The ability of statins to protect low density lipoprotein from oxidation in hypercholesterolemic patients.
OBJECTIVE
It is unclear at the present time whether hydroxy-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors; statins) exert a protective effect on low-density lipoproteins (LDL) oxidation in vivo. In addition, it is speculated that pharmacological differences between statins may account for differences in their antioxidative capacities. This is of clinical relevance, because there is strong evidence that oxidized LDL initiates the atherosclerosis process.


METHODS
In a controlled, randomized, double-blind study we compared the effects of three different statins (simvastatin, pravastatin and atorvastatin) on the ability to protect LDL from oxidation in 70 hypercholesterolemic but otherwise healthy subjects. Statins were administered in doses which were nearly equi-effective in lowering LDL-cholesterol. Changes in LDL oxidation were measured using diene conjugation (DIENES) and thiobarbituric acid reactive substances (TBARS) at entry and three months after beginning therapy with the statins.


RESULTS
Levels of DIENES, usually generated during the early phases of lipid peroxidation, were significantly reduced by 10.2 +/- 5.5% (mean +/- SEM; p < 0.03), 6.0 +/- 2.0% (p < 0.005) versus baseline in the case of pravastatin and atorvastatin but simvastatin had no significant effect with a mean reduction of 5.5 +/- 6.4% (p > 0.23). Levels of TBARS, reflecting late phases of LDL oxidation, showed no significant changes against baseline (p > 0.34). Pooled data (n = 70) indicated that statins reduce DIENES levels by approximately 9% versus baseline (p < 0.005) but had no significant effect on TBARS levels (p > 0.29) after three months of therapy.


CONCLUSIONS
This study showed that atorvastatin and pravastatin were capable of protecting LDL from oxidation in vivo in the early treatment phase. Pooled data levels of DIENES were significantly affected by statin therapy over a period of 3 months. No protective effect appeared to be present in the late phases of oxidation evaluated using measurement of TBARS but it should be noted that the clinical impact of such observations are currently discussed controversially in the literature.
Thallinger
C
C
Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria.
Urbauer
E
E
Lackner
E
E
Graselli
U
U
Kostner
K
K
Wolzt
M
M
Joukhadar
C
C
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D017035:Pravastatin / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D017392:Thiobarbituric Acid Reactive Substances; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin