease and tooth infection are common in primary care, and both significantly reduce quality of life. Our study aimed to examine signs of vascular inflammation associated with loss of tooth vitality before and after a single tooth extraction. MethodsAn observational cohort study was performed with adults who had a nonvital tooth and an indicated desire for tooth extraction. Concentrations of total cholesterol, high-density lipoprotein-cholesterol, high-sensitivity C-reactive protein (hs-CRP), myeloperoxidase (MPO), and troponin T were measured in venous blood serum or plasma at baseline and 6-weeks after tooth extraction. ResultsCirculating hs-CRP levels were > 3 mg/dL in 15 participants (68.2%) and MPO levels were > 350 pmol/L in 9 (40.9%) of 22 participants at baseline. After tooth extraction (n = 18), MPO levels decreased significantly compared with baseline (P < .00006) and hs-CRP levels moved directionally downward. The response rate for MPO was 88.9% (confidence interval: 65.1%-98.6%) from visit 1 to visit 2. Those with high MPO levels at baseline demonstrated larger reductions in MPO levels by visit 2 than those with lower baseline MPO levels (r = .81; P < .0001). A total of 13 individuals (72.2%) achieved MPO levels < 350 pmol/L and 11 (61.1%) achieved hs-CRP levels < 3 mg/dL at visit 2. Total cholesterol, high-density lipoprotein-cholesterol, and troponin T levels did not significantly change from visit 1 to visit 2. ConclusionA link between dental infection and circulating levels of inflammation was observed, suggesting that oral infection could be a risk factor for atherosclerotic cardiovascular disease.

Plasma Myeloperoxidase as a Potential Biomarker of Patient Response to Anti-Dementia Treatment in Alzheimer's Disease.

Myeloperoxidase (MPO), a neutrophil-derived pro-inflammatory protein, co-localizes with amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Anti-dementia treatment may facilitate efflux of Aβ and associated plaque proteins from the brain to the peripheral circulation, therefore providing potential biomarkers for the monitoring of donor response to drug treatment. We investigated the diagnostic utility of MPO as a biomarker of AD, and how anti-dementia treatment alters plasma MPO concentration. Thirty-two AD patients were recruited, and plasma collected pre-drug administration (baseline), and 1- and 6-months post-treatment. All patients received cholinesterase inhibitors (ChEIs). At baseline and 6 months, patients underwent neuropsychological assessment. Forty-nine elderly healthy individuals with normal cognitive status served as controls. Plasma MPO concentration was measured by ELISA. AD drug naïve patients had similar plasma MPO concentration to their control counterparts (p &gt; 0.05). Baseline MPO levels positively correlated with Neuropsychiatric Inventory score (r = 0.5080; p = 0.011) and carer distress (r = 0.5022; p = 0.012). Following 1-month ChEI treatment, 84.4% of AD patients exhibited increased plasma MPO levels (p &lt; 0.001), which decreased at 6 months (p &lt; 0.001). MPO concentration at 1 month was greatest in AD patients whose memory deteriorated during the study period (p = 0.028), and for AD patients with deterioration in Cornell assessment score (p = 0.044). Whereas baseline MPO levels did not differentiate between healthy and AD populations, baseline MPO positively correlated with initial Neuropsychiatric Inventory evaluation. Post-treatment, transient MPO upregulation in ChEI-treated patients may reflect worse therapeutic outcome. Further studies are required to assess the potential of plasma MPO as an AD therapeutic biomarker.

P5542Predictors of the risk of recurrent cardiovascular events in patients with unstable angina with conservative treatment strategy

Abstract Objective To identify independent predictors of the risk of recurrent cardiovascular events in patients (pts) with unstable angina (UA) in a conservative treatment strategy. Material and methods The study involved 236 patients with UA with low risk according to GRACE scale and conservative treatment strategy. The end points were: recurrent UA, myocardial infarction (MI), death. The mean age was 60.2±7.3 years. All pts were performed general blood analysis, determination of troponin I, BNP, C-reactive protein, myeloperoxidase, von Willebrand factor, fibrinogen, antithrombin III and also the performance of the thrombin generation test, aggregatogram on aggregometry Multiplate impedance and ECG, EchoCG, Holter ECG. Results Cardiovascular events developed in 104 (44%) pts during 5 years of follow-up, and in the first year of follow - up-in 58 people (24.6%), followed annually by 10–14% of events for the year. MI developed in 21 pts (8.9%), recurrent angina in 75 (31.8%) pts, 51 (21.6%) pts underwent coronary artery stenting, and 26 (11%) pts underwent coronary bypass surgery, 8 (3.4%) patients died. Having studied all the objective data of the observed patients, we concluded that independent predictors of the risk of recurrent cardiovascular events were: previous MI (RR=2,8; 95% CI 1,32–6,08; p=0,0028), type II Diabetes (RR=3,1; 95% CI 1,78- 5,37; p=0,0001), first-time angina pectoris (RR=3,7; 95% CI 2,68–5,85; p=0,001, smoking (RR=2,1; 95% CI 1,21–3,74; p=0,0129), baseline myeloperoxidase &gt;316 pmol/l (RR=3,1; 95% CI 1,29–4,74; p=0,029), high sensitive CRP &gt;3,8 g/l (RR=3,9; 95% CI 2, 44–6,14; p=0,0001), mean platelet volume &gt;9,6fl (RR=2,9; 95% CI 1,49–5,52; p=0,0006), area under the curve ADP- test AUC &gt;60 U (RR=3,4; 95% CI 2, 3–5,2; p=0,002). Conclusions Cardiovascular events developed in 44% of pts over 5 years of follow-up. Independent predictors of adverse outcomes in pts with UA with low risk according to GRACE scale were: previous MI, type II Diabetes mellitus, first-time angina pectoris, smoking, baseline myeloperoxidase levels&gt;316 pmol/l, highly sensitive CRP&gt;3.8 g/l, MPV&gt;9.6fl, and the area under the ADP test curve &gt;60 U.

Prognostic value of myeloperoxidase concentration in patients with acute coronary syndrome

Objective: To evaluate the difference of plasma myeloperoxidase (MPO) level in different types of acute coronary syndrome (ACS) patients, and the value of baseline MPO level in predicting short-term and long-term outcomes in patients with ACS. Methods: The study cohort was derived from "the 12th Five-Year" National Science and Technology Support Program Project "Study on Comprehensive Intervention and Prognosis of Acute Coronary Syndrome" . We enrolled all hospitalized ACS patients who were enrolled in "the 12th Five-Year" cohort from January 1, 2011 to December 31, 2013. A total of 630 patients from 20 centers were enrolled. According to the diagnosis, the patients were divided into two groups: ST-segment elevation myocardial infarction (STEMI) group and non-ST-elevation acute coronary syndrome (NSTE-ACS) group. Plasma levels of MPO were measured by ELISA method. Cardiovascular events in the hospital were recorded. All patients were followed-up by telephone, follow-up ended December 31, 2015. The occurrence of major adverse cardiovascular events (MACE, defined as cardiac death, recurrent myocardial infarction, unscheduled coronary revascularization procedure and stroke) and all-cause death were recorded. Logistic regression analysis and Cox regression analysis were used to evaluate the predictive value of baseline MPO levels obtained during hospitalization and the long-term outcomes of ACS patients. Results: A total of 597 ACS patients were enrolled in final analysis. Level of plasma MPO in STEMI patients was significantly higher than that of NSTE-ACS patients (34.02(19.31, 67.87) μg/L vs. 27.25(16.69, 52.92) μg/L, P=0.028) . MPO was not related to the in-hospital cardiovascular events (OR=0.797, 95%CI 0.366-1.737, P=0.569). Follow up was completed in 476 patients, median follow-up time was 796 (32, 1 816) days. There were 23 all-cause deaths and 51 MACE. Plasma MPO level was not an independent predictor for all-cause death (HR=1.434, 95%CI 0.502-4.100, P=0.501) and MACE (HR=1.271, 95%CI 0.662-2.442, P=0.471). Conclusion: In hospitalized ACS patients, level of plasma MPO was significantly higher in STEMI patients than in NSTE-ACS patients, but MPO could not predict the short-term or long-term outcomes in patients with ACS.

Myeloperoxidase levels predict accelerated progression of coronary atherosclerosis in diabetic patients: Insights from intravascular ultrasound

ObjectiveWhile inflammation has been proposed to contribute to the adverse cardiovascular outcome in diabetic patients, the specific pathways involved have not been elucidated. The leukocyte derived product, myeloperoxidase (MPO), has been implicated in all stages of atherosclerosis. The relationship between MPO and accelerated disease progression observed in diabetic patients has not been studied. MethodsWe investigated the relationship between MPO and disease progression in diabetic patients. 881 patients with angiographic coronary artery disease underwent serial evaluation of atherosclerotic burden with intravascular ultrasound. Disease progression in diabetic (n = 199) and non-diabetic (n = 682) patients, stratified by baseline MPO levels was investigated. ResultsMPO levels were similar in patients with and without diabetes (1362 vs. 1255 pmol/L, p = 0.43). No relationship was observed between increasing quartiles of MPO and either baseline (p = 0.81) or serial changes (p = 0.43) in levels of percent atheroma volume (PAV) in non-diabetic patients. In contrast, increasing MPO quartiles were associated with accelerated PAV progression in diabetic patients (p = 0.03). While optimal control of lipid and the use of high-dose statin were associated with less disease progression, a greater benefit was observed in diabetic patients with lower compared with higher MPO levels at baseline. ConclusionsIncreasing MPO levels are associated with greater progression of atherosclerosis in diabetic patients. This finding indicates the potential importance of MPO pathways in diabetic cardiovascular disease.

Polyunsaturated omega-3 fatty acids reduce lipoprotein-associated phospholipase A2 in patients with stable angina

Background and AimsIncreased consumption of omega-3 polyunsaturated fatty acids (PUFA) together with lifestyle measures and medications is recommended for the prevention of cardiovascular diseases. However, the exact mechanisms underlying observed benefits are not well defined. To this aim, we evaluated the effects of omega-3 PUFA in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) on lipoprotein associated phospholipase A2 (Lp-PLA2) mass and activity and their relation to oxidized low-density lipoproteins (oxy-LDL). Methods and ResultsIn a prospective, double-blind, placebo-controlled, randomized study Lp-PLA2, oxy-LDL, myeloperoxidase and interleukin-6 were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n = 30) or placebo (n = 24). Treatment with omega-3 PUFA resulted in reduction of Lp-PLA2 mass by 10.7%, activity by 9.3 (p = 0.026 for both) and oxy-LDL by 10.9% (p = 0.014) at 30 days, with no change in myeloperoxidase and interleukin-6. Compared with placebo, patients receiving omega-3 PUFA had lower Lp-PLA2 mass by 9.42%, activity by 9.2 (p = 0.041 for both) and oxy-LDL by 12.3% (p = 0.10) after one month, but not at 3–5 days. There were no correlations between Lp-PLA2 and both myeloperoxidase and oxy-LDL throughout the study. The multivariate model showed that only treatment with omega-3 PUFA and baseline myeloperoxidase levels were independent predictors of Lp-PLA2 mass changes at one month (R2 = 0.37, P = 0.005). ConclusionsAdministration of omega-3 PUFA can decrease Lp-PLA2 in patients with stable angina undergoing PCI. This novel effect may contribute to the benefits derived from omega-3 PUF.

Diagnostic and Prognostic Performance of Myeloperoxidase Plasma Levels Compared With Sensitive Troponins in Patients Admitted With Acute Onset Chest Pain

Activation of leukocytes with release of myeloperoxidase (MPO) has been linked to acute coronary disease. To date, studies investigating the diagnostic and prognostic performance of circulating MPO in patients with chest pain (CP) are mainly retrospective, of low size, and lack a cut-off value for MPO. Herein, we prospectively assess the diagnostic and prognostic properties of MPO compared with sensitive troponin I (sTNI) in patients admitted to the emergency room with CP. One thousand, eight hundred and eighteen consecutive patients (mean age, 61.4±13.5 years; 33.6% female) admitted for CP underwent determination of MPO, sTnI, and B-natriuretic peptide plasma levels at admission and 3 hours and 6 hours thereafter. A cut-off for MPO was defined in 5000 population-based subjects. Baseline MPO levels were elevated in patients with acute myocardial infarction compared with patients with noncoronary CP. For all time-points accuracy of MPO was inferior to sTNI for predicting AMI. The sensitivity of MPO to diagnose AMI at presentation was 73.5% compared with 90.7% for sTNI, and the specificity of MPO was 45.5% as opposed to 90.2%. B-natriuretic peptide levels also failed to demonstrate independent diagnostic information. Both MPO and B-natriuretic peptide were predictive for increased risk of adverse events at 30 days and 6 months, whereas their predictive value was weakened after covariate adjustment. The data demonstrate that MPO and B-natriuretic peptide fail to provide incremental information for patients with acute onset CP when added to sensitive troponin. However, there is a potential value for both biomarkers as prognostic markers.

Usefulness of Baseline Plasma Myeloperoxidase Levels as an Independent Predictor of Myocardial Infarction at Two Years in Patients Presenting With Acute Coronary Syndrome

Baseline plasma myeloperoxidase (MPO) levels have been shown to independently predict the early risk of myocardial infarction (MI) in patients presenting with chest pain. In addition, baseline MPO levels have been demonstrated to predict the development of adverse cardiac events up to 6 months after an acute coronary syndrome (ACS). However, in contrast to other biomarkers, there are no data about the long-term independent predictive value of baseline MPO values in patients with ACS. The present study investigated the long-term prognostic significance of baseline MPO levels in a well-characterized cohort of 193 men with ACS who were referred for coronary angiography at a Veterans Administration Medical Center. All patients were followed prospectively for the development of death and MI, and follow-up data were available for all patients at 24 months. After controlling for different baseline clinical, laboratory, and angiographic variables, baseline plasma MPO values were a strong and independent predictor of MI at 24 months by multivariate analysis. Using the median MPO value of the entire cohort of patients (i.e., 20.34 ng/ml) as a prespecified cutoff, the MI-free survival at 24 months for the group whose baseline MPO values were < or =20.34 ng/ml was 88% compared with 74% in those whose values were >20.34 ng/ml (p = 0.0249 by log-rank test). In conclusion, these data demonstrate that baseline MPO levels independently predict MI at 2 years in patients with ACS.

Vaginal myeloperoxidase and flora in the pig‐tailed macaque

Myeloperoxidase (MPO) is an enzyme in neutrophils and monocytes which reacts with H2O2 and chloride to kill microbes after phagocytosis. Instillation of MPO into the vagina may augment vaginal defenses against sexually transmitted diseases, since the normal vaginal flora is characterized by the presence of H2O2-producing lactobacilli. We assessed the menstrual cycle stage, vaginal flora, pH, macroscopic appearance, and endogenous MPO in the adult female pig-tailed macaque (Macaca nemestrina) at baseline (n = 26; 60 observations) and at 0, 4, and 24 hours in untreated animals (n = 6) or in animals treated with intravaginal MPO gel at time 0 (n = 5). Baseline MPO levels were highly variable, and there was no detectable effect of cycle stage. In untreated animals, there was no significant effect of vaginal swab collection on vaginal flora or MPO levels. MPO treatment did not reduce vaginal H2O2-producing organisms, and vaginal MPO levels tended to increase at 4 hours in treated animals. Vaginal/cervical colposcopic changes were not detected in either group.