Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

C-reactive protein in cardiovascular disease

David A Morrow, MD, MPH
Section Editor
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Deputy Editor
Brian C Downey, MD, FACC


Experimental and clinical evidence accumulated since 1990 have established inflammatory processes as important contributors to atherogenesis, as well as to the vulnerability of an atherosclerotic lesion to rupture or erosion. (See "The role of the vulnerable plaque in acute coronary syndromes".)

Based upon this evidence, protein markers of inflammation have been studied as noninvasive indicators of underlying atherosclerosis in apparently healthy individuals and of the risk of recurrent events in patients with established atherosclerotic vascular disease. The most extensively studied biomarker of inflammation in cardiovascular diseases is C-reactive protein (CRP), for which standardized high-sensitivity assays (hs-CRP) are widely available [1,2].

CRP is an acute phase protein that is produced predominantly by hepatocytes under the influence of cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha [3]. (See "Acute phase reactants".)

Despite a lack of specificity for the cause of inflammation, data from more than 30 epidemiologic studies have shown a significant association between elevated serum or plasma concentrations of CRP and the prevalence of underlying atherosclerosis, the risk of recurrent cardiovascular events among patients with established disease, and the incidence of first cardiovascular events among individuals at risk for atherosclerosis [4,5]. In addition, a number of drugs used in the treatment of cardiovascular disease reduce serum CRP. It is therefore possible that reduced inflammation contributes to the beneficial effects of these medications. However, despite the consistent epidemiological evidence, there is, at present, no established role for routine measurement of hs-CRP in patients with cardiovascular disease.

These issues as well as the mechanisms of association with cardiovascular risk will be reviewed here. The application of CRP measurement for screening for cardiovascular risk is discussed elsewhere. (See "Screening for cardiovascular risk with C-reactive protein".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 19, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Roberts WL, Moulton L, Law TC, et al. Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2. Clin Chem 2001; 47:418.
  2. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107:363.
  3. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci 1982; 389:39.
  4. 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.
  5. Zacho J, Tybjaerg-Hansen A, Jensen JS, et al. Genetically elevated C-reactive protein and ischemic vascular disease. N Engl J Med 2008; 359:1897.
  6. Libby P. Inflammation in atherosclerosis. Nature 2002; 420:868.
  7. Nilsson J. CRP--marker or maker of cardiovascular disease? Arterioscler Thromb Vasc Biol 2005; 25:1527.
  8. Scirica BM, Morrow DA. Is C-reactive protein an innocent bystander or proatherogenic culprit? The verdict is still out. Circulation 2006; 113:2128.
  9. 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.
  10. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001; 103:1194.
  11. Bisoendial RJ, Kastelein JJ, Levels JH, et al. Activation of inflammation and coagulation after infusion of C-reactive protein in humans. Circ Res 2005; 96:714.
  12. Schwedler SB, Amann K, Wernicke K, et al. Native C-reactive protein increases whereas modified C-reactive protein reduces atherosclerosis in apolipoprotein E-knockout mice. Circulation 2005; 112:1016.
  13. 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.
  14. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102:2165.
  15. Pasceri V, Cheng JS, Willerson JT, Yeh ET. Modulation of C-reactive protein-mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 2001; 103:2531.
  16. Lagrand WK, Niessen HW, Wolbink GJ, et al. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997; 95:97.
  17. Griselli M, Herbert J, Hutchinson WL, et al. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999; 190:1733.
  18. Pepys MB, Hirschfield GM, Tennent GA, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 2006; 440:1217.
  19. Kitsis RN, Jialal I. Limiting myocardial damage during acute myocardial infarction by inhibiting C-reactive protein. N Engl J Med 2006; 355:513.
  20. Clapp BR, Hirschfield GM, Storry C, et al. Inflammation and endothelial function: direct vascular effects of human C-reactive protein on nitric oxide bioavailability. Circulation 2005; 111:1530.
  21. Paffen E, Vos HL, Bertina RM. C-reactive protein does not directly induce tissue factor in human monocytes. Arterioscler Thromb Vasc Biol 2004; 24:975.
  22. Taylor KE, Giddings JC, van den Berg CW. C-reactive protein-induced in vitro endothelial cell activation is an artefact caused by azide and lipopolysaccharide. Arterioscler Thromb Vasc Biol 2005; 25:1225.
  23. Pepys MB, Hawkins PN, Kahan MC, et al. Proinflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products, not by C-reactive protein itself. Circ Res 2005; 97:e97.
  24. Pai JK, Mukamal KJ, Rexrode KM, Rimm EB. C-reactive protein (CRP) gene polymorphisms, CRP levels, and risk of incident coronary heart disease in two nested case-control studies. PLoS One 2008; 3:e1395.
  25. Lawlor DA, Harbord RM, Timpson NJ, et al. The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants. PLoS One 2008; 3:e3011.
  26. Elliott P, Chambers JC, Zhang W, et al. Genetic Loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 2009; 302:37.
  27. Schunkert H, Samani NJ. Elevated C-reactive protein in atherosclerosis--chicken or egg? N Engl J Med 2008; 359:1953.
  28. Albert CM, Ma J, Rifai N, et al. Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105:2595.
  29. Wu KC, Gerstenblith G, Guallar E, et al. Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death. Circ Cardiovasc Imaging 2012; 5:178.
  30. 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.
  31. Venugopal SK, Devaraj S, Yuhanna I, et al. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002; 106:1439.
  32. Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in "active" coronary artery disease. Am J Cardiol 1990; 65:168.
  33. Liuzzo G, Biasucci LM, Rebuzzi AG, et al. Plasma protein acute-phase response in unstable angina is not induced by ischemic injury. Circulation 1996; 94:2373.
  34. Zebrack JS, Muhlestein JB, Horne BD, et al. C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina. J Am Coll Cardiol 2002; 39:632.
  35. Sabatine MS, Morrow DA, Jablonski KA, et al. 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 2007; 115:1528.
  36. Khera A, de Lemos JA, Peshock RM, et al. Relationship between C-reactive protein and subclinical atherosclerosis: the Dallas Heart Study. Circulation 2006; 113:38.
  37. Bogaty P, Poirier P, Simard S, et al. Biological profiles in subjects with recurrent acute coronary events compared with subjects with long-standing stable angina. Circulation 2001; 103:3062.
  38. Haverkate F, Thompson SG, Pyke SD, et al. 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 1997; 349:462.
  39. Tomoda H, Aoki N. Prognostic value of C-reactive protein levels within six hours after the onset of acute myocardial infarction. Am Heart J 2000; 140:324.
  40. Thompson SG, Kienast J, Pyke SD, et al. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. N Engl J Med 1995; 332:635.
  41. 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.
  42. Arroyo-Espliguero R, Avanzas P, Cosín-Sales J, et al. C-reactive protein elevation and disease activity in patients with coronary artery disease. Eur Heart J 2004; 25:401.
  43. Zouridakis E, Avanzas P, Arroyo-Espliguero R, et al. Markers of inflammation and rapid coronary artery disease progression in patients with stable angina pectoris. Circulation 2004; 110:1747.
  44. Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994; 331:417.
  45. Liuzzo G, Biasucci LM, Gallimore JR, et al. Enhanced inflammatory response in patients with preinfarction unstable angina. J Am Coll Cardiol 1999; 34:1696.
  46. Biasucci LM, Vitelli A, Liuzzo G, et al. Elevated levels of interleukin-6 in unstable angina. Circulation 1996; 94:874.
  47. Liuzzo G, Buffon A, Biasucci LM, et al. Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. Circulation 1998; 98:2370.
  48. Biasucci LM, Koenig W, Mair J, et al. How to use C-reactive protein in acute coronary care. Eur Heart J 2013; 34:3687.
  49. Buffon A, Biasucci LM, Liuzzo G, et al. Widespread coronary inflammation in unstable angina. N Engl J Med 2002; 347:5.
  50. Cristell N, Cianflone D, Durante A, et al. High-sensitivity C-reactive protein is within normal levels at the very onset of first ST-segment elevation acute myocardial infarction in 41% of cases: a multiethnic case-control study. J Am Coll Cardiol 2011; 58:2654.
  51. Morrow DA, Rifai N, Antman EM, et al. 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 1998; 31:1460.
  52. Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. Circulation 1997; 96:4204.
  53. Lindahl B, Toss H, Siegbahn A, et al. 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 2000; 343:1139.
  54. Heeschen C, Hamm CW, Bruemmer J, Simoons ML. Predictive value of C-reactive protein and troponin T in patients with unstable angina: a comparative analysis. CAPTURE Investigators. Chimeric c7E3 AntiPlatelet Therapy in Unstable angina REfractory to standard treatment trial. J Am Coll Cardiol 2000; 35:1535.
  55. Biasucci LM, Liuzzo G, Grillo RL, et al. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999; 99:855.
  56. James SK, Armstrong P, Barnathan E, et al. Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: a GUSTO-IV substudy. J Am Coll Cardiol 2003; 41:916.
  57. Scirica BM, Cannon CP, Sabatine MS, et al. Concentrations of C-reactive protein and B-type natriuretic peptide 30 days after acute coronary syndromes independently predict hospitalization for heart failure and cardiovascular death. Clin Chem 2009; 55:265.
  58. Suleiman M, Khatib R, Agmon Y, et al. Early inflammation and risk of long-term development of heart failure and mortality in survivors of acute myocardial infarction predictive role of C-reactive protein. J Am Coll Cardiol 2006; 47:962.
  59. Makrygiannis SS, Ampartzidou OS, Zairis MN, et al. Prognostic usefulness of serial C-reactive protein measurements in ST-elevation acute myocardial infarction. Am J Cardiol 2013; 111:26.
  60. Lim P, Moutereau S, Simon T, et al. Usefulness of fetuin-A and C-reactive protein concentrations for prediction of outcome in acute coronary syndromes (from the French Registry of Acute ST-Elevation Non-ST-Elevation Myocardial Infarction [FAST-MI]). Am J Cardiol 2013; 111:31.
  61. 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.
  62. Zebrack JS, Anderson JL, Maycock CA, et al. Usefulness of high-sensitivity C-reactive protein in predicting long-term risk of death or acute myocardial infarction in patients with unstable or stable angina pectoris or acute myocardial infarction. Am J Cardiol 2002; 89:145.
  63. Mega JL, Morrow DA, De Lemos JA, et al. B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction: an ENTIRE-TIMI-23 substudy. J Am Coll Cardiol 2004; 44:335.
  64. Nikfardjam M, Müllner M, Schreiber W, et al. The association between C-reactive protein on admission and mortality in patients with acute myocardial infarction. J Intern Med 2000; 247:341.
  65. Zebrack JS, Anderson JL. Should C-reactive protein be measured routinely during acute myocardial infarction? Am J Med 2003; 115:735.
  66. Milazzo D, Biasucci LM, Luciani N, et al. Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events. Am J Cardiol 1999; 84:459.
  67. Buffon A, Liuzzo G, Biasucci LM, et al. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999; 34:1512.
  68. Saleh N, Svane B, Jensen J, et al. Stent implantation, but not pathogen burden, is associated with plasma C-reactive protein and interleukin-6 levels after percutaneous coronary intervention in patients with stable angina pectoris. Am Heart J 2005; 149:876.
  69. Chew DP, Bhatt DL, Robbins MA, et al. Incremental prognostic value of elevated baseline C-reactive protein among established markers of risk in percutaneous coronary intervention. Circulation 2001; 104:992.
  70. Mueller C, Buettner HJ, Hodgson JM, et al. Inflammation and long-term mortality after non-ST elevation acute coronary syndrome treated with a very early invasive strategy in 1042 consecutive patients. Circulation 2002; 105:1412.
  71. Walter DH, Fichtlscherer S, Sellwig M, et al. Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation. J Am Coll Cardiol 2001; 37:839.
  72. Zairis MN, Ambrose JA, Manousakis SJ, et al. The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting: The Global Evaluation of New Events and Restenosis After Stent Implantation Study. J Am Coll Cardiol 2002; 40:1375.
  73. Park DW, Lee SW, Yun SC, et al. A point-of-care platelet function assay and C-reactive protein for prediction of major cardiovascular events after drug-eluting stent implantation. J Am Coll Cardiol 2011; 58:2630.
  74. Anand IS, Latini R, Florea VG, et al. C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation 2005; 112:1428.
  75. Lamblin N, Mouquet F, Hennache B, et al. High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure. Eur Heart J 2005; 26:2245.
  76. Park JJ, Choi DJ, Yoon CH, et al. Prognostic value of C-reactive protein as an inflammatory and N-terminal probrain natriuretic peptide as a neurohumoral marker in acute heart failure (from the Korean Heart Failure registry). Am J Cardiol 2014; 113:511.
  77. Hashimoto H, Kitagawa K, Hougaku H, et al. C-reactive protein is an independent predictor of the rate of increase in early carotid atherosclerosis. Circulation 2001; 104:63.
  78. Ford ES, Giles WH. Serum C-reactive protein and self-reported stroke: findings from the Third National Health and Nutrition Examination Survey. Arterioscler Thromb Vasc Biol 2000; 20:1052.
  79. Muir KW, Weir CJ, Alwan W, et al. C-reactive protein and outcome after ischemic stroke. Stroke 1999; 30:981.
  80. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001; 32:917.
  81. Winbeck K, Poppert H, Etgen T, et al. Prognostic relevance of early serial C-reactive protein measurements after first ischemic stroke. Stroke 2002; 33:2459.
  82. Bos MJ, Schipper CM, Koudstaal PJ, et al. High serum C-reactive protein level is not an independent predictor for stroke: the Rotterdam Study. Circulation 2006; 114:1591.
  83. Eisenberg MS, Chen HJ, Warshofsky MK, et al. Elevated levels of plasma C-reactive protein are associated with decreased graft survival in cardiac transplant recipients. Circulation 2000; 102:2100.
  84. Labarrere CA, Lee JB, Nelson DR, et al. C-reactive protein, arterial endothelial activation, and development of transplant coronary artery disease: a prospective study. Lancet 2002; 360:1462.
  85. Rossi E, Biasucci LM, Citterio F, et al. Risk of myocardial infarction and angina in patients with severe peripheral vascular disease: predictive role of C-reactive protein. Circulation 2002; 105:800.
  86. Chung MK, Martin DO, Sprecher D, et al. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001; 104:2886.
  87. Aviles RJ, Martin DO, Apperson-Hansen C, et al. Inflammation as a risk factor for atrial fibrillation. Circulation 2003; 108:3006.
  88. Conway DS, Buggins P, Hughes E, Lip GY. Predictive value of indexes of inflammation and hypercoagulability on success of cardioversion of persistent atrial fibrillation. Am J Cardiol 2004; 94:508.
  89. Malouf JF, Kanagala R, Al Atawi FO, et al. High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion. J Am Coll Cardiol 2005; 46:1284.
  90. Am J Cardiol 2007; 99:1941.
  91. Jialal I, Stein D, Balis D, et al. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001; 103:1933.
  92. Plenge JK, Hernandez TL, Weil KM, et al. Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002; 106:1447.
  93. Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999; 100:230.
  94. Albert MA, Danielson E, Rifai N, et al. 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.
  95. Ferro D, Parrotto S, Basili S, et al. Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia. J Am Coll Cardiol 2000; 36:427.
  96. Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine production by pravastatin. Lancet 1999; 353:983.
  97. Kleemann R, Verschuren L, de Rooij BJ, et al. Evidence for anti-inflammatory activity of statins and PPARalpha activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro. Blood 2004; 103:4188.
  98. de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292:1307.
  99. Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005; 352:20.
  100. 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.
  101. Walter DH, Fichtlscherer S, Britten MB, et al. Statin therapy, inflammation and recurrent coronary events in patients following coronary stent implantation. J Am Coll Cardiol 2001; 38:2006.
  102. Chan AW, Bhatt DL, Chew DP, et al. Relation of inflammation and benefit of statins after percutaneous coronary interventions. Circulation 2003; 107:1750.
  103. 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.
  104. Morrow DA, de Lemos JA, Sabatine MS, et al. Clinical relevance of C-reactive protein during follow-up of patients with acute coronary syndromes in the Aggrastat-to-Zocor Trial. Circulation 2006; 114:281.
  105. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 2005; 352:29.
  106. Sever PS, Poulter NR, Chang CL, et al. Evaluation of C-reactive protein before and on-treatment as a predictor of benefit of atorvastatin: a cohort analysis from the Anglo-Scandinavian Cardiac Outcomes Trial lipid-lowering arm. J Am Coll Cardiol 2013; 62:717.
  107. Ridker PM, Morrow DA, Rose LM, et al. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol 2005; 45:1644.
  108. Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation 2015; 132:1224.
  109. 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.
  110. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336:973.
  111. Ikonomidis I, Andreotti F, Economou E, et al. Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999; 100:793.
  112. Kennon S, Price CP, Mills PG, et al. The effect of aspirin on C-reactive protein as a marker of risk in unstable angina. J Am Coll Cardiol 2001; 37:1266.
  113. 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.
  114. Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002; 106:679.
  115. Pfützner A, Marx N, Lübben G, et al. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. J Am Coll Cardiol 2005; 45:1925.
  116. Sidhu JS, Cowan D, Kaski JC. The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 2003; 42:1757.
  117. Hanefeld M, Marx N, Pfützner A, et al. Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study. J Am Coll Cardiol 2007; 49:290.
  118. Jenkins NP, Keevil BG, Hutchinson IV, Brooks NH. Beta-blockers are associated with lower C-reactive protein concentrations in patients with coronary artery disease. Am J Med 2002; 112:269.
  119. Ridker PM, Hennekens CH, Rifai N, et al. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100:713.
  120. 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.
  121. Cushman M, Legault C, Barrett-Connor E, et al. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999; 100:717.
  122. Jenkins DJ, Kendall CW, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA 2003; 290:502.
  123. Seshadri P, Iqbal N, Stern L, et al. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med 2004; 117:398.
  124. King DE, Egan BM, Woolson RF, et al. Effect of a high-fiber diet vs a fiber-supplemented diet on C-reactive protein level. Arch Intern Med 2007; 167:502.
  125. de Winter RJ, Fischer J, Bholasingh R, et al. C-Reactive protein and cardiac troponin T in risk stratification: differences in optimal timing of tests early after the onset of chest pain. Clin Chem 2000; 46:1597.