What does an elevated Myeloperoxidase (MPO) level indicate in a patient with a history of metabolic syndrome or cardiovascular disease?

What Myeloperoxidase (MPO) Tells You

Elevated MPO indicates increased oxidative stress and inflammation, serving as a powerful independent predictor of cardiovascular events and mortality in patients with metabolic syndrome or established cardiovascular disease. 1

MPO as a Biomarker of Oxidative Stress and Inflammation

MPO is a heme peroxidase enzyme released primarily by activated neutrophils and monocytes during inflammatory responses. 2 In the context of metabolic syndrome and cardiovascular disease, elevated MPO levels signal:

• Active oxidative stress: MPO catalyzes chlorinating reactions that generate highly reactive oxidant species, making it one of the most important phagocyte-derived oxidants in the human body. 1
• Inflammatory activation: MPO secretion directly links oxidative stress to both inflammation and endothelial dysfunction, creating a pathophysiologic bridge between these processes. 1
• Tissue damage potential: MPO-derived reactive species can attack and modify every known cellular component, including lipoproteins, proteins, and nucleic acids. 2

Prognostic Significance in Cardiovascular Disease

Elevated MPO independently predicts major adverse cardiovascular events and mortality, even after adjusting for traditional risk factors. 3

In Stable Coronary Artery Disease

• Patients with plasma MPO >322 pmol/L have a 71% increased risk of death, myocardial infarction, or stroke over 3 years, independent of traditional cardiac risk factors, creatinine clearance, B-type natriuretic peptide, and high-sensitivity C-reactive protein. 3
• MPO provides additive prognostic value beyond inflammatory markers alone—patients with elevated hsCRP but low MPO have lower event rates than those with both markers elevated. 3

In Acute Myocardial Infarction

• Above-median MPO levels (>55 ng/ml) independently predict 5-year mortality with an odds ratio of 1.8. 4
• The combination of elevated MPO with either elevated NT-proBNP or reduced left ventricular ejection fraction identifies patients at significantly greater mortality risk. 4

In Asymptomatic Individuals

• MPO at or above the median (257 pM) doubles the risk of incident cardiovascular events (4.6% vs 2.3%) over 3.8 years, even after adjusting for age, sex, coronary artery calcium, and traditional risk factors. 5
• The highest risk group has both elevated MPO and coronary artery calcium ≥100: these patients have a 19.5-fold increased risk of cardiovascular events compared to those with minimal calcium and low MPO. 5

Mechanistic Links to Cardiovascular Pathophysiology

MPO is not merely a marker but likely a direct mediator of cardiovascular disease through multiple mechanisms: 2, 6

• Lipoprotein modification: MPO generates dysfunctional, highly atherogenic lipoproteins through oxidative modification. 2
• Endothelial dysfunction: MPO reduces nitric oxide availability and impairs vasoreactivity. 2
• Plaque instability: MPO-derived oxidants promote atherosclerotic plaque destabilization. 2
• Protein oxidation: Increased formation of 3-chlorotyrosine (a specific marker of MPO-catalyzed oxidation) has been demonstrated in dialysis patients and correlates with cardiovascular risk. 1

Clinical Context in Metabolic Syndrome

In patients with metabolic syndrome, elevated MPO reflects the intersection of multiple pathophysiologic processes: 1, 2

• Chronic low-grade inflammation: Metabolic syndrome components (obesity, insulin resistance, dyslipidemia, hypertension) all promote inflammatory activation and MPO release. 2
• Increased cardiometabolic risk: Elevated MPO may represent the cumulative burden of metabolic abnormalities and comorbidities that coexist with inflammation and oxidative stress. 2
• Accelerated atherosclerosis: The combination of metabolic syndrome and elevated MPO creates a particularly high-risk phenotype for cardiovascular events. 5

Practical Clinical Interpretation

When you see elevated MPO in a patient with metabolic syndrome or cardiovascular disease, it tells you:

• The patient has active oxidative stress and inflammation beyond what traditional risk factors capture. 3
• Cardiovascular risk is substantially elevated, independent of lipid levels, blood pressure, or glucose control. 3
• The patient may benefit from aggressive risk factor modification targeting inflammation and oxidative stress pathways. 2, 6
• Prognosis is worse, particularly when combined with other high-risk markers like elevated natriuretic peptides, reduced ejection fraction, or significant coronary calcification. 5, 4

Important Caveats

• MPO levels can be elevated in chronic kidney disease due to uremia, chronic inflammation, and dialysis-related factors, which may complicate interpretation in this population. 1
• While MPO is a strong predictor of cardiovascular events, therapeutic MPO inhibition has not yet been validated in clinical trials for improving cardiovascular outcomes. 2, 6
• MPO should be interpreted in the context of other cardiovascular risk markers rather than in isolation—its greatest prognostic value emerges when combined with measures of subclinical atherosclerosis or cardiac dysfunction. 5, 4