Effect of plasma cholesterol reduction by pravastatin on the functional properties of forearm arteries in hypercholesterolemic patients

Background and Aim: Since functional properties in the vasculature of hyper cholesterolemic subjects are impaired, a six-month pravastatin treatment (2 0 mg/die) was tested in an open design, on the impaired unstimulated forear m arterial compliance (Un-FAC((AUC))) of 14 asymptomatic type IIa familial hypercholesterolemic patients. In order to evaluate whether FAC((AUC)) chan ges might be related to the extent of cholesterol reduction achieved, this evaluation was carried out in five severely hypercholesterolemic patients, undergoing LDL-apheresis. Methods and Results: Arterial functional properties, ie FAC((AUC)) response s to glyceryl trinitrate (GTN-FAC((AUC))) and acetylcholine (ACh-FAC((AUC)) ), four patients) and the effects on rest and peak forearm blood flow and v ascular resistance were evaluated on the non-dominant arm using plethysmogr aphic methods, that also allow the direct assessment of the non-linear "com pliance-blood pressure" curve. Selective LDL-apheresis was performed by usi ng a dextran-sulphate column. Pravastatin effectively lowered plasma total (-16%, p=0.002) and LDL choles terol levels (-22%, p=0.006 vs baseline). Rest and peak flow, basal and pos t ischemic vascular resistance were not affected as well as Un-FAC((AUC)) a nd GTN-FAC((AUC)).However, in the four hypercholesterolemic patients underg oing ACh infusion, there was an improvement in the ACh-FAC((AUC)) Of border line statistical significativity (p=0.056). LDL-apheresis reduced plasma to tal and LDL cholesterol levels by 55% and 59%, without affecting blood pres sure. In this series of five patients Un-FAC((AUC)) increased the Un-FAC((A UC)) rise being inversely related to the absolute reduction of plasma total (r=0.92, p<0.05) and LDL cholesterol (r=0.89, p<0.05) levels. Conclusions: In hypercholesterolemic patients a short-term hypocholesterole mic treatment with pravastatin, although able to improve the lipid profile, cannot alter significantly and GTN- blood flow vascular resistance, Un-FAC ((AUC)) and GTN-FAC((AUC)). A possible selective improvement in the ACh-rec eptor-activated signal transduction pathway has been observed and the impor tance of a drastic reduction of cholesterol concentrations in order to affe ct the Un-FAC((AUC)) is suggested. (C) 1999, Medikal Press.