Global Reach 2018: Reduced Flow-Mediated Dilation Stimulated by Sustained Increases in Shear Stress in High-Altitude Excessive Erythrocytosis

Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g dl-1 in adult males) is a maladaptive high-altitude pathology associated with increased cardiovascular risk and reduced reactive hyperemia flow-mediated dilation; however, whether a similar impairment occurs in response to more commonly-encountered sustained increases in shear stress (SS-FMD) over a range of overlapping stimuli is unknown. We characterized SS-FMD in response to handgrip exercise in Andeans with and without EE in Cerro de Pasco, Peru (4330 m). Andean highlanders with (n=17, Hb=23.2±1.2 g dl-1) and without EE (n=23, Hb=18.7±1.9 g dl-1) performed three-minutes of rhythmic handgrip exercise at 20%, 35%, and 50% of maximum voluntary contraction (MVC). Duplex ultrasound was used to continuously record blood velocity and diameter in the brachial artery, and blood viscosity was measured to accurately calculate shear stress. Although baseline shear stress did not differ, Andeans with EE had 22% lower shear stress than Andeans without at 50% MVC (P=0.004). At 35% and 50% MVC, SS-FMD was 2.1±2.0% and 2.8±2.7% in Andeans with EE compared to 4.1±3.4% and 7.5±4.5% in those without (P=0.048 and P<0.001). The stimulus-response slope (∆shear stress versus ∆diameter) was lower in Andeans with EE compared to Andeans without (P=0.028). This slope was inversely related to Hb in Andeans with EE (r2=0.396, P=0.007). A reduced SS-FMD in response to small muscle mass exercise in Andeans with EE indicates a generalized reduction in endothelial sensitivity to shear stress, which may contribute to increased cardiovascular risk in this population.