Influence of withdrawal of statin treatment on proinflammatory response and fibrinolytic activity in humans: an effect independent on cholesterol elevation

Background: In addition to lowering lipid profile, statins have pleiotropic effects on improving vascular function. Changes of these pleiotropic effects and their relationship to lipid profile after withdrawal of statin treatment remained unclear. Methods: We investigated the changes of lipid profile and plasma concentrations of human soluble vascular cell adhesion molecule-1 (sVCAM-1) and human tissue type plasminogen activator (tPA) after withdrawal of statin treatment. Twenty-two patients (14 F, 8 M, aged 63 13 years) with hypercholesterolemia were treated with atorvastatin (ATOR; 10 mg/day) for 12 weeks. Blood samplings for serum lipid and markers were collected before, after and withdrawal of statin treatment. Results: The total cholesterol, LDL-cholesterol and sVCAM-1 (from 394.4 +/- 251.7 to 321.0 +/- 198.9 ng/ml,p < 0.05) all decreased significantly and the tPA (from 9.47 +/- 3.57 to 11.62 +/- 3.99 ng/ml,p < 0.05) increased significantly after atorvastatin treatment. During the following 3 days after withdrawal of atorvastatin, the total cholesterol and LDL-cholesterol did not show any significant change. However, the plasma sVCAM-1 significantly elevated on day 2 (from 321.0 +/- 198.9 to 371.2 +/- 220.4 ng/ml,p < 0.05) and the plasma tPA significantly decreased on day 1 (from 11.62 +/- 3.99 to 10.52 +/- 3.55 ng/ml,p < 0.05) and day 3 (from 11.62 +/- 3.99 to 10.27 +/- 3.69 ng/ml,p < 0.05). Both the significant elevation of sVCAM-1 and decrease of tPA after withdrawal of atorvastatin treatment occurred within 3 days, while the serum cholesterol and LDL-chol levels did not have any significant change and were still within the therapeutic range. Conclusions: After 12 weeks of atorvastatin treatment, the beneficial pleiotropic effects can be demonstrated simultaneously with lowering the lipid profile. However, after withdrawal of atorvastatin, the beneficial pleiotropic effects are abrogated rapidly within days and are independent on elevation of serum cholesterol. (c) 2004 Elsevier Ireland Ltd. All rights reserved.