Circulating extracellular vesicles correlate with nocturnal blood pressure and vascular organ damage and may serve as an integrative biomarker of vascular health.

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Council on Science and Technology, Mexico (CONACYT). Background Elevated blood pressure (BP) has been associated with increased levels of circulating extracellular vesicles (EVs) which could potentially serve as a novel integrative biomarker for vascular health. Purpose The present study therefore aimed to assess the relationship between increased EV release, blood pressure and macrovascular organ damage. Methods A total of 83 patients with BP ranging from normal to high were included in the present analysis. Extracellular vesicles were evaluated by flow cytometry (CD41+/Annexin v+). BP evaluation included unobserved automated office BP (AOBP) and ambulatory BP monitoring (24hr-BP, day-BP and night-BP). Carotid-femoral pulse wave velocity (PWV) was measured by the SphygmoCor XCEL as a marker of macrovascular organ damage. Results Hypertensive patients (n = 73, BP 132.9 ± 17.4/79.4 ± 14.0) compared to normotensive patients (n = 10, BP 113.4 ± 10.4/71.3 ± 9.6) had higher levels of EVs (10.6 ± 8.2 vs 6.5 ± 4.5 EV/µL; p = 0.02). Circulating EVs were positively correlated with nocturnal systolic BP (r= 0.3; p = 0.01) and night-time dipping (r= -0.26; p = 0.02) in univariable analysis. In contrast, systolic AOBP, 24hr-BP and day-BP did not show significant associations. No significant correlations were found with diastolic BP. EVs were significantly correlated with PWV (r = 0.26 p = 0.02).While all BP measures were associated with PWV, average systolic night-time BP demonstrated the strongest correlation with PWV (r = 0.55; p < 0.001) compared to systolic AOBP (r = 0.51; p < 0.001), 24hr-BP (r = 0.46; p < 0.001), and average day-BP (r = 0.48; p < 0.001). Multivariable regression models confirmed robustness of the models. Conclusion We demonstrate a close positive relationship between a variety of BP measures and levels of circulating EVs as well as macrovascular damage assessed by PWV. The strongest correlation with EVs was found for average systolic nocturnal BP. Given that average nocturnal BP is the strongest predictor of CV events, EVs may serve as a useful integrative marker of vascular health and useful biomarker for CV risk assessment, a proposition that will need to be tested in prospective clinical trials. Abstract Figure.