Effect of plasma cholesterol reduction by pravastatin on the functional properties of forearm arteries in hypercholesterolemic patients.
OBJECTIVE
Since functional properties in the vasculature of hypercholesterolemic subjects are impaired, a six-month pravastatin treatment (20 mg/die) was tested in an open design, on the impaired unstimulated forearm arterial compliance (Un-FAC(AUC)) of 14 asymptomatic type IIa familial hypercholesterolemic patients. In order to evaluate whether FAC(AUC) changes might be related to the extent of cholesterol reduction achieved, this evaluation was carried out in five severely hypercholesterolemic patients, undergoing LDL-apheresis.


RESULTS
Arterial functional properties, i.e. FAC(AUC) responses to glyceryl trinitrate (GTN-FAC(AUC)) and acetylcholine (ACh-FAC(AUC), four patients) and the effects on rest and peak forearm blood flow and vascular resistance were evaluated on the non-dominant arm using plethysmographic methods, that also allow the direct assessment of the non-linear "compliance-blood pressure" curve. Selective LDL-apheresis was performed by using a dextran-sulphate column. Pravastatin effectively lowered plasma total (-16%, p = 0.002) and LDL cholesterol levels (-22%, p = 0.006 vs baseline). Rest and peak flow, basal and post ischemic vascular resistance were not affected as well as Un-FAC(AUC) and GTN-FAC(AUC). However, in the four hypercholesterolemic patients undergoing ACh infusion, there was an improvement in the ACh-FAC(AUC) of borderline statistical significativity (p = 0.056). LDL-apheresis reduced plasma total and LDL cholesterol levels by 55% and 59%, without affecting blood pressure. In this series of five patients Un-FAC(AUC) increased, the Un-FAC(AUC) 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 hypocholesterolemic treatment with pravastatin, although able to improve the lipid profile, cannot alter significantly blood flow, vascular resistance, Un-FAC(AUC) and GTN-FAC(AUC). A possible selective improvement in the ACh-receptor-activated signal transduction pathway has been observed and the importance of a drastic reduction of cholesterol concentrations in order to affect the Un-FAC(AUC) is suggested.
Baldassarre
D
D
E. Grossi Paoletti Center, Institute of Pharmacological Sciences, University of Milan, Italy.
Busnach
G
G
Amato
M
M
Pazzucconi
F
F
Sirtori
C R
CR
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D001781:Blood Component Removal; D001916:Brachial Artery / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D010991:Plethysmography; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D014665:Vasodilator Agents; D005996:Nitroglycerin; D017035:Pravastatin; D000109:Acetylcholine