Peripheral vasoactivity in familial hypercholesterolemic subjects treated with heparin-induced extracorporeal LDL precipitation (HELP)

Abstract

Hypercholesterolemia is associated with abnormalities in arterial vasoactivity which can be reversed with cholesterol-reducing therapies. Heparin-induced extracorporeal LDL precipitation (HELP), an invasive method for treating refractory hypercholesterolemia, causes regression of both xanthomas and atherosclerosis, but its effect on vasoactivity has not been investigated. We tested the effects of HELP on vasoactivity with an ultrasound system for continuous measurement of arterial flow velocity and end-diastolic diameter. We measured brachial artery vasoactivity before, during, and after a 5 min forearm vascular occlusion. Vasoactivity measurements were acquired from 6 subjects with familial hypercholesterolemia (FH) who had been treated chronically with HELP, immediately before and after each of 4 treatments, and from 12 age- and sex-matched normocholesterolemic subjects (2 matched with each HELP subject). Peak arterial dilation after cuff release, relative to the pre-occlusion diameter, was similar for the pre-treatment, post-treatment, and normocholesterolemic groups (0.29 mm pre-treatment, 0.30 mm post-treatment and 0.33 mm normocholesterolemic, P=NS). The slope of arterial diameter during occlusion was also similar for the three groups (−0.10 μm/s pre-treatment, 0.02 μm/s post-treatment, and 0.06 μm/s normocholesterolemic, P=NS). These two parameters are known to be decreased in hypercholesterolemic subjects to an extent which could be readily detected by the power of this study. Interestingly, one homozygous FH subject consistently demonstrated significant improvement in these two parameters immediately after HELP, suggesting an individual difference in arterial physiology. On average, FH patients treated chronically with HELP have similar vasoactivity to age- and sex-matched subjects with low risk for atherosclerosis. This result, in light of the many studies that have associated hypercholesterolemia with abnormal vasoactivity, suggests that chronic HELP therapy improves vasoactivity in patients with severe hypercholesterolemia.