Free Myeloperoxidase Levels Show Promise for Predicting Risk of Cardiovascular, All-Cause Mortality

Monitoring changes in levels of free myeloperoxidase (MPO) may help identify patients with increased mortality risk, according to a new study published in Plos One.

Previous studies have indicated that major adverse cardiac events (MACE), such as spontaneous thrombosis or myocardial infarction (MI), are influenced by vascular inflammation. At the site of inflammation, MPO is released into circulation by neutrophils as a part of bodily defense efforts. Due to this process, past research has identified MPO as a keen marker for cardiovascular risk; however, the potential benefits of lowering MPO have not been investigated.

In a retrospective study, researchers were analyzed whether reductions in MPO could be associated with decreases in MACE or all-cause mortality. Patient data from 2011 to 2015 were gathered from the Cleveland HeartLab. The cohort consisted of 3657 patients and included individuals who received MPO measurements and had low-density lipoprotein-cholesterol levels (LDL-C; the management of which has been crucial for preventing and treating certain cardiovascular diseases) at or above 90 mg/dL.

After evaluating a portion of the cohort to establish baseline values of MPO and rates of MACE, MPO levels were rated as either high (≥ 540 pmol/L), moderate (470-539 pmol/L), or low (< 470 pmol/L). A total of 2310 patients (63%) were categorized as having high MPO values, 659 (18%) as moderate, and 689 (19%) as low.

During a median follow-up time of 6.5 years (from initial MPO measurements), the cohort had an event rate of 13.2%. Rates of MACE per every 1000 patient years totaled at 21.5, most of which resulted in death (79.1%). Higher MPO levels were associated with greater incidences and all-cause death (21.2; 95% CI, 19.0-23.7). Moderate MPO levels registered less incidences and all-cause death (14.6; 95% CI, 11.5–18.5), followed by those with low MPO levels (2.3; 95% CI, 1.2-4.6).

Researchers found a statistically significant connection between baseline MPO levels and cardiovascular and non-cardiovascular death alike. Most notably, in follow-ups, a 100 pmol/L MPO decrease was linked to a 5% reduction in mortality over 5 years (HR, 0.95; 95% CI, 0.93-0.97). Therefore, they ascertained that reversing chronic activation of neutrophils is connected to improved patient outcomes. In fact, the measuring of free MPO to analyze chronic neutrophil activation could theoretically provide major benefits for identifying mortality risks in a patient’s next 5 years, according to the authors.

A limitation the authors noted was their inability to obtain specific drug therapy information for each of their patients. Despite this shortcoming, their results produced major evidence for how tracking free MPO and chronic neutrophil activation aids in identify patients’ risks of death. In all their results, elevated MPO levels correlated with increased mortality, whereas lower MPO levels continually trended toward lower overall mortality risk.

The authors also point out increasing evidence that suggests elevated inflammatory markers—like MPO—can indicate a patient’s risk of cancer. Considering this wealth of research alongside their findings, they conclude by emphasizing that “patients who develop elevated MPO warrant greater investigation for potential etiologies that could lead to adverse events... The dichotomy of outcomes between those with and without elevated markers of inflammation suggests that measures of inflammation could serve to identify patients who need more aggressive investigation and care and could be used to close gaps in care.”

Reference

Penn MS, MacRae C, Goldfaden RF, et al. Association of chronic neutrophil activation with risk of mortality. Plos One. Published online July 20, 2023. doi.org/10.1371/journal.pone.0288712