Association of chronic neutrophil activation with risk of mortality

PLoS One. 2023 Jul 20;18(7):e0288712. doi: 10.1371/journal.pone.0288712. eCollection 2023.

Abstract

Background: Levels of free myeloperoxidase (MPO), a cardiovascular risk marker, have been reported to decline with standard care. Whether such declines signify decreased risk of mortality remains unknown.

Design: Cox proportional hazard models were generated using data from a retrospective cohort study of prospectively collected measures.

Participants: Patients (3,658) who had MPO measurements and LDL-C ≥ 90 mg/dL during 2011-2015 were selected based on a stratified random sampling on MPO risk level. Baseline MPO was either low (<470 pmol/L), moderate (470-539 pmol/L), or high (≥540 pmol/L).

Main outcomes and measures: First occurrence of MACE (myocardial infarction, stroke, coronary revascularization, or all-cause death).

Results: Mean age was 66.5 years, and 64.7% were women. During a mean 6.5-year follow-up, crude incidence per 1000 patient years was driven by death. The incidence and all-cause death was highest for patients with high MPO (21.2; 95% CI, 19.0-23.7), then moderate (14.6; 95% CI, 11.5-18.5) and low (2.3; 95% CI, 1.2-4.6) MPO. After adjusting for age, sex, and cardiovascular risk factors, risk of cardiovascular death did not differ significantly between patients with high and low MPO (HR, 1.57; 95% CI, 0.56-4.39), but patients with high MPO had greater risk of non-cardiovascular (HR, 6.15; 95% CI, 2.27-16.64) and all-cause (HR, 3.83; 95% CI, 1.88-7.78) death. During follow-up, a 100 pmol/L decrease in MPO correlated with a 5% reduction in mortality (HR, 0.95; 95% CI, 0.93-0.97) over 5 years.

Conclusions: Free circulating MPO is a strong marker of risk of mortality. Monitoring changes in MPO levels over time may provide insight into changes in physiology that mark a patient for increased risk of mortality.

MeSH terms

  • Aged
  • Cardiovascular Diseases*
  • Female
  • Humans
  • Male
  • Myocardial Infarction*
  • Neutrophil Activation
  • Retrospective Studies
  • Risk Factors
  • Stroke*

Grants and funding

Dr. Penn is the founder of Cleveland HeartLab, Inc and a consulting Medical Director for Quest Diagnostics Center of Excellence for Cardiometabolic Testing at Cleveland HeartLab. Dr. Saghir is an employee of Quest Diagnostics, including salary and equity holdings. Dr. David Wrenn is an employee of Quest Diagnostics, including salary and equity holdings. Dr. Klemes is the Chief Medical Officer of MDVIP, Inc. The funders had no role in the no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data collection and analyses were performed by Authors who did not work for either of the funders.