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With regards to assessment of cardiovascular risk, hsCRP levels add prognostic information to that obtained from the Framingham risk score (1).

Statin drugs are cholesterol-lowering agents that also lower CRP levels (2), and the Cholesterol and Recurrent Events (CARE) trial showed that statin therapy reduced the risk of recurrent coronary events, with a more pronounced risk-lowering effect seen in patients with inflammation (3). With the AFCAPS/TexCAPS study published in 2001, it became apparent that the protection afforded by statins in the primary prevention of cardiovascular events was seen not only in patients with high LDL-cholesterol but also in those with low LDL-cholesterol and high hsCRP levels (4). The JUPITER trial is currently underway to investigate the role of statin therapy in the primary prevention of cardiovascular events in subjects with low LDL-cholesterol and high hsCRP levels.

The Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22 (PROVE IT–TIMI 22) trial was first reported by Cannon and colleagues in 2004, and showed that in patients with acute coronary syndromes, aggressive statin therapy with 80mg atorvastatin caused a relative risk reduction for major cardiovascular events or all-cause death of 16 percent compared to moderate statin therapy with 40mg pravastatin (5).

Based on these initial findings it became of interest to find out whether some of the cardiovascular protection from statins could be explained on the basis of CRP lowering after adjustment for achieved LDL-cholesterol levels, and whether the greater reduction in cardiovascular risk due to aggressive versus moderate statin therapy could be explained at least in part by differences in CRP lowering.

In this talk Dr. Ridker reviews data from 2 newly published studies on the effects of aggressive versus moderate statin therapy in patients with established heart disease. In the first study, patients with acute coronary syndromes from the PROVE IT-TIMI 22 trial were tested for cholesterol and CRP thirty days after starting statin therapy, and a risk reduction for recurrent myocardial infarction or coronary death was observed that was attributable to CRP-lowering at all levels of achieved LDL-cholesterol, suggesting that both CRP and cholesterol should be monitored in patients on statin therapy (6). The second study, the REVERSAL trial, used intravascular ultrasound measurements to investigate the progression of atherosclerosis in patients with stable coronary artery disease, and found a reduction in the rate of atherosclerosis progression in patients achieving greater LDL- and CRP-lowering with statin therapy (7).

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

- Recent trials demonstrating the lowering of cardiovascular risk with statin therapy (primary and secondary prevention)
- New results from the PROVE IT-TIMI 22 trial on the effects of LDL-C- and CRP-lowering on the risk of recurrent MI/ coronary death
- New evidence from the REVERSAL study on the role of LDL-C- and CRP-lowering in slowing the rate of atherosclerosis progression

1. Paul M Ridker, MD; Peter W.F. Wilson, MD; Scott M. Grundy, MD.Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk? Circulation. 2004;109:2818-2825.

2. Paul M. Ridker, MD; Nader Rifai, PhD; Marc A. Pfeffer, MD; Frank Sacks, MD; Eugene Braunwald, MD; for the Cholesterol and Recurrent Events (CARE) Investigators.Long-Term Effects of Pravastatin on Plasma Concentration of C-reactive Protein Circulation. 1999;100:230-235.

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) Investigators.Inflammation, Pravastatin, and the Risk of Coronary Events After Myocardial Infarction in Patients With Average Cholesterol Levels Circulation. 1998;98:839-844.


4. 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 Investigators.Measurement of C-Reactive Protein for the Targeting of Statin Therapy in the Primary Prevention of Acute Coronary Events
NEJM.2001;344:1959-1965.

5. Christopher P. Cannon, M.D., Eugene Braunwald, M.D., Carolyn H. McCabe, B.S., Daniel J. Rader, M.D., Jean L. Rouleau, M.D., Rene Belder, M.D., Steven V. Joyal, M.D., Karen A. Hill, B.A., Marc A. Pfeffer, M.D., Ph.D., Allan M. Skene, Ph.D., for the Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators.Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary SyndromesNEJM.2004;350:1495-1504.

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) Investigators.C-Reactive Protein Levels and Outcomes after Statin TherapyNEJM.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) Investigators.Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery DiseaseNEJM.2005;352:29-38.