Comparison effect of atorvastatin (10 versus 80 mg) on biomarkers of inflammation and oxidative stress in subjects with metabolic syndrome.
Metabolic syndrome (MS), characterized by low-grade inflammation, confers an increased risk for cardiovascular disease. Statins, in addition to having lipid-lowering effects, have pleiotropic effects and decrease biomarkers of inflammation and oxidative stress. The Treating to New Target Study showed a greater decrease in low-density lipoprotein (LDL) cholesterol and cardiovascular events with atorvastatin 80 mg versus 10 mg in patients with MS with coronary heart disease. However, part of this benefit could be caused by the greater pleiotropic effects of the higher dose of atorvastatin. The dose-response effect of atorvastatin on biomarkers of inflammation and oxidative stress has not been investigated in subjects with MS. Thus, the dose-response effect of atorvastatin on biomarkers of inflammation (high-sensitivity C-reactive protein [hs-CRP], matrix metalloproteinase-9, and nuclear factor-kappaB [NF-kB] activity) and oxidative stress (oxidized LDL, urinary nitrotyrosine, F2-isoprostanes, and monocyte superoxide release) was tested in a randomized double-blind clinical trial in subjects with MS. Seventy subjects were randomly assigned to receive placebo or atorvastatin 10 or 80 mg/day for 12 weeks. A strong dose-response (atorvastatin 10 compared with 80 mg, p <0.05) was observed for changes in total, LDL (32% and 44% reduction), non-high-density lipoprotein (28% and 40% reduction), and oxidized LDL cholesterol (24% and 39% reduction) at atorvastatin 10 and 80 mg, respectively. Hs-CRP, matrix metalloproteinase-9, and NF-kB significantly decreased in the 80-mg atorvastatin group compared with baseline. In conclusion, this randomized trial of subjects with MS showed the superiority of atorvastatin 80 mg compared with its 10-mg dose in decreasing oxidized LDL, hs-CRP, matrix metalloproteinase-9, and NF-kB activity.
Singh
Uma
U
The Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, California, USA.
Devaraj
Sridevi
S
Jialal
Ishwarlal
I
Siegel
David
D
D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D000069059:Atorvastatin; D015415:Biomarkers / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D028441:F2-Isoprostanes / Q000032:analysis; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology*; D020959:Polyethylene / Q000032:analysis; D011758:Pyrroles / Q000008:administration & dosage*; D013481:Superoxides / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000652:urine
D000924:Anticholesteremic Agents; D015415:Biomarkers; D028441:F2-Isoprostanes; D006538:Heptanoic Acids; D016328:NF-kappa B; D011758:Pyrroles; D013481:Superoxides; D014443:Tyrosine; D020959:Polyethylene; D002097:C-Reactive Protein; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9