Hypertension Related Netosis Is Strongly Dependent on Nighttime Blood Pressure in a Cohort of Newly Diagnosed, Treatment Naïve Hypertensive Patients

Objective: Over the last years, accumulating evidence has highlighted the key role of immunity in the inflammatory environment of essential hypertension (EH). Neutrophil extracellular traps (NETs) formation represents a protective innate immune mechanism of the neutrophils. However, excessive release of NETs (NETosis) has been shown to exert a potent pro-inflammatory and pro-thrombotic effect. Even though NETosis is increasingly implicated in the thrombo-inflammatory environment of cardiovascular disease, experimental and clinical data regarding the association between NETs and EH are scarce. 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 and central BP parameters were measured with the Mobil-O-Graph device. Plasma levels of NETs including myeloperoxidase (MPO)-DNA were determined by ELISA. Results: A total of 139 individuals including 99 UHTs and 40 NTs were included in the study. Levels of MPO-DNA were increased in UHTs compared to NTs (p<0.001). In multivariate analysis after adjustment for confounding variables (body mass index, hemoglobin, uric acid, high sensitivity c-reactive protein), hypertension was the strongest independent predictor of incident NETosis (p<0.001). Among the ambulatory BP indices, peripheral nighttime systolic BP (F:5.937; p=0.016) and central nighttime diastolic BP (F:4.751; p=0.031) were the strongest prognosticators of hypertension related NETosis (Optimal Scaling ANOVA; p=0.028). Conclusions: In a cohort of newly diagnosed, treatment-naïve hypertensive patients, nighttime BP indices are the strongest factors that can predict, independently, an increased NETosis, adding to the superior significance of nocturnal BP in cardiovascular prognosis. Further research is needed to clarify the association of NETs with hypertension as well as hypertension-mediated target organ damage.