Early, Intensive and Long-term Statin Therapy in Acute Coronary Syndrome: Focus on Anti-inflammatory Mechanisms
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.
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: c-reactive protein (crp); coronary heart disease (chd); lipopolysaccharide (lps); thrombogenesis; thrombolysis; tumor necrosis factor; vulnerable plaque
Document Type: Review Article
Affiliations: Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People's Republic of China.
Publication date: 01 July 2005
- Vascular Disease Prevention publishes reviews as well as original papers to update all those concerned with this topic at the clinical or scientific level. In addition to clinically relevant topics, we consider reviews and original papers dealing with the more scientific aspects of vascular disease prevention. This includes the evaluation of emerging vascular risk factors, research dealing with the pathogenesis of atherosclerosis and the investigation of new treatment options both at the clinical and scientific level (e.g. epidemiology, patient-based studies, experimental models, in vitro experiments or molecular research). Therefore, another function of Vascular Disease Prevention is to bridge the gap between clinical practice and ongoing laboratory-based research.
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