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(Circulation. 2005;111:1735-1737.)
© 2005 American Heart Association, Inc.

Editorial

Should Treatment of Sepsis Include Statins?

Ascan Warnholtz, MD; Sabine Genth-Zotz, MD; Thomas Münzel, MD

From II Medizinische Klinik, Klinikum der Johannes Gutenberg-Universität Mainz, Mainz, Germany.

Correspondence to Thomas Münzel, MD, II Medizinische Klinik, Klinikum der Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, D-55131 Mainz, Germany. E-mail tmuenzel@uni-mainz.de

Key Words: Editorials • sepsis • statins • endotoxins • drugs, antiinflammatory

An extract of the first 250 words of the full text is provided, because this article has no abstract.

During the past decade, HMG-CoA reductase inhibitors (statins) have been shown to improve survival in patients with cardiovascular disease. Initially, the beneficial effects of statins were attributed simply to lipid reduction¹; however, more recent data suggest that "pleiotropic" properties such as improvement of endothelial dysfunction, increased nitric oxide bioavailability, and antioxidative and antiinflammatory properties may contribute to the improvement of prognosis in patients with coronary artery disease. Many of these pleiotropic effects of statins are mediated by the ability to block the synthesis of important isoprenoid intermediates, which have been shown to serve as lipid attachments for a variety of intracellular signaling molecules. In particular, the inhibition of the small guanosine triphosphate–binding proteins rho, ras, and rac, the membrane localization of which depends on isoprenylation, may play an important role in mediating the direct effects of statins on the vascular wall. Thus, the characteristics of this class of drugs may explain the dramatic effects on the progression of atherosclerosis and therefore on survival in patients with established coronary artery disease.

See p 1841

Chronic inflammation and activation of the coagulation system is thought to contribute significantly to the progression of atherosclerosis and to the induction of acute cardiovascular events.² Although inflammatory markers such as C-reactive protein (CRP) have been demonstrated to be predictive of clinical atherosclerosis, the exact pathogenetic role of inflammation in the atherosclerotic process is not yet fully understood. One possible proinflammatory mechanism may be chronic exposure to endotoxin, also known as lipopolysaccharide (LPS).^3,4 In a prospective . . . [Full Text of this Article]

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