Associations between Circulating VEGFR2hi-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease

Abstract

Background. Neutrophils expressing vascular endothelial growth factor receptor (VEGFR) represent a distinct subtype of neutrophils with proangiogenic properties. The purpose of this study was to identify the interrelations between circulating CD16hiCD11bhiCD62LloCXCR2hiVEGFR2hi-neutrophils and indicators of carotid plaque burden in patients without atherosclerotic cardiovascular diseases (ASCVD). Methods. The study included 145 patients, 51.7% men and 48.3% women, median age—49.0 years. All patients underwent carotid duplex ultrasound scanning. The maximal carotid plaque thickness was used as an indicator of carotid plaque burden. Also, carotid intima-media thickness (cIMT) and femoral IMT were measured. The phenotyping of neutrophil subpopulations was executed by the flow cytometry via the Navios 6/2. Results. The subpopulation of VEGFR2hi-neutrophils accounted for about 5% of the total pool of circulating neutrophils. A decrease in VEGFR2hi-neutrophils with an increase in carotid plaque burden was statistically significant ( $p=0.036$ ). A decrease in VEGFR2hi- $\text{neutrophils}<4.52\%$ allowed to predict the presence of plaque with a maximum $\text{height}>2.1$  mm (Q4), with sensitivity of 78.9% and specificity of 61.5% (AUC 0.693; 95% CI 0.575-0.811; $p=0.007$ ). Inverse correlations were established between the carotid and femoral IMT and the absolute and relative number of VEGFR2hi-neutrophils ( $p<0.01$ ). Conclusion. In patients aged 40-64 years without established ASCVD, with an increase in indicators of the carotid plaque burden, a significant decrease in the proportion of circulating VEGFR2hi-neutrophils was noticed. A decrease in the relative number of VEGFR2hi-neutrophils of less than 4.52% made it possible to predict the presence of extent carotid atherosclerosis with sensitivity of 78.9% and specificity of 61.5%.