title: High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy.
abstract: There is compelling experimental and clinical evidence suggesting a crucial role for inflammation in the initiation and also the progression of atherosclerosis. Numerous biomarkers involved at various levels of the inflammation cascade have been shown to be associated with adverse cardiovascular outcomes. Yet, to date, it is not clear whether inflammation simply accompanies the atherosclerotic process or represents a major driver. Among all blood biomarkers, C-reactive protein (CRP), the classical acute phase reactant that can be measured with high-sensitivity (hs) assays seems to be the most promising candidate. It has already found its way into the guidelines in primary prevention. Hs-CRP can also be used to identify a high-risk group for recurrent events in patients with manifest atherosclerosis. Several post hoc analyses of large-scale randomized clinical trials testing various statins have indicated that, besides low density lipoprotein (LDL) cholesterol, hs-CRP levels might also further aid in tailoring statin treatment. The large JUPITER trial has prospectively confirmed these findings in primary prevention in patients with elevated hs-CRP but normal LDL cholesterol levels. Still, statin therapy is not a specific anti-inflammatory regime acting on the inflammation cascade. Thus, to directly test the inflammation hypothesis, a novel, more proximally located cytokine-based approach is needed. Canakinumab, a fully human monoclonal antibody against interleukin-1β, might represent a promising compound in this regard and provide a proof of concept. If successful, this may become a novel strategy to treat high-risk patients with stable atherosclerotic disease to prevent recurrent events on top of standard medical care.
authors: Department of Internal Medicine II - Cardiology, University of Ulm Medical Center, Albert Einstein-Allee 23, D-89081 Ulm, Germany. Electronic address: wolfgang.koenig@uniklinik-ulm.de.
authors: Wolfgang
authors: W
authors: Koenig
mesh_terms: D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D006801:Humans; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
keywords: A-to-Z; ACS; AHA; ASCOT; Aggrastat-to-Zocor; American Heart Association; Anglo-Scandinavian Cardiac Outcomes Trial; Atherosclerosis; Biomarkers; C-reactive protein; CAD; CARE; CHD; CI; CRP; CVD; Canakinumab; Cardiovascular disease; Cholesterol and Recurrent Events; ECAT; European Concerted Action on Thrombosis and Disabilities; FRS; Framingham Risk Score; GPx-1; GRACE; GWAS; Global Registry of Acute Coronary Events; HAECs; HDL; HPS; Heart Protection Study; Hs-CRP; IL; Inflammation; JUPITER; Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin; LDL; LOX-1; Lp-PLA(2); MCP-1; MMPs; MPO; PAPP-A; PROCAM; PROVE-IT TIMI 22; PlGF; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22; Prospective Cardiovascular Münster; SAA; SCORE; SNP; SOLID-TIMI; STABILITY; STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY; Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction; Systematic COronary Risk Evaluation; THROMBO; TIMI; TNF-α; Thrombogenic Risk Factor; Thrombolysis in Myocardial Infarction; ULSAM; Uppsala Longitudinal Study of Adult Men; VILCAD; acute coronary syndrome; cardiovascular disease; confidence interval; coronary artery disease; coronary heart disease; genome-wide association and replication study; glutathione peroxidase; high-density lipoprotein; high-sensitivity C-reactive protein; human aortic endothelial cells; interleukin; lectin-type oxidized LDL receptor 1; lipoprotein associated phospholipase A(2); low-density lipoprotein; matrix metalloproteinases; monocyte chemoattractant protein-1; myeloperoxidase; oxLDL; oxidized LDL; placental growth factor; pregnancy-associated plasma protein-A; sICAM-1; sVCAM-1; serum amyloid A protein; single-nucleotide polymorphism; soluble intercellular adhesion molecule-1; soluble vascular cell adhesion molecule; the Vienna and Ludwigshafen Coronary Artery Disease; tumor necrosis factor-α