C-reactive protein and cardiovascular disease: New insights from an old molecule

QJM: An International Journal of Medicine

Volumn 96, Issue 11, 2003, Pages 793-807

  Hirschfield, G M ^a   Pepys, M B ^a  

^a ROYAL FREE AND UNIVERSITY COLLEGE MEDICAL SCHOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABCIXIMAB; ACUTE PHASE PROTEIN; ANTITHROMBOCYTIC AGENT; C REACTIVE PROTEIN; CHIMERIC ANTIBODY; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INTERCELLULAR ADHESION MOLECULE 1; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; MEVINOLIN;

ACUTE HEART INFARCTION; ATHEROSCLEROTIC PLAQUE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; COMPLEMENT ACTIVATION; CORONARY ARTERY THROMBOSIS; DIFFERENTIAL DIAGNOSIS; DISEASE MARKER; DRUG TARGETING; HEART MUSCLE ISCHEMIA; HUMAN; INFLAMMATION; METABOLISM; MOLECULAR BIOLOGY; OUTCOMES RESEARCH; PATHOGENESIS; PATIENT MONITORING; PREDICTION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN BLOOD LEVEL; PROTEIN SYNTHESIS; REGULATORY MECHANISM; REVIEW; SENSITIVITY ANALYSIS; UNSTABLE ANGINA PECTORIS;

EID: 0242636458     PISSN: 14602725     EISSN: None     Source Type: Journal    
DOI: 10.1093/qjmed/hcg134     Document Type: Review

References (177)

1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340:448-54.
2. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med 1999; 340:115-26.
3. Lusis AJ. Atherosclerosis. Nature 2000; 407:233-41.
4. Spodick DH. Inflammation and the onset of myocardial infarction. Ann Intern Med 1985; 102:699-702.
5. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 2002; 105:1135-43.
6. Tillett WS, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med 1930; 52:561-71.
7. Pepys MB, Baltz ML. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol 1983; 34:141-212.
8. Srinivasan N, Rufino SD, Pepys MB, Wood SP, Blundell TL. A superfamily of proteins with the lectin fold. Chemtracts-Biochem Mol Biol 1996; 6:149-64.
9. Shine B, de Beer FC, Pepys MB. Solid phase radioimmunoassays for C-reactive protein. Clin Chim Acta 1981; 117:13-23.
10. Kushner I, Broder ML, Karp D. Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J Clin Invest 1978; 61:235-42.
11. Hutchinson WL, Koenig W, Fröhlich M, Sund M, Lowe GDO, Pepys MB. Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population. Clin Chem 2000; 46:934-8.
12. Vigushin DM, Pepys MB, Hawkins PN. Metabolic and scintigraphic studies of radioiodinated human C-reactive protein in health and disease. J Clin Invest 1993; 91:1351-7.
13. Hutchinson WL, Noble GE, Hawkins PN, Pepys MB. The pentraxins, C-reactive protein and serum amyloid P component, are cleared and catabolized by hepatocytes in vivo. J Clin Invest 1994; 94:1390-6.
14. Pepys MB. C-reactive protein fifty years on. Lancet 1981 i:653-6.
15. Pepys MB. The acute phase response and C-reactive protein. In: Warrell DA, Cox TM, Firth JD, Benz EJ, Jr, eds. Oxford Textbook of Medicine, 4th edn. Oxford, Oxford University Press, 2003:150-6.
16. Pepys MB, Lanham JG, de Beer FC. C-reactive protein in systemic lupus erythematosus. In: Hughes GRV, ed. Clinics in the Rheumatic Diseases, No. 1. Eastbourne, WB Saunders, 1982:91-103.
17. Starke ID, de Beer FC, Donnelly JP, Catovsky D, Goldman JM, Galton DG, Pepys MB. Serum C-reactive protein levels in the management of infection in acute leukaemia. Eur J Cancer 1984; 20:319-25.
18. Osmand AP, Friedenson B, Gewurz H, Painter RH, Hofmann T, Shelton E. Characterisation of C-reactive protein and the complement subcomponent Clt as homologous proteins displaying cyclic pentameric symmetry (pentraxins). Proc Natl Acad Sci USA 1977; 74:739-43.
19. Robey FA, Liu T-Y. Limulin: a C-reactive protein from Limulus polyphemus. J Biol Chem 1981; 256:969-75.
20. Pepys MB, Booth DR, Hutchinson WL, Gallimore JR, Collins PM, Hohenester E. Amyloid P component. A critical review. Amyloid: Int J Exp Clin Invest 1997; 4:274-95.
21. Pepys MB, Baltz M, Gomer K, Davies AJS, Doenhoff M. Serum amyloid P-component is an acute-phase reactant in the mouse. Nature 1979; 278:259-61.
22. Pepys MB. Isolation of serum amyloid P component (protein SAP) in the mouse. Immunology 1979; 37:637-41.
23. Lin CS, Xia D, Yun JS, Wagner T, Magnuson T, Mold C, Samols D. Expression of rabbit C-reactive protein in transgenic mice. Immunol Cell Biol 1995; 73:521-31.
24. Ciliberto G, Arcone R, Wagner EF, Ruther U. Inducible and tissue-specific expression of human C-reactive protein in transgenic mice. EMBO J 1987; 6:4017-22.
25. Pepys MB, Rowe IF, Baltz ML. C-reactive protein: binding to lipids and lipoproteins. Int Rev Exp Pathol 1985; 27:83-111.
26. Volanakis JE, Wirtz KWA. Interaction of C-reactive protein with artificial phosphatidylcholine bilayers. Nature 1979; 281:155-7.
27. Du Clos TW. C-reactive protein reacts with the U1 small nuclear ribonucleoprotein. J Immunol 1989; 143:2553-9.
28. Pepys MB, Booth SE, Tennent GA, Butler PJG, Williams DG. Binding of pentraxins to different nuclear structures: C-reactive protein binds to small nuclear ribonucleoprotein particles, serum amyloid P component binds to chromatin and nucleoli. Clin Exp Immunol 1994; 97:152-7.
29. Gershov D, Kim S, Brot N, Elkon KB. C-reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an anti-inflammatory innate immune response: implications for systemic autoimmunity. J Exp Med 2000; 192:1353-63.
30. Steel DM, Whitehead AS. The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A protein. Immunol Today 1994; 15:81-8.
31. Du Clos TW. Function of C-reactive protein. Ann Med 2000; 32:274-8.
32. Kaplan MH, Volanakis JE. Interaction of C-reactive protein complexes with the complement system. I. Consumption of human complement associated with the reaction of C-reactive protein with pneumococcal C-polysaccharide and with the choline phosphatides, lecithin and sphingomyelin. J Immunol 1974; 112:2135-47.
33. Volanakis JE, Kaplan MH. Interaction of C-reactive protein complexes with the complement system. II. Consumption of guinea-pig complement by CRP complexes: requirement for human Clq. J Immunol 1974; 113:9-17.
34. Siegel J, Rent R, Gewurz H. Interactions of C-reactive protein with the complement system. I. Protamine-induced consumption of complement in acute phase sera. J Exp Med 1974; 140:631-47.
35. Osmand AP, Mortensen RF, Siegel J, Gewurz H. Interactions of C-reactive protein with the complement system. III. Complement-dependent passive hemolysis initiated by CRP. J Exp Med 1975; 142:1065-77.
36. Mold C, Gewurz H, Du Clos TW. Regulation of complement activation by C-reactive protein. Immunopharmacology 1999; 42:23-30.
37. Bickerstaff MCM, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, Mitchell DA, Cook HT, Butler PJG, Walport MJ, Pepys MB. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nature Med 1999; 5:694-7.
38. Janeway CA, Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20:197-216.
39. Boes M, Prodeus AP, Schmidt T, Carroll MC, Chen J. A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J Exp Med 1998; 188:2381-6.
40. Pepys MB. Role of complement in the induction of immunological responses. Transplant Rev 1976; 32:93-120.
41. Nielsen CH, Fischer EM, Leslie RGQ. The role of complement in the acquired immune response. Immunology 2000; 100:4-12.
42. Mold C, Nakayama S, Holzer TJ, Gewurz H, Du Clos TW. C-reactive protein is protective against Streptococcus pneumoniae infection in mice. J Exp Med 1981; 154:1703-8.
43. Briles DE, Forman C, Hudak S, Claflin JL. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J Exp Med 1982; 156:1177-85.
44. Yother J, Volanakis JE, Briles DE. Human C-reactive protein is protective against fatal Streptococcus pneumoniae infection in mice. J Immunol 1982; 128:2374-6.
45. Harnett W, Harnett MM. Phosphorylcholine: friend or foe of the immune system? Immunol Today 1999; 20:125-9.
46. Weiser JN, Pan N, McGowan KL, Musher D, Martin A, Richards J. Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 1998; 187:631-40.
47. Lysenko E, Richards JC, Cox AD, Stewart A, Martin A, Kapoor M, Weiser JN. The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killing. Mol Microbiol 2000; 35:234-45.
48. de Beer FC, Soutar AK, Baltz ML, Trayner I, Feinstein A, Pepys MB. Low density and very low density lipoproteins are selectively bound by aggregated C-reactive protein. J Exp Med 1982; 156:230-42.
49. Rowe IF, Soutar AK, Trayner IM, Thompson GR, Pepys MB. Circulating human C-reactive protein binds very low density lipoproteins. Clin Exp Immunol 1984; 58:237-44.
50. Chang MK, Binder CJ, Torzewski M, Witztum JL. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci USA 2002; 99:13043-8.
51. Shaw PX, Horkko S, Chang MK, Curtiss LK, Palinski W, Silverman GJ, Witztum JL. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest 2000; 105:1731-40.
52. Pepys MB. C-reactive protein, amyloidosis and the acute phase response. The Goulstonian Lecture. In: Sarner M, ed. Advanced Medicine. Tunbridge Wells, Pitman Books, 1982:208-30.
53. Hughes GRV. Hughes syndrome: the antiphospholipid syndrome. J R Coll Physicians Lond 1998; 32:260-4.
54. Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure 1999; 7:169-77.
55. Shrive AK, Cheetham GMT, Holden D, Myles DAA, Turnell WG, Volanakis JE, Pepys MB, Bloomer AC, Greenhough TJ. Three-dimensional structure of human C-reactive protein. Nature Struct Biology 1996; 3:346-54.
56. Agrawal A, Simpson MJ, Black S, Carey MP, Samols D. A C-reactive protein mutant that does not bind to phosphocholine and pneumococcal C-polysaccharide. J Immunol 2002; 169:3217-22.
57. Agrawal A, Shrive AK, Greenhough TJ, Volanakis JE. Topology and structure of the C1q-binding site on C-reactive protein. J Immunol 2001; 166:3998-4004.
58. Whitehead AS, Bruns GAP, Markham AF, Colten HR, Woods DE. Isolation of human C-reactive protein complementary DNA and localization of the gene to chromosome 1. Science 1983; 221:69-71.
59. Mantzouranis EC, Dowton SB, Whitehead AS, Edge MD, Bruns GAP, Colten HR. Human serum amyloid P component. cDNA isolation, complete sequence of pre-serum amyloid P component, and localization of the gene to chromosome 1. J Biol Chem 1985; 260:7752-6.
60. Hurlimann J, Thorbecke G, Hochwald G. The liver as the site of C-reactive protein formation. J Exp Med 1966; 123:365-78.
61. Murphy TM, Baum LL, Beaman KD. Extrahepatic transcription of human C-reactive protein. J Exp Med 1991; 173:495-8.
62. Yasojima K, Schwab C, McGeer EG, McGeer PL. Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer's disease. Brain Res 2000; 887:80-9.
63. Gould JM, Weiser JN. Expression of C-reactive protein in the human respiratory tract. Infect Immun 2001; 69:1747-54.
64. Yasojima K, Schwab C, McGeer EG, McGeer PL. Generation of C-reactive protein and complement components in atherosclerotic plaques. Am J Pathol 2001; 158:1039-51.
65. Gould JM, Weiser JN. The inhibitory effect of C-reactive protein on bacterial phosphorylcholine platelet-activating factor receptor-mediated adherence is blocked by surfactant. J Infect Dis 2002; 186:361-71.
66. Mackiewicz A, Speroff T, Ganapathi MK, Kushner I. Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol 1991; 146:3032-7.
67. Cha-Molstad H, Agrawal A, Zhang D, Samols D, Kushner I. The Rel family member P50 mediates cytokine-induced C-reactive protein expression by a novel mechanism. J Immunol 2000; 165:4592-7.
68. Agrawal A, Cha-Molstad H, Samols D, Kushner I. Transactivation of C-reactive protein by IL-6 requires synergistic interaction of CCAAT/enhancer binding protein beta (C/EBP beta) and Rel p50. J Immunol 2001; 166:2378-84.
69. Yue CC, Muller-Greven J, Dailey P, Lozanski G, Anderson V, Macintyre S. Identification of a C-reactive protein binding site in two hepatic carboxylesterases capable of retaining C-reactive protein within the endoplasmic reticulum. J Biol Chem 1996; 271:22245-50.
70. Wilkins J, Gallimore JR, Moore EG, Pepys MB. Rapid automated high sensitivity enzyme immunoassay of C-reactive protein. Clin Chem 1998; 44:1358-61.
71. MacGregor AJ, Gallimore J, Spector TD, Pepys MB. Genetic factors determine baseline levels of C-reactive protein and serum amyloid A. Ann Rheum Dis 1999; 58 (Suppl.):43 [abstract 139].
72. Pankow JS, Folsom AR, Cushman M, Borecki IB, Hopkins PN, Eckfeldt JH, Tracy RP. Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis 2001; 154:681-9.
73. Berger P, McConnell JP, Nunn M, Kornman KS, Sorrell J, Stephenson K, Duff GW. C-reactive protein levels are influenced by common IL-1 gene variations. Cytokine 2002; 17:171-4.
74. Vickers MA, Green FR, Terry C, Mayosi BM, Julier C, Lathrop M, Ratcliffe PJ, Watkins HC, Keavney B. Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 2002; 53:1029-34.
75. Zee RY, Ridker PM. Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis 2002; 162:217-19.
76. Szalai AJ, McCrory MA, Cooper GS, Wu J, Kimberly RP. Association between baseline levels of C-reactive protein (CRP) and a dinucleotide repeat polymorphism in the intron of the CRP gene. Genes Immun 2002; 3:14-19.
77. Roy S, Hill AV, Knox K, Griffiths D, Crook D. Research pointers: association of common genetic variant with susceptibility to invasive pneumococcal disease. Br Med J 2002; 324:1369.
78. Berk BC, Weintraub WS, Alexander RW. Elevation of C-reactive protein in 'active' coronary artery disease. Am J Cardiol 1990; 65:168-72.
79. Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994; 331:417-24.
80. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW. Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 1995; 332:635-41.
81. 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; 144:537-47.
82. Tracy RP, Kuller LH, Psaty BM, Cushman M, Meilahn EN, Smith N. C-reactive protein and incidence of cardiovascular disease in older women: the rural health promotion project and the cardiovascular health study. Circulation 1996; 93:622.
83. Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349:462-6.
84. 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; 336:973-9.
85. Koenig W, Sund M, Fröhlich M, Fischer H-G, Löwel H, Döring A, Hutchinson WL, Pepys MB. 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; 99:237-42.
86. Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. Br Med J 2000; 321:199-204.
87. 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; 342:836-43.
88. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. J Am Coll Cardiol 1998; 279:1477-82.
89. Danesh J, Muir J, Wong Y-K, Ward M, Gallimore JR, Pepys MB. Risk factors for coronary heart disease and acute-phase proteins. A population-based study. Eur Heart J 1999; 20:954-9.
90. Bhakdi S, Torzewski M, Klouche M, Hemmes M. Complement and atherogenesis. Binding of CRP to degraded, nonoxidized LDL enhances complement activation. Arterioscler Thromb Vasc Biol 1999; 19:2348-54.
91. Torzewski J, Torzewski M, Bowyer DE, Fröhlich M, Koenig W, Waltenberger J, Fitzsimmons C, Hombach V. 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; 18:1386-92.
92. Zhang YX, Cliff WJ, Schoefl GI, Higgins G. Coronary C-reactive protein distribution: its relation to development of atherosclerosis. Atherosclerosis 1999; 145:375-9.
93. Lagrand WK, Visser CA, Hermens WT, Niessen HWM, Verheugt FWA, Wolbink G-J, Hack CE. C-reactive protein as a cardiovascular risk factor. More than an epiphenomenon? Circulation 1999; 100:96-102.
94. de Beer FC, Hind CRK, Fox KM, Allan R, Maseri A, Pepys MB. Measurement of serum C-reactive protein concentration in myocardial ischaemia and infarction. Br Heart J 1982; 47:239-43.
95. Pietilä KO, Harmoinen AP, Jokiniitty J, Pasternack AI. Serum C-reactive protein concentration in acute myocardial infarction and its relationship to mortality during 24 months of follow-up in patients under thrombolytic treatment. Eur Heart J 1996; 17:1345-9.
96. Ueda S, Ikeda U, Yamamoto K, Takahashi M, Nishinaga M, Nago N, Shimada K. C-reactive protein as a predictor of cardiac rupture after acute myocardial infarction. Am Heart J 1996; 131:857-60.
97. Anzai T, Yoshikawa T, Shiraki H, Asakura Y, Akaishi M, Mitamura H, Ogawa S. C-reactive protein as a predictor of infarct expansion and cardiac rupture after a first Q-wave acute myocardial infarction. Circulation 1997; 96:778-84.
98. Kushner I, Rakita L, Kaplan MH. Studies of acute phase protein. II. Localization of Cx-reactive protein in heart in induced myocardial infarction in rabbits. J Clin Invest 1963; 42:286-92.
99. Lagrand WK, Niessen HWM, Wolbink G-J, Jaspars LH, Visser CA, Verheugt FWA, Meijer CJLM, Hack CE. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction. Circulation 1997; 95:97-103.
100. Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction. J Exp Med 1999; 190:1733-9.
101. Rebuzzi AG, Quaranta G, Liuzzo G, Caligiuri G, Lanza GA, Gallimore JR, Grillo RL, Cianflone D, Biasucci LM, Maseri A. Incremental prognostic value of serum levels of troponin T and C-reactive protein on admission in patients with unstable angina pectoris. Am J Cardiol 1998; 82:715-19.
102. Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A. Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 1999; 99:855-60.
103. Buffon A, Liuzzo G, Biasucci LM, Pasqualetti P, Ramazzotti V, Rebuzzi AG, Crea F, Maseri A. Preprocedural serum levels of C-reactive protein predict early complications and late restenosis after coronary angioplasty. J Am Coll Cardiol 1999; 34:1512-21.
104. Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke 1999; 30:981-5.
105. Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001; 32:917-24.
106. Winbeck K, Poppert H, Etgen T, Conrad B, Sander D. Prognostic relevance of early serial C-reactive protein measurements after first ischemic stroke. Stroke 2002; 33:2459-64.
107. Arici M, Walls J. End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link? Kidney Int 2001; 59:407-14.
108. Hunt ME, O'Malley PG, Vernalis MN, Feuerstein IM, Taylor AJ. C-reactive protein is not associated with the presence or extent of calcified subclinical atherosclerosis. Am Heart J 2001; 141:206-10.
109. Wang TJ, Larson MG, Levy D, Benjamin EJ, Kupka MJ, Manning WJ, Clouse ME, D'Agostino RB, Wilson PW, O'Donnell CJ. C-reactive protein is associated with subclinical epicardial coronary calcification in men and women: the Framingham Heart Study. Circulation 2002; 106:1189-91.
110. Buffon A, Biasucci LM, Liuzzo G, D'Onofrio G, Crea F, Maseri A. Widespread coronary inflammation in unstable angina. N Engl J Med 2002; 347:5-12.
111. 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; 35:1535-42.
112. Lenderink T, Boersma E, Heeschen C, Vahanian A, de Boer MJ, Umans V, van den Brand MJ, Hamm CW, Simoons ML. Elevated troponin T and C-reactive protein predict impaired outcome for 4 years in patients with refractory unstable angina, and troponin T predicts benefit of treatment with abciximab in combination with PTCA. Eur Heart J 2003; 24:77-85.
113. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282:2131-5.
114. Fröhlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H, Muche R, Brenner H, Koenig W. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000; 23:1835-9.
115. Chambers JC, Eda S, Bassett P, Karim Y, Thompson SG, Gallimore JR, Pepys MB, Kooner JS. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation 2001; 104:145-50.
116. 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 14719 initially healthy American women. Circulation 2003; 107:391-7.
117. Ford ES. Body mass index, diabetes, and C-reactive protein among U.S. adults. Diabetes Care 1999; 22:1971-7.
118. Yudkin JS, Stehouwer CDA, Emeis JJ, Coppack SW. 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 1999; 19:972-8.
119. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, O'Reilly DS, Packard CJ, Sattar N. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 2002; 51:1596-600.
120. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, Reaven P. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 2002; 106:2908-12.
121. Fröhlich M, Döring A, Imhof A, Hutchinson WL, Pepys MB, Koenig W. Oral contraceptive use is associated with a systemic acute phase response. Fibrinolysis and Proteolysis 1999; 13:239-44.
122. Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Study. Circulation 1999; 100:717-22.
123. Ridker PM, Hennekens CH, Rifai N, Buring JE, Manson JE. Hormone replacement therapy and increased plasma concentration of C-reactive protein. Circulation 1999; 100:713-16.
124. van Baal WM, Kenemans P, van der Mooren MJ, Kessel H, Emeis JJ, Stehouwer CDA. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thromb Haemost 1999; 81:925-8.
125. Decensi A, Omodei U, Robertson C, Bonanni B, Guerrieri-Gonzaga A, Ramazzotto F, Johansson H, Mora S, Sandri MT, Cazzaniga M, Franchi M, Pecorelli S. Effect of transdermal estradiol and oral conjugated estrogen on C-reactive protein in retinoid-placebo trial in healthy women. Circulation 2002; 106:1224-8.
126. de Maat MP, Kluft C. Determinants of C-reactive protein concentration in blood. Ital Heart J 2001; 2:189-95.
127. Chung MK, Martin DO, Sprecher D, Wazni O, Kanderian A, Carnes CA, Bauer JA, Tchou PJ, Niebauer MJ, Natale A, Van Wagoner DR. C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation. Circulation 2001 ; 104:2886-91.
128. Dernellis J, Panaretou M. C-reactive protein and paroxysmal atrial fibrillation: evidence of the implication of an inflammatory process in paroxysmal atrial fibrillation. Acta Cardiol 2001; 56:375-80.
129. Heilbronn LK, Noakes M, Clifton PM. Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women. Arterioscler Thromb Vasc Biol 2001; 21:968-70.
130. Tchernof A, Nolan A, Sites CK, Ades PA, Poehlman ET. Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 2002; 105:564-9.
131. Imhof A, Froehlich M, Brenner H, Boeing H, Pepys MB, Koenig W. Effect of alcohol consumption on systemic markers of inflammation. Lancet 2001; 357:763-7.
132. Albert MA, Glynn RJ, Ridker PM. Alcohol consumption and plasma concentration of C-reactive protein. Circulation 2003; 107:443-7.
133. Ford ES. Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults. Epidemiology 2002; 13:561-8.
134. Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN. Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol 2002; 22:1869-76.
135. Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation 1999; 100:230-5.
136. 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.
137. Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S. Effect of hydroxymethyl glutaryl coenzyme a reductase inhibitor therapy on high sensitive C-reactive protein levels. Circulation 2001; 103:1933-5.
138. Ridker PM, Rifai N, Lowenthal SP. Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia. Circulation 2001; 103:1191-3.
139. Plenge JK, Hernandez TL, Weil KM, Poirier P, Grunwald GK, Marcovina SM, Eckel RH. Simvastatin lowers C-reactive protein within 14 days: an effect independent of low-density lipoprotein cholesterol reduction. Circulation 2002; 106:1447-52.
140. Munford RS. Statins and the acute-phase response. N Engl J Med 2001; 344:2016-18.
141. Kleemann R, Gervois PP, Verschuren L, Staels B, Princen HMG, Kooistra T. Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB ∼C/EBP-β complex formation. Blood 2003; 101:545-51.
142. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM, Jr. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med 2001; 344:1959-65.
143. Ridker PM. Should statin therapy be considered for patients with elevated C-reactive protein? The need for a definitive clinical trial. Eur Heart J 2001 ; 22:2135-7.
144. 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; 347:1557-65.
145. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, 3rd., Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC, Jr., Taubert K, Tracy RP, Vinicor F. 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.
146. Pepys MB, Berger A. The renaissance of C reaction protein. It may be a marker not only of acute illness but also of future cardiovascular disease. BMJ 2001; 322:4-5.
147. Schmiedt W, Kinscherf R, Deigner HP, Kamencic H, Nauen O, Kilo J, Oelert H, Metz J, Bhakdi S. Complement C6 deficiency protects against diet-induced atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol 1998; 18:1790-5.
148. Buono C, Come CE, Witztum JL, Maguire GF, Connelly PW, Carroll M, Lichtman AH. Influence of C3 deficiency on atherosclerosis. Circulation 2002; 105:3025-31.
149. Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82:513-20.
150. Nakagomi A, Freedman SB, Geczy CL. Interferon-γ and lipopolysaccharide potentiate monocyte tissue factor induction by C-reactive protein: relationship with age, sex, and hormone replacement treatment. Circulation 2000; 101:1785-91.
151. Bharadwaj D, Stein M-P, Volzer M, Mold C, Du Clos TW. The major receptor for C-reactive protein on leukocytes is Fcγ receptor II. J Exp Med 1999; 190:585-90.
152. Stein M-P, Edberg JC, Kimberly RP, Mangan EK, Bharadwaj D, Mold C, Du Clos TW. C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific. J Clin Invest 2000; 105:369-76.
153. Torzewski M, Rist C, Mortensen RF, Zwaka TP, Bienek M, Waltenberger J, Koenig W, Schmitz G, Hombach V, Torzewski J. C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis. Arterioscler Thromb Vasc Biol 2000; 20:2094-9.
154. Bodman-Smith KB, Melendez AJ, Campbell I, Harrison PT, Allen JM, Raynes JG. C-reactive protein-mediated phagocytosis and phospholipase D signalling through the high-affinity receptor for immunoglobulin G (FcgammaRI). Immunology 2002; 107:252-60.
155. Hundt M, Zielinska-Skowronek M, Schmidt RE. Lack of specific receptors for C-reactive protein on white blood cells. Eur J Immunol 2001; 31:3475-83.
156. Saeland E, van Royen A, Hendriksen K, Vile-Weekhout H, Rijkers GT, Sanders LA, van de Winkel JG. Human C-reactive protein does not bind to FcgammaRIIa on phagocytic cells. J Clin Invest 2001; 107:641-3.
157. Fichtlscherer S, Rosenberger G, Walter DH, Breuer S, Dimmeler S, Zeiher AM. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 2000; 102:1000-6.
158. Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, Donald AE, Palacios M, Griffin GE, Deanfield JE, MacAllister RJ, Vallance P. Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 2000; 102:994-9.
159. Ikeda U, Maeda Y, Yamamoto K, Shimada K. C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes. Cardiovasc Res 2002; 56:86-92.
160. 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; 106:1439-41.
161. Verma S, Wang CH, Li SH, Dumont AS, Fedak PW, Badiwala MV, Dhillon B, Weisel RD, Li RK, Mickle DA, Stewart DJ. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002; 106:913-19.
162. Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102:2165-8.
163. 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; 103:2531-4.
164. Verma S, Li SH, Badiwala MV, Weisel RD, Fedak PW, Li RK, Dhillon B, Mickle DA. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 2002; 105:1890-6.
165. Wang CH, Li SH, Weisel RD, Fedak PW, Dumont AS, Szmitko P, Li RK, Mickle DA, Verma S. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 2003; 107:1783-90.
166. 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.
167. Labarrere CA, Lee JB, Nelson DR, Al-Hassani M, Miller SJ, Pitts DE. C-reactive protein, arterial endothelial activation, and development of transplant coronary artery disease: a prospective study. Lancet 2002; 360:1462-7.
168. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001; 103:1194-7.
169. Fu T, Borensztajn J. Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions. Biochem J 2002; 366:195-201.
170. de Beer FC, Baltz ML, Munn EA, Feinstein A, Taylor J, Bruton C, Clamp JR, Pepys MB. Isolation and characterisation of C-reactive protein and serum amyloid P component in the rat. Immunology 1982; 45:55-70.
171. Hill JH, Ward PA. The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats. J Exp Med 1971; 133:885-900.
172. Maroko PR, Carpenter CB, Chiariello M, Fishbein MC, Radvany P, Knostman JD, Hale SL. Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion. J Clin Invest 1978; 61:661-70.
173. Pinckard RN, O'Rourke RA, Crawford MH, Grover FS, McManus LM, Ghidoni JJ, Storrs SB, Olson MS. Complement localization and mediation of ischemic injury in baboon myocardium. J Clin Invest 1980; 66:1050-6.
174. Weisman HF, Bartow T, Leppo MK, Marsh HC, Carson GR, Concino MF, Boyle MP, Roux KH, Weisfeldt ML, Fearon DT. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science 1990; 249:146-51.
175. Nijmeijer R, Lagrand WK, Visser CA, Meijer CJ, Niessen HW, Hack CE. CRP, a major culprit in complement-mediated tissue damage in acute myocardial infarction? Int Immunopharmacol 2001; 1:403-14.
176. Pepys MB. The Lumleian Lecture. C-reactive protein and amyloidosis: from proteins to drugs? In: Williams G, ed. Horizons in Medicine. London, Royal College of Physicians of London, 1999:397-414.
177. Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature 2002; 417:254-9.