Need to Test the Arterial Inflammation Hypothesis
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Despite intensive basic and clinical investigation, coronary artery disease remains the principal cause of death and disability in the United States. In recent years, the appreciation of arterial inflammation as an important risk factor has had considerable implications for changing our approach to managing these patients.1,2⇓ Arterial inflammation has emerged as central to the progression of atherothrombosis.3 Of the markers of inflammation, the high-sensitivity C-reactive protein (CRP) is the most studied, with evidence that it may also play a direct pathogenic role in atherosclerotic lesion formation.4– 11⇓⇓⇓⇓⇓⇓⇓ In the absence of active infection, measurements of CRP are reasonably reproducible, comparable to measurements of total cholesterol.12,13⇓ Additionally, elevated CRP appears to be a more potent risk factor than other mediators of inflammation, such as tumor necrosis factor-α, interleukin-6, or serum amyloid A.4,14⇓ A group of pharmacotherapies that are currently available, such as aspirin, statins, angiotensin converting enzyme inhibitors (ACE-Is), thienopyridines, and peroxisome proliferator-activated receptor (PPAR) agonists have been shown, in addition to their other properties, to reduce CRP and/or arterial inflammation. Although it is clear that elevated CRP denotes increased risk and emerging evidence suggests that there are novel therapies that result in lowering of CRP, the most important unanswered question is whether suppression of inflammation and consequent lowering of CRP will translate into a decrease in clinical events.15 Surprisingly, despite the importance of the question, the “inflammation hypothesis” of intentional CRP suppression as compared with standard care has not yet been tested. Such a prospective study of patients with established cardiovascular disease and elevated baseline CRP in which incremental pharmacotherapy would be guided by reassessments of the CRP marker could allow formulation of a rational therapeutic strategy instead of an approach of “polypharmacy” for …