Correlation between inflammation and oxidative stress in normocholesterolemic coronary artery disease patients 'on' and 'off atorvastatin for short time intervals

Aim of the study: To assess whether variations in antioxidant and anti-inflammatory parameters occur with short term administration and discontinuation of atorvastatin in normocholesterolemic coronary artery disease (CAD) patients. Methods: Forty CAD patients with near normal serum cholesterol levels (total cholesterol < 240 mg/dl, LDL cholesterol < 130 mg/dl) were continuously enrolled and randomized to groups A & B (20 patients taking atorvastatin) and groups C & D (20 patients not taking atorvastatin). Atorvastatin (10 mg/day) was continued in group A, withdrawn in group B and started in groups C & D for 6 weeks. Thereafter atorvastatin was withdrawn in group A and C, restarted in group B, and continued in group D for further 6 weeks. CRP, FRAP and TBARS were assessed at baseline, 6 weeks and 12 weeks in all the groups. Results: Baseline CRP, TBARS and FRAP levels were significantly different (p < 0.05) between groups A & B and C & D at the time of enrollment, indicating lower levels of oxidative stress (FRAP-172.40 +/- 23.41 nmol Fe2+/l VS 142.62 +/- 15.73 nmol Fe2+/l and TBARS-3.66 +/- 1.14 nmol/nd vs 6.11 +/- 1.85 nmol/ml) and low grade inflammation (CRP-1.38 +/- 0.69 mg/l vs 3.19 +/- 1.77 mg/l) in statin treated groups. In group B, discontinuation resulted in increase in CRP (2.87 +/- 0.98 mg/l) and TBARS (5.75 +/- 1.35 nmol/ml) and decrease in FRAP (133.132 +/- 13.32 nmol Fe2+/l) and whereas group A patients did not show significant variation in values compared to baseline (CRP-1.36 +/- 0.33 mg/l, FRAP-155.45 +/- 19.51 and TBARS-4.22 +/- 0.81). Administration of atorvastatin caused a marked reduction in oxidative stress and inflammation in groups C & D (CRP-1.13 +/- 0.99 mg/l & 1.73 +/- 1.60 mg/l, FRAP-166.54 +/- 34.11 & 177.44 +/- 13.31 nmol Fe(2+)A, TBARS-4.66 +/- 2.33 & 3.55 +/- 1.25 nmol/ml respectively). The values returned to pretreatment levels on discontinuation of the drug in group C (CRP-2.61 +/- 1.28 mg/l, FRAP-138.49 +/- 19.62 nmol Fe2+/l, TBARS-6.13 +/- 0.74 nmol/ml) whereas the decline was maintained in group D (CRP-1.62 +/- 1.48 mg/l, FRAP-173.07 +/- 9.03 nmol Fe2+/l, TBARS-3.75 +/- 1.03 nmol/ml). Conclusion: Administration and withdrawal of atorvastatin caused changes in markers of oxidative stress which closely correlated with changes in marker of inflammation. Further, the salutary effects were of quick onset, but were rapidly reversed on withdrawal of atorvastatin.