If you reply, please remove the newsgroup, you don't normally post to. The Newsweek special double Edition For years now high cholesterol has sounded like a death knell. But if Paul Ridler is right, the real risk factor for heart disease and stroke is something else - C-reactive protein (CRP), Ridker, a cardiologist at Brigham and Women's Hopsital, -you found that people with low cholesterol weren't necessarily healthy R: they may be at very high risk. In our study, people with low LDL and high CRP had more cardio-vascular events than people with high LDL and low CRP. - what causes high CRP? R: Half of it is genetic. The other half is _link_ed to smoking, diet , obesity. Our genetic adaptations from millions of years ago - strong inflammatory responses and the ability to store fat - are maladaptive now that starvation and infections aren't life-threatening issues in the US. - How will new findings abiut CRP affect the way we treat heart disease? R-These data challenge our federal guidelines. For instance, statins lower CRP, but their pre_script_ion guidelines only consider cholesterol. We need to go beyond that. * * * * * * * * * * * * **
http://jama.ama-assn.org/issues/v286n1/abs/joc10590.html Effect of Statin Therapy on C-Reactive Protein Levels The Pravastatin Inflammation/CRP Evaluation (PRINCE): A Randomized Trial and Cohort Study Michelle A. Albert, MD; Ellie Danielson, MIA; Nader Rifai, PhD; Paul M Ridker, MD; for the PRINCE Investigators Context Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk, and retrospective studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may lower CRP in a manner largely independent of low-density lipoprotein cholesterol (LDL-C). However, prospective trial data directly evaluating this anti-inflammatory effect of statins are not available. _object_ive To test the hypothesis that pravastatin has anti-inflammatory effects as evidenced by CRP reduction. Design, Setting, and Participants Community-_base_d, prospective, randomized, double-blind trial including 1702 men and women with no prior history of cardiovascular disease (primary prevention cohort) and open-label study including 1182 patients with known cardiovascular disease (secondary prevention cohort) who provided at least _base_line and 12-week blood samples. The study was conducted in US office-_base_d practices from February to December 2000. Interventions Participants in the double-blind primary prevention trial were randomly assigned to receive 40 mg/d of pravastatin (n = 865) or placebo (n = 837) for 24 weeks. Participants in the secondary prevention cohort received 40 mg/d of open-label pravastatin for 24 weeks. Main Outcome Measure Change in CRP levels from _base_line to 24 weeks. Results In the primary prevention trial, compared with placebo, pravastatin reduced median CRP levels by 16.9% (P<.001) at 24 weeks, reflecting a decrease of 0.02 mg/dL in the pravastatin group while no change in CRP levels was observed in the placebo group. This effect was seen as early as 12 weeks (median reduction in CRP with pravastatin, 14.7%; P<.001) and was present among all prespecified subgroups according to sex, age, smoking status, body mass index, _base_line lipid levels, presence of diabetes, and use of aspirin or hormone replacement therapy. No significant association was observed between _base_line CRP and _base_line LDL-C levels, end-of-study CRP and end-of-study LDL-C levels, or change in CRP and change in LDL-C levels over time. In linear regression analyses, the only significant predictors of change in CRP on a log scale were randomized pravastatin allocation and _base_line CRP levels (P<.001 for both). Similar reductions in CRP levels were observed at 12 weeks (-14.3%) and 24 weeks (-13.1%) in the secondary prevention cohort treated with pravastatin (P<.005 for both). Conclusions In this prospective trial, pravastatin reduced CRP levels at both 12 and 24 weeks in a largely LDL-C–independent manner. These data provide evidence that statins may have anti-inflammatory effects in addition to lipid-lowering effects. JAMA. 2001;286:64-70 View Full Text Author/Article Information Author Affiliations: Center for Cardiovascular Disease Prevention, Divisions of Cardiology and Preventive Medicine, Brigham and Women's Hospital (Drs Albert and Ridker and Ms Danielson), Department of Laboratory Medicine, Children's Hospital Medical Center (Dr Rifai), and the Leducq Center for Cardiovascular Research, Harvard Medical School (Drs Albert, Rifai, and Ridker), Boston, Mass. Corresponding Author and Reprints: Paul M Ridker, MD, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02215 (e-mail:
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). Author Contributions: Dr Ridker, as principal investigator of the PRINCE study, had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analyses. Study concept and design: Albert, Ridker. Analysis and interpretation of data: Albert, Rifai, Ridker. Drafting of the manu_script_: Albert, Ridker. Critical revision of the manu_script_ for important intellectual content: Albert, Danielson, Rifai, Ridker. Obtained funding: Ridker. Administrative, technical, or material support: Danielson, Rifai. Study supervision: Ridker. Financial Disclosure: Dr Ridker is named as a co-inventor on pending patents filed by Brigham and Women's Hospital, which relate to use of inflammatory biomarkers in cardiovascular disease. Funding/Support: This study was supported by an investigator-initiated grant from Bristol-Myers Squibb, Princeton NJ. Disclaimer: The PRINCE trial was investigator initiated, coordinated, and performed centrally within the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, and was run with full independence. The research group wrote all the protocols and manuals, holds all the primary data forms, and performed all the analyses. In addition to providing funding, the study sponsor, Bristol-Myers Squibb, also provided active drug and blinded placebo. The Pravastatin Inflammation/CRP Evaluation (PRINCE) could not have been conducted without the dedication and commitment of the PRINCE Investigators, who represent 1143 community-_base_d investigators in 49 states and the District of Columbia. The full list of the names of the PRINCE Investigators and the participating clinical sites is available in pdf format joc10590w.pdf and also on request from Dr Ridker. Pravastatin Inflammation/CRP Evaluation Trial Chairman: Paul M Ridker. Steering Committee: Michelle A. Albert, Paul H. Chew, Ellie Danielson, Paul M Ridker (chair), Harriet Samuelson, Joan E. Staggers. Data Coordinating Center: David Bates, Ellie Danielson, Robert Glynn, Kathleen McKenna, Kim Taylor. Laboratory Coordinating Center: Shake Ayanian, Gail Borkowski, Stephanie Chuive, Tony Laurinaitis, Nader Rifai.
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