Objective--During hypoxia, active substances released by the endothelium play a key role in the cardiovascular and respiratory responses elicited to optimize oxygen delivery. As hypercholesterolemia is a major cause of endothelial dysfunction, it may interfere with these responses.

Methods and Results--We studied cardiovascular and ventilatory responses to acute systemic hypoxia in 14 patients with hypercholesterolemia (HC) and 13 control (CO) subjects. Oxygen saturation decreased similarly in both groups. Diastolic blood pressure increased only in the HC group (P=0.0002) and, despite systolic blood pressure increases both in HC groups, 140±4 (95% confidence interval [CI],131 to 149 mm Hg) to 154±4 mm Hg (95% CI,145 to 164 mm Hg), and in the CO group, 133±3 (95% CI,126 to 140 mm Hg) to 140±4 mm Hg (95% CI,132 to 148 mm Hg), the HC group showed an enhanced pressor response (P=0.03, group comparison). Both groups had increased forearm blood flow, but the decrease in forearm vascular resistance in the CO group, 40±5 (95% CI, 30 to 51 UR) to 31±4 UR (95% CI,23 to 39 UR) (P=0.0001) was not seen in the HC group, 29±3 (95% CI, 22 to 37 UR) to 26±3 UR (95% CI, 20 to 33 UR), (P=0.03, group comparison).

Conclusions--Hypercholesterolemic patients demonstrate a hyperreactive pressor response and absence of forearm vasodilation during acute systemic hypoxia.