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Inflammation and atherosclerosis

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Abstract

Inflammation plays a pivotal role in all stages of atherogenesis, from foam cell to plaque formation to rupture and ultimately to thrombosis. Insight gained from recent basic and clinical data linking inflammation to atherosclerosis has yielded important diagnostic and prognostic information. Low-grade chronic inflammation as measured by high sensitivity C-reactive protein predicts future risk of acute coronary syndrome independent of traditional cardiovascular risk factors. In addition, individuals with higher “inflammatory burden” gain the largest absolute risk reduction with aggressive risk-lowering therapy. The link between inflammation and atherosclerosis provides a new venue for future pharmacologic agents that may slow the progression of atherosclerosis by inhibiting inflammation.

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References

  1. Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002, 105:1135–1143.

    Article  PubMed  CAS  Google Scholar 

  2. Libby P: Molecular bases of the acute coronary syndromes. Circulation 1995, 91:2844–2850.

    PubMed  CAS  Google Scholar 

  3. Qiao JH, Fishbein MC: The severity of coronary atherosclerosis at sites of plaque rupture with occlusive thrombosis. J Am Coll Cardiol 1991, 17:1138–1142.

    Article  PubMed  CAS  Google Scholar 

  4. Giroud D, Li JM, Urban P, et al.: Relation of the site of acute myocardial infarction to the most severe coronary arterial stenosis at prior angiography. Am J Cardiol 1992, 69:729–732.

    Article  PubMed  CAS  Google Scholar 

  5. Rioufol G, Finet G, Ginon I, et al.: Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 2002, 106:804–808.

    Article  PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. Buffon A, Biasucci LM, Liuzzo G, et al.: Widespread coronary inflammation in unstable angina. N Engl J Med 2002, 347:5–12.

    Article  PubMed  Google Scholar 

  8. Steinberg D, Parthasarathy S, Carew TE, et al.: Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989, 320:915–924.

    Article  PubMed  CAS  Google Scholar 

  9. Chisolm GM 3rd, Hazen SL, Fox PL, Cathcart MK: The oxidation of lipoproteins by monocytes-macrophages. Biochemical and biological mechanisms. J Biol Chem 1999, 274:25959–25962.

    Article  PubMed  CAS  Google Scholar 

  10. Chisolm GM, Steinberg D: The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 2000, 28:1815–1826.

    Article  PubMed  CAS  Google Scholar 

  11. Hulthe J, Fagerberg B: Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR Study). Arterioscler Thromb Vasc Biol 2002, 22:1162–1167.

    Article  PubMed  CAS  Google Scholar 

  12. Huber J, Boechzelt H, Karten B, et al.: Oxidized cholesteryl linoleates stimulate endothelial cells to bind monocytes via the extracellular signal-regulated kinase 1/2 pathway. Arterioscler Thromb Vasc Biol 2002, 22:581–586.

    Article  PubMed  CAS  Google Scholar 

  13. Boring L, Gosling J, Cleary M, Charo IF: Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998, 394:894–897.

    Article  PubMed  CAS  Google Scholar 

  14. Yamada Y, Doi T, Hamakubo T, Kodama T: Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system. Cell Mol Life Sci 1998, 54:628–640.

    Article  PubMed  CAS  Google Scholar 

  15. Libby P: Atherosclerosis: the new view. Sci Am 2002, 286:46–55.

    PubMed  Google Scholar 

  16. Ross R: Atherosclerosis—an inflammatory disease. N Engl J Med 1999, 340:115–126.

    Article  PubMed  CAS  Google Scholar 

  17. van der Wal AC, Becker AE, van der Loos CM, Das PK: Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994, 89:36–44.

    PubMed  Google Scholar 

  18. Hansson GK, Holm J, Jonasson L: Detection of activated T lymphocytes in the human atherosclerotic plaque. Am J Pathol 1989, 135:169–175.

    PubMed  CAS  Google Scholar 

  19. Mach F, Schonbeck U, Libby P: CD40 signaling in vascular cells: a key role in atherosclerosis? Atherosclerosis 1998, 137(suppl):S89-S95.

    Article  PubMed  CAS  Google Scholar 

  20. Bhatt DL, Topol EJ: Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003, 2:15–28.

    Article  PubMed  CAS  Google Scholar 

  21. Schonbeck U, Sukhova GK, Shimizu K, et al.: Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice. Proc Natl Acad Sci U S A 2000, 97:7458–7463.

    Article  PubMed  CAS  Google Scholar 

  22. Asakura M, Ueda Y, Yamaguchi O, et al.: Extensive development of vulnerable plaques as a pan-coronary process in patients with myocardial infarction: an angioscopic study. J Am Coll Cardiol 2001, 37:1284–1288.

    Article  PubMed  CAS  Google Scholar 

  23. Libby P, Aikawa M: Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med 2002, 8:1257–1262.

    Article  PubMed  CAS  Google Scholar 

  24. Virmani R, Burke AP, Farb A, Kolodgie FD: Pathology of the unstable plaque. Prog Cardiovasc Dis 2002, 44:349–356.

    Article  PubMed  Google Scholar 

  25. Rajavashisth TB, Liao JK, Galis ZS, et al.: Inflammatory cytokines and oxidized low density lipoproteins increase endothelial cell expression of membrane type 1-matrix metalloproteinase. J Biol Chem 1999, 274:11924–11929.

    Article  PubMed  CAS  Google Scholar 

  26. Jeziorska M, Woolley DE: Local neovascularization and cellular composition within vulnerable regions of atherosclerotic plaques of human carotid arteries. J Pathol 1999, 188:189–196.

    Article  PubMed  CAS  Google Scholar 

  27. de Boer OJ, van der Wal AC, Teeling P, Becker AE: Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? Cardiovasc Res 1999, 41:443–449.

    Article  PubMed  Google Scholar 

  28. Inoue M, Itoh H, Ueda M, et al.: Vascular endothelial growth factor (VEGF) expression in human coronary atherosclerotic lesions: possible pathophysiological significance of VEGF in progression of atherosclerosis. Circulation 1998, 98:2108–2116.

    PubMed  CAS  Google Scholar 

  29. Moulton KS, Heller E, Konerding MA, et al.: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999, 99:1726–1732.

    PubMed  CAS  Google Scholar 

  30. Libby P: Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001, 104:365–372.

    PubMed  CAS  Google Scholar 

  31. Libby P, Geng YJ, Aikawa M, et al.: Macrophages and atherosclerotic plaque stability. Curr Opin Lipidol 1996, 7:330–335.

    PubMed  CAS  Google Scholar 

  32. Smith JD, Trogan E, Ginsberg M, et al.: Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci U S A 1995, 92:8264–8268.

    Article  PubMed  CAS  Google Scholar 

  33. Davies MJ: A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation 1990, 82(suppl 3):II38-II46.

    PubMed  CAS  Google Scholar 

  34. Selwyn AP: Prothrombotic and antithrombotic pathways in acute coronary syndromes. Am J Cardiol 2003, 91:3H-11H.

    Article  PubMed  CAS  Google Scholar 

  35. Henn V, Slupsky JR, Grafe M, et al.: CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998, 391:591–594.

    Article  PubMed  CAS  Google Scholar 

  36. Celi A, Pellegrini G, Lorenzet R, et al.: P-selectin induces the expression of tissue factor on monocytes. Proc Natl Acad Sci U S A 1994, 91:8767–8771.

    Article  PubMed  CAS  Google Scholar 

  37. Rinder HM, Bonan JL, Rinder CS, et al.: Dynamics of leukocyte-platelet adhesion in whole blood. Blood 1991, 78:1730–1737.

    PubMed  CAS  Google Scholar 

  38. Lindemann S, Tolley ND, Dixon DA, et al.: Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001, 154:485–490.

    Article  PubMed  CAS  Google Scholar 

  39. Quinn MJ, Plow EF, Topol EJ: Platelet glycoprotein IIb/IIIa inhibitors: recognition of a two-edged sword? Circulation 2002, 106:379–385.

    Article  PubMed  CAS  Google Scholar 

  40. Freedman JE, Loscalzo J: Platelet-monocyte aggregates: bridging thrombosis and inflammation. Circulation 2002, 105:2130–2132.

    Article  PubMed  Google Scholar 

  41. Osterud B: The role of platelets in decrypting monocyte tissue factor. Dis Mon 2003, 49:7–13.

    Article  PubMed  Google Scholar 

  42. Furman MI, Benoit SE, Barnard MR, et al.: Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 1998, 31:352–358.

    Article  PubMed  CAS  Google Scholar 

  43. Ott I, Neumann FJ, Gawaz M, et al.: Increased neutrophil-platelet adhesion in patients with unstable angina. Circulation 1996, 94:1239–1246.

    PubMed  CAS  Google Scholar 

  44. Sheth SS, Deluna A, Allayee H, Lusis AJ: Understanding atherosclerosis through mouse genetics. Curr Opin Lipidol 2002, 13:181–189.

    Article  PubMed  CAS  Google Scholar 

  45. Glass CK, Witztum JL: Atherosclerosis: the road ahead. Cell 2001, 104:503–516.

    Article  PubMed  CAS  Google Scholar 

  46. Steinberg D, Witztum JL: Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation 2002, 105:2107–2111.

    Article  PubMed  Google Scholar 

  47. Abu-Soud HM, Hazen SL: Nitric oxide is a physiological substrate for mammalian peroxidases. J Biol Chem 2000, 275:37524–37532.

    Article  PubMed  CAS  Google Scholar 

  48. Shishehbor MH, Aviles RJ, Brennan ML, et al.: Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy. JAMA 2003, 289:1675–1680.

    Article  PubMed  CAS  Google Scholar 

  49. Mackness MI, Mackness B, Durrington PN: Paraoxonase and coronary heart disease. Atheroscler Suppl 2002, 3:49–55.

    Article  PubMed  CAS  Google Scholar 

  50. Dichtl W, Nilsson L, Goncalves I, et al.: Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells. Circ Res 1999, 84:1085–1094.

    PubMed  CAS  Google Scholar 

  51. Basta G, Lazzerini G, Massaro M, et al.: Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation 2002, 105:816–822.

    Article  PubMed  CAS  Google Scholar 

  52. Yamagishi S, Inagaki Y, Okamoto T, et al.: Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human-cultured mesangial cells. J Biol Chem 2002, 277:20309–20315.

    Article  PubMed  CAS  Google Scholar 

  53. Avogaro A, Pagnin E, Calo L: Monocyte NADPH oxidase subunit p22(phox) and inducible hemeoxygenase-1 gene expressions are increased in type II diabetic patients: relationship with oxidative stress. J Clin Endocrinol Metab 2003, 88:1753–1759.

    Article  PubMed  CAS  Google Scholar 

  54. Reckelhoff JF, Romero JC: Role of oxidative stress in angiotensin-induced hypertension. Am J Physiol Reg Integr Comp Physiol 2003, 284:R893-R912.

    CAS  Google Scholar 

  55. Ruiz-Ortega M, Lorenzo O, Ruperez M, et al.: Renin-angiotensin system and renal damage: emerging data on angiotensin II as a proinflammatory mediator. Contrib Nephrol 2001, 135:123–137.

    Article  PubMed  CAS  Google Scholar 

  56. Jacoby DS, Rader DJ: Renin-angiotensin system and atherothrombotic disease: from genes to treatment. Arch Intern Med 2003, 163:1155–1164.

    Article  PubMed  CAS  Google Scholar 

  57. Costanzo A, Moretti F, Burgio VL, et al.: Endothelial activation by angiotensin II through NFkappaB and p38 pathways: Involvement of NFkappaB-inducible kinase (NIK), free oxygen radicals, and selective inhibition by aspirin. J Cell Physiol 2003, 195:402–410.

    Article  PubMed  CAS  Google Scholar 

  58. Danesh J, Collins R, Peto R: Chronic infections and coronary heart disease: is there a link? Lancet 1997, 350:430–436.

    Article  PubMed  CAS  Google Scholar 

  59. Zahn R, Schneider S, Frilling B, et al.: Antibiotic therapy after acute myocardial infarction: a prospective randomized study. Circulation 2003, 107:1253–1259.

    Article  PubMed  Google Scholar 

  60. Anderson JL, Muhlestein JB, Carlquist J, et al.: Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study. Circulation 1999, 99:1540–1547.

    PubMed  CAS  Google Scholar 

  61. Sinisalo J, Mattila K, Valtonen V, et al.: Effect of 3 months of antimicrobial treatment with clarithromycin in acute non-q-wave coronary syndrome. Circulation 2002, 105:1555–1160.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  63. Zhang R, Brennan ML, Fu X, et al.: Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 2001, 286:2136–2142.

    Article  PubMed  CAS  Google Scholar 

  64. Ridker PM, Stampfer MJ, Rifai N: Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease. JAMA 2001, 285:2481–2485.

    Article  PubMed  CAS  Google Scholar 

  65. Pasceri V, Willerson JT, Yeh ET: Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000, 102:2165–2168.

    PubMed  CAS  Google Scholar 

  66. Nakajima T, Schulte S, Warrington KJ, et al.: T-cell-mediated lysis of endothelial cells in acute coronary syndromes. Circulation 2002, 105:570–575.

    Article  PubMed  CAS  Google Scholar 

  67. 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.

    PubMed  CAS  Google Scholar 

  68. 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.

    Article  PubMed  CAS  Google Scholar 

  69. 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.

    Article  PubMed  CAS  Google Scholar 

  70. Jarvisalo MJ, Harmoinen A, Hakanen M, et al.: Elevated serum C-reactive protein levels and early arterial changes in healthy children. Arterioscler Thromb Vasc Biol 2002, 22:1323–1328.

    Article  PubMed  CAS  Google Scholar 

  71. 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, 104:992–997.

    PubMed  CAS  Google Scholar 

  72. 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, 349:462–466.

    Article  PubMed  CAS  Google Scholar 

  73. 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, 35:1535–1542.

    Article  PubMed  CAS  Google Scholar 

  74. 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, 89:145–149.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  76. 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.

    Article  PubMed  Google Scholar 

  77. 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.

    Article  PubMed  Google Scholar 

  78. Shishehbor MH, Bhatt DL, Topol EJ: Using C-reactive protein to assess cardiovascular disease risk. Cleve Clin J Med 2003, 70:634–640.

    Article  PubMed  Google Scholar 

  79. Yeh ET, Willerson JT: Coming of age of C-reactive protein: using inflammation markers in cardiology. Circulation 2003, 107:370–371.

    Article  PubMed  Google Scholar 

  80. Ikonomidis I, Andreotti F, Economou E, et al.: Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin. Circulation 1999, 100:793–798.

    PubMed  CAS  Google Scholar 

  81. Bhatt DL, Topol EJ: Need to test the arterial inflammation hypothesis. Circulation 2002, 106:136–140.

    Article  PubMed  Google Scholar 

  82. Chan AW, Bhatt DL, Chew DP, et al.: Relation of inflammation and benefit of statins after percutaneous coronary interventions. Circulation 2003, 107:1750–1756.

    Article  PubMed  CAS  Google Scholar 

  83. 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, 106:679–684.

    Article  PubMed  CAS  Google Scholar 

  84. Niwa S, Totsuka T, Hayashi S: Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol 1996, 18:669–675.

    Article  PubMed  CAS  Google Scholar 

  85. Munford RS: Statins and the acute-phase response. N Engl J Med 2001, 344:2016–2018.

    Article  PubMed  CAS  Google Scholar 

  86. Liao JK: Isoprenoids as mediators of the biological effects of statins. J Clin Invest 2002, 110:285–288.

    Article  PubMed  CAS  Google Scholar 

  87. Laufs U, La Fata V, Plutzky J, Liao JK: Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998, 97:1129–1135.

    PubMed  CAS  Google Scholar 

  88. Shishehbor MH, Brennan ML, Aviles RJ, et al.: Statins promote potent systemic antioxidant effects through specific inflammatory pathways. Circulation 2003, 108:426–431.

    Article  PubMed  CAS  Google Scholar 

  89. 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.

    Article  PubMed  CAS  Google Scholar 

  90. 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, 100:230–235.

    PubMed  CAS  Google Scholar 

  91. 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, 336:973–979.

    Article  PubMed  CAS  Google Scholar 

  92. Fukai T, Siegfried MR, Ushio-Fukai M, et al.: Modulation of extracellular superoxide dismutase expression by angiotensin II and hypertension. Circ Res 1999, 85:23–28.

    PubMed  CAS  Google Scholar 

  93. Han Y, Runge MS, Brasier AR: Angiotensin II induces interleukin-6 transcription in vascular smooth muscle cells through pleiotropic activation of nuclear factor-kappa B transcription factors. Circ Res 1999, 84:695–703.

    PubMed  CAS  Google Scholar 

  94. Kranzhofer R, Schmidt J, Pfeiffer CA, et al.: Angiotensin induces inflammatory activation of human vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 1999, 19:1623–1629.

    PubMed  CAS  Google Scholar 

  95. Hernandez-Presa MA, Bustos C, Ortego M, et al.: ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen I in a rabbit model of atherosclerosis. Am J Pathol 1998, 153:1825–1837.

    PubMed  CAS  Google Scholar 

  96. Jackson SM, Parhami F, Xi XP, et al.: Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 1999, 19:2094–2104.

    PubMed  CAS  Google Scholar 

  97. Phipps RP: Atherosclerosis: the emerging role of inflammation and the CD40-CD40 ligand system. Proc Natl Acad Sci U S A 2000, 97:6930–6932.

    Article  PubMed  CAS  Google Scholar 

  98. Hermann A, Rauch BH, Braun M, et al.: Platelet CD40 ligand (CD40L)—subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets 2001, 12:74–82.

    Article  PubMed  CAS  Google Scholar 

  99. Moshfegh K, Redondo M, Julmy F, et al.: Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction: enhanced inhibitory effects of combination therapy. J Am Coll Cardiol 2000, 36:699–705.

    Article  PubMed  CAS  Google Scholar 

  100. Schonbeck U, Varo N, Libby P, et al.: Soluble CD40L and cardiovascular risk in women. Circulation 2001, 104:2266–2268.

    PubMed  CAS  Google Scholar 

  101. Bhatt DL: Diffuse coronary disease and atherothrombosis: a rationale for long-term therapy to prevent recurrent ischemic events. J Invasive Cardiol 2003, 15(suppl B):3B-9B, discussion 9B–10B.

    PubMed  Google Scholar 

  102. 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.

    Article  PubMed  CAS  Google Scholar 

  103. 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, 22:2135–2137.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F25, 44195, Cleveland, OH, USA

    Mehdi H. Shishehbor DO & Deepak L. Bhatt MD

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Shishehbor, M.H., Bhatt, D.L. Inflammation and atherosclerosis. Curr Atheroscler Rep 6, 131–139 (2004). https://doi.org/10.1007/s11883-004-0102-x

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