Effect of atorvastatin and fish oil on plasma high-sensitivity C-reactive protein concentrations in individuals with visceral obesity.
BACKGROUND
Chronic low-grade inflammation may contribute to the increased risk of atherosclerosis in visceral obesity. Statin and fish oil have been reported to have antiinflammatory effects. We studied whether dyslipidemic, obese individuals have increased plasma high-sensitivity C-reactive protein (hs-CRP) concentrations and whether treatment with atorvastatin and fish oil lowered plasma hs-CRP concentrations.


METHODS
We compared plasma hs-CRP, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) concentrations in 48 obese individuals with the concentrations in 10 lean normolipidemic men. The obese individuals were then randomized to treatment with atorvastatin (40 mg/day), fish oil (4 g/day), atorvastatin plus fish oil, or matching placebo for 6 weeks.


RESULTS
Compared with controls, obese individuals had increased hs-CRP [geometric mean, 2.19 mg/L (95% confidence interval, 2.15-3.15 mg/L) vs 0.49 mg/L (0.30- 0.93 mg/L); P <0.001] and IL-6 [351 pg/L (318-449 pg/L) vs 251 pg/L (211-305 pg/L); P <0.01]. Atorvastatin treatment had a significant main effect of decreasing plasma hs-CRP (-0.87 mg/L; 95% confidence interval, -0.10 to -1.60 mg/L; P <0.01) and IL-6 (-70 pg/L; 10 to -140 pg/L; P <0.01), but this was not seen with fish oil. The reductions in hs-CRP with atorvastatin were not significantly correlated to changes in plasma lipids, IL-6, insulin resistance, or cholesterogenesis. Plasma TNF-alpha concentrations in obese individuals, however, were neither statistically different from concentrations in the lean controls nor altered with atorvastatin or fish oil treatment.


CONCLUSIONS
This study shows that visceral obesity is associated with increased plasma hs-CRP and IL-6 and, hence, a low-grade chronic inflammatory state and that treatment with atorvastatin or atorvastatin with fish oil, but not fish oil alone, reverses this abnormality.
Chan
Dick C
DC
University Department of Medicine, University of Western Australia and the Western Australia Institute for Medical Research, Royal Perth Hospital, Perth, Western Australia WA 6847, Australia.
Watts
Gerald F
GF
Barrett
P Hugh R
PH
Beilin
Lawrence J
LJ
Mori
Trevor A
TA
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003124:Colorimetry; D003430:Cross-Sectional Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007118:Immunoassay; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000924:Anticholesteremic Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D005395:Fish Oils; D006538:Heptanoic Acids; D015850:Interleukin-6; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases