Evaluation of neutrophil oxidative burst capacity in relation to major adverse cardiac events and infection in patients with cardiovascular disease

BACKGROUND: Neutrophils are key in acute and chronic cardiovascular diseases (CVD) by mediating inflammation during myocardial infarction, stroke, and heart failure. Reactive oxygen species (ROS) generated by neutrophil NADPH oxidase 2 (NOX2) have been linked to CVD pathology by inducing tissue injury via oxidative stress. There is, however, only limited data investigating the impact of neutrophil-derived ROS on clinical outcome in patients with CVD. This study measured neutrophil oxidative burst capacity (NOBC) in patients with CVD and evaluated its association with major adverse cardiac events (MACE) and infection. METHODS: In a population of 201 (median age 69 years (interquartile range (IQR) = 61-80 years); 33.4% female) out of 1128 patients from the prospective all-comer Essen Coronary Artery Registry II (ECAD II registry), NOBC was measured using a Seahorse XF analyzer with phorbol-12-myristat-13-acetat (PMA) stimulation. Based on NOBC values, the study collective was divided by median split. The primary endpoint was MACE, comprising of acute myocardial infarction, acute ischemic stroke, or hospitalization for heart failure, with a median follow-up time of 287 days (IQR = 225-349 days). A secondary endpoint occurrence of infection was assessed with a median follow-up time of 273 days (IQR = 214-332 days). RESULTS: Patients with low NOBC showed 20% lower values (98.8 nmol (IQR = 92.9-104.2 nmol; high NOBC) vs. 79.4 nmol (IQR = 71.8-84.9 nmol; low NOBC); p < 0,001). In this group, we observed a significantly higher portion of females (26.7% (high NOBC) vs. 41.0% (low NOBC); p = 0.03). Despite lower CCL2 and hemoglobin levels in patients with low NOBC, further inflammatory markers were unaltered. Occurrence of MACE (hazard ratio (HR) = 2.78; 95% confidence interval (CI) 1.17-6.63; p = 0.02) and infection (HR = 3.67; 95% CI = 1.16-11.62; p = 0.03) was significantly increased in patients with low NOBC. The latter remained significant, while the association between low NOBC and incidence of MACE lost its significance after adjustment for anemia and further confounders. CONCLUSION: Incidence of MACE and infection was increased in patients with low NOBC. Whether low NOBC is directly associated with patient outcome or acts in combination with other factors remains unclear.