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C-reactive Information and Courses from MediaLab, Inc.

These are the MediaLab courses that cover C-reactive and links to relevant pages within the course.

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Cardiac Biomarkers
Screening Biomarkers

Previously, screening for cardiovascular disease (CVD) focused on hyperlipidemia, obesity, and hypertension. However, approximately one half of AMIs occur in healthy men and women with normal or only slightly elevated plasma lipids. With new insights into cardiac disease and the ACS, novel biomarkers such as inflammatory markers, hormones, and other biomolecules indicating myocardial stress are required. Some new screening markers are in use today and many more are in study and evaluation for future use. New screening markers for CVD and ACS are: Highly Sensitive C-Reactive Protein (hs-CRP) Homocysteine Ischemial Modified Albumin (IMA) Myeloperoxidase (MPO)

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High Sensitivity C-Reactive Protein (hs-CRP)

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to injury or tissue damage. It has been assayed for many years as a non-specific marker of acute inflammatory diseases, infections, neoplastic diseases, and other conditions where inflammation occurs. It is still assayed in this manner as a marker of inflammation by immunoassay methods that are sensitive to concentrations of 5-20 mg/L. Atherosclerosis is a subclinical chronic inflammatory condition. Highly sensitive measurements of CRP have been developed to detect this protein in lower levels that are sensitive to 0.5-10.0 mg/L. This assay is referred to as high sensitivity C-reactive protein (hs-CRP).

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References

Arneson W, Brickell J, eds.Clinical Chemistry: A Laboratory Perspective. Philadelphia: FA Davis; 2007.Burtis CA, Ashwoood ER, Burns DE, eds. Tietz Fundamentals of Clinical Chemistry. 6th ed. St. Louis, MO: Elsevier Saunders; 2008.Carreiro-Lewandowski E. Update on cardiac markers. Lab Med. 2006;37:597-605.D'Amore PJ. Evolution of C-reactive protein as a cardiac risk factor. Lab Med. 2005;36:234-238.Dotsenko O, Chackathayil J, Lip GY. Cardiac biomarkers:myths, facts and future horizons. Expert Review of Molecular Diagnostics. 2007;7:693-697.Foley, K. BNP: a novel biomarker. Advance for Medical Laboratory Professionals. August 25, 2008:9.Kaplan LA, Pesce AJ, Kazmierczak SC, eds. Clinical Chemistry Theory, Analysis, Correlation. St. Louis, MO: Mosby Elsevier Science; 2007. McDowell J. Reviewing the evidence for BNP, NT-proBNP testing. Clin Lab News. 2006;32:1, 3, 5.Rollins G. cTn and MI - what's the diagnosis? Clin Lab News. 2009;35:1, 3-4.Rollins, G. The BNP debate. Clin Lab News. 2009;35:1,3-4.Schreiber D, Miller SM. Use of cardiac markers in the emergency department. eMedicine. Updated July 2009. Available at: http://emedicine.medscape.com/article/811905-print.Accessed March 25, 2013. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Circulation 2007;116:2634-2653.

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Emerging Cardiovascular Risk Markers
High Sensitivity-C-Reactive Protein

C-reactive protein (CRP) is a very sensitive acute phase reactant. Serum CRP levels increase following a variety of pro-inflammatory events such as infection, tissue necrosis, trauma, surgery and even malignancy. CRP levels can increase quickly and dramatically (often 100 fold) during inflammation. CRP can activate compliment, bind Fc receptors and can function as an opsonin, enhancing phagocytosis with certain infections. Measurement of CRP is not new, it has been on clinical laboratory testing menus for decades. However, a newer version of the CRP test is now in use to assess cardiovascular risk.High sensitivity-CRP (hs-CRP) assays have been developed that are more sensitive to the more subtle changes that can occur during chronic vascular inflammation. (Recall that atherosclerosis is an inflammatory process.) By measuring hsCRP we can get a glimpse at vascular function. CRP has been shown to be an independent risk factor for atherosclerotic disease and cardiac death. A 2002 prospective study of more than 27,000 patients showed that the CRP concentration is a stronger predictor of cardiovascular events than the LDL-cholesterol level.

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Which of the following is FALSE concerning CRP or hs-CRP?View Page
References

Atherosclerosis. U.S. Department of Health & Human Services National Institutes of Health. Available at http://www.nhlbi.nih.gov/health/dci/Diseases/Atherosclerosis/Atherosclerosis_WhatIs.html Accessed March 25, 2013.Daniels LB, Barrett-Connor E, Sarno M, Laughlin GA,Bettencourt R, Wolfert RL. Lipoprotein-associated phospholipase A2 (Lp-PLA2) independently predicts incident coronary heart disease (CHD) in an apparently healthy older population: The Rancho Bernardo study. J Am Coll Cardiol. 2008;51:913-919.Executive Summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001; 285:2486-2497. Frostegard, J, Wu R, Lemne C, Thulin T, Witztum JL and de Faire U. Circulating oxidized low-density lipoprotein is increased in hypertension, Clin Sci 2003; 105, 615.Garza CA, Montoir VM, McConnell JP, et al. Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review. Mayo Clin Proc. 2007;82(2):159-165.Interpretive Handbook, (MC0440rev0407) Mayo Clinic, RochesterMN;2007. Maksimowicz-McKinnon K, Bhatt DL, Calabrese LH: Recent advances in vascular inflammation: C-reactive protein and other inflammatory biomarkers. Curr Opin Rheumatol. 2004;16:18-24.Mora S, Szklo M, Otvos JD, et al. LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the multi-ethnic study of atherosclerosis. Atherosclerosis. 2007;192:211-217.NACB Laboratory Medicine Practice Guidelines. Emerging biomarkers of cardiovascular disease and stroke. NationalAcademy of Clinical Biochemistry Laboratory Medicine Practice Guidelines. 2006.PLACtest animation, diaDexus. http://www.plactest.com/laboratorians/action.php Accessed March 25, 2013.Rifai N, Warnick GR. Lipids, lipoproteins, apolipoproteins, and other cardiovascular risk factors. In: BurtisCA, Ashwood ER. BrunsDE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis, MO: Elsevier Saunders: 2006; chap. 26.Ridker PM, Rifai N, Rose L, et al. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002;347:1557-1565.Sniderman AD. Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: Implications for clinical practice. J Clin Lipidol 2008;2:36-42.Tsimikas, S, Brilakis ES, Miller ER, et al. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease, N Engl J Med: 2005;353:46.Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol. 2003; 41: 360.Tsimikas, S, Lau HK, Han KR, et al. Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): Short-term and long-term immunologic responses to oxidized low-density lipoprotein. Circulation. 2004;109, 3164.Tsimikas S, Witztum JL, Miller ER, Sasiela WJ, et al. High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial, Circulation: 2004;110, 1406. Walldius G, Jungner I, Holme I, et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet. 2001;358:2026-2033.Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937-952.

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General Laboratory Question Bank - Review Mode (no CE)
The assay which is most helpful in identifying specific allergens is:View Page
C-reactive protein:View Page

Metabolic Syndrome
References

Armstrong C. Practice guidelines AHA and NHLBI review diagnosis and management of the metabolic syndrome. Am Fam Physician. 2006;74:891-1062.D'Amore PJ. Evolution of c-reactive protein as a cardiac risk factor. Lab Med. 2005;36:234-238.Devaraj, S, Swarbrick MM, Singh U et al. CRP and adiponectin and its oligomers in the metabolic syndrome evaluation of new laboratory-based biomarkers. Am J Clin Pathol. 2008;129:815-822.Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415-1428.Expert Panel in Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (authors). Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA.2001;285:2486-2497.Gade W, Gade J, Collins M et al. Failures of feedback: rush hour along the highway to obesity. Clin Lab Sci. 2010;23:39-50.Gade W, Gade J, Collins M et al. Beyond obesity: the diagnosis and pathophysiology of metabolic syndrome. Clin Lab Sci. 2010;23:51-61.Grundy SM. Does a diagnosis of metabolic syndrome have value in clinical practice? Am J Clin Nutr. 2006;83:1248-1251.Grundy SM, Brewer HB, Cleeman JI, et al. Definition of metabolic syndrome: report of the national heart, lung, and blood institute/american heart association conference on scientific issues related to definition. Circulation. 2004;109:433-438.Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735-2752.Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2004;89:2595-2600.Mathew B, Francis L, Kayalar A, et al. Obesity: effects on cardiovascular disease and its diagnosis. J Am Board Fam Med. 2008;21:562-568.Metabolic Syndrome. National Heart Lung and Blood Institute. Diseases and Conditions Index. Available at http://www.nhlbi.nih.gov/health/dci/Diseases/ms/ms_whatis.html. Accessed December 5, 2011.Mittal S. The Metabolic Syndrome in Clinical Practice. London, England. Springer-Verlag Springer Science; 2008.Molinaro RJ. Metabolic syndrome: an update on prevalence, criteria, and laboratory testing. MLO. 2007;39:24-27.Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol. 2006;64:355-365.

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IL-6

IL-6 responds to tissue injury. IL-6 is synthesized and secreted by many different cells in addition to adipocytes including immune cells, fibroblasts, endothelial cells and skeletal muscle. IL-6 is increased in obesity and insulin resistance and those with elevated levels are at higher risk for type 2 diabetes and myocardial infarction. Similar to TNF-a, IL-6 increases NEFA release and reduces adiponectin secretion. IL-6 increases insulin resistance by inhibiting insulin receptor signal transduction in liver cells. It also increases other inflammatory cytokines, interleukin-1 (IL-1) and TNF-a, and stimulates the liver to produce C-reactive protein (CRP), an important protein marker of inflammation.

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Which adipokine is synthesized and released by adipocytes and many other body cell types, is an inflammatory cytokine that stimulates the liver to produce C-reactive protein (CRP), and is increased in obesity and insulin resistance?View Page
Risk Factors

According to the American Heart Association, the risk factors for metabolic syndrome include:Abdominal obesity (excessive fat tissue in and around the abdomen) Atherogenic dyslipidemia (blood fat disorders – high triglycerides, low HDL cholesterol and high LDL cholesterol – that foster plaque buildups in artery walls) Elevated blood pressure Insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar) Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor–1 in the blood) Proinflammatory state (e.g., elevated high sensitivity C-reactive protein in the blood) Reference: Metabolic syndrome.The American Heart Association website. Available at:http://www.heart.org/HEARTORG/Conditions/More/MetabolicSyndrome/Metabolic-Syndrome_UCM_002080_SubHomePage.jsp#. Accessed December 5, 2011.

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C-Reactive Protein (CRP)

CRP is an important acute phase reactant protein synthesized and released by the liver. In obesity, increased secretion of cytokines results in increased stimulation of the liver and increased CRP. Elevated CRP levels are a marker of inflammation. In metabolic syndrome and obesity, CRP levels can be used to identify a proinflammatory state. Increased CRP levels are correlated with an increased risk for cardiovascular disease, particularly myocardial infarction and stroke.

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Which of the following most likely causes the hypertension that often occurs in metabolic syndrome?View Page


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