Cardio IQ Myeloperoxidase (MPO)

Cardio IQ Myeloperoxidase (MPO)

This test is used to predict risk of cardiovascular disease, including coronary artery disease and acute coronary syndrome in both primary and secondary prevention.

HLA-B27

Test Summary

 

Cardio IQ® Myeloperoxidase (MPO)

Test Code: 92814

 

Clinical use

  • Predict risk of cardiovascular disease, including coronary artery disease (CAD) and acute coronary syndrome (ACS), in both primary and secondary prevention

Clinical background

Myeloperoxidase (MPO) is a leukocyte-derived inflammatory enzyme that can play a direct role in the pathogenesis of cardiovascular disease (CVD). MPO is also involved in the destabilization and rupture of vulnerable atherosclerotic plaque by reducing fibrous cap thickness and increasing the likelihood of thrombotic events.1 In circulation, MPO has oxidative properties and can promote oxidation of lipids, HDL dysfunction, and decreased nitric oxide, promoting endothelial dysfunction.1,2

MPO elevation in the bloodstream has been linked to increased risk for coronary artery disease (CAD), major adverse cardiovascular events (MACE), and acute coronary syndrome (ACS) and provides prognostic insight in both primary and secondary prevention.1,2 Asymptomatic individuals with elevated MPO levels are more than 2 times as likely to have a CVD event compared to individuals with low MPO levels.1 Elevated MPO is also associated with a risk for mortality, and a reduction of MPO correlates with decreased risk for mortality.3 Elevated plasma levels of MPO have been linked to (1) increased risk for MACE and death in individuals with confirmed CAD and ST-segment elevation myocardial infarction (STEMI),4 and (2) recurrent ACS in individuals with non–ST-segment elevation.2

MPO enhances cardiovascular risk prediction when used independently and alongside standard biomarkers, such as high-sensitivity C-reactive protein,5 high-sensitivity troponin T,1 B-type natriuretic peptide (BNP),6 and trimethylamine N-oxide (TMAO).4

The Quest Cardiometabolic Center of Excellence at Cleveland HeartLab offers the Cardio IQ® Myeloperoxidase (MPO) test; the test directly measures the amount of MPO protein that is outside of white blood cells (WBCs) in the blood stream, which indicates cardiovascular risk.

The physiology of WBC activation and MPO elevation are driven by risk factors that may be nonoptimal. These include poor lifestyle habits, dyslipidemia, hypertension, insulin resistance, periodontal disease, and other comorbidities like type 2 diabetes and chronic kidney disease.7 Additional etiologies can cause WBC activation in circulation and subsequent MPO elevation, including vasculitis, neurodegenerative disorders, cancer,3,7 strenuous exercise,2,8 and chronic inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.7

Individuals suitable for testing

  • Individuals with 1 or more risk factors for the development of cardiovascular disease (CVD)
  • Individuals with CAD or risk equivalents

Methods

  • Turbidimetric immunoassay (TIA); latex particle coated with a polyclonal antibody
  • Analytical sensitivity: 20 pmol/L
  • Reportable range: 20 to 5,000 pmol/L

Interpretive information

The following risk cut-offs are used for MPO:3

  • Low risk: <470 pmol/L
  • Moderate risk: 470-539 pmol/L
  • High risk: ≥540 pmol/L

Compared with patients in the low-risk category, MPO levels independently predict that patients in the high-risk category have a 6.2 (95% CI, 2.3-16.6)-fold greater risk of non-CVD death and a 3.8 (95% CI, 1.9-7.8)-fold greater risk of all-cause death using a fully adjusted model; CV death correlated with MPO levels over time, though the adjusted 1.6 (95% CI, 1.9-7.8)-fold greater risk of CV death was not statistically significant.3 These estimates are based on a population of >3,600 patients (65% female, mean age 67 years, mean 6.5-year follow-up, LDL-C ≥90 mg/dL) who had relatively low incidence of cardiovascular disease (2%-4%) for their age and risk profile.3 Decreasing MPO by 100 pmol/L reduced all-cause mortality by 5% over 5 years.3

Relative risk estimates for increased MPO for cardiovascular risk were assessed in stable, ambulatory patients without acute coronary syndrome who underwent elective diagnostic coronary angiography and were assessed for risk of incident MACE at 3 years. The patients demonstrated increased event rates per increasing quartile of MPO concentration (P<.01)9 and 1.3-fold increased risk of MACE at higher MPO levels independent of other risk factors (P<.04).10 Reference range studies of apparently healthy donors using previously employed immunoassays were correlated with the current TIA (95% concordance, data on file).

References

  1. Lin W, Chen H, Chen X, et al. The roles of neutrophil-derived myeloperoxidase (MPO) in diseases: the new progress. Antioxidants. 2024;13(1):132. doi:10.3390/antiox13010132
  2. Ndrepepa G. Myeloperoxidase – a bridge linking inflammation and oxidative stress with cardiovascular disease. Clin Chim Acta. 2019;493:36-51. doi:10.1016/j.cca.2019.02.022
  3. Penn MS, MacRae C, Goldfaden RF, et al. Association of chronic neutrophil activation with risk of mortality. PLOS ONE. 2023;18(7):e0288712. doi:10.1371/journal.pone.0288712
  4. Tan Y, Zhou J, Yang S, et al. Addition of plasma myeloperoxidase and trimethylamine N-oxide to the GRACE score improves prediction of near-term major adverse cardiovascular events in patients with ST-segment elevation myocardial infarction. Front Pharmacol. 2021;12:632075. doi:10.3389/fphar.2021.632075
  5. Penn MS, Yenikomshian MA, Cummings AKG, et al. The economic impact of implementing a multiple inflammatory biomarker-based approach to identify, treat, and reduce cardiovascular risk. J Méd Econ. 2015;18(7):483-491. doi:10.3111/13696998.2015.1029490
  6. Ibrahim NE, Januzzi JL. Established and emerging roles of biomarkers in heart failure. Circ Res. 2018;123(5):614-629. doi:10.1161/circresaha.118.312706
  7. Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Méd Sci. 2018;6(2):33. doi:10.3390/medsci6020033
  8. Carrera-Quintanar L, Funes L, Herranz-López M, et al. Antioxidant supplementation modulates neutrophil inflammatory response to exercise-induced stress. Antioxidants. 2020;9(12):1242. doi:10.3390/antiox9121242
  9. Tang WW, Wu Y, Nicholls SJ, et al. Plasma myeloperoxidase predicts incident cardiovascular risks in stable patients undergoing medical management for coronary artery disease. Clin Chem. 2011;57(1):33-39. doi:10.1373/clinchem.2010.152827
  10. Tang WHW, Iqbal N, Wu Y, et al. Usefulness of cardiac biomarker score for risk stratification in stable patients undergoing elective cardiac evaluation across glycemic status. Am J Cardiol. 2013;111(4):465-470. doi:10.1016/j.amjcard.2012.10.027
     

Content reviewed 10/2024

top of page

This test is used to predict risk of cardiovascular disease, including coronary artery disease and acute coronary syndrome in both primary and secondary prevention.

HLA-B27

Test Summary

 

Cardio IQ® Myeloperoxidase (MPO)

Test Code: 92814

 

Clinical use

  • Predict risk of cardiovascular disease, including coronary artery disease (CAD) and acute coronary syndrome (ACS), in both primary and secondary prevention

Clinical background

Myeloperoxidase (MPO) is a leukocyte-derived inflammatory enzyme that can play a direct role in the pathogenesis of cardiovascular disease (CVD). MPO is also involved in the destabilization and rupture of vulnerable atherosclerotic plaque by reducing fibrous cap thickness and increasing the likelihood of thrombotic events.1 In circulation, MPO has oxidative properties and can promote oxidation of lipids, HDL dysfunction, and decreased nitric oxide, promoting endothelial dysfunction.1,2

MPO elevation in the bloodstream has been linked to increased risk for coronary artery disease (CAD), major adverse cardiovascular events (MACE), and acute coronary syndrome (ACS) and provides prognostic insight in both primary and secondary prevention.1,2 Asymptomatic individuals with elevated MPO levels are more than 2 times as likely to have a CVD event compared to individuals with low MPO levels.1 Elevated MPO is also associated with a risk for mortality, and a reduction of MPO correlates with decreased risk for mortality.3 Elevated plasma levels of MPO have been linked to (1) increased risk for MACE and death in individuals with confirmed CAD and ST-segment elevation myocardial infarction (STEMI),4 and (2) recurrent ACS in individuals with non–ST-segment elevation.2

MPO enhances cardiovascular risk prediction when used independently and alongside standard biomarkers, such as high-sensitivity C-reactive protein,5 high-sensitivity troponin T,1 B-type natriuretic peptide (BNP),6 and trimethylamine N-oxide (TMAO).4

The Quest Cardiometabolic Center of Excellence at Cleveland HeartLab offers the Cardio IQ® Myeloperoxidase (MPO) test; the test directly measures the amount of MPO protein that is outside of white blood cells (WBCs) in the blood stream, which indicates cardiovascular risk.

The physiology of WBC activation and MPO elevation are driven by risk factors that may be nonoptimal. These include poor lifestyle habits, dyslipidemia, hypertension, insulin resistance, periodontal disease, and other comorbidities like type 2 diabetes and chronic kidney disease.7 Additional etiologies can cause WBC activation in circulation and subsequent MPO elevation, including vasculitis, neurodegenerative disorders, cancer,3,7 strenuous exercise,2,8 and chronic inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.7

Individuals suitable for testing

  • Individuals with 1 or more risk factors for the development of cardiovascular disease (CVD)
  • Individuals with CAD or risk equivalents

Methods

  • Turbidimetric immunoassay (TIA); latex particle coated with a polyclonal antibody
  • Analytical sensitivity: 20 pmol/L
  • Reportable range: 20 to 5,000 pmol/L

Interpretive information

The following risk cut-offs are used for MPO:3

  • Low risk: <470 pmol/L
  • Moderate risk: 470-539 pmol/L
  • High risk: ≥540 pmol/L

Compared with patients in the low-risk category, MPO levels independently predict that patients in the high-risk category have a 6.2 (95% CI, 2.3-16.6)-fold greater risk of non-CVD death and a 3.8 (95% CI, 1.9-7.8)-fold greater risk of all-cause death using a fully adjusted model; CV death correlated with MPO levels over time, though the adjusted 1.6 (95% CI, 1.9-7.8)-fold greater risk of CV death was not statistically significant.3 These estimates are based on a population of >3,600 patients (65% female, mean age 67 years, mean 6.5-year follow-up, LDL-C ≥90 mg/dL) who had relatively low incidence of cardiovascular disease (2%-4%) for their age and risk profile.3 Decreasing MPO by 100 pmol/L reduced all-cause mortality by 5% over 5 years.3

Relative risk estimates for increased MPO for cardiovascular risk were assessed in stable, ambulatory patients without acute coronary syndrome who underwent elective diagnostic coronary angiography and were assessed for risk of incident MACE at 3 years. The patients demonstrated increased event rates per increasing quartile of MPO concentration (P<.01)9 and 1.3-fold increased risk of MACE at higher MPO levels independent of other risk factors (P<.04).10 Reference range studies of apparently healthy donors using previously employed immunoassays were correlated with the current TIA (95% concordance, data on file).

References

  1. Lin W, Chen H, Chen X, et al. The roles of neutrophil-derived myeloperoxidase (MPO) in diseases: the new progress. Antioxidants. 2024;13(1):132. doi:10.3390/antiox13010132
  2. Ndrepepa G. Myeloperoxidase – a bridge linking inflammation and oxidative stress with cardiovascular disease. Clin Chim Acta. 2019;493:36-51. doi:10.1016/j.cca.2019.02.022
  3. Penn MS, MacRae C, Goldfaden RF, et al. Association of chronic neutrophil activation with risk of mortality. PLOS ONE. 2023;18(7):e0288712. doi:10.1371/journal.pone.0288712
  4. Tan Y, Zhou J, Yang S, et al. Addition of plasma myeloperoxidase and trimethylamine N-oxide to the GRACE score improves prediction of near-term major adverse cardiovascular events in patients with ST-segment elevation myocardial infarction. Front Pharmacol. 2021;12:632075. doi:10.3389/fphar.2021.632075
  5. Penn MS, Yenikomshian MA, Cummings AKG, et al. The economic impact of implementing a multiple inflammatory biomarker-based approach to identify, treat, and reduce cardiovascular risk. J Méd Econ. 2015;18(7):483-491. doi:10.3111/13696998.2015.1029490
  6. Ibrahim NE, Januzzi JL. Established and emerging roles of biomarkers in heart failure. Circ Res. 2018;123(5):614-629. doi:10.1161/circresaha.118.312706
  7. Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Méd Sci. 2018;6(2):33. doi:10.3390/medsci6020033
  8. Carrera-Quintanar L, Funes L, Herranz-López M, et al. Antioxidant supplementation modulates neutrophil inflammatory response to exercise-induced stress. Antioxidants. 2020;9(12):1242. doi:10.3390/antiox9121242
  9. Tang WW, Wu Y, Nicholls SJ, et al. Plasma myeloperoxidase predicts incident cardiovascular risks in stable patients undergoing medical management for coronary artery disease. Clin Chem. 2011;57(1):33-39. doi:10.1373/clinchem.2010.152827
  10. Tang WHW, Iqbal N, Wu Y, et al. Usefulness of cardiac biomarker score for risk stratification in stable patients undergoing elective cardiac evaluation across glycemic status. Am J Cardiol. 2013;111(4):465-470. doi:10.1016/j.amjcard.2012.10.027
     

Content reviewed 10/2024

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

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