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Semin Vasc Med 2002; 02(4): 401-416
DOI: 10.1055/s-2002-36769
DOI: 10.1055/s-2002-36769
Infective Agents and Cardiovascular Disease
Further Information
Publication History
Publication Date:
22 January 2003 (online)
ABSTRACT
As a consequence of seminal laboratory and experimental work conducted in the 1970s, infections have recently been recognized among possible risk factors for atherosclerosis and its clinical cardiovascular disease manifestations. The infectious hypothesis also relates to modern atherogenesis theories that consider the crucial role of inflammation in the initial development as well as in the natural history of the atherosclerotic plaque. During the last 2 decades, numerous clinical and epidemiologic studies have explored the association between markers of chronic infections in relation to a variety of clinical and subclinical cardiovascular disease outcomes. These studies have focused on a variety of agents including herpesvirus (especially cytomegalovirus), Chlamydia pneumonia, Helicobacter pylori, and periodontal pathogens, and have produced inconsistent results. Some of the limitations and methodological issues in interpreting the existing epidemiologic evidence are discussed in this article. In addition, other supporting evidence is presented here, including pathology studies documenting the presence of infectious agents' DNA in atherosclerotic plaque tissue and experimental infection models in animal studies. Areas for future research are discussed in light of the strengths and limitations of the existing evidence.
KEYWORD
Atherosclerosis - bias - Chlamydia pneumoniae, cardiovascular disease - coronary disease - cytomegalovirus - epidemiologic studies - infections - inflammation
REFERENCES
- 1 Nieto F J. Infections and atherosclerosis: new clues from an old hypothesis?. Am J Epidemiol . 1998; 148 937-948
- 2 Braunwald E. Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med . 1997; 337 1360-1369
- 3 Hennekens C H. Increasing burden of cardiovascular disease: current knowledge and future directions for research on risk factors. Circulation . 1998; 97 1095-1102
- 4 Nieto F J. Cardiovascular disease and risk factor epidemiology: a look back at the epidemic of the 20th century. Am J Public Health . 1999; 89 292-294
- 5 Libby P, Egan D, Skarlatos S. Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation . 1997; 96 4095-4103
- 6 Nicholson A C, Hajjar D P. Herpesvirus in atherosclerosis and thrombosis: etiologic agents or ubiquitous bystanders?. Arterioscler Thromb Vasc Biol . 1998; 18 339-348
- 7 Mehta J L, Saldeen T G, Rand K. Interactive role of infection, inflammation and traditional risk factors in atherosclerosis and coronary artery disease. J Am Coll Cardiol . 1998; 31 1217-1225
- 8 Epstein S E, Zhou Y F, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation . 1999; 100 e20-e28
- 9 Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med . 1999; 340 115-126
- 10 Benditt E P, Benditt J M. Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci U S A . 1973; 70 1753-1756
- 11 Benditt E P, Barrett T, McDougall J K. Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci USA . 1983; 80 6386-6389
- 12 Hendrix M G, Salimans M M, van Boven P C, Bruggeman C A. High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol . 1990; 136 23-28
- 13 Hendrix M G, Daemen M, Bruggeman C A. Cytomegalovirus nucleic acid distribution within the human vascular tree. Am J Pathol . 1991; 138 563-567
- 14 Melnick J L, Hu C, Burek J, Adam E, DeBakey M E. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol . 1994; 42 170-174
- 15 Melnick J L, Adam E, DeBakey M E. Cytomegalovirus and atherosclerosis. Arch Immunol Ther Exp (Warsz) . 1996; 44 297-302
- 16 Campbell L A, O'Brien E R, Cappuccio A L. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis . 1995; 172 585-588
- 17 Blasi F, Denti F, Erba M. Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. J Clin Microbiol . 1996; 34 2766-2769
- 18 Grayston J T, Kuo C C, Coulson A S. Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. Circulation . 1995; 92 3397-3400
- 19 Kuo C C, Shor A, Campbell L A, Fukushi H, Patton D L, Grayston J T. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis . 1993; 167 841-849
- 20 Kuo C C, Grayston J T, Campbell L A, Goo Y A, Wissler R W, Benditt E P. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). Proc Natl Acad Sci U S A . 1995; 92 6911-6914
- 21 Danesh J, Appleby P. Persistent infection and vascular disease: a systematic review. Exp Opin Invest Drugs . 1998; 7 691-713
- 22 Vink A, Poppen M, Schoneveld A H. Distribution of Chlamydia pneumoniae in the human arterial system and its relation to the local amount of atherosclerosis within the individual. Circulation . 2001; 103 1613-1617
- 23 Radke P W, Merkelbach-Bruse S, Messmer B J. Infectious agents in coronary lesions obtained by endatherectomy: pattern of distribution, coinfection, and clinical findings. Coron Artery Dis . 2001; 12 1-6
- 24 Dobrilovic N, Vadlamani L, Meyer M, Wright C B. Chlamydia pneumoniae in atherosclerotic carotid artery plaques: high prevalence among heavy smokers. Am Surg . 2001; 67 589-593
- 25 Chiu B, Viira E, Tucker W, Fong I W. Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. Circulation . 1997; 96 2144-2148
- 26 Farsak B, Yildirir A, Akyon Y. Detection of Chlamydia pneumoniae and Helicobacter pylori DNA in human atherosclerotic plaques by PCR. J Clin Microbiol . 2000; 38 4408-4411
- 27 Danesh J, Koreth J, Youngman L. Is Helicobacter pylori a factor in coronary atherosclerosis?. J Clin Microbiol . 1999; 37 1651
- 28 Haraszthy V I, Zambon J J, Trevisan M, Zeid M, Genco R J. Identification of periodontal pathogens in atheromatous plaques. J Periodontol . 2000; 71 1554-1560
- 29 Shor A. A pathologist's view of organisms and human atherosclerosis. J Infect Dis . 2001; 183 1428-1429
- 30 Tumilowicz J J, Gawlik M E, Powell B B, Trentin J J. Replication of cytomegalovirus in human arterial smooth muscle cells. J Virol . 1985; 56 839-845
- 31 Bruggeman C. Cytomegalovirus is involved in vascular pathology. Am Heart J . 1999; 138 S473-S475
- 32 Gaydos C A, Summersgill J T, Sahney N N, Ramirez J A, Quinn T C. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun . 1996; 64 1614-1620
- 33 Knoebel E, Vijayagopal P, Figueroa 2nd E J, Martin D H. In vitro infection of smooth muscle cells by Chlamydia pneumoniae. Infect Immun . 1997; 65 503-506
- 34 Guetta E, Guetta V, Shibutani T, Epstein S E. Monocytes harboring cytomegalovirus: interactions with endothelial cells, smooth muscle cells, and oxidized low-density lipoprotein. Possible mechanisms for activating virus delivered by monocytes to sites of vascular injury. Circ Res . 1997; 81 8-16
- 35 Span A H, Van Boven P C, Bruggeman C A. The effect of cytomegalovirus infection on the adherence of polymorphonuclear leucocytes to endothelial cells. Eur J Clin Invest . 1989; 19 542-548
- 36 Zajac B A, O'Neill K, Friedman H M, MacGregor R R. Increased adherence of human granulocytes to herpes simplex virus type 1 infected endothelial cells. In Vitro Cell Dev Biol . 1988; 24 321-325
- 37 Kaukoranta-Tolvanen S S, Teppo A M, Laitinen K, Saikku P, Linnavuori K, Leinonen M. Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response. Microb Pathog . 1996; 21 215-221
- 38 Shahgasempour S, Woodroffe S B, Garnett H M. Alterations in the expression of ELAM-1, ICAM-1 and VCAM-1 after in vitro infection of endothelial cells with a clinical isolate of human cytomegalovirus. Microbiol Immunol . 1997; 41 121-129
- 39 Kovacs A, Weber M L, Burns L J, Jacob H S, Vercellotti G M. Cytoplasmic sequestration of p53 in cytomegalovirus-infected human endothelial cells. Am J Pathol . 1996; 149 1531-1539
- 40 Speir E, Modali R, Huang E S. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science . 1994; 265 391-394
- 41 Tanaka K, Zou J P, Takeda K. Effects of human cytomegalovirus immediate-early proteins on p53-mediated apoptosis in coronary artery smooth muscle cells. Circulation . 1999; 99 1656-1659
- 42 Zhou Y F, Yu Z X, Wanishsawad C, Shou M, Epstein S E. The immediate early gene products of human cytomegalovirus increase vascular smooth muscle cell migration, proliferation, and expression of PDGF beta-receptor. Biochem Biophys Res Commun . 1999; 256 608-613
- 43 Fabricant C G, Krook L, Gillespie J H. Virus-induced cholesterol crystals. Science . 1973; 181 566-567
- 44 Hajjar D P, Fabricant C G, Minick C R, Fabricant J. Virus-induced atherosclerosis. Herpesvirus infection alters aortic cholesterol metabolism and accumulation. Am J Pathol . 1986; 122 62-70
- 45 Fabricant C G, Fabricant J. Atherosclerosis induced by infection with Marek's disease herpesvirus in chickens. Am Heart J . 1999; 138 S465-S468
- 46 Zhou Y F, Guetta E, Yu Z X, Finkel T, Epstein S E. Human cytomegalovirus increases modified low-density lipoprotein uptake and scavenger receptor mRNA expression in vascular smooth muscle cells. J Clin Invest . 1996; 98 2129-2138
- 47 Steinberg D, Parthasarathy S, Carew T E, Khoo J C, Witztum J L. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med . 1989; 320 915-924
- 48 Kalayoglu M V, Byrne G I. A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun . 1998; 66 5067-5072
- 49 Kalayoglu M V, Byrne G I. Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis . 1998; 177 725-729
- 50 Kalayoglu M V, Hoerneman B, LaVerda D, Morrison S G, Morrison R P, Byrne G I. Cellular oxidation of low-density lipoprotein by Chlamydia pneumoniae. J Infect Dis . 1999; 180 780-790
- 51 Byrne G I, Kalayoglu M V. Chlamydia pneumoniae and atherosclerosis: links to the disease process. Am Heart J . 1999; 138 S488-S490
- 52 Bruggeman C A, Debie W H, Muller A D, Schutte B, van Dam-Mieras C M. Cytomegalovirus alters the von Willebrand's factor content in human endothelial cells. Thromb Haemost . 1988; 59 264-268
- 53 Van Dam-Mieras C M, Bruggeman C A, Muller A D, Debie W H, Zwaal R F. Induction of endothelial cell procoagulant activity by cytomegalovirus infection. Thromb Res . 1987; 47 69-75
- 54 Vercellotti G M. Proinflammatory and procoagulant effects of herpes simplex infection on human endothelium [published erratum appears in Blood Cells 1991;17:442]. Blood Cells . 1990; 16 209-216
- 55 Vercellotti G M. Effects of viral activation of the vessel wall on inflammation and thrombosis. Blood Coagul Fibrinolysis . 1998; 9(Suppl 2) S3-S6
- 56 Nieto F J, Sorlie P, Comstock G W. Cytomegalovirus infection, lipoprotein(a), and hypercoagulability: an atherogenic link?. Arterioscler Thromb Vasc Biol . 1997; 17 1780-1785
- 57 Kol A, Sukhova G K, Lichtman A H, 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
- 58 Kol A, Bourcier T, Lichtman A H, 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
- 59 Mayr M, Metzler B, Kiechl S. Endothelial cytotoxicity mediated by serum antibodies to heat shock proteins of Escherichia coli and Chlamydia pneumoniae: immune reactions to heat shock proteins as a possible link between infection and atherosclerosis. Circulation . 1999; 99 1560-1566
- 60 Srivastava P K, Menoret A, Basu S, Binder R J, McQuade K L. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity . 1998; 8 657-665
- 61 Bukau B, Horwich A L. The Hsp70 and Hsp60 chaperone machines. Cell . 1998; 92 351-366
- 62 Williams R S. Heat shock protein 47: a chaperone for the fibrous cap?. Circulation . 2000; 101 1227-1228
- 63 Benjamin I J, McMillan D R. Stress (heat shock) proteins: molecular chaperones in cardiovascular biology and disease. Circ Res . 1998; 83 117-132
- 64 Pockley A G, Wu R, Lemne C, Kiessling R, Ulf De F, Frostegard J. Circulating heat shock protein 60 is associated with early cardiovascular disease. Hypertension . 2000; 36 303-307
- 65 Xu Q, Schett G, Perschinka H. Serum soluble heat shock protein 60 is elevated in subjects with atherosclerosis in a general population. Circulation . 2000; 102 14-20
- 66 Wick G, Perschinka H, Xu Q. Autoimmunity and atherosclerosis. Am Heart J . 1999; 138 S444-S449
- 67 Fabricant C G, Fabricant J, Minick C R, Litrenta M M. Virus-induced atherosclerosis in chickens. J Exp Med . 1978; 148 335-340
- 68 Span A H, Grauls G, Bosman F, van Boven P C, Bruggeman C A. Cytomegalovirus infection induces vascular injury in the rat. Atherosclerosis . 1992; 93 41-52
- 69 Zhou Y F, Shou M, Guetta E. Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall. Circulation . 1999; 100 1569-1575
- 70 Zhou Y F, Shou M, Harrell R F, Yu Z X, Unger E F, Epstein S E. Chronic non-vascular cytomegalovirus infection: effects on the neointimal response to experimental vascular injury. Cardiovasc Res . 2000; 45 1019-1025
- 71 Berencsi K, Endresz V, Klurfeld D, Kari L, Kritchevsky D, Gonczol E. Early atherosclerotic plaques in the aorta following cytomegalovirus infection of mice. Cell Adhes Commun . 1998; 5 39-47
- 72 Muhlestein J B, Anderson J L, Hammond E H. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation . 1998; 97 633-636
- 73 Hu H, Pierce G N, Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest . 1999; 103 747-753
- 74 Liu L, Hu H, Ji H, Murdin A D, Pierce G N, Zhong G. Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR-/- mouse model within six months. Mol Cell Biochem . 2000; 215 123-128
- 75 Moazed T C, Campbell L A, Rosenfeld M E, Grayston J T, Kuo C C. Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis . 1999; 180 238-241
- 76 Aalto-Setala K, Laitinen K, Erkkila L. Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol . 2001; 21 578-584
- 77 Caligiuri G, Rottenberg M, Nicoletti A, Wigzell H, Hansson G K. Chlamydia pneumoniae infection does not induce or modify atherosclerosis in mice. Circulation . 2001; 103 2834-2838
- 78 Benson R, Smith K, Semenov H. Experimental arteritis and arteriosclerosis associated with streptococcal inoculations. Arch Pathol . 1931; 12 924-940
- 79 Jones N, Rogers A. The incidence of streptococcal infection in cardiovascular sclerosis. Ann Intern Med . 1935; 8 834-853
- 80 Jones N, Rogers A. Chronic infections and atherosclerosis. Arch Pathol . 1948; 27 271-277
- 81 Virus infections and atherosclerosis. Lancet . 1978; 2 821-822
- 82 Adam E, Melnick J L, Probtsfield J L. High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet . 1987; 2 291-293
- 83 Saikku P, Leinonen M, Mattila K. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet . 1988; 2 983-986
- 84 Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link?. Lancet . 1997; 350 430-436
- 85 Danesh J, Whincup P, Walker M. Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. BMJ . 2000; 321 208-213
- 86 Nieto F J, Folsom A R, Sorlie P D, Grayston J T, Wang S P, Chambless L E. Chlamydia pneumoniae infection and incident coronary heart disease: the Atherosclerosis Risk in Communities Study. Am J Epidemiol . 1999; 150 149-156
- 87 Siscovick D S, Schwartz S M, Corey L. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the cardiovascular health study. Circulation . 2000; 102 2335-2340
- 88 Ridker P M, Kundsin R B, Stampfer M J, Poulin S, Hennekens C H. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation . 1999; 99 1161-1164
- 89 Ridker P M, Hennekens C H, Buring J E, Kundsin R, Shih J. Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women. Ann Intern Med . 1999; 131 573-577
- 90 Strachan D P, Carrington D, Mendall M A. Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the Caerphilly prospective heart disease study. BMJ . 1999; 318 1035-1039
- 91 Wald N J, Law M R, Morris J K, Zhou X, Wong Y, Ward M E. Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study. BMJ . 2000; 321 204-207
- 92 Fagerberg B, Gnarpe J, Gnarpe H, Agewall S, Wikstrand J. Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension. Stroke . 1999; 30 299-305
- 93 Ridker P M, Hennekens C H, Stampfer M J, Wang F. Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation . 1998; 98 2796-2799
- 94 Strachan D P, Carrington D, Mendall M A, Butland B K, Sweetnam P M, Elwood P C. Cytomegalovirus seropositivity and incident ischaemic heart disease in the Caerphilly prospective heart disease study. Heart . 1999; 81 248-251
- 95 Sorlie P D, Nieto F J, Adam E, Folsom A R, Shahar E, Massing M. A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study. Arch Intern Med . 2000; 160 2027-2032
- 96 Muhlestein J B, Horne B D, Carlquist J F. Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation . 2000; 102 1917-1923
- 97 Mendall M A, Goggin P M, Molineaux N. Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J . 1994; 71 437-439
- 98 Folsom A R, Nieto F J, Sorlie P, Chambless L E, Graham D Y. Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk In Communities (ARIC) Study Investigators. Circulation . 1998; 98 845-850
- 99 Ridker P M, Danesh J, Youngman L. A prospective study of Helicobacter pylori seropositivity and the risk for future myocardial infarction among socioeconomically similar US men. Ann Intern Med . 2001; 135 184-188
- 100 Strachan D P, Mendall M A, Carrington D. Relation of Helicobacter pylori infection to 13-year mortality and incident ischemic heart disease in the Caerphilly prospective heart disease study. Circulation . 1998; 98 1286-1290
- 101 Roivainen M, Alfthan G, Jousilahti P, Kimpimaki M, Hovi T, Tuomilehto J. Enterovirus infections as a possible risk factor for myocardial infarction. Circulation . 1998; 98 2534-2537
- 102 Roivainen M. Enteroviruses and myocardial infarction. Am Heart J . 1999; 138 S479-S483
- 103 Roivainen M, Viik-Kajander M, Palosuo T. Infections, inflammation, and the risk of coronary heart disease. Circulation . 2000; 101 252-257
- 104 Lovey P Y, Morabia A, Bleed D, Peter O, Dupuis G, Petite J. Long-term vascular complications of Coxiella burnetii infection in Switzerland: cohort study. BMJ . 1999; 319 284-286
- 105 Mattila K J, Valle M S, Nieminen M S, Valtonen V V, Hietaniemi K L. Dental infections and coronary atherosclerosis. Atherosclerosis . 1993; 103 205-211
- 106 Mattila K J, Nieminen M S, Valtonen V V. Association between dental health and acute myocardial infarction. BMJ . 1989; 298 779-781
- 107 Emingil G, Buduneli E, Aliyev A, Akilli A, Atilla G. Association between periodontal disease and acute myocardial infarction. J Periodontol . 2000; 71 1882-1886
- 108 Beck J, Garcia R, Heiss G, Vokonas P S, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol . 1996; 67 1123-1137
- 109 Wu T, Trevisan M, Genco R J, Dorn J P, Falkner K L, Sempos C T. Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study. Arch Intern Med . 2000; 160 2749-2755
- 110 Howell T H, Ridker P M, Ajani U A, Hennekens C H, Christen W G. Periodontal disease and risk of subsequent cardiovascular disease in U.S male physicians. J Am Coll Cardiol . 2001; 37 445-450
- 111 Hujoel P P, Drangsholt M, Spiekerman C, DeRouen T A. Periodontal disease and coronary heart disease risk. JAMA . 2000; 284 1406-1410
- 112 Genco R J, Trevisan M, Wu T, Beck J D. Periodontal disease and risk of coronary heart disease. JAMA . 2001; 285 40-41
- 113 Zhu J, Quyyumi A A, Norman J E. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. Am J Cardiol . 2000; 85 140-146
- 114 Zhu J, Nieto F J, Horne B D, Anderson J L, Muhlestein J B, Epstein S E. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation . 2001; 103 45-51
- 115 Rupprecht H J, Blankenberg S, Bickel C. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation . 2001; 104 25-31
- 116 Strong J P, McGill Jr C H. The pediatric aspects of atherosclerosis. J Atheroscler Res . 1969; 9 251-265
- 117 Strong J P, Malcom G T, McMahan C A. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA . 1999; 281 727-735
- 118 The ARIC investigators. The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. Am J Epidemiol . 1989; 129 687-702
- 119 Sharrett A R. Invasive versus noninvasive studies of risk factors and atherosclerosis. Circulation . 1993; 87 II48-53
- 120 Melnick S L, Shahar E, Folsom A R. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk In Communities (ARIC) Study Investigators. Am J Med . 1993; 95 499-504
- 121 Sorlie P D, Adam E, Melnick S L. Cytomegalovirus/ herpesvirus and carotid atherosclerosis: the ARIC Study. J Med Virol . 1994; 42 33-37
- 122 Kawamoto R, Doi T, Tokunaga H, Konishi I. An association between an antibody against Chlamydia pneumoniae and common carotid atherosclerosis. Intern Med . 2001; 40 208-213
- 123 Nieto F J, Adam E, Sorlie P. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation . 1996; 94 922-927
- 124 Kiechl S, Egger G, Mayr M. Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. Circulation . 2001; 103 1064-1070
- 125 Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. Circulation . 2001; 103 1390-1395
- 126 Zhou Y F, Leon M B, Waclawiw M A. Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med . 1996; 335 624-630
- 127 Blum A, Giladi M, Weinberg M. High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis. Am J Cardiol . 1998; 81 866-868
- 128 Manegold C, Alwazzeh M, Jablonowski H. Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty. Circulation . 1999; 99 1290-1294
- 129 Schiele F, Batur M K, Seronde M F. Cytomegalovirus, Chlamydia pneumoniae, and Helicobacter pylori IgG antibodies and restenosis after stent implantation: an angiographic and intravascular ultrasound study. Heart . 2001; 85 304-311
- 130 Grattan M T, Moreno-Cabral C E, Starnes V A, Oyer P E, Stinson E B, Shumway N E. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA . 1989; 261 3561-3566
- 131 Hauptman P J, Davis S F, Miller L, Yeung A C. The role of nonimmune risk factors in the development and progression of graft arteriosclerosis: preliminary insights from a multicenter intravascular ultrasound study. Multicenter Intravascular Ultrasound Transplant Study Group. J Heart Lung Transplant . 1995; 14 S238-S242
- 132 Koskinen P, Lemstrom K, Mattila S, Hayry P, Nieminen M S. Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft. Clin Transplant . 1996; 10 487-493
- 133 Gao H Z, Hunt S A, Alderman E L, Liang D, Yeung A C, Schroeder J S. Relation of donor age and pre-existing coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease. J Am Coll Cardiol . 1997; 29 623-629
- 134 Everett J P, Hershberger R E, Norman D J. Prolonged cytomegalovirus infection with viremia is associated with development of cardiac allograft vasculopathy. J Heart Lung Transplant . 1992; 11 S133-S137
- 135 Gaudin P B, Rayburn B K, Hutchins G M. Peritransplant injury to the myocardium associated with the development of accelerated arteriosclerosis in heart transplant recipients. Am J Surg Pathol . 1994; 18 338-346
- 136 McDonald K, Rector T S, Braulin E A, Kubo S H, Olivari M T. Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol . 1989; 64 359-362
- 137 Tikkanen J, Kallio E, Pulkkinen V, Bruggeman C, Koskinen P, Lemstrom K. Cytomegalovirus infection-enhanced chronic rejection in the rat is prevented by antiviral prophylaxis. Transplant Proc . 2001; 33 1801
- 138 Hosenpud J D. Coronary artery disease after heart transplantation and its relation to cytomegalovirus. Am Heart J . 1999; 138 S469-S472
- 139 Koskinen P K, Kallio E A, Tikkanen J M, Sihvola R K, Hayry P J, Lemstrom K B. Cytomegalovirus infection and cardiac allograft vasculopathy. Transplant Infect Dis . 1999; 1 115-126
- 140 Weis M, von Scheidt W. Coronary artery disease in the transplanted heart. Ann Rev Med . 2000; 51 81-100
- 141 Billingham M E. Graft coronary disease: the lesions and the patients. Transplant Proc . 1989; 21 3665-3666
- 142 Weis M, von Scheidt W. Cardiac allograft vasculopathy: a review. Circulation . 1997; 96 2069-2077
- 143 Gupta S, Leatham E W, Carrington D, Mendall M A, Kaski J C, Camm A J. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation . 1997; 96 404-407
- 144 Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B. Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet . 1997; 350 404-407
- 145 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
- 146 Anderson J L, Muhlestein J B, Carlquist J. 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
- 147 Grayston J T. Antibiotic treatment of Chlamydia pneumoniae for secondary prevention of cardiovascular events. Circulation . 1998; 97 1669-1670
- 148 Meier C R, Derby L E, Jick S S, Vasilakis C, Jick H. Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA . 1999; 281 427-431
- 149 Folsom A R. Antibiotics for prevention of myocardial infarction?. <~>Not yet! JAMA . 1999; 281 461-462
- 150 Jackson L A, Smith N L, Heckbert S R, Grayston J T, Siscovick D S, Psaty B M. Lack of association between first myocardial infarction and past use of erythromycin, tetracycline, or doxycycline. Emerg Infect Dis . 1999; 5 281-284
- 151 Karvonen M, Tuomilehto J, Pitkaniemi J, Naukkarinen A, Saikku P. Importance of smoking for Chlamydia pneumoniae seropositivity. Int J Epidemiol . 1994; 23 1315-1321
- 152 Hahn D L, Golubjatnikov R. Smoking is a potential confounder of the Chlamydia pneumoniae-coronary artery disease association. Arterioscler Thromb . 1992; 12 945-947
- 153 Hoffmeister A, Rothenbacher D, Bode G. Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid profile. Arterioscler Thromb Vasc Biol . 2001; 21 427-432
- 154 Laurila A, Bloigu A, Nayha S, Hassi J, Leinonen M, Saikku P. Chlamydia pneumoniae antibodies and serum lipids in Finnish men: cross sectional study. BMJ . 1997; 314 1456-1457
- 155 Ridker P M. Inflammation, infection, and cardiovascular risk: how good is the clinical evidence?. Circulation . 1998; 97 1671-1674
- 156 West R. Commentary: adjustment for potential confounders may have been taken too far. BMJ . 2000; 321 213
- 157 Gullen W H, Bearman J E, Johnson E A. Effects of misclassification in epidemiologic studies. Public Health Rep . 1968; 83 914-918
- 158 Smieja M, Chong S, Natarajan M, Petrich A, Rainen L, Mahony J B. Circulating nucleic acids of Chlamydia pneumoniae and cytomegalovirus in patients undergoing coronary angiography. J Clin Microbiol . 2001; 39 596-600
- 159 Wong Y K, Dawkins K D, Ward M E. Circulating Chlamydia pneumoniae DNA as a predictor of coronary artery disease. J Am Coll Cardiol . 1999; 34 1435-1439
- 160 Nieminen M S, Mattila K, Valtonen V. Infection and inflammation as risk factors for myocardial infarction. Eur Heart J . 1993; 14(Suppl K) 12-16
- 161 Syrjanen J, Valtonen V V, Iivanainen M, Kaste M, Huttunen J K. Preceding infection as an important risk factor for ischaemic brain infarction in young and middle-aged patients. Br Med J Clin Res Ed . 1988; 296 1156-1160
- 162 Labro M T. Anti-inflammatory activity of macrolides: a new therapeutic potential?. J Antimicrob Chemother . 1998; 41(Suppl B) 37-46
- 163 Black P N. Anti-inflammatory effects of macrolide antibiotics. Eur Respir J . 1997; 10 971-972
- 164 Thom D H, Grayston J T, Siscovick D S, Wang S P, Weiss N S, Daling J R. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA . 1992; 268 68-72
- 165 Miettinen H, Lehto S, Saikku P. Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland. Eur Heart J . 1996; 17 682-688
- 166 Burian K, Kis Z, Virok D. Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis. Circulation . 2001; 103 1503-1508