Myeloperoxidase Improves Risk Stratification in Patients with Ischemia and Normal Cardiac Troponin I Concentrations

Apple, Fred S.; Smith, Stephen W.; Pearce, Lesly A.; Schulz, Karen; Ler, Ranka; Murakami, MaryAnn M.

doi:10.1373/clinchem.2010.158014

Cited by 20 publications

(9 citation statements)

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“…Systemic concentrations of MPO have been reported to predict prospective clinical risk in patients who present for assessment of chest pain of suspected cardiac etiology (30) . The current findings use an assay cleared by the FDA and extend observations from early reports from investigators who used a research-grade MPO assay (28, 30) , as well as building on subsequent studies demonstrating the incremental prognostic value of a single measure of plasma MPO compared with cardiac troponin measurements (34) , to suggest that serial monitoring of MPO concentrations provides incremental ability to predict the risk of cardiovascular events. The present observations also confirm previous findings of a rapid increase in MPO concentrations in patients presenting with acute coronary syndromes (35) .…”

Section: Discussionsupporting

confidence: 72%

Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

et al. 2011

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BACKGROUND Although myeloperoxidase (MPO) monitoring is predictive for cardiovascular outcomes in suspected acute coronary syndromes, the value of serial testing is unknown. METHODS We investigated the relationship between serial MPO concentrations in 490 individuals with acute chest pain and incident major adverse cardiac events (MACE) during 6 months of follow-up. We measured MPO with the CardioMPO assay, and cardiac troponin I (cTnI), with the Abbott Architect assay. RESULTS Plasma MPO concentrations during the first 16 h were higher in individuals who experienced MACE. Higher MPO quartiles predicted a greater likelihood of 6-month MACE at baseline [OR (95% CI), 2.4 (1.4 – 4.1), P = 0.001 for highest vs lowest quartile] and all subsequent time points, with strongest predictive ability found in 16-h postbaseline samples [9.9 (4.7–20.9), P < 0.001 for highest vs lowest quartile]. MPO was predictive for MACE among individuals whose cTnI remained within reference intervals (<0.028 μg/L). The lowest rate of missed cases was found when MPO was <640 pmol/L at baseline and all other time points. Serial MPO monitoring predicted MACE risk better than baseline MPO measurements alone (c statistic 0.813 vs 0.602; P = 0.002), including in individuals whose cTnI remained within reference intervals (c statistic 0.903; P = 0.009). Combined serial cTnI and MPO testing improved accuracy for predicting 6-month MACE, reduced the number of missed MACE events from cTnI testing alone, and improved risk classification in 26.1% of patients. CONCLUSIONS MPO concentrations are predictive of outcome up to 16 h after presentation with chest pain and predict events missed by cTnI testing, supporting a potential role in rapid patient triage.

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Section: Discussionsupporting

confidence: 72%

Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

et al. 2011

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“…In individuals with chest pain MPO concentrations at presentation of patients were predictive of major adverse coronary events after 30 days and 6 months [10,22]. In another study [29] the authors reported that MPO levels predicted short-term risk of major adverse coronary events even in patients with normal cardiac TnT levels.…”

Section: Discussionmentioning

confidence: 99%

Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography—The LURIC study

Scharnagl

Kleber

Genser

et al. 2014

International Journal of Cardiology

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BackgroundThe phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.Methods and resultsMPO plasma concentrations along with eight MPO polymorphisms were determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years). MPO concentrations were positively associated with age, diabetes, smoking, markers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After adjustment for cardiovascular risk factors MPO concentrations in the highest versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09–1.67) for total mortality. In the adjusted model the hazard ratio for cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07–1.88). Five MPO polymorphisms were positively associated with MPO concentrations but not with mortality. Using Mendelian randomization, we did not obtain evidence for a causal association of MPO with either total or cardiovascular mortality.ConclusionsMPO concentrations but not genetic variants at the MPO locus are independently associated with risk for total and cardiovascular mortality in coronary artery disease patients.

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“…Later, in a subsequent study by the same author regarding the clinical utility of MPO for the risk stratification in patients with ischemia, suggestive of ACS and with normal cTnI concentrations at admission, MPO was a powerful predictor of MACE. The combined use of cTnI and MPO identified a significantly greater proportion of patients at risk of MACE during the 30-day follow-up, however when these markers were considered separately, the adjusted HR for MACE was significantly higher for troponin 104 . A reliable assessment of this study is hampered by the lack of information of the heparin administration before or at the time of admission, which is known to significantly affect the concentration of MPO 105,106 .…”

Section: Role Of Mpo In Patients With Acute Chest Painmentioning

confidence: 88%

Critical appraisal of inflammatory markers in cardiovascular risk stratification

Krintus¹,

Koziński²,

Kubica

et al. 2014

Critical Reviews in Clinical Laboratory Sciences

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Despite great progress in prevention strategies, pharmacotherapy and interventional treatment of coronary artery disease (CAD), cardiovascular events still constitute the leading cause of mortality and morbidity in the modern world. Traditional risk factors, including hypertension, diabetes mellitus, smoking, obesity, dyslipidemia, and positive family history account for the occurrence of the majority of these events, but not all of them. Adequate risk assessment remains the most challenging in individuals classified into low or intermediate risk categories. Inflammation plays a key role in the initiation and promotion of atherosclerosis and may lead to acute coronary syndrome (ACS) by the induction of plaque instability. For this reason, numerous inflammatory markers have been extensively investigated as potential candidates for the enhancement of cardiovascular risk assessment. This review aims to critically assess the clinical utility of well-established (C-reactive protein [CRP] and fibrinogen), newer (lipoprotein-associated phospholipase A2 [Lp-PLA2] and myeloperoxidase [MPO]) and novel (growth differentiation factor-15 [GDF-15]) inflammatory markers which, reflect different pathophysiological pathways underlying CAD. Although according to the traditional approach all discussed inflammatory markers were shown to be associated with the risk of future cardiovascular events in individuals with and without CAD, their clear clinical utility remains not fully elucidated. Current recommendations of numerous scientific societies predominantly advocate routine assessment of CRP in healthy people with intermediate cardiovascular risk. However, these recommendations substantially vary in their strength among particular societies. These discrepancies have a multifactorial background, including: (i) the strong prognostic value of CRP supported by solid scientific evidence and proven to be comparable in magnitude with that of total and high-density lipoprotein cholesterol, or hypertension, (ii) favourable analytical characteristics of commercially available CRP assays, (iii) lack of CRP specificity and causal relationship between CRP concentration and cardiovascular risk, and (iv) CRP dependence on other classical risk factors. Of major importance, CRP measurement in healthy men ≥50 years of age or healthy women ≥60 years of age with low-density lipoprotein cholesterol <130 mg/dL may be helpful in the selection of patients for statin therapy. Additionally, evaluation of CRP and fibrinogen or Lp-PLA2 may be considered to facilitate risk stratification in ACS patients and in healthy individuals with intermediate cardiovascular risk, respectively. Nevertheless, the clinical utility of CRP requires further investigation in a broad spectrum of CAD patients, while other promising inflammatory markers, particularly GDF-15 and Lp-PLA2, should be tested in individuals both with and without established CAD. Further studies should also focus on novel performance metrics such as measures of discrimination, calibration and reclassific...

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Myeloperoxidase Improves Risk Stratification in Patients with Ischemia and Normal Cardiac Troponin I Concentrations

Abstract: BACKGROUND:We assessed the ability of myeloperoxidase (MPO) to identify the risk for major adverse cardiac events (MACE) in patients who present with ischemic symptoms suggestive of acute coronary syndrome and have a normal cardiac troponin I (cTnI) value.

Cited by 20 publications

References 20 publications

Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

Risk Prediction with Serial Myeloperoxidase Monitoring in Patients with Acute Chest Pain

Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography—The LURIC study

Critical appraisal of inflammatory markers in cardiovascular risk stratification

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