[Effect of high doses of atorvastatin on the endothelial function of the coronary arteries].
OBJECTIVE
The aim of this study is to investigate the role of high doses of atorvastatin (80 mg per day) in the treatment of endothelium dysfunction of the coronary arteries.


METHODS
Intracoronary acethylcholine test was performed for 28 (16 in treatment group and 12 in control group) patients who had normal coronary angiogram or minimal lesions (stenosis <50%) and symptomatic coronary heart disease. Acetylcholine was given into left coronary artery in three stages (2 min each) at estimated intracoronary concentrations 10(-6) mol/l, 3.3x10(-6) mol/l,and 10(-5) mol/l. Treatment group patients were given atorvastatin 80 mg per day. Intracoronary acetylcholine test was repeated after six months. The target segment was the segment that exhibited the maximal constrictive response at baseline in a given patient.


RESULTS
Total cholesterol was reduced by 40.6+/-11.2% (p<0.001), low density lipoproteins cholesterol by 55.4+/-14% (p<0.001), triglycerides by 29.6% (p<0.05) and high density lipoproteins cholesterol was increased by 24.7% (p<0.05) in atorvastatin group after 6 months of therapy. No significant lipid changes were observed in the control group. Sixteen target segments in the treatment group and 12 segments in the control group were selected for primary efficacy parameter. The vasoconstrictor reaction to acetylcholine was similar at baseline in both groups: -16.8%+/-11.6% of diameter in atorvastatin group and -14.2%+/-13.7% in control group (p=0.58) at dose 10(-6) mol/l, -43.5%+/-21.2% in atorvastatin group and -41.2%+/-22.4% in control group (p=0.79) at dose 3.3x10(-6) mol/l, -64.5%+/-12.4% in atorvastatin group and -57.4%+/-15.6% in control group (p=0.35) at dose 10(-5) mol/l. Treatment with high doses of atorvastatin markedly decreased acetylcholine - induced vasoconstriction: -6.5%+/-14.5% of diameter in atorvastatin group versus -18.3%+/-14.0% in control group (p=0.04) at dose 10(-6) mol/l, -19.7%+/-22.8% in atorvastatin group versus -40.0%+/-25.0% in control group (p=0.034) at dose 3.3x10(-6) mol/l, -29.9%+/-21.3% in atorvastatin group (6 segments) versus -48.7%+/-19.0% in control group (3 segments, p=0.24) at dose 10(-5) mol/l.


CONCLUSIONS
Treatment with high doses of atorvastatin significantly improves endothelium-mediated response to acetylcholine in the coronary arteries of the patients with minimal lesions.
Simaitis
Audrius
A
Klaipeda Seamen's Hospital, Vilnius University, Liepojos pl. 45, 5809 Klaipeda, Lithuania. audrsima@takas.lt
Laucevicius
Aleksandras
A
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003627:Data Interpretation, Statistical; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage*; D012044:Regression Analysis; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D000109:Acetylcholine