C-reactive protein: risk factor, biomarker and/or therapeutic target?
The inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) has been proposed as a novel instrument to assess cardiovascular risk, to determine the need for statin therapy in specific individual otherwise not deemed to meet current criteria, and to represent a potential target of treatment. CRP is predominantly secreted by the liver and adipose tissues in response to inflammatory stress and is regulated, in great part, by interleukin-6. The issues of CRP as a causal factor (rather than a biomarker) has been addressed by three types of studies: animal models, in which CRP was injected; transgenic mice over-expressing human CRP; and Mendelian randomization studies. All indicate that CRP may not have a direct role in promoting atherosclerosis but, instead, serves as a marker of vascular inflammation and the presence of atherosclerosis. Several clinical studies have shown that individuals reaching both low-density lipoprotein cholesterol (LDL-C) and hsCRP targets (LDL-C less than 2.0 mmol/L and hsCRP less than 2 mg/L) have the lowest event rate, suggesting that hsCRP may become a secondary target of treatment after LDL-C. The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study showed that apparently healthy men and women with elevated hsCRP, but normal LDL-C (less than 3.4 mmol/L), had an overall 44% reduction in the primary end points with rosuvastatin 20 mg/day. The results of this study have now been incorporated in the new Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease.
Genest
Jacques
J
Faculty of Medicine, McGill University, Montreal, Quebec, Canada. Jacques.genest@muhc.mcgill.ca
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control*; D006801:Humans; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D002097:C-Reactive Protein