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. 2009 Feb 3;24(10):642–650. doi: 10.1002/clc.4960241003

Assessment of subclinical atherosclerosis and cardiovascular risk

R Michael BENITEZ 1,, Robert A Vogel 1
PMCID: PMC6654927  PMID: 11594409

Abstract

Conventional cardiac risk factors do not fully explain the incidence of coronary artery disease and coronary events. Risk stratification and therapy based solely on these conventional risk factors may exclude a population who would otherwise benefit from lifestyle and risk factor modification. Recent efforts to improve our ability to recognize individuals and populations at increased risk of coronary events have focused on the noninvasive imaging of atherosclerosis, both in coronary and extracoronary arterial beds, or the identification of “non‐traditional” serum markers. We review the complimentary role of these newer methods of risk stratification in the context of conventional risk factor evaluation.

Keywords: cardiac risk, electron‐beam computed tomography, magnetic resonance angiography, brachial artery reactivity

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References

  • 1. Braunwald E: Shattuck Lecture—Cardiovascular medicine at the turn of the millennium: Triumphs, concerns, and opportunities. N Engl J Med 1997; 337: 1360–1369 [DOI] [PubMed] [Google Scholar]
  • 2. Pearson A, Laurora I, Chu H, Kafonek: The lipid treatment assessment project (L‐TAP). Arch Intern Med 2000; 160: 459–467 [DOI] [PubMed] [Google Scholar]
  • 3. Schrott HG, Bittner V, Vittinghoff E, Herrington DM, Hulley S: Adherence to national cholesterol education program treatment goals in postmenopausal women with heart disease. The heart and estrogen/progestin replacement study (HERS). The HERS research group. J Am Med Assoc 1997; 277: 1281–1286 [PubMed] [Google Scholar]
  • 4. Oliver MF, Samuel E, Morley P, Young GP, Kapur PL: Detection of coronary artery calcification during life. Lancet 1964; 1: 891–895 [DOI] [PubMed] [Google Scholar]
  • 5. Margolis JR, Chen J, Kong Y: The diagnostic and prognostic significance of coronary artery calcification: A report of 800 cases. Radiology 1980; 137: 609–616 [DOI] [PubMed] [Google Scholar]
  • 6. Shemesh J, Tenenbaum A, Fisman E, Apter S, Rath S, Rozeenman J, Itzchak Y, Motro M: Absence of coronary calcification on double‐helical CT scans: Predictor of angiographically normal coronary arteries in elderly women? Radiology 1996; 199: 665–668 [DOI] [PubMed] [Google Scholar]
  • 7. Shemesh J, Fisman E, Tenenbaum A, Apter S, Leibovitch L, Rath S, Itzchak Y, Motro M: Coronary artery calcification in women with syndrome X: Usefulness of double‐helical CT for detection. Radiology 1997; 205: 697–700 [DOI] [PubMed] [Google Scholar]
  • 8. Baskin KM, Stanford W, Thompson BH, Hoffman E, Tajik J, Heery SD: Comparison of electron beam and helical computed tomography in assessment of coronary artery calcification (abstr). Circulation 1995; 92 (suppl I): I–651 [Google Scholar]
  • 9. Budhoff MJ, Georgiou D, Brody A, Agatston AS, Kennedy J, Wolfkiel C, Stanford W, Shields P, Lewis RJ, Janowitz WR, Rich S, Brundage BH: Ultrafast computed tomography as a diagnostic modality in the detection of CAD: A multicenter study. Circulation 1996; 93: 898–904 [DOI] [PubMed] [Google Scholar]
  • 10. Borman JL, Stanford W, Stenberg RG, Winniford MD, Berbaum KS. Talman CL, Galvin JR: Ultrafast tomographic detection of coronary artery calcification as an indicator of stenosis. Am J Card Imaging 1992; 6: 191–196 [Google Scholar]
  • 11. Chou T, Redberg R, Eitetsu K, Durairaj A, Messenger JC, Sudhir K, Kane JP, Malloy MJ: Screening for coronary artery atherosclerosis by detection of calcium on electron beam computed tomography: Correlation with intravascular ultrasound in asymptomatic patients with primary hyperlipidemia (abstr). Circulation 1996; 94 (supplI): I–360 [Google Scholar]
  • 12. Devries S, Wolfkiel C, Fusman B, Bakdash H, Ahmed A, Levy P, Chomka E, Kondos G, Zajac E, Rich S: Influence of age and gender on the presence of coronary calcium detected by ultrafast computed tomography. J Am Med Assoc 1995; 25: 76–82 [DOI] [PubMed] [Google Scholar]
  • 13. Guerci AD, Spadaro LA, Goodman K, Lledo‐Perez A, Newstein D, Lerner G, Arad Y: Comparison of electron beam computed tomography scanning and conventional risk factor assessment for the prediction of angiographic coronary artery disease. J Am Coll Cardiol 1998; 32: 673–679 [DOI] [PubMed] [Google Scholar]
  • 14. Schmermund A, Denktas AE, Rumberger JA, Christian TF, Sheedy PF, Bailey KR, Schwartz RS: Independent and incremental value of coronary artery calcium for predicting the extent of angiographic coronary artery disease. J Am Coll Cardiol 1999; 34: 777–786 [DOI] [PubMed] [Google Scholar]
  • 15. Kennedy J, Shavelle R, Wang S, Budoff M, Detrano RC: Coronary calcium and standard risk factors in symptomatic patients referred for coronary angiography. Am Heart J 1998; 135: 696–702 [DOI] [PubMed] [Google Scholar]
  • 16. Detrano R, Hsiai T, Wang S, Puentes G, Fallavollita J, Shields R Stanford W, Wolfkiel C, Georgiou D, Budoff M, Reed J: Prognostic value of coronary calcification and angiographic stenoses in patients undergoing coronary angiography. J Am Coll Cardiol 1996; 27: 285–290 [DOI] [PubMed] [Google Scholar]
  • 17. Detrano RC, Wong ND, Doherty TM, Shavelle RM, Tang W, Ginzton LE, Budoff MJ, Narahara KA: Coronary calcium does not accurately predict near‐term future coronary events in high‐risk adults. Circulation 1999; 99: 2633–2638 [DOI] [PubMed] [Google Scholar]
  • 18. Arad Y, Spadaro LA, Goodman K, Lledo‐Perez A, Sherman S, Lerner G, Guerci AD: Predictive value of electron beam computed tomography of the coronary arteries—19 month follow up of 1,173 asymptomatic subjects. Circulation 1996; 93: 1951–1953 [DOI] [PubMed] [Google Scholar]
  • 19. Grover SA, Coupal L, Hu X: Identifying adults at increased risk of coronary disease. J Am Med Assoc 1995; 274: 801–806 [PubMed] [Google Scholar]
  • 20. Secci A, Wong N, Tang W, Wang S, Doherty T, Detrano R: Electron beam computed tomographic coronary calcium as a predictor of coronary events. Comparison of two protocols. Circulation 1997; 96: 1122–1129 [DOI] [PubMed] [Google Scholar]
  • 21. Callister TQ, Cooil B, Raya SP, Lippolis NJ, Russo DJ, Raggi P: Coronary artery disease: Improved reproducibility of calcium scoring with an electron beam CT volumetric method. Radiology 1998; 208: 807–814 [DOI] [PubMed] [Google Scholar]
  • 22. O'Rourke RA, Brundage BH, Froehlicher VF, Greenland P, Grundy SM, Hachamovitch R, Pohost GM, Shaw LJ, Weintraub WS, Winters WL, Forrester JS, Douglas PS, Faxon DP, Fisher JD, Gregoratos G, Hochman JS, Hutter AM, Kaul S, Wolk MJ: American College of Cardiology/American Heart Association expert consensus document on electron‐beam computed tomography for the diagnosis and prognosis of coronary artery disease. Circulation 2000; 102: 126–140 [DOI] [PubMed] [Google Scholar]
  • 23. Van Geuns RJ, de Bruin HG, Rensing BJ, van Ooijen PM, Oudkerk M, de Feyter PJ: Magnetic resonance imaging of the coronary arteries: Clinical results from three dimensional evaluation of a respiratory gated technique. Heart 1999; 82 (4):515–519 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Regenfus M, Ropers D, Achenbach S, Kessler W, Laub G, Daniel W, Moshage W: Noninvasive detection of coronary artery stenosis using contrast‐enhanced three‐dimensional breath‐hold magnetic resonance coronary angiography. J Am Coll Cardiol 2000; 36: 44–50 [DOI] [PubMed] [Google Scholar]
  • 25. Kessler W, Laub G, Achenbach S, Ropers D, Moshage W, Daniel WG: Coronary arteries: MR angiography with fast contrast enhanced three dimensional breath hold imaging—initial experience. Radiology 1999; 210 (2): 566–572 [DOI] [PubMed] [Google Scholar]
  • 26. Taylor AM, Keegan J, Jhooti P, Gatehouse PD, Firmin DN, Pennell DJ: Differences between normal subjects and patients with coronary artery disease for three different MR coronary angiography respiratory suppression techniques. J Magnet Reson Imag 1999; 9 (6): 786–793 [DOI] [PubMed] [Google Scholar]
  • 27. Sakuma H, Takeda K, Higgins CB: Fast magnetic resonance imaging of the heart. Eur J Radiol 1999; 29: 101–113 [DOI] [PubMed] [Google Scholar]
  • 28. Duerinckx AJ: Coronary MR angiography. Radiol Clin North Am 1999; 37: 273–318 [DOI] [PubMed] [Google Scholar]
  • 29. Hundley WG, Hamilton CA, Clarke GD, Hillis LD, Herrington DM, Lange RA, Applegate RJ, Thomas MS, Payne J, Link KM, Peshock RM: Visualization of functional assessment of proximal and middle left anterior descending coronary stenoses in humans with magnetic resonance imaging. Circulation 1999; 99 (25): 3248–3254 [DOI] [PubMed] [Google Scholar]
  • 30. Simon A, Giral P, Levenson J: Extracoronary atherosclerotic plaque at multiple sites and total coronary calcification deposit in asymptomatic men. Circulation 1995; 92: 1414–1421 [DOI] [PubMed] [Google Scholar]
  • 31. Mitchell JR, Schwartz CJ: Relationship between arterial disease at different sites. Br Med J 1962; 1: 1293–1301 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32. Geroulakos G, O'Gorman D, Kalodiki E, Sheridan DJ, Nicolaides AN: The carotid intima‐media thickness as a marker of the presence of severe symptomatic coronary artery disease. Eur Heart J 1994; 15: 781–785 [DOI] [PubMed] [Google Scholar]
  • 33. Crouse JR, Craven TE, Hagaman AP, Bond MG: Association of coronary disease with segment specific intimal‐medial thickening of the extracranial carotid artery. Circulation 1995; 92: 1141–1147 [DOI] [PubMed] [Google Scholar]
  • 34. Blankenhorn DH, Selzer RH, Crawford DW, Barth JD, Liu CH, Mack WJ, Alaupovic P: Beneficial effects of colestipol‐niacin therapy on the common carotid. Circulation 1993; 88: 20–28 [DOI] [PubMed] [Google Scholar]
  • 35. Crouse JR, Byington RP, Bond MG, Espeland MA, Craven TE, Sprinkle JW, McGovern ME, Furberg CD: Pravastatin, lipids and atherosclerosis in the carotid arteries (PLAC‐II). Am J Cardiol 1995; 75: 445–459 [DOI] [PubMed] [Google Scholar]
  • 36. Furberg CD, Adams HP, Appelgate WB, Byington RP, Espeland MA, Hartwell T, Hunninghake DB, Lefkowitz DS, Probstfield J, Riley WA: Effect of lovastatin on early carotid atherosclerosis and clinical events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation 1994; 90: 1679–1687 [DOI] [PubMed] [Google Scholar]
  • 37. Salonen R, Nyyssonen K, Porkkala E, Rmmukainen J, Belder R, Park JS, Salonen JT: Kuopio Atherosclerosis Prevention Study (KAPS)—a population based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation 1995; 92: 1758–1764 [DOI] [PubMed] [Google Scholar]
  • 38. Gostomyzyk JG, Heller WD, Gerhardt P, Lee PN, Keil U: B‐scan ultrasound examination of the carotid arteries within a representative population (MONICA project Augsburg). Klin Wochenschr 1988; 66 (suppl II): 58–65 [PubMed] [Google Scholar]
  • 39. Craven TE, Ryu JE, Espeland MA, Kahl FR, McKinney WM, Toole JF, McMahan MR, Thompson CJ, Heiss G, Crouse JR: Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis: A case control study. Circulation 1990; 82: 1230–1242 [DOI] [PubMed] [Google Scholar]
  • 40. Geroulakos G, O'Gorman D, Nicolaides A, Sheridan D, Elkeles R, Shaper AG: Carotid intimal‐medial thickness: Correlation with the British Regional heart study risk score. J Intern Med 1994; 235: 431–433 [DOI] [PubMed] [Google Scholar]
  • 41. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX: Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: The atherosclerosis risk in communities (ARIC) study, 1987–1993. Am J Epidemiol 1997; 146: 483–494 [DOI] [PubMed] [Google Scholar]
  • 42. Salonen JT, Salonen R: Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb 1991: 11 (5): 1245–1249 [DOI] [PubMed] [Google Scholar]
  • 43. Simons P, Algra A, Bots ML. Banga JD, Grobbee DE, van der Graaf Y: Common carotid intima‐media thickness and arterial stiffness—indicators of cardiovascular risk in high‐risk patients. The SMART study (Second Manifestations of ARTerial disease). Circulation 1999; 100: 951–957 [DOI] [PubMed] [Google Scholar]
  • 44. Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, Azen SP: The role of carotid arterial intima‐medial thickness in predicting clinical coronary events. Ann Intern Med 1998; 128: 262–269 [DOI] [PubMed] [Google Scholar]
  • 45. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P: Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med 1986; 315: 1046–1051 [DOI] [PubMed] [Google Scholar]
  • 46. Zeiher AM, Drexler H, Wollschlager H, Just H: Modulation of coronary vasomotor tone in humans: Progressive endothelial dysfunction with different stages of coronary atherosclerosis. Circulation 1991; 83: 391–401 [DOI] [PubMed] [Google Scholar]
  • 47. Yasue H, Matsuyama K, Okumura K, Morikami Y, Ogawa H: Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment: Possible role of early coronary atherosclerosis. Circulation 1990; 81: 482–490 [DOI] [PubMed] [Google Scholar]
  • 48. Anderson TJ, Uehata A, Gerhard MD, Mederdith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC: Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol 1995; 26: 1235–1241 [DOI] [PubMed] [Google Scholar]
  • 49. Takase B, Uehata A, Akima T, Nagai T, Nishioka T, Hamabe A, Satomura K, Ohsuzu F, Kurita A: Endothelium‐dependent flow‐mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 1998; 82: 1535–1539, A7–8 [DOI] [PubMed] [Google Scholar]
  • 50. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE: Non‐invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992; 340: 1111–1115 [DOI] [PubMed] [Google Scholar]
  • 51. Celermajer DS, Sorensen KE, Bull C, Robinson J, Deanfiled JE: Endothelium‐dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol 1994; 24: 1468–1474 [DOI] [PubMed] [Google Scholar]
  • 52. Jensen‐Urstad K, Johansson J, Jensen‐Urstad M: Vascular function correlates with risk factors for cardiovascular disease in a healthy population of 35–year‐old subjects. J Intern Med 1997; 241: 507–513 [DOI] [PubMed] [Google Scholar]
  • 53. Clarkson P, Celermajer DS, Powe AJ, Donald AE, Henry RM, Deanfield JE: Endothelium‐dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease. Circulation 1997; 96: 3378–3383 [DOI] [PubMed] [Google Scholar]
  • 54. Correti MC, Plotnick GD, Vogel RA: Smoking correlates with flow‐mediated brachial artery vasoactivity but not cold pressor vasoactivity in men with coronary artery disease. Int J Card Imaging 1998; 14: 11–17 [DOI] [PubMed] [Google Scholar]
  • 55. Yataco AR, Corretti MC, Gardner AW, Womack CJ, Katzel LI: Endothelial reactivity and cardiac risk factors in older patients with peripheral arterial disease. Am J Cardiol 1999; 83: 754–758 [DOI] [PubMed] [Google Scholar]
  • 56. Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, Jubb M, World M, Deanfield JE: Exercise training enhances endothelial function in young men. J Am Coll Cardiol 1999; 33: 1379–1385 [DOI] [PubMed] [Google Scholar]
  • 57. Plotnick GD, Corretti MC, Vogel RA: Effect of antioxidant vitamins on the transient impairment of endothelium‐dependent brachial artery vasoactivity following a single high‐fat meal. J Am Med Assoc 1997; 278: 1682–1686 [PubMed] [Google Scholar]
  • 58. Lundman P, Eriksson M, Schenck‐Gustafsson K, Karpe F, Tornvall P: Transient triglyceridemia decreases vascular reactivity in young, healthy men without risk factors for coronary heart disease. Circulation 1997; 96: 3266–3268 [DOI] [PubMed] [Google Scholar]
  • 59. Jodoin I, Bussieres LM, Tardif JC, Juneau M: Effect of a short‐term primary prevention program on endothelium‐dependent vasodilation in adults at risk for atherosclerosis. Can J Cardiol 1999; 15: 83–88 [PubMed] [Google Scholar]
  • 60. Vogel RA, Corretti MC, Plotnick GD: Changes in flow‐mediated brachial artery vasoreactivity with lowering of desirable cholesterol levels in healthy middle‐aged men. Am J Cardiol 1996; 77: 37–40 [DOI] [PubMed] [Google Scholar]
  • 61. Dupuis J, Tardif JC, Cernacek P, Théroux P: Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. Circulation 1999; 99: 3227–3233 [DOI] [PubMed] [Google Scholar]
  • 62. Corretti MC, Plotnick GD, Vogel RA: Correlation of cold pressor and flow‐mediated brachial artery diameter responses with the presence of coronary artery disease. Am J Cardiol 1995; 75: 783–787 [DOI] [PubMed] [Google Scholar]
  • 63. Neunteufl T, Katzenschlager R, Hassan A, Klaar U, Schwarzacher S, Glogar D, Bauer P, Weidinger F: Systemic endothelial dysfunction is related to the extent and severity of coronary of coronary artery disease. Atherosclerosis 1997; 129: 111–118 [DOI] [PubMed] [Google Scholar]
  • 64. Kaku B, Mizuno S, Ohsato K, Murakami T, Moriuchi I, Arai Y, Nio Y, Hirase H, Nagata M, Takahashi Y, Ohnaka M: The correlation between stenosis index and flow‐mediated dilation of the brachial Jpn Circ J 1998; 62: 425–430 [DOI] [PubMed] [Google Scholar]
  • 65. Enderle MD, Schroeder S, Ossen R, Meisner C, Baumbach A, Haering HU, Karsch KR, Pfohl M: Comparison of peripheral endothelial dysfunction and intimal media thickness in patients with suspected coronary artery disease. Heart 1998; 80: 349–354 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66. Lieberman EH, Gerhard MD, Uehata A, Selwyn AP, Ganz P, Yeung AC, Creager MA: Flow‐induced vasodilation of the human brachial artery is impaired in patients < 40 years of age with coronary artery disease. Am J Cardiol 1996; 78: 1210–1214 [DOI] [PubMed] [Google Scholar]
  • 67. Maseri A: Inflammation, atherosclerosis, and ischemic events—exploring the hidden side of the moon. N Engl J Med 1997; 336: 1014–1016 [DOI] [PubMed] [Google Scholar]
  • 68. Shor A, Kuo CC, Patton DL: Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atheromatous plaques. S Afr Med J 1992; 82: 158–161 [PubMed] [Google Scholar]
  • 69. Coombes BK, Mahoney JB: Chlamydia pneumoniae infection of human endothelial cells induces proliferation of smooth muscle cells via an endothelial cell‐derived soluble factor(s). Infect Immun 1999; 67: 2909–2915 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70. Krull M, Klucken A, Wupperman F, Fuhrmann O, Margerl C, Seybold J, Hippenstiel S, Hegemann JH, Jantos CA, Suttorp N: Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae. J Immunol 1999; 162: 4834–4841 [PubMed] [Google Scholar]
  • 71. Kalayoglu MV, Hoerneman B, La Verda D, Morrison SG, Morrison RP, Byrne GI: Cellular oxidation of low‐density lipoprotein by Chlamydia pneumoniae. J Infect Dis 1999; 180: 780–790 [DOI] [PubMed] [Google Scholar]
  • 72. Kalayoglu MV, Byrne GI: A Chlamydia pneumoniae component that induces macrophage foam cell formation is a chlamydial lipopolysaccharide. Infect Immun 1998; 66: 5067–5072 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73. Kol A, Sukhova GK, Lichtman AH, Libby P: Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor alpha and matrix metalloproteinase expression. Circulation 1998; 98: 300–307 [DOI] [PubMed] [Google Scholar]
  • 74. Kol A, Bourcier T, Lichtman AH, Libby P: Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Invest 1999; 103: 571–577 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75. Dechend R, Maass M, Gieffers J, Dietz R, Scheidereit C, Leutz A, Gulba DC: Chlamydia pneumoniae infection of vascular smooth muscle and endothelial cells activates NF‐Kappa B and induces tissue factor and PAI‐1 expression: A potential link to arteriosclerosis. Circulation 1999; 100: 1369–1373 [DOI] [PubMed] [Google Scholar]
  • 76. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ: Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997; 96: 404–407 [DOI] [PubMed] [Google Scholar]
  • 77. Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan S, Nielson C, Hall S, Brady J, Egger M, Home B, Lim T: 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 Infarction with Chlamydia (ACADEMIC) Study. Circulation 1999; 99: 1540–1547 [DOI] [PubMed] [Google Scholar]
  • 78. Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B: Treatment with the antibiotic roxithromycin in patients with acute non‐Q wave coronary syndromes. The final report of the ROXIS study. Eur Heart J 1999; 20: 121–127 [DOI] [PubMed] [Google Scholar]
  • 79. 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 [DOI] [PubMed] [Google Scholar]
  • 80. Kloner RA, Giacomelli F, Alker KJ, Hale SL, Matthews R, Bellows S: Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion. Circulation 1991; 84: 1758–1772 [DOI] [PubMed] [Google Scholar]
  • 81. Friedman GD, Klatsky AL, Siegelaub AB: The leukocyte count as a predictor of myocardial infarction. N Engl J Med 1974; 290: 1275–1278 [DOI] [PubMed] [Google Scholar]
  • 82. Zalokar JB, Richard JL, Claude JR: Leukocyte count, smoking and myocardial infarction. N Engl J Med 1981; 304: 402–408 [DOI] [PubMed] [Google Scholar]
  • 83. Grimm RH, Neaton JD, Ludwig H: Prognostic importance of the white blood cell count for coronary, cancer, and all‐cause mortality. J Am Med Assoc 1985; 254: 1932–1937 [PubMed] [Google Scholar]
  • 84. Prentice RL, Szatrowski TP, Fujikuru T, Kato H, Mason MW, Hamilton HH: Leukocyte counts and coronary heart disease in a Japanese cohort. Am J Epidemiol 1982; 116: 496–506 [DOI] [PubMed] [Google Scholar]
  • 85. Kannel WB, Anderson K, Wilson PW: White blood cell count and cardiovascular disease—insights from the Framingham Study. J Am Med Assoc 1992; 267: 1253–1256 [PubMed] [Google Scholar]
  • 86. Manttari M, Manninen V, Koskinen P, Huttunen JK, Oksanen E, Tenkanen L, Heinonen OP, Frick MH: Leukocytes as a coronary risk factor in a dyslipidemic male population. Am Heart J 1992; 123: 873–877 [DOI] [PubMed] [Google Scholar]
  • 87. 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 [DOI] [PubMed] [Google Scholar]
  • 88. 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 [DOI] [PubMed] [Google Scholar]
  • 89. 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 [DOI] [PubMed] [Google Scholar]
  • 90. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring 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 Augsburg cohort study, 1984–1992. Circulation 1999; 99: 237–242 [DOI] [PubMed] [Google Scholar]
  • 91. Ridker PM, Buring JE, Shih J, Mafias 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 [DOI] [PubMed] [Google Scholar]
  • 92. Grundy SM, Pasternak R, Greenland P, Smith S, Fuster V: Assessment of cardiovascular risk by use of multiple‐risk‐factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology. J Am Coll Cardiol 1999; 34: 1348–1359 [DOI] [PubMed] [Google Scholar]
  • 93. Ernst E, Koenig W: Fibrinogen and cardiovascular risk. Vase Med 1997; 2: 115–125 [DOI] [PubMed] [Google Scholar]
  • 94. Danesh J, Muir J, Wong YK, 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: 954–959 [DOI] [PubMed] [Google Scholar]
  • 95. Lindberg G, Rastam L, Nilsson‐Ehle P, Lundblad A, Ranstam J, Folsom AR, Burke GL: Serum sialic acid and sialoglycoproteins in asymptomatic carotid artery atherosclerosis. ARIC investigators. Atherosclerosis Risk in Communities. Atherosclerosis 1999; 146: 65–69 [DOI] [PubMed] [Google Scholar]
  • 96. De Maat MP, Kastelein JJ, Jukema JW, Zwinderman AH, Jansen H, Groenemeier B, Bruschke AV, Kluft C: 455G/A polymorphism of the beta‐fibrinogen gene is associated with the progression of coronary atherosclerosis in symptomatic men: Proposed role for an acute phase reaction pattern of fibrinogen. REGRESS group. Arterioscler Thromb Vasc Biol 1998; 2: 265–271 [DOI] [PubMed] [Google Scholar]
  • 97. Wu KK, Aleksic N: Platelet glycoprotein polymorphism and risk for coronary heart disease. Blood Coagul Fibrinol 1999: 10 (suppl 1): S63–S65 [PubMed] [Google Scholar]
  • 98. De Maat MP, Bladbjerg EM, Johansen LG, de Knijff P, Gram J, Kluft C, Jesperen J: DNA polymorphisms and plasma levels of vascular disease risk factors in Greenland Inuit: Is there a relation with the low risk of cardiovascular disease in Inuit? Thromb Haemost 1999; 81: 547–552 [PubMed] [Google Scholar]
  • 99. Junker R, Heinrich J, Schulte H, van de Loo J, Assmann G: Coagulation factor VII and the risk of coronary heart disease in healthy men. Arterioscler Thromb Vasc Biol 1997; 17: 1539–1544 [DOI] [PubMed] [Google Scholar]
  • 100. De Maat MP, Green F, de Knijff P, Jespersen J, Kluft C: Factor VII polymorphisms in populations with different risks of cardiovascular disease. Arterioscler Thromb Vasc Biol 1997; 17: 1918–1923 [DOI] [PubMed] [Google Scholar]
  • 101. Ghaddar HM, Folsom AR, Aleksic N, Heame LB, Chambless LE, Morrissey JH, Wu KK: Correlation of factor Vila values with factor VII gene polymorphism, fasting and postprandial triglyceride levels, and subclinical atherosclerosis. Circulation 1998; 98: 2815–2821 [DOI] [PubMed] [Google Scholar]
  • 102. Folsom AR, Rosamond WD, Shahar E, Coooper LS, Aleksic N, Nieto FJ, Rasmussen ML, Wu KK: Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) study investigators. Circulation 1999; 100: 736–742 [DOI] [PubMed] [Google Scholar]
  • 103. Wu KK: Hemostatic tests in the prediction of atherothrombotic disease. Int J Clin Lab Res 1997; 27: 145–152 [DOI] [PubMed] [Google Scholar]
  • 104. Koenig W, Sund M, Filipiak B, Doring A, Lowel H, Ernst E: Plasma viscosity and the risk of coronary heart disease: Results from the MONICA Augsburg cohort study, 1984–1992. Arterioscler Thmmb Vase Biol 1998; 18: 768–772 [DOI] [PubMed] [Google Scholar]
  • 105. Saloma V, Matei C, Aleksic N, Sansores‐Garcia L, Folsom AR, Juneja H, Chabless LE, Wu KK: Soluble thrombomodulin as a predictor of incident coronary heart disease and symptomless carotid artery atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) Study: A case‐cohort study. Lancet 1999; 353: 1729–1734 [DOI] [PubMed] [Google Scholar]
  • 106. McCully KS: Vascular pathology of homocysteinemia. Am J Pathol 1969: 56: 111–128 [PMC free article] [PubMed] [Google Scholar]
  • 107. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, Andria G, Boers GH, Bromberg IL, Cerone R: Natural history of homocysteinuria due to cystathione beta synthase deficiency. Am J Hum Genet 1985; 37: 1–25 [PMC free article] [PubMed] [Google Scholar]
  • 108. Rolland PH, Friggi A, Barlaiter A, Piquet P, Latrille V, Faye MM, Guillou J, Charpiot P, Bodard H, Ghiringhelli O: Hyperhomo‐cysteinemia induced vascular damage in the minipig. Captopril‐hydrochlorothiazide combination prevents elastic alterations. Circulation 1995; 91: 1161–1174 [DOI] [PubMed] [Google Scholar]
  • 109. Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR, Hiestad DD: Vascular dysfunction in monkeys with diet‐induced hyperhomocysteinemia. J Clin Invest 1996; 98: 328–329 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 110. Chambers JC, McGregor A, Jean‐Marie J, Kooner JS: Acute hyperhomocysteinemia and endothelial dysfunction. Lancet 1998; 351: 36–37 [DOI] [PubMed] [Google Scholar]
  • 111. Malinow MR, Bostom AG, Krauss RM: Homocysteine, diet, and cardiovascular diseases: A statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 1999; 99: 178–182 [DOI] [PubMed] [Google Scholar]
  • 112. 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 (18):1837–1847 [DOI] [PubMed] [Google Scholar]

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