LEVELS OF NEUTROPHIL EXTRACELLULAR TRAPS ARE ASSOCIATED WITH MARKERS OF VASCULAR DAMAGE IN A POPULATION OF NORMOTENSIVES AND TREATMENT-NAÏVE HYPERTENSIVES

Objective: Accumulating evidence has demonstrated the critical role of immunity in the inflammatory environment of essential hypertension (EH). Neutrophil extracellular traps (NETs), an otherwise defense innate immune mechanism of the neutrophils, has been shown to exert a potent pro-inflammatory and pro-thrombotic effect in cardiovascular disease. NETs levels have been also found to be increased in hypertensive patients compared to normotensives and to be correlated with blood pressure (BP) parameters. The purpose of this study was to explore the association of NETs’ levels with markers of micro- and macro- vascular damage. Design and method: We recruited newly diagnosed, untreated hypertensives (UHTs) without overt cardiovascular disease and healthy, normotensive individuals (NTs). Office BP was measured according to guidelines. Ambulatory peripheral and central BP parameters were measured with the Mobil-O-Graph device. Plasma levels of NETs including myeloperoxidase (MPO)-DNA were determined by ELISA. Carotid stiffness including mean pulse wave velocity (PWV) of both carotid arteries was assessed by using a high-definition echo-tracking system (Aloka Pro Sound A7, Ultrasound System, Tokyo, Japan). Skin microvascular function was assessed using laser speckle contrast imaging (LSCI) (PeriCam PSI system, Perimed, Järfälla, Sweden) coupled with post-occlusive reactive hyperemia (PORH). Results: A total of 139 individuals including 99 UHTs and 40 NTs were included in the study. In univariate analysis, MPO-DNA complexes levels were positively associated with mean carotid PWV (p=0.033) and baseline flux (p=0.017), and negatively associated with baseline to peak flux (p=0.020) and CVC increase (p=0.034). In multivariate analysis after adjustment for hypertension, body mass index, hemoglobin, uric acid, and high-sensitivity C-reactive protein, MPO-DNA complexes load was documented as a strong and independent predictor of carotid PWV. Conclusions: In a cohort of normotensives and newly diagnosed, treatment-naïve hypertensive patients MPO-DNA complexes were significantly associated with surrogate markers of micro- and macrovascular damage. Interestingly, NETs burden could predict carotid stiffness, therefore suggesting a potential role of NETs as a surrogate marker of early macrovascular damage in hypertensive patients.