SINGLE LDL APHERESIS IMPROVES ENDOTHELIUM-DEPENDENT VASODILATATION INHYPERCHOLESTEROLEMIC HUMANS

Background Although long-term lipid-lowering therapy improves endothel ium-dependent vasodilatation in humans, it remains unknown whether the short-term removal of LDL per se ameliorates endothelial dysfunction. Methods and Results To examine the effects of a single session of LDL apheresis on endothelial function in patients with hypercholesterolem ia, we measured forearm blood flow (FBF) by strain-gauge plethysmograp hy before and after single LDL apheresis while infusing acetylcholine (ACh; 4 to 24 mu g/min) and sodium nitroprusside (SNP; 0.2 to 1.2 mu g /min). The single session of LDL apheresis reduced total LDL (from 142 .2+/-15.0 to 32.6+/-5.0 mg/mL, P<.0005) and oxidized LDL (from 111.6+/ -22.8 to 30.0+/-5.4 ng/mL, P<.005). Although ACh and SNP increased FBF dose-dependently before and after LDL apheresis, the endothelium-depe ndent vasodilatation responses to ACh were significantly augmented (P< .01) after the single session of LDL apheresis without changes in the endothelium-independent vasodilatation responses to SNP. The plasma le vels of total and oxidized LDL correlated with the degree of ACh-induc ed vasodilatation. Furthermore, the local production of nitrate/nitrit e, metabolites of NO, during ACh infusion was significantly (P<.05) au gmented by LDL apheresis, and there was a significant correlation betw een the degree of ACh-induced vasodilatation and the production in nit rate/nitrite (r=.99, P<.0005). Conclusions We demonstrated that even a single session of LDL apheresis with the reduction of total LDL and o xidized LDL improved endothelial function. Our results suggest that to tal LDL and/or oxidized LDL may directly impair endothelial function i n the human forearm vessel.