Antioxidant Effects of Statins in Patients with Atherosclerotic Cerebrovascular Disease
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Background and Purpose Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropicand low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that highdose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke afterstatin use. This study evaluated changes in oxidative stress markers after short-term use of ahigh-dose statin in patients with atherosclerotic stroke. Methods Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and1 month after dosing, and the serum levels of four oxidative stress markers–malondialdehyde(MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)–were evaluated to determine the oxidation of MDA and lipids, proteins,and DNA, respectively, at both of those time points. Results The baseline levels and the degrees of reduction after statin use differed among theoxidative stress markers measured. MDA and PCO levels were associated with infarct volumeson diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin usedecreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While thereduction in MDA levels after statin use was not associated with changes in cholesterol, that inoxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL(r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05). Conclusions The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidativestress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidationvia lipid-lowering-dependent and -independent mechanisms, but not against protein or DNAoxidation in atherosclerotic stroke patients.
Abstract
Background and Purpose Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropicand low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that highdose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke afterstatin use. This study evaluated changes in oxidative stress markers after short-term use of ahigh-dose statin in patients with atherosclerotic stroke. Methods Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and1 month after dosing, and the serum levels of four oxidative stress markers–malondialdehyde(MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)–were evaluated to determine the oxidation of MDA and lipids, proteins,and DNA, respectively, at both of those time points. Results The baseline levels and the degrees of reduction after statin use differed among theoxidative stress markers measured. MDA and PCO levels were associated with infarct volumeson diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin usedecreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While thereduction in MDA levels after statin use was not associated with changes in cholesterol, that inoxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL(r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05). Conclusions The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidativestress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidationvia lipid-lowering-dependent and -independent mechanisms, but not against protein or DNAoxidation in atherosclerotic stroke patients.
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