Beneficial effects of atorvastatin on myocardial regions with initially low vasodilatory capacity at various stages of coronary artery disease.
OBJECTIVE
The aim of this study was to analyse non-invasively the regional effect of therapy with an HMG-CoA reductase inhibitor on myocardial blood flow in patients with coronary artery disease (CAD) with special reference to segments with initially substantially impaired vasodilation.


METHODS
The study included 26 patients with untreated hypercholesterolaemia. Coronary angiography revealed CAD in nine patients with stenosis >50% and wall irregularities or minimal stenosis <30% in 17 patients. Before and 4.6+/-1.8 months after atorvastatin therapy, ( 13)N-ammonia positron emission tomography (PET) studies were performed at rest and under pharmacological stress. Minimum coronary vascular resistance (MCR) and coronary flow reserve (CFR) were determined. Segments were divided into those with normal or near-normal (MBF during adenosine > or =2.0 ml/min/g) and those with abnormal (MBF<2.0 ml/min/g) vasodilator flow response. In CAD patients, 156 segments were analysed, 85 of which had abnormal MBF; in the non-obstructive group, 59 of 297 segments had abnormal MBF.


RESULTS
LDL cholesterol decreased after atorvastatin therapy from 186+/-43 mg/dl to 101+/-26 mg/dl (p<0.001). In normal segments no significant changes in MBF, CFR and MCR were found. However, initially abnormal segments showed significant improvements in MCR (15%, p<0.0001) and MBF during adenosine (30%, p<0.0001) after therapy.


CONCLUSIONS
The improvement in regional coronary vasodilator function after atorvastatin in patients with coronary atherosclerosis may be caused, at least in part, by increased flow-mediated (endothelium-dependent) dilation of the total arteriolar and arterial vascular system. These data further support the concept of non-invasive management of stable CAD by statin therapy and life-style modification guided by PET.
Wielepp
Peter
P
Institute of Molecular Biophysics, Radiopharmacy and Nuclear Medicinea, Ruhr-University Bochum, Bad Oeynhausen, Germany. peter.wielepp@gmx.de
Baller
Detlev
D
Gleichmann
Ulrich
U
Pulawski
Ewa
E
Horstkotte
Dieter
D
Burchert
Wolfgang
W
D000368:Aged; D000069059:Atorvastatin; D001783:Blood Flow Velocity; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000187:drug effects; D018450:Disease Progression; D005080:Exercise Test; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D011877:Radionuclide Imaging; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000209:etiology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin