C-Reactive Protein as a Tool for Risk Assessment in Primary Prevention

  • Shari S. Bassuk
  • Paul M. Ridker
Part of the Contemporary Cardiology book series (CONCARD)


High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy persons without a history of cardiovascular disease, as well as recurrent events and death in patients with acute or stable coronary syndromes. hsCRP adds prognostic value at all levels of low-density lipoprotein cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. Among apparently healthy men and women, hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L distinguish those at low, moderate, and high risk for future cardiovascular disease, respectively. In clinical settings, hsCRP should be used in conjunction with lipid evaluation as part of global risk assessment. Improved knowledge of cardiovascular risk should lead to better compliance with lifestyle and pharmacological interventions designed to prevent future cardiovascular events.

Key Words

C-reactive protein cardiovascular disease clinical medicine epidemiology inflammation risk assessment 


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  1. 1.
    Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837–1847.PubMedGoogle Scholar
  2. 2.
    Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA 2003;290:898–904.PubMedCrossRefGoogle Scholar
  3. 3.
    Greenland P, Knoll MD, Stamler J, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA 2003;290:891–897.PubMedCrossRefGoogle Scholar
  4. 4.
    Ridker PM. Evaluating novel cardiovascular risk factors: can we better predict heart attacks? Ann Intern Med 1999;130:933–937.PubMedGoogle Scholar
  5. 5.
    Hackam DG, Anand SS. Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence. JAMA 2003;290:932–940.PubMedCrossRefGoogle Scholar
  6. 6.
    Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol 2004;29:439–493.PubMedGoogle Scholar
  7. 7.
    Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Res 2001;89:763–771.PubMedCrossRefGoogle Scholar
  8. 8.
    Blake GJ, Ridker PM. Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med 2002;252:283–294.PubMedCrossRefGoogle Scholar
  9. 9.
    Pearson TA, Mensah GA, Alexander RW, et al. 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 2003;107:499–511.PubMedCrossRefGoogle Scholar
  10. 10.
    Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836–843.PubMedCrossRefGoogle Scholar
  11. 11.
    Ridker PM, Stampfer MJ, Rifai N. Novel risk factors for systemic atherosclerosis: a comparison of Creactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001;285:2481–2485.PubMedCrossRefGoogle Scholar
  12. 12.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000;101:1767–1772.PubMedGoogle Scholar
  14. 14.
    Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of tumor necrosis factoralpha and increased risk of recurrent coronary events after myocardial infarction. Circulation 2000;101:2149–2153.PubMedGoogle Scholar
  15. 15.
    Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 1998;351:88–92.PubMedCrossRefGoogle Scholar
  16. 16.
    Pradhan AD, Rifai N, Ridker PM. Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men. Circulation 2002;106:820–825.PubMedCrossRefGoogle Scholar
  17. 17.
    Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation 2001;103:491–495.PubMedGoogle Scholar
  18. 18.
    Schonbeck U, Varo N, Libby P, Buring J, Ridker PM. Soluble CD40L and cardiovascular risk in women. Circulation 2001;104:2266–2268.PubMedCrossRefGoogle Scholar
  19. 19.
    Brown DA, Breit SN, Buring J, et al. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women: a nested case-control study. Lancet 2002;359:2159–2163.PubMedCrossRefGoogle Scholar
  20. 20.
    Packard CJ, O’Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med 2000;343:1148–1155.PubMedCrossRefGoogle Scholar
  21. 21.
    Ballantyne CM, Hoogeveen RC, Bang H, et al. 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 2004;109:837–842.PubMedCrossRefGoogle Scholar
  22. 22.
    Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1997;96:1102–1108.PubMedGoogle Scholar
  23. 23.
    Malik I, Danesh J, Whincup P, et al. Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 2001;358:971–976.PubMedCrossRefGoogle Scholar
  24. 24.
    Folsom AR. Hemostatic risk factors for atherothrombotic disease: an epidemiologic view. Thromb Haemost 2001;86:366–373.PubMedGoogle Scholar
  25. 25.
    Calabro P, Willerson JT, Yeh ET. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation 2003;108:1930–1932.PubMedCrossRefGoogle Scholar
  26. 26.
    Jabs WJ, Theissing E, Nitschke M, et al. Local generation of C-reactive protein in diseased coronary artery venous bypass grafts and normal vascular tissue. Circulation 2003;108:1428–1431.PubMedCrossRefGoogle Scholar
  27. 27.
    Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol 2001;158:1039–1051.PubMedGoogle Scholar
  28. 28.
    Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165–2168.PubMedGoogle Scholar
  29. 29.
    Pasceri V, Cheng JS, Willerson JT, Yeh ET, Chang J. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001;103:2531–2534.PubMedGoogle Scholar
  30. 30.
    Verma S, Li SH, Badiwala MV, et al. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002;105:1890–1896.PubMedCrossRefGoogle Scholar
  31. 31.
    Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003;107:398–404.PubMedCrossRefGoogle Scholar
  32. 32.
    Venugopal SK, Devaraj S, Yuhanna I, Shaul P, Jialal I. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002;106:1439–1441.PubMedCrossRefGoogle Scholar
  33. 33.
    Verma S, Wang CH, Li SH, et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002;106:913–919.PubMedCrossRefGoogle Scholar
  34. 34.
    Nakagomi A, Freedman SB, Geczy CL. Interferon-gamma and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment. Circulation 2000;101:1785–1791.PubMedGoogle Scholar
  35. 35.
    Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001;103:1194–1197.PubMedGoogle Scholar
  36. 36.
    Torzewski J, Torzewski M, Bowyer DE, et al. C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol 1998;18:1386–1392.PubMedGoogle Scholar
  37. 37.
    Danenberg HD, Szalai AJ, Swaminathan RV, et al. Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 2003;108:512–515.PubMedCrossRefGoogle Scholar
  38. 38.
    Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol 1996;144:537–547.PubMedGoogle Scholar
  39. 39.
    Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973–979.PubMedCrossRefGoogle Scholar
  40. 40.
    Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998;97:2007–2011.PubMedGoogle Scholar
  41. 41.
    Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 1998;98:731–733.PubMedGoogle Scholar
  42. 42.
    Rifai N, Buring JE, Lee IM, Manson JE, Ridker PM. Is C-reactive protein specific for vascular disease in women? Ann Intern Med 2002;136:529–533.PubMedGoogle Scholar
  43. 43.
    Tracy RP, Lemaitre RN, Psaty BM, et al. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Arterioscler Thromb Vasc Biol 1997;17:1121–1127.PubMedGoogle Scholar
  44. 44.
    Koenig W, Sund M, Frohlich M, et al. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999;99:237–242.PubMedGoogle Scholar
  45. 45.
    Danesh J, Whincup P, Walker M, et al. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000;321:199–204.PubMedCrossRefGoogle Scholar
  46. 46.
    Mendall MA, Strachan DP, Butland BK, et al. C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart J 2000;21:1584–1590.PubMedCrossRefGoogle Scholar
  47. 47.
    Roivainen M, Viik-Kajander M, Palosuo T, et al. Infections, inflammation, and the risk of coronary heart disease. Circulation 2000;101:252–257.PubMedGoogle Scholar
  48. 48.
    Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001;344:1959–1965.PubMedCrossRefGoogle Scholar
  49. 49.
    Lowe GD, Yarnell JW, Rumley A, Bainton D, Sweetnam PM. C-reactive protein, fibrin D-dimer, and incident ischemic heart disease in the Speedwell study: are inflammation and fibrin turnover linked in pathogenesis? Arterioscler Thromb Vasc Biol 2001;21:603–610.PubMedGoogle Scholar
  50. 50.
    Park R, Detrano R, Xiang M, et al. Combined use of computed tomography coronary calcium scores and C-reactive protein levels in predicting cardiovascular events in nondiabetic individuals. Circulation 2002;106:2073–2077.PubMedCrossRefGoogle Scholar
  51. 51.
    Folsom AR, Aleksic N, Catellier D, Juneja HS, Wu KK. C-reactive protein and incident coronary heart disease in the Atherosclerosis Risk In Communities (ARIC) study. Am Heart J 2002;144:233–238.PubMedCrossRefGoogle Scholar
  52. 52.
    Pradhan AD, Manson JE, Rossouw JE, et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study. JAMA 2002;288:980–987.PubMedCrossRefGoogle Scholar
  53. 53.
    Sakkinen P, Abbott RD, Curb JD, Rodriguez BL, Yano K, Tracy RP. C-reactive protein and myocardial infarction. J Clin Epidemiol 2002;55:445–451.PubMedCrossRefGoogle Scholar
  54. 54.
    Witherell HL, Smith KL, Friedman GD, et al. C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction. Ann Epidemiol 2003;13:170–177.PubMedCrossRefGoogle Scholar
  55. 55.
    van der Meer IM, de Maat MP, Kiliaan AJ, van der Kuip DA, Hofman A, Witteman JC. The value of C-reactive protein in cardiovascular risk prediction: the Rotterdam Study. Arch Intern Med 2003;163:1323–1328.PubMedCrossRefGoogle Scholar
  56. 56.
    Koenig W, Lowel H, Baumert J, Meisinger C. C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment. Circulation 2004;109:1349–1353.PubMedCrossRefGoogle Scholar
  57. 57.
    Danesh J, Wheeler JG, Hirschfield GM, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004;350:1387–1397.PubMedCrossRefGoogle Scholar
  58. 58.
    Pai JK, Pischon T, Ma J, et al. Inflammatory markers and risk of coronary heart disease in men and women. N Engl J Med 2004;351:2599–2610.PubMedCrossRefGoogle Scholar
  59. 59.
    Gussekloo J, Schaap MC, Frohlich M, Blauw GJ, Westendorp RG. C-reactive protein is a strong but nonspecific risk factor for fatal stroke in elderly persons. Arterioscler Thromb Vasc Biol 2000;20:1047–1051.PubMedGoogle Scholar
  60. 60.
    Rost NS, Wolf PA, Kase CS, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham Study. Stroke 2001;32:2575–2579.PubMedCrossRefGoogle Scholar
  61. 61.
    Curb JD, Abbott RD, Rodriguez BL, et al. C-reactive protein and the future risk of thromboembolic stroke in healthy men. Circulation 2003;107:2016–2020.PubMedCrossRefGoogle Scholar
  62. 62.
    Cao JJ, Thach C, Manolio TA, et al. C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study. Circulation 2003;108:166–170.PubMedCrossRefGoogle Scholar
  63. 63.
    Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation 1998;97:425–428.PubMedGoogle Scholar
  64. 64.
    Vasan RS, Sullivan LM, Roubenoff R, et al. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation 2003;107:1486–1491.PubMedCrossRefGoogle Scholar
  65. 65.
    Cesari M, Penninx BW, Newman AB, et al. Inflammatory markers and onset of cardiovascular events: results from the Health ABC study. Circulation 2003;108:2317–2322.PubMedCrossRefGoogle Scholar
  66. 66.
    Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003;108:3006–3010.PubMedCrossRefGoogle Scholar
  67. 67.
    Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002;105:2595–2599.PubMedCrossRefGoogle Scholar
  68. 68.
    Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. 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.Google Scholar
  69. 69.
    Ridker PM, Cook NR. Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham risk scores. Circulation 2004;109:1955–1959.PubMedCrossRefGoogle Scholar
  70. 70.
    Ridker PM, Wilson PW, Grundy SM. Should C-reactive protein be added to metabolic syndrome and to assessment of global cardiovascular risk? Circulation 2004;109:2818–2825.PubMedCrossRefGoogle Scholar
  71. 71.
    Albert MA, Glynn RJ, Ridker PM. Plasma concentration of C-reactive protein and the calculated Framingham Coronary Heart Disease Risk Score. Circulation 2003;108:161–165.PubMedCrossRefGoogle Scholar
  72. 72.
    Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709–2716.PubMedCrossRefGoogle Scholar
  73. 73.
    Sesso HD, Buring JE, Rifai N, Blake GJ, Gaziano JM, Ridker PM. C-reactive protein and the risk of developing hypertension. JAMA 2003;290:2945–2951.PubMedCrossRefGoogle Scholar
  74. 74.
    Pradhan AD, Cook NR, Buring JE, Manson JE, Ridker PM. C-reactive protein is independently associated with fasting insulin in nondiabetic women. Arterioscler Thromb Vasc Biol 2003;23:650–655.PubMedCrossRefGoogle Scholar
  75. 75.
    Ridker PM, Buring JE, Cook NR, Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14,719 initially healthy American women. Circulation 2003;107:391–397.PubMedCrossRefGoogle Scholar
  76. 76.
    Sattar N, Gaw A, Scherbakova O, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation 2003;108:414–419.PubMedCrossRefGoogle Scholar
  77. 77.
    Rutter MK, Meigs JB, Sullivan LM, D’Agostino RB Sr, Wilson PW. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004;110:380–385.PubMedCrossRefGoogle Scholar
  78. 78.
    Schulze MB, Rimm EB, Li T, Rifai N, Stampfer MJ, Hu FB. C-reactive protein and incident cardiovascular events among men with diabetes. Diabetes Care 2004;27:889–894.PubMedCrossRefGoogle Scholar
  79. 79.
    Freeman DJ, Norrie J, Caslake MJ, et al. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 2002;51:1596–1600.PubMedCrossRefGoogle Scholar
  80. 80.
    Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin-6, and risk of developing type 2 diabetes mellitus. JAMA 2001;286:327–334.PubMedCrossRefGoogle Scholar
  81. 81.
    Hu FB, Meigs JB, Li TY, Rifai N, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 2004;53:693–700.PubMedCrossRefGoogle Scholar
  82. 82.
    Barzilay JI, Abraham L, Heckbert SR, et al. The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study. Diabetes 2001;50:2384–2389.PubMedCrossRefGoogle Scholar
  83. 83.
    Thorand B, Lowel H, Schneider A, et al. C-reactive protein as a predictor for incident diabetes mellitus among middle-aged men: results from the MONICA Augsburg cohort study, 1984–1998. Arch Intern Med 2003;163:93–99.PubMedCrossRefGoogle Scholar
  84. 84.
    Festa A, D’Agostino R Jr, Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the Insulin Resistance Atherosclerosis Study. Diabetes 2002;51:1131–1137.PubMedCrossRefGoogle Scholar
  85. 85.
    Muntner P, Hamm LL, Kusek JW, Chen J, Whelton PK, He J. The prevalence of nontraditional risk factors for coronary heart disease in patients with chronic kidney disease. Ann Intern Med 2004;140:9–17.PubMedGoogle Scholar
  86. 86.
    deFilippi C, Wasserman S, Rosanio S, et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003;290:353–359.PubMedCrossRefGoogle Scholar
  87. 87.
    Wang TJ, Nam BH, Wilson PW, et al. Association of C-reactive protein with carotid atherosclerosis in men and women: the Framingham Heart Study. Arterioscler Thromb Vasc Biol 2002;22:1662–1667.PubMedCrossRefGoogle Scholar
  88. 88.
    Wang TJ, Larson MG, Levy D, et al. C-reactive protein is associated with subclinical epicardial coronary calcification in men and women: the Framingham Heart Study. Circulation 2002;106:1189–1191.PubMedCrossRefGoogle Scholar
  89. 89.
    van der Meer IM, de Maat MP, Bots ML, et al. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study. Arterioscler Thromb Vasc Biol 2002;22:838–842.PubMedCrossRefGoogle Scholar
  90. 90.
    Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004;291:1071–1080.PubMedCrossRefGoogle Scholar
  91. 91.
    Folsom AR, Pankow JS, Tracy RP, et al. Association of C-reactive protein with markers of prevalent atherosclerotic disease. Am J Cardiol 2001;88:112–117.PubMedCrossRefGoogle Scholar
  92. 92.
    Reilly MP, Wolfe ML, Localio AR, Rader DJ. C-reactive protein and coronary artery calcification: the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA). Arterioscler Thromb Vasc Biol 2003;23:1851–1856.PubMedCrossRefGoogle Scholar
  93. 93.
    Burke AP, Tracy RP, Kolodgie F, et al. Elevated C-reactive protein values and atherosclerosis in sudden coronary death: association with different pathologies. Circulation 2002;105:2019–2023.PubMedCrossRefGoogle Scholar
  94. 94.
    Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998;98:839–844.PubMedGoogle Scholar
  95. 95.
    Retterstol L, Eikvar L, Bohn M, Bakken A, Erikssen J, Berg K. C-reactive protein predicts death in patients with previous premature myocardial infarction—a 10-year follow-up study. Atherosclerosis 2002;160:433–440.PubMedCrossRefGoogle Scholar
  96. 96.
    Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352:20–28.PubMedCrossRefGoogle Scholar
  97. 97.
    Harb TS, Zareba W, Moss AJ, et al. Association of C-reactive protein and serum amyloid A with recurrent coronary events in stable patients after healing of acute myocardial infarction. Am J Cardiol 2002;89:216–221.PubMedCrossRefGoogle Scholar
  98. 98.
    Tice JA, Browner W, Tracy RP, Cummings SR. The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women. Am J Med 2003;114:199–205.PubMedCrossRefGoogle Scholar
  99. 99.
    Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003;107:363–369.PubMedCrossRefGoogle Scholar
  100. 100.
    Blake GJ, Ridker PM, Kuntz KM. Projected life-expectancy gains with statin therapy for individuals with elevated C-reactive protein levels. J Am Coll Cardiol 2002;40:49–55.PubMedCrossRefGoogle Scholar
  101. 101.
    Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein: the Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999;100:230–235.PubMedGoogle Scholar
  102. 102.
    Balk EM, Lau J, Goudas LC, et al. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med 2003;139:670–682.PubMedGoogle Scholar
  103. 103.
    Albert MA, Danielson E, Rifai N, Ridker PM. Effect of statin therapy on C-reactive protein levels: the Pravastatin Inflammation/CRP Evaluation (PRINCE), a randomized trial and cohort study. JAMA 2001;286:64–70.PubMedCrossRefGoogle Scholar
  104. 104.
    Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001;103:1191–1193.PubMedGoogle Scholar
  105. 105.
    Bays HE, Stein EA, Shah AK, Maccubbin DL, Mitchel YB, Mercuri M. Effects of simvastatin on C-reactive protein in mixed hyperlipidemic and hypertriglyceridemic patients. Am J Cardiol 2002;90: 942–946.PubMedCrossRefGoogle Scholar
  106. 106.
    Ballantyne CM, Houri J, Notarbartolo A, et al. Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial. Circulation 2003;107:2409–2415.PubMedCrossRefGoogle Scholar
  107. 107.
    Kinlay S, Timms T, Clark M, et al. Comparison of effect of intensive lipid lowering with atorvastatin to less intensive lowering with lovastatin on C-reactive protein in patients with stable angina pectoris and inducible myocardial ischemia. Am J Cardiol 2002;89:1205–1207.PubMedCrossRefGoogle Scholar
  108. 108.
    Kinlay S, Schwartz GG, Olsson AG, et al. High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation 2003;108:1560–1566.PubMedCrossRefGoogle Scholar
  109. 109.
    Gagne C, Bays HE, Weiss SR, et al. Efficacy and safety of ezetimibe added to ongoing statin therapy for treatment of patients with primary hypercholesterolemia. Am J Cardiol 2002;90:1084–1091.PubMedCrossRefGoogle Scholar
  110. 110.
    Ridker PM. 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 2003;108:2292–2297.PubMedCrossRefGoogle Scholar
  111. 111.
    Chew DP, Bhatt DL, Robbins MA, et al. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol 2001;88:672–674.PubMedCrossRefGoogle Scholar
  112. 112.
    Lincoff AM, Kereiakes DJ, Mascelli MA, et al. Abciximab suppresses the rise in levels of circulating inflammatory markers after percutaneous coronary revascularization. Circulation 2001;104:163–167.PubMedGoogle Scholar
  113. 113.
    Vivekananthan DP, Bhatt DL, Chew DP, et al. Effect of clopidogrel pretreatment on periprocedural rise in C-reactive protein after percutaneous coronary intervention. Am J Cardiol 2004;94:358–360.PubMedCrossRefGoogle Scholar
  114. 114.
    Di Napoli M, Papa F. Inflammation, hemostatic markers, and antithrombotic agents in relation to longterm risk of new cardiovascular events in first-ever ischemic stroke patients. Stroke 2002;33:1763–1771.PubMedCrossRefGoogle Scholar
  115. 115.
    Ikonomidis I, Andreotti F, Economou E, Stefanadis C, Toutouzas P, Nihoyannopoulos P. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999;100:793–798.PubMedGoogle Scholar
  116. 116.
    Feldman M, Jialal I, Devaraj S, Cryer B. Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay. J Am Coll Cardiol 2001;37:2036–2041.PubMedCrossRefGoogle Scholar
  117. 117.
    Feng D, Tracy RP, Lipinska I, Murillo J, McKenna C, Tofler GH. Effect of short-term aspirin use on C-reactive protein. J Thromb Thrombolysis 2000;9:37–41.PubMedCrossRefGoogle Scholar
  118. 118.
    Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002;106:679–684.PubMedCrossRefGoogle Scholar
  119. 119.
    Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999;100:713–716.PubMedGoogle Scholar
  120. 120.
    Cushman M, Legault C, Barrett-Connor E, et al. Effect of postmenopausal hormones on inflammationsensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999;100:717–722.PubMedGoogle Scholar
  121. 121.
    Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003;349:523–534.PubMedCrossRefGoogle Scholar
  122. 122.
    Wassertheil-Smoller S, Hendrix SL, Limacher M, et al. Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial. JAMA 2003;289:2673–2684.PubMedCrossRefGoogle Scholar
  123. 123.
    Herrington DM, Brosnihan KB, Pusser BE, et al. Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal women. J Clin Endocrinol Metab 2001;86:4216–4222.PubMedCrossRefGoogle Scholar
  124. 124.
    Vongpatanasin W, Tuncel M, Wang Z, Arbique D, Mehrad B, Jialal I. Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women. J Am Coll Cardiol 2003;41:1358–1363.PubMedCrossRefGoogle Scholar
  125. 125.
    Ridker PM. Cardiology Patient Page. C-reactive protein: a simple test to help predict risk of heart attack and stroke. Circulation 2003;108:e81–e85.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Shari S. Bassuk
    • 1
  • Paul M. Ridker
    • 2
    • 3
  1. 1.Division of Preventive MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBoston
  2. 2.Division of Cardiovascular Disease PreventionBrigham and Women’s Hospital, Harvard Medical SchoolBoston
  3. 3.Center for Cardiovascular Disease Prevention, Donald W. Reynolds Center for Cardiovascular ResearchBoston

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