Comparison Effect of Atorvastatin (10 versus 80 mg) on Biomarkers of Inflammation and Oxidative Stress in Subjects With Metabolic Syndrome

Uma Singh, Sridevi Devaraj, Ishwarlal Jialal, David Siegel

Research output: Contribution to journalArticle

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Abstract

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-κB [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.

Original languageEnglish (US)
Pages (from-to)321-325
Number of pages5
JournalAmerican Journal of Cardiology
Volume102
Issue number3
DOIs
StatePublished - Aug 1 2008

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Oxidative Stress
Biomarkers
Inflammation
NF-kappa B
Matrix Metalloproteinase 9
C-Reactive Protein
LDL Cholesterol
F2-Isoprostanes
Atorvastatin Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL Lipoproteins
Superoxides
Lipoproteins
Coronary Disease
Monocytes
Cardiovascular Diseases
Placebos
Clinical Trials
Lipids
oxidized low density lipoprotein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Comparison Effect of Atorvastatin (10 versus 80 mg) on Biomarkers of Inflammation and Oxidative Stress in Subjects With Metabolic Syndrome. / Singh, Uma; Devaraj, Sridevi; Jialal, Ishwarlal; Siegel, David.

In: American Journal of Cardiology, Vol. 102, No. 3, 01.08.2008, p. 321-325.

Research output: Contribution to journalArticle

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abstract = "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-κB [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.",
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