Early, Intensive and Long-term Statin Therapy in Acute Coronary Syndrome: Focus on Anti-inflammatory Mechanisms

Author(s): Jian-Jun Li, Sheng-Shou Hu.

Journal Name: Vascular Disease Prevention

Volume 2 , Issue 3 , 2005

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Abstract:

An acceptable concept is that the acute coronary syndrome (ACS) is related to erosion or rupture of vulnerable plaques leading to intracoronary thrombosis as a result of the activation of the coagulation cascade and platelet aggregation. Clinical trials and animal models suggest an inflammatory etiology in ACS. This concept is supported by evidence showing that a reduction in serum inflammatory marker levels significantly decreased coronary events in patients with ACS. Statins can lower the circulating levels of inflammatory markers and rapidly improve endothelial function with a concurrent decrease in vascular events. This may explain the accumulating evidence indicating that statins, like aspirin, should be given intensively and early in patients with ACS. Long-term statin therapy will also decrease subsequent coronary events. Our recent findings show that simvastatin induced significant reductions in C-reactive protein (CRP) levels and endothelin-1 (ET-1) on day 14. A rapid reduction in CRP could even be achieved within 24 h following a single, high dose of simvastatin (80 mg) which also positively influenced short-term clinical outcomes. In addition, our in vitro data demonstrated that simvastatin could significantly inhibit the release of interleukin-6 (IL-6) in cultured blood monocytes induced by CRP as well as lipopolysaccharide (LPS) in dose-dependent manner. We also showed that fluvastatin significantly inhibited the induction of tumor necrosis factor-α (TNF-α), and activation of nuclear factor-kappa B (NF-kB) in cultured human vascular endothelial cells stimulated by CRP. These findings provide an insight into the antiinflammatory and anti-atherosclerotic actions of statins. Based on available evidence and in the light of the understanding that statins have potential pleiotropic effects, especially as anti-inflammatory agents, early, intensive and long-term statin therapy has become accepted in patients with ACS.

Keywords: coronary heart disease (chd), thrombogenesis, vulnerable plaque, c-reactive protein (crp), lipopolysaccharide (lps), tumor necrosis factor, thrombolysis

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Article Details

VOLUME: 2
ISSUE: 3
Year: 2005
Page: [181 - 186]
Pages: 6
DOI: 10.2174/1567270010502030181
Price: $58