Rapid effect of pravastatin on endothelial function and lipid peroxidation in unstable angina.
BACKGROUND
Oxidative stress contributes to endothelial dysfunction, an important step to the pathogenesis of atherosclerosis and coronary events. Latest studies revealed the existence of pleiotropic and especially antioxidant properties of statins. We sought to examine the effects of pravastatin on lipid peroxidation and endothelial function, independently from lipid-lowering, in patients with unstable angina (UA).


METHODS
Thirty-seven patients (males), 64.46+/-9.09 years, suffering from UA enrolled in the study. Patients were not on statin medication before admission and they received after randomization either 40 mg pravastatin daily (group A, n = 20), or placebo (group B, n = 17). Malondialdehyde (MDA) concentration, an index of lipid peroxidation and plaque instability, flow-mediated dilatation (FMD) of the brachial artery and blood lipids were measured on the second day of hospitalization and 10 days later.


RESULTS
MDA decreased significantly in both groups (A, p = 0.008; B, p = 0.003). FMD increased significantly in group A (p = 0.007), whereas in group B it did not change. Serum lipids remained unaltered in all three groups.


CONCLUSIONS
Pravastatin administration improved FMD within 10 days and this favorable effect occurred before any significant reduction in blood lipids, revealing its pleiotropic effects during the early phase of an acute coronary syndrome. Circulating lipid peroxidation products in patients with UA decreased significantly during the same period independently of endothelial function and pravastatin therapy.
Karatzis
Emmanouil
E
Vascular Laboratory, Department of Clinical Therapeutics, Alexandra University Hospital, 12 Iridanou str., Athens 11528, Greece.
Lekakis
John
J
Papamichael
Christos
C
Andreadou
Ioanna
I
Cimponeriu
Adriana
A
Aznaouridis
Konstantinos
K
Papaioannou
Theodoros G
TG
Protogerou
Athanassios
A
Mavrikakis
Myron
M
D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy* / Q000503:physiopathology; D001916:Brachial Artery / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde; D008875:Middle Aged; D009687:Nuclear Proteins / Q000187:drug effects; D018384:Oxidative Stress; D010919:Placebos; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009687:Nuclear Proteins; D010919:Placebos; D008315:Malondialdehyde; D017035:Pravastatin