TY - JOUR

T1 - Global REACH 2018

T2 - High Blood Viscosity and Hemoglobin Concentration Contribute to Reduced Flow-Mediated Dilation in High-Altitude Excessive Erythrocytosis

AU - Tremblay, Joshua C

AU - Hoiland, Ryan L

AU - Howe, Connor A

AU - Coombs, Geoff B

AU - Vizcardo-Galindo, Gustavo A

AU - Figueroa-Mujíca, Rómulo J

AU - Bermudez, Daniela

AU - Gibbons, Travis D

AU - Stacey, Benjamin S

AU - Bailey, Damian M

AU - Tymko, Michael M

AU - MacLeod, David B

AU - Gasho, Chris

AU - Villafuerte, Francisco C

AU - Pyke, Kyra E

AU - Ainslie, Philip N

PY - 2019/6

Y1 - 2019/6

N2 - Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk in highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) in male Andeans with and without EE. We hypothesized that FMD would be impaired in Andeans with EE after accounting for shear stress and that FMD would improve after isovolemic hemodilution. Brachial artery shear stress and FMD were assessed in 23 male Andeans without EE (age: 40±15 years [mean±SD]; Hb<21 g/dL) and 19 male Andeans with EE (age: 43±14 years; Hb≥21 g/dL) in Cerro de Pasco, Peru (4330 m). Shear stress was quantified from Duplex ultrasound measures of shear rate and blood viscosity. In a subset of participants (n=8), FMD was performed before and after isovolemic hemodilution with blood volume replaced by an equal volume of human serum albumin. Blood viscosity and Hb were 48% and 23% higher (both P<0.001) and FMD was 28% lower after adjusting for the shear stress stimulus ( P=0.013) in Andeans with EE compared to those without. FMD was inversely correlated with blood viscosity ( r2=0.303; P<0.001) and Hb ( r2=0.230; P=0.001). Isovolemic hemodilution decreased blood viscosity by 30±10% and Hb by 14±5% (both P<0.001) and improved shear stress stimulus-adjusted FMD from 2.7±1.9% to 4.3±1.9% ( P=0.022). Hyperviscosity, high Hb, or both, actively contribute to acutely reversible impairments in FMD in EE, suggesting that this plays a pathogenic role in the increased cardiovascular risk.

AB - Excessive erythrocytosis (EE; hemoglobin concentration [Hb] ≥21 g/dL in adult males) is associated with increased cardiovascular risk in highlander Andeans. We sought to quantify shear stress and assess endothelial function via flow-mediated dilation (FMD) in male Andeans with and without EE. We hypothesized that FMD would be impaired in Andeans with EE after accounting for shear stress and that FMD would improve after isovolemic hemodilution. Brachial artery shear stress and FMD were assessed in 23 male Andeans without EE (age: 40±15 years [mean±SD]; Hb<21 g/dL) and 19 male Andeans with EE (age: 43±14 years; Hb≥21 g/dL) in Cerro de Pasco, Peru (4330 m). Shear stress was quantified from Duplex ultrasound measures of shear rate and blood viscosity. In a subset of participants (n=8), FMD was performed before and after isovolemic hemodilution with blood volume replaced by an equal volume of human serum albumin. Blood viscosity and Hb were 48% and 23% higher (both P<0.001) and FMD was 28% lower after adjusting for the shear stress stimulus ( P=0.013) in Andeans with EE compared to those without. FMD was inversely correlated with blood viscosity ( r2=0.303; P<0.001) and Hb ( r2=0.230; P=0.001). Isovolemic hemodilution decreased blood viscosity by 30±10% and Hb by 14±5% (both P<0.001) and improved shear stress stimulus-adjusted FMD from 2.7±1.9% to 4.3±1.9% ( P=0.022). Hyperviscosity, high Hb, or both, actively contribute to acutely reversible impairments in FMD in EE, suggesting that this plays a pathogenic role in the increased cardiovascular risk.

KW - Adult

KW - Altitude

KW - Blood Viscosity/physiology

KW - Brachial Artery/diagnostic imaging

KW - Endothelium, Vascular/physiopathology

KW - Hemoglobins/metabolism

KW - Humans

KW - Male

KW - Polycythemia/blood

KW - Regional Blood Flow/physiology

KW - Risk Factors

KW - Ultrasonography, Doppler

KW - Vasodilation/physiology

U2 - 10.1161/HYPERTENSIONAHA.119.12780

DO - 10.1161/HYPERTENSIONAHA.119.12780

M3 - Article

C2 - 31006327

VL - 73

SP - 1327

EP - 1335

JO - Hypertension (Dallas, Tex. : 1979)

JF - Hypertension (Dallas, Tex. : 1979)

SN - 0194-911X

IS - 6

ER -