In this presentation Dr. Koenig discusses the potential for inflammation as a target to be addressed in addition to LDL cholesterol (LDL-C) in patients with coronary heart disease.

Statins not only lower LDL-C but also have other antiatherosclerotic properties related to improvement in endothelial function, anti-thrombogenicity and anti-inflammatory effects. How do statins reduce acute coronary syndromes? Of interest are animal and human studies showing anti-inflammatory effects of statins which promote plaque stabilization (1,2).

Statins also reduce systemic inflammation, and as seen in the CARE trial, the efficacy of statin therapy in terms of reduced risk of recurrent coronary events after myocardial infarction, was greater in those with evidence of inflammation by elevated C-reactive protein (CRP) and serum amyloid A levels (3). A number of studies have documented the magnitude of CRP lowering achieved with different statins, and interestingly, the mechanism whereby statins reduce IL-6-induced CRP production in human hepatocytes has recently been elucidated (4).

Could CRP be a target for statin therapy? A number of post hoc analyses from recent clinical trials suggest this may well be the case. In the large AFCAPS/TexCAPS trial for example, which was five-year randomized trial of lovastatin for the primary prevention of acute coronary events, it was found that statin therapy may also be effective among persons with relatively low lipid levels but with elevated levels of C-reactive protein (5). This served as the basis of the ongoing JUPITER study. More recent data supporting CRP as a potential target for statin therapy come from trials such as PROVE-IT and REVERSAL (6,7).

Dr. Koenig also discusses other frequently prescribed cardiovascular drugs affecting the inflammatory response in atherothrombogenesis, and ends with some concluding comments.

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After viewing this presentation the participant will be able to discuss:

- The role of inflammation in atherogenesis
- The antiatherosclerotic properties of statins
- The mechanism of statin-induced reduction of CRP release by human hepatocytes
- Post hoc analyses from recent clinical trials suggesting that CRP may become a target for intervention

1. M. Aikawa and P. Libby Vascular inflammation and activation: new targets for lipid lowering Eur Heart Journal 2001;3(suppl B): B3-B11.

2. Milita Crisby, MD; Gunilla Nordin-Fredriksson, MD; Prediman K. Shah, MD; Juliana Yano, BS; Jenny Zhu, BS; Jan Nilsson, MD, PhDPravastatin Treatment Increases Collagen Content and Decreases Lipid Content, Inflammation, Metalloproteinases, and Cell Death in Human Carotid Plaques: Implications for Plaque Stabilization Circulation. 2001;103:926.

3. Paul M. Ridker, MD; Nader Rifai, PhD; Marc A. Pfeffer, MD; Frank M. Sacks, MD; Lemuel A. Moye, MD, PhD; Steven Goldman, MD; Greg C. Flaker, MD; Eugene Braunwald, MD; ; for the Cholesterol and Recurrent Events (CARE) InvestigatorsInflammation, Pravastatin, and the Risk of Coronary Events After Myocardial Infarction in Patients With Average Cholesterol Levels Circulation. 1998;98:839-844.

4. Claire Arnaud; Fabienne Burger; Sabine Steffens; Niels R. Veillard; Tuan Huy Nguyen; Didier Trono; François Mach Statins Reduce Interleukin-6–Induced C-Reactive Protein in Human Hepatocytes: New Evidence for Direct Antiinflammatory Effects of Statins Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1231.

5. Paul M. Ridker, M.D., M.P.H., Nader Rifai, Ph.D., Michael Clearfield, D.O., John R. Downs, M.D., Stephen E. Weis, D.O., J. Shawn Miles, M.D., Antonio M. Gotto, Jr., M.D., D.Phil., for the Air Force/Texas Coronary Atherosclerosis Prevention Study InvestigatorsMeasurement of C-Reactive Protein for the Targeting of Statin Therapy in the Primary Prevention of Acute Coronary EventsNEJM 2001;344:1959-1965.

6. Paul M Ridker, M.D., Christopher P. Cannon, M.D., David Morrow, M.D., Nader Rifai, Ph.D., Lynda M. Rose, M.S., Carolyn H. McCabe, B.S., Marc A. Pfeffer, M.D., Ph.D., Eugene Braunwald, M.D., for the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) InvestigatorsC-Reactive Protein Levels and Outcomes after Statin Therapy NEJM 2005;352:20-28.

7. Steven E. Nissen, M.D., E. Murat Tuzcu, M.D., Paul Schoenhagen, M.D., Tim Crowe, B.S., William J. Sasiela, Ph.D., John Tsai, M.D., John Orazem, Ph.D., Raymond D. Magorien, M.D., Charles O'Shaughnessy, M.D., Peter Ganz, M.D., for the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) InvestigatorsStatin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease NEJM 2005;352:29-38.