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The use of high-sensitivity assays for C-reactive protein in clinical practice

Abstract

High-sensitivity assays that accurately measure levels of the inflammatory biomarker C-reactive protein have been proposed for use in assessments of risk for cardiovascular disease (CVD). A growing body of evidence supports recommendations for these tests in selected asymptomatic individuals deemed to be at intermediate risk of CVD according to traditional risk-factor assessments and who do not already warrant chronic treatment with aspirin and statin therapy. Data suggests that these high-sensitivity assays should be used in combination with measurements of LDL-cholesterol levels to assist risk stratification of selected patients for prevention of CVD.

Key Points

  • In asymptomatic individuals, C-reactive protein (CRP) levels are associated with risk of cardiovascular disease, including both coronary events and stroke, independent of traditional risk factors

  • High-sensitivity CRP assay results add predictive power to current coronary risk scores for some intermediate-risk individuals and, in some individuals, could highlight a need for treatment with chronic aspirin and statin therapy if not already on therapy

  • CRP levels are associated with clinical outcomes in high-risk individuals treated with statin therapy and, in some individuals, measurement of CRP in conjunction with LDL cholesterol could be useful

  • CRP levels are associated with incident diabetes mellitus and cardiovascular disease outcomes in individuals with the metabolic syndrome

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References

  1. Thom T et al. (2006) Heart disease and stroke statistics—2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113: e85–e151

    PubMed  Google Scholar 

  2. Greenland P et al. (2003) Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 290: 891–897

    Article  PubMed  Google Scholar 

  3. Khot UN et al. (2003) Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 290: 898–904

    Article  PubMed  Google Scholar 

  4. Lloyd-Jones DM et al. (1999) Lifetime risk of developing coronary heart disease. Lancet 353: 89–92

    Article  CAS  PubMed  Google Scholar 

  5. Pasternak RC et al. (2003) 34th Bethesda conference: task force #1—identification of coronary heart disease risk: is there a detection gap? J Am Coll Cardiol 41: 1863–1874

    Article  PubMed  Google Scholar 

  6. Ford ES et al. (2004) The distribution of 10-year risk for coronary heart disease among US adults: findings from the National Health and Nutrition Examination Survey III. J Am Coll Cardiol 43: 1791–1796

    Article  PubMed  Google Scholar 

  7. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) 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) final report. Circulation 106: 3143–3421

  8. Wilson PW et al. (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97: 1837–1847

    Article  CAS  PubMed  Google Scholar 

  9. D'Agostino RB Sr et al. for the CHD Risk Prediction Group (2001) Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA 286: 180–187

    Article  PubMed  Google Scholar 

  10. Berman DS and Wong ND (2004) Implications of estimating coronary heart disease risk in the US population. J Am Coll Cardiol 43: 1797–1798

    Article  PubMed  Google Scholar 

  11. Vasan RS (2006) Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 113: 2335–2362

    Article  PubMed  Google Scholar 

  12. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352: 1685–1695

    Article  CAS  PubMed  Google Scholar 

  13. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340: 115–126

    Article  CAS  PubMed  Google Scholar 

  14. Libby P and Ridker PM (2006) Inflammation and atherothrombosis: from population biology and bench research to clinical practice. J Am Coll Cardiol 48 (Suppl 9): A33–A46

    Article  CAS  Google Scholar 

  15. Pearson TA et al. for the Centers for Disease Control and Prevention and the American Heart Association (2003) Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107: 499–511

    Article  PubMed  Google Scholar 

  16. Ridker PM et al. for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators (2001) Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 344: 1959–1965

    Article  CAS  PubMed  Google Scholar 

  17. Ballantyne CM et al. (2004) Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation 109: 837–842

    Article  CAS  PubMed  Google Scholar 

  18. Danesh J et al. (2000) Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 321: 199–204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lowe GD et al. (2004) C-reactive protein, fibrin D-dimer, and risk of ischemic heart disease: the Caerphilly and Speedwell studies. Arterioscler Thromb Vasc Biol 24: 1957–1962

    Article  CAS  PubMed  Google Scholar 

  20. Cushman M et al. (2005) C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study. Circulation 112: 25–31

    Article  CAS  PubMed  Google Scholar 

  21. Tzoulaki I et al. (2007) Relative value of inflammatory, hemostatic, and rheological factors for incident myocardial infarction and stroke: the Edinburgh Artery Study. Circulation 115: 2119–2127

    Article  PubMed  Google Scholar 

  22. Boekholdt SM et al. (2006) C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: the EPIC-Norfolk prospective population study 1993–2003. Atherosclerosis 187: 415–422

    Article  CAS  PubMed  Google Scholar 

  23. Wilson PW et al. (2006) Increased CRP and long term risk for cardiovascular events in middle age men and women [abstract #4070]. Circulation 114 (Suppl): II877–II878

    Google Scholar 

  24. Sakkinen P et al. (2002) C-reactive protein and myocardial infarction. J Clin Epidemiol 55: 445–451

    Article  PubMed  Google Scholar 

  25. Pai JK et al. (2004) Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 351: 2599–2610

    Article  CAS  PubMed  Google Scholar 

  26. Laaksonen DE et al. (2005) C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study. Eur Heart J 26: 1783–1789

    Article  CAS  PubMed  Google Scholar 

  27. Koenig W et al. (2006) Increased concentrations of C-reactive protein and IL-6 but not IL-18 are independently associated with incident coronary events in middle-aged men and women: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Arterioscler Thromb Vasc Biol 26: 2745–2751

    Article  CAS  PubMed  Google Scholar 

  28. Ridker PM et al. (1997) Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 336: 973–979

    Article  CAS  PubMed  Google Scholar 

  29. Luc G et al. for the PRIME Study Group (2003) C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME study. Arterioscler Thromb Vasc Biol 23: 1255–1261

    Article  CAS  PubMed  Google Scholar 

  30. Sattar N et al. for the PROSPER Study Group (2007) C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Circulation 115: 981–989

    Article  CAS  PubMed  Google Scholar 

  31. Danesh J et al. (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350: 1387–1397

    Article  CAS  PubMed  Google Scholar 

  32. Tice JA et al. (2003) The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women. Am J Med 114: 199–205

    Article  CAS  PubMed  Google Scholar 

  33. Pradhan AD et al. (2002) Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. JAMA 288: 980–987

    Article  CAS  PubMed  Google Scholar 

  34. Ridker PM et al. (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347: 1557–1565

    Article  CAS  PubMed  Google Scholar 

  35. Lowe GD et al. for the West of Scotland Coronary Prevention Study Group (2004) Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease. Arterioscler Thromb Vasc Biol 24: 1529–1534

    Article  CAS  PubMed  Google Scholar 

  36. Wilson PW et al. (2005) C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study. Arch Intern Med 165: 2473–2478

    Article  CAS  PubMed  Google Scholar 

  37. Kuller LH et al. (1996) Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study: multiple risk factor intervention trial. Am J Epidemiol 144: 537–547

    Article  CAS  PubMed  Google Scholar 

  38. Cesari M et al. (2003) Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 108: 2317–2322

    Article  CAS  PubMed  Google Scholar 

  39. Jager A et al. (1999) von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscler Thromb Vasc Biol 19: 3071–3078

    Article  CAS  PubMed  Google Scholar 

  40. Harris TB et al. (1999) Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 106: 506–512

    Article  CAS  PubMed  Google Scholar 

  41. Hu FB et al. (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53: 693–700

    Article  CAS  PubMed  Google Scholar 

  42. Pirro M et al. (2001) Age and duration of follow-up as modulators of the risk for ischemic heart disease associated with high plasma C-reactive protein levels in men. Arch Intern Med 161: 2474–2480

    Article  CAS  PubMed  Google Scholar 

  43. van der Meer IM et al. (2003) The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study. Arch Intern Med 163: 1323–1328

    Article  PubMed  Google Scholar 

  44. Doggen CJ et al. (2000) C-reactive protein, cardiovascular risk factors and the association with myocardial infarction in men. J Intern Med 248: 406–414

    Article  CAS  PubMed  Google Scholar 

  45. Cook NR et al. (2006) The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 145: 21–29

    Article  CAS  PubMed  Google Scholar 

  46. Ridker PM et al. (2007) Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA 297: 611–619

    Article  CAS  PubMed  Google Scholar 

  47. Koenig W et al. (2004) C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany. Circulation 109: 1349–1353

    Article  PubMed  Google Scholar 

  48. Wang TJ et al. (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355: 2631–2639

    Article  CAS  PubMed  Google Scholar 

  49. Gail MH and Pfeiffer RM (2005) On criteria for evaluating models of absolute risk. Biostatistics 6: 227–239

    Article  PubMed  Google Scholar 

  50. Harrell FE Jr (2001) Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis. New York: Springer–Verlag New York Inc

    Book  Google Scholar 

  51. Cook NR (2007) Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation 115: 928–935

    Article  PubMed  Google Scholar 

  52. Pencina MJ et al. (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27: 157–172

    Article  PubMed  Google Scholar 

  53. Ballantyne CM et al. (2005) Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the atherosclerosis risk in communities (ARIC) study. Arch Intern Med 165: 2479–2484

    Article  CAS  PubMed  Google Scholar 

  54. Cao JJ et al. (2003) C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation 108: 166–170

    Article  CAS  PubMed  Google Scholar 

  55. Rost NS et al. (2001) Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke 32: 2575–2579

    Article  CAS  PubMed  Google Scholar 

  56. Wakugawa Y et al. (2006) C-reactive protein and risk of first-ever ischemic and hemorrhagic stroke in a general Japanese population: the Hisayama Study. Stroke 37: 27–32

    Article  CAS  PubMed  Google Scholar 

  57. Ford ES and Giles WH (2000) Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey. Arterioscler Thromb Vasc Biol 20: 1052–1056

    Article  CAS  PubMed  Google Scholar 

  58. Kistorp C et al. (2005) N-terminal pro-brain natriuretic peptide, C-reactive protein, and urinary albumin levels as predictors of mortality and cardiovascular events in older adults. JAMA 293: 1609–1616

    Article  CAS  PubMed  Google Scholar 

  59. Gussekloo J et al. (2000) C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons. Arterioscler Thromb Vasc Biol 20: 1047–1051

    Article  CAS  PubMed  Google Scholar 

  60. Bos MJ et al. (2006) High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study. Circulation 114: 1591–1598

    Article  CAS  PubMed  Google Scholar 

  61. Duncan BB et al. for the Atherosclerosis Risk in Communities Study (2003) Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 52: 1799–1805

    Article  CAS  PubMed  Google Scholar 

  62. Wang Z and Hoy WE (2007) C-reactive protein and the risk of developing type 2 diabetes in Aboriginal Australians. Diabetes Res Clin Pract 76: 37–43

    Article  CAS  PubMed  Google Scholar 

  63. Barzilay JI et al. (2001) The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. Diabetes 50: 2384–2389

    Article  CAS  PubMed  Google Scholar 

  64. Spranger J et al. (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52: 812–817

    Article  CAS  PubMed  Google Scholar 

  65. Doi Y et al. (2005) Elevated C-reactive protein is a predictor of the development of diabetes in a general Japanese population: the Hisayama Study. Diabetes Care 28: 2497–2500

    Article  CAS  PubMed  Google Scholar 

  66. Festa A et al. for the Insulin Resistance Atherosclerosis Study (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51: 1131–1137

    Article  CAS  PubMed  Google Scholar 

  67. Nakanishi S et al. (2003) Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans. Diabetes Care 26: 2754–2757

    Article  CAS  PubMed  Google Scholar 

  68. Laaksonen DE et al. (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47: 1403–1410

    Article  CAS  PubMed  Google Scholar 

  69. Han TS et al. (2002) Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25: 2016–2021

    Article  CAS  PubMed  Google Scholar 

  70. Thorand B et al. (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30: 854–860

    Article  CAS  PubMed  Google Scholar 

  71. Pradhan AD et al. (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286: 327–334

    Article  CAS  PubMed  Google Scholar 

  72. Freeman DJ et al. for the West of Scotland Coronary Prevention Study (2002) C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51: 1596–1600

    Article  CAS  PubMed  Google Scholar 

  73. Ridker PM et al. (2004) Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 109: 2818–2825

    Article  CAS  PubMed  Google Scholar 

  74. Malik S et al. (2005) Cardiovascular disease in U.S. patients with metabolic syndrome, diabetes, and elevated C-reactive protein. Diabetes Care 28: 690–693

    Article  CAS  PubMed  Google Scholar 

  75. Wannamethee SG et al. (2005) The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men. Atherosclerosis 181: 101–108

    Article  CAS  PubMed  Google Scholar 

  76. Yudkin JS et al. (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19: 972–978

    Article  CAS  PubMed  Google Scholar 

  77. Bazzano LA et al. (2003) Relationship between cigarette smoking and novel risk factors for cardiovascular disease in the United States. Ann Intern Med 138: 891–897

    Article  PubMed  Google Scholar 

  78. Bermudez EA et al. (2002) Relation between markers of systemic vascular inflammation and smoking in women. Am J Cardiol 89: 1117–1119

    Article  PubMed  Google Scholar 

  79. Esposito K et al. (2003) Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289: 1799–1804

    Article  CAS  PubMed  Google Scholar 

  80. Mora S et al. (2006) Association of physical activity and body mass index with novel and traditional cardiovascular biomarkers in women. JAMA 295: 1412–1419

    Article  CAS  PubMed  Google Scholar 

  81. Tchernof A et al. (2002) Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 105: 564–569

    Article  PubMed  Google Scholar 

  82. Wannamethee SG et al. (2002) Physical activity and hemostatic and inflammatory variables in elderly men. Circulation 105: 1785–1790

    Article  PubMed  Google Scholar 

  83. Wannamethee SG et al. (2005) Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease. Eur Heart J 26: 1765–1773

    Article  CAS  PubMed  Google Scholar 

  84. Hamer M (2007) The relative influences of fitness and fatness on inflammatory factors. Prev Med 44: 3–11

    Article  PubMed  Google Scholar 

  85. Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107: 363–369

    Article  PubMed  Google Scholar 

  86. Tsimikas S et al. (2006) C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 47 (Suppl 8): C19–C31

    Article  CAS  PubMed  Google Scholar 

  87. Nissen SE et al. for the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352: 29–38

    Article  CAS  PubMed  Google Scholar 

  88. Ridker PM et al. for the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) Investigators (2005) C-reactive protein levels and outcomes after statin therapy. N Engl J Med 352: 20–28

    Article  CAS  PubMed  Google Scholar 

  89. Arnaud C et al. (2005) Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arterioscler Thromb Vasc Biol 25: 1231–1236

    Article  CAS  PubMed  Google Scholar 

  90. Jain MK and Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4: 977–987

    Article  CAS  PubMed  Google Scholar 

  91. Schönbeck U and Libby P (2004) Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation 109 (Suppl 1): II18–II26

    PubMed  Google Scholar 

  92. Ridker PM et al. (1998) Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events (CARE) investigators. Circulation 98: 839–844

    Article  CAS  PubMed  Google Scholar 

  93. Ridker PM for the JUPITER Study Group (2003) Rosuvastatin in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein: rationale and design of the JUPITER trial. Circulation 108: 2292–2297

    Article  PubMed  Google Scholar 

  94. Haverkate F et al. (1997) Production of C-reactive protein and risk of coronary events in stable and unstable angina: European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349: 462–466

    Article  CAS  PubMed  Google Scholar 

  95. Lindahl B et al. (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. N Engl J Med 343: 1139–1147

    Article  CAS  PubMed  Google Scholar 

  96. Liuzzo G et al. (1994) The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 331: 417–424

    Article  CAS  PubMed  Google Scholar 

  97. Morrow DA et al. (2006) Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation 114: 281–288

    Article  CAS  PubMed  Google Scholar 

  98. Morrow DA et al. (1998) C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIMI 11A substudy (Thrombolysis in Myocardial Infarction). J Am Coll Cardiol 31: 1460–1465

    Article  CAS  PubMed  Google Scholar 

  99. Sabatine MS et al. (2002) Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide. Circulation 105: 1760–1763

    Article  CAS  PubMed  Google Scholar 

  100. Mega JL et al. (2006) Cholesterol, C-reactive protein, and cerebrovascular events following intensive and moderate statin therapy. J Thromb Thrombolysis 22: 71–76

    Article  CAS  PubMed  Google Scholar 

  101. Albert MA et al. (2004) C-reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study). Am J Cardiol 93: 1238–1242

    Article  CAS  PubMed  Google Scholar 

  102. Albert MA and Ridker PM (2006) C-reactive protein as a risk predictor: do race/ethnicity and gender make a difference? Circulation 114: e67–e74

    PubMed  Google Scholar 

  103. Ridker PM and Cook N (2004) Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores. Circulation 109: 1955–1959

    Article  PubMed  Google Scholar 

  104. Sabatine MS et al. for the PEACE Investigators (2007) Prognostic significance of the Centers for Disease Control/American Heart Association high-sensitivity C-reactive protein cut points for cardiovascular and other outcomes in patients with stable coronary artery disease. Circulation 115: 1528–1536

    Article  PubMed  Google Scholar 

  105. Zieske AW et al. for the Pathobiological Determinants of Atherosclerosis in Youth Research Group (2005) Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol 25: 1237–1243

    Article  CAS  PubMed  Google Scholar 

  106. Fröhlich M et al. (2002) Lack of seasonal variation in C-reactive protein. Clin Chem 48: 575–577

    Article  PubMed  Google Scholar 

  107. Sung KC (2006) Seasonal variation of C-reactive protein in apparently healthy Koreans. Int J Cardiol 107: 338–342

    Article  PubMed  Google Scholar 

  108. Heikkilä K et al. (2007) A systematic review of the association between circulating concentrations of C reactive protein and cancer. J Epidemiol Community Health 61: 824–833

    Article  PubMed  PubMed Central  Google Scholar 

  109. Koenig W et al. (2008) Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA Augsburg Cohort Study, 1984–1998. Clin Chem 54: 335–342

    Article  CAS  PubMed  Google Scholar 

  110. Marsik C et al. (2008) C-reactive protein and all-cause mortality in a large hospital-based cohort. Clin Chem 54: 343–349

    Article  CAS  PubMed  Google Scholar 

  111. Blake GJ et al. (2003) Potential cost-effectiveness of C-reactive protein screening followed by targeted statin therapy for the primary prevention of cardiovascular disease among patients without overt hyperlipidemia. Am J Med 114: 485–494

    Article  PubMed  Google Scholar 

  112. Ridker PM et al. (2005) Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA 294: 326–333

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Charles P Vega, University of California, Irvine, CA, and A Del Negro, Medscape Cardiology, New York, NY, are the authors of and are solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Correspondence to Kiran Musunuru.

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K Musunuru has served as a consultant for Alnylam Pharmaceuticals within the last year. TJ Gluckman has received honoraria from Sanofi-Aventis and Pfizer and has served as a consultant for Merck within the last year. MH Davidson has received honoraria from and served as a consultant for diaDexus within the last year. They declare no conflicts of interest pertaining to this topic. The other authors declared no competing interests.

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Musunuru, K., Kral, B., Blumenthal, R. et al. The use of high-sensitivity assays for C-reactive protein in clinical practice. Nat Rev Cardiol 5, 621–635 (2008). https://doi.org/10.1038/ncpcardio1322

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