Pravastatin and functional properties of forearm arteries in hypercholesterolemic patients

Studies in the experimental animal and in hypercholesterolemic patients have shown that reduction of serum cholesterol may improve defective endothelium-dependent vasodilation of arterial beds. In this study we have investigated, according to an open design, whether six month pravastatin treatment (20 mg/die) was able to restore the impaired unstimulated forearm arterial compliance (Un-FAC(AUC)) in 14 asymptomatic type IIa hypercholesterolemic patients. The effects of pravastatin on FAC(AUC) responses to glyceryl trinitrate (GTN-FAC(AUC)) and acetylcholine (ACh-FAC(AUC)) and the effects on the characteristics of rest and post-ischaemic forearm blood flow and vascular resistance were also investigated. An additional group of five severely hypercholesterolemic patients was also selected and the effect of LDL-apheresis on the Un-FAC(AUC) evaluated. At the end of treatment a significant decrease of plasma LDL-C levels (22%, p=0.006 vs baseline) was found. In contrast, heart rate, blood pressure, rest flow, basal forearm vascular resistance, peak flow, minimal resistances, total-time of hyperemia and unstimulated or GTN-stimulated FAC(AUC) were not affected by the treatment. Instead, a modest effect of pravastatin on the response to Ach was observed; pravastatin treatment increased the dose-response curve to ACh, but the difference observed was of borderline statistical significance (p=0.06). In three out of the five patients exposed to treatment with LDL-apheresis, an immediate post-apheresis improvement of Un-FAC(AUC) was demonstrated; moreover, a strong inverse correlation was found between the increase in Un-FAC(AUC) after LDL-apheresis and the reduction of total and LDL cholesterol (r=0.92 and 0.89, respectively; both p<0.05). In conclusion, these data suggest that in hypercholesterolemic patients a short term hypocholesterolemic treatment with pravastatin, although improving the plasma lipid profile, does not alter significantly the functional properties of forearm arteries. Furthermore, the results obtained with patients treated with LDL-apheresis suggest that FAC(AUC) changes are related to the cholesterol reduction achieved.