Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients.

Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40-64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12-24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0-467.0 cells/µL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642-0.815) versus 0.637 (0.539-0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression.

Circulating Ageing Neutrophils as a Marker of Asymptomatic Polyvascular Atherosclerosis in Statin-Naïve Patients without Established Cardiovascular Disease.

BACKGROUND: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). METHODS: The study was carried out on 151 statin-naïve patients aged 40-64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). RESULTS: The number of CD62LloCXCR4hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62LloCXCR4hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4-50.5% and specificity of 80.0-92.1%, in two vascular beds with sensitivity of 44.7-84.4% and specificity of 80.8-33.3%. CONCLUSION: In statin-naïve patients 40-64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62LloCXCR4hi-neutrophils. It was also concluded that the increase in the number of circulating CD62LloCXCR4hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617-0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis.

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

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-neutrophils < 4.52% allowed to predict the presence of plaque with a maximum 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%.