Levels of adhesion molecules do not decrease after 3 months of statin therapy in moderate hypercholesterolaemia

Abstract

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4-4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2-4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6-6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n =19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.

Reduction of oxidative stress and modulation of autoantibodies against modified low‐density lipoprotein after rosuvastatin therapy

“…The increase in ICAM‐1 concentrations (7.9%) after 24 weeks found in our study is higher, as reported by Jilma et al. [44], in patients with moderate hypercholesterolaemia. In this study, a modest increase in ICAM‐1 (2.1%), VCAM‐1 (2.7%) and E‐selectin (1.7%) was found after 3 months’ treatment with standard doses of three different statins.…”

Statins as antiinflammatory and immunomodulatory agents: A future in rheumatologic therapy?

“…Shed (soluble) adhesion molecules are well-known markers for atherosclerotic disease (36)(37)(38), and several studies indicated that statins down-regulate circulating soluble ICAM-1, vascular cell adhesion molecule 1 (39)(40)(41), and E-and P-selectin (42,43). However, not all studies that examined the effects of statins on the soluble levels of these molecules have replicated these findings (44,45).…”

ICAM-1: Contribution to Vascular Inflammation and Early Atherosclerosis

“…Increased levels of sICAM-1 were also found in type 2 diabetic patients (Becker, van Hinsbergh et al 2002). Serum levels of sICAM-1 in cardiovascular patients treated with statins were confirmed to be lower in some groups (Romano, Mezzetti et al 2000;Blann, Gurney et al 2001;Bickel, Rupprecht et al 2002), whereas some studies could not find a significant reduction (Rauch, Osende et al 2000;Jilma, Joukhadar et al 2003).…”