In addition to lowering cholesterol, statins effectively lower C-reactive protein (CRP) levels. The effects of withdrawal from long-term statin therapy on CRP are unknown. This study examined the effect of withdrawal from 4 years of statin treatment on CRP. We prospectively evaluated the effects of withdrawal from pravastatin (40 mg) treatment on CRP levels in 566 subjects who participated in a randomized, placebo-controlled trial. Median (interquartile range) CRP levels before randomization were 1.29 mg/L (0.63 to 2.73) and mean low-density lipoprotein (LDL) cholesterol was 4.06 +/- 0.92 mmol/L. Four years after randomization, placebo-treated patients (n = 266) had a nonsignificant 9% increase in CRP, whereas there was a 12% decrease (p = 0.001) in the pravastatin-treated patients (n = 300). LDL cholesterol only decreased in pravastatin-treated patients (-27%; p <0.001). Withdrawal from pravastatin led to a significant increase in both CRP and LDL cholesterol to approximately pretreatment levels (p <0.05 and <0.001, respectively). Changes in CRP after withdrawal from pravastatin could not be predicted by the change in LDL cholesterol. The difference between the pravastatin and placebo groups in terms of change in CRP by withdrawal was consistent and persisted in analysis corrected for body mass index, smoking status, blood pressure, and baseline levels of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, or triglycerides. In conclusion, withdrawal from pravastatin treatment resulted in an increase in CRP to approximately baseline levels, which is not related to the increase in LDL cholesterol. (c) 2007 Elsevier Inc. All rights reserved.