![]() 8 Some of these cytokines, such as IL-1β, also have a short half-life. 5–7 Analyte stability for these molecules is a major limitation in routine clinical settings because serum and plasma must be rapidly separated from blood cells and assayed immediately or frozen to at least −70☌ to prevent analyte degradation. At present, these assays remain research tools for clinical and preanalytical reasons. Improvements in assay techniques, such as an automated microplate system, chemiluminescent assays, and multiplex assays, have resulted in reasonably acceptable within- and between-run precision for a number of assays, even at the low concentrations needed in the context of atherosclerosis. Because cytokines are confined primarily to the research laboratory, they typically are assayed with ELISA techniques. The cytokines and chemokines that have been investigated as possibly being related to atherosclerosis include several interleukins (IL-1β, IL-6, IL-8, IL-10, and IL-18), TNF-α, and monocyte chemoattractant protein-1. This interest has led to the development of a variety of commercial assays for these markers. Although the initial interest in these markers was confined to the basic research arena, there has been a significant and expanding interest in the clinical application of these markers, despite a lack of consensus about which markers are of clinical use and in what clinical context they should be measured. Among these markers are nonspecific acute-phase reactants such as fibrinogen, CRP, and serum amyloid A (SAA), which, when present in low concentrations, are reflective of a low-grade chronic inflammatory disease more specific primary inflammatory signals, including cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and vascular adhesion molecules such as soluble intercellular adhesion molecule-1. A variety of markers associated with inflammation in the arterial wall, which also are detectable in the circulation, have thus been evaluated as potential indicators for predicting risk of coronary events. ![]() The laboratory group primarily focused on the availability of commercial assays, their limitations and strengths, ability to standardize assay results, assay performance, and how results should be interpreted for assessing the risk of future CVD.Īs our knowledge of the atherosclerotic process has improved in recent years, evidence suggests that after initiation, inflammation plays a significant role in the development of this disease. The markers were divided into 3 groups of molecules: cytokines and chemokines, soluble adhesion molecules, and acute-phase reactants. The Laboratory Science Discussion Group was charged with reviewing the available analytical data on inflammatory markers and recommending those, if any, that were ready to move from the research setting into the routine clinical laboratory. Performance goals for CRP measurement, similar to those developed for total cholesterol, HDL and LDL cholesterol, and triglycerides, need to be developed with a view toward better characterization of the total allowable error required to measure CRP reliably. It should be recognized that other acute inflammatory conditions may result in mildly to moderately increased CRP levels, such as inflammatory bowel disease, 2 rheumatoid arthritis, 3 and long-term alcoholism. On the basis of the CRP population distributions, the following tertiles are recommended for categorizing patients: low risk, 3.0 mg/L. Risk assessment should be modeled after the lipids approach via 3 risk categories: low risk, average risk, and high risk. If the CRP level is >10 mg/L, then the test should be repeated and the patient examined for sources of infection or inflammation.ĬRP results should be expressed only as milligrams per liter and expressed to 1 decimal point. To obtain a CRP concentration in metabolically stable patients, 2 measurements, fasting or nonfasting, should be made (optimally 2 weeks apart) and the results averaged. Of the inflammatory markers identified, C-reactive protein (CRP) has the analyte and assay characteristics that are the most conducive for use in practice. Customer Service and Ordering Information.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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