Changes of plasma inflammatory markers after withdrawal of statin therapy in patients with hyperlipidemia

Background: Atherosclerosis has been considered to be an inflammatory process. In addition to its lipid-lowering properties, statin has been shown to decrease the concentrations of inflammatory markers resulting in reduction of cardiovascular events. Emerging data suggest that withdrawal of statin might be associated with increased cardiac events. The mechanism for this phenomenon, however, is still unclear. We investigated whether acute termination of statin treatment Could result in rebound of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), in patients with hyperlipidemia. Methods: Seventeen patients (11 men and 6 women, mean age 51 +/- 7 years) with hyperlipidemia were given 40 mg/day of pravastatin for 6 weeks. The concentrations of plasma CRP and IL-6 were evaluated before receiving the statin therapy, immediately after 6 weeks of pravastatin therapy, and at days 1, 3 and 7 after withdrawal of pravastatin therapy. The lipid profile was also evaluated at baseline, 6 weeks of therapy, and at day 7 after terminating pravastatin. Results: Pravastatin therapy induced significant reductions in total cholesterol (TC, 6.88 +/- 0.36 vs. 5.27 +/- 0.23 mmol/L, p < 0.01), low-density lipoprotein (LDL) cholesterol (4.28 +/- 0.25 vs. 3.06 +/- 0.14 mmol/l, p < 0.01), CRP (0.28 +/- 0.16 vs. 0.20 +/- 0.08 mg/l, p < 0.01), and IL-6 (8.4 +/- 0.6 vs. 6.7 +/- 0.4 pg/dl, p < 0.01). Although the TC and LDL-cholesterol did not change during the 7-day period after withdrawal of pravastatin therapy, the concentrations of CRP and IL-6 increased at day 3 (CRP: 0.20 +/- 0.08 vs. 0.27 +/- 0.12 mg/l, and IL-6: 6.7 0.4 vs. 7.7 +/- 0.6 pg/dl, p < 0.05 respectively) and at day 7 (CRP: 0.20 +/- 0.08 vs. 0.30 +/- 0.14 mg/l, and IL-6: 6.7 +/- 0.4 vs. 8.7 +/- 0.8pg/dl, p < 0.01 respectively) after withdrawal of pravastatin therapy. No correlation between increase of CRP as well as IL-6 and small changes of LDL-cholesterol concentrations was found after withdrawal of pravastatin therapy at day 7 (r = -0.021 and r = -0.044 respectively, p > 0.05 respectively). Conclusions: 6 weeks after pravastatin therapy could significant modify the lipid profile and decrease the inflammatory markers including CRP and IL-6 in patients with hyperlididemia. Moreover, statin therapy discontinuation could induce a rebound phenomenon of inflammatory response representing an increase in some inflammatory markers, which is independent of changes of lipid parameters. (c) 2005 Elsevier B.V. All rights reserved.