Association of chronic neutrophil activation with risk of mortality

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.