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The pravastatin inflammation CRP evaluation (PRINCE): rationale and design
M A Albert1, J Staggers, P Chew
1Center for Cardiovascular Disease Prevention, Division of Cardiology and Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, USA. maalbert@bics.bwh.harvard.edu
Insights
Pravastatin may reduce inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP). The PRINCE trial investigates pravastatin
Area of Science:
- Cardiology
- Pharmacology
- Inflammation Research
Background:
- Statins, including HMG CoA reductase inhibitors, reduce coronary events in primary and secondary prevention.
- Beyond cholesterol reduction, statins exhibit anti-inflammatory properties potentially stabilizing atherosclerotic plaques.
- High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker predicting vascular risk, with statin efficacy potentially linked to baseline hs-CRP levels.
Purpose of the Study:
- To evaluate the effects of pravastatin on hs-CRP levels in individuals with and without coronary artery disease.
- To determine the time course and magnitude of pravastatin's effect on hs-CRP.
- To assess if pravastatin's effect on hs-CRP is independent of its lipid-lowering effects.
Main Methods:
- The PRavastatin Inflammation CRP Evaluation (PRINCE) trial is a multicenter, community-based study.
- Participants include individuals with (n=1182) and without (n=1702) coronary artery disease.
- Lipid profiles and hs-CRP levels were measured at baseline, 12, and 24 weeks. Patients with coronary artery disease received 40 mg/d pravastatin; others were randomized to placebo or 40 mg/d pravastatin.
Main Results:
- Data on the main results are not yet available in the provided abstract.
Conclusions:
- Pravastatin's impact on hs-CRP levels and its independence from LDL cholesterol changes will be clarified by the PRINCE trial.
- Identifying individuals with elevated hs-CRP and normal cholesterol may improve risk stratification for statin therapy.
- Nearly 50% of US myocardial infarctions occur in individuals with normal cholesterol levels, highlighting the need for alternative risk markers.
Background:
Randomized, controlled trials demonstrate that HMG CoA reductase inhibition reduces coronary event rates in both primary and secondary prevention. In addition to reducing cholesterol levels, laboratory evidence suggests that statins also have anti-inflammatory activity, a property that may be critical for maintaining plaque stability. Recently, the inflammatory marker high-sensitivity C-reactive protein (hs-CRP) has been shown to predict vascular risk in individuals with and without hyperlipidemia. Furthermore, in the Cholesterol and Recurrent Events (CARE) trial, the relative efficacy of pravastatin in reducing events was greatest among those with elevated levels of hs-CRP. However, the time course and magnitude of this effect in both primary and secondary prevention is controversial.
Methods:
PRavastatin Inflammation CRP Evaluation (PRINCE) is an investigator-initiated, multicenter, community-based trial that will evaluate the effects of pravastatin on hs-CRP in up to 1182 individuals with coronary artery disease and up to 1702 individuals without coronary artery disease. Lipid profiles and hs-CRP levels will be obtained at baseline, 12 weeks, and 24 weeks in all study participants. Patients with known coronary artery disease will receive 40 mg/d pravastatin, whereas those without coronary artery disease will be randomly assigned to receive placebo or 40 mg/d pravastatin.
Conclusions:
The potential clinical impact of the PRINCE trial is substantial because nearly 50% of myocardial infarctions in the United States occur in persons with normal cholesterol levels, and inflammatory markers such as hs-CRP may provide a means to detect such individuals at high risk who do not currently qualify for statin therapy. The PRINCE trial will determine the time course of effect of this statin on hs-CRP and whether any observed effect on hs-CRP is independent of pravastatin-induced changes in low-density lipoprotein cholesterol.