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Emerg Infect Dis. 2001 Sep-Oct; 7(5): 780–788.
PMCID: PMC2631877

Potential infectious etiologies of atherosclerosis: a multifactorial perspective.

Abstract

Coronary heart disease (CHD) contributes substantially to illness and death worldwide. Experimental studies demonstrate that infection can stimulate atherogenic processes. This review presents a spectrum of data regarding the link between CHD and infection. In addition, the need for improved diagnostic tools, the significance of multiple pathogens, and potential intervention strategies are discussed.

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Selected References

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  • Decline in deaths from heart disease and stroke--United States, 1900-1999. MMWR Morb Mortal Wkly Rep. 1999 Aug 6;48(30):649–656. [PubMed]
  • Reddy KS, Yusuf S. Emerging epidemic of cardiovascular disease in developing countries. Circulation. 1998 Feb 17;97(6):596–601. [PubMed]
  • Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115–126. [PubMed]
  • Gaydos CA, Quinn TC. The role of Chlamydia pneumoniae in cardiovascular disease. Adv Intern Med. 2000;45:139–173. [PubMed]
  • Muhlestein JB. Chronic infection and coronary artery disease. Med Clin North Am. 2000 Jan;84(1):123–148. [PubMed]
  • Nieto FJ. Infections and atherosclerosis: new clues from an old hypothesis? Am J Epidemiol. 1998 Nov 15;148(10):937–948. [PubMed]
  • Clinton SK, Fleet JC, Loppnow H, Salomon RN, Clark BD, Cannon JG, Shaw AR, Dinarello CA, Libby P. Interleukin-1 gene expression in rabbit vascular tissue in vivo. Am J Pathol. 1991 Apr;138(4):1005–1014. [PubMed]
  • Campbell LA, Kuo CC, Grayston JT. Chlamydia pneumoniae and cardiovascular disease. Emerg Infect Dis. 1998 Oct-Dec;4(4):571–579. [PMC free article] [PubMed]
  • Mattila KJ, Valtonen VV, Nieminen MS, Asikainen S. Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. Clin Infect Dis. 1998 Mar;26(3):719–734. [PubMed]
  • Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet. 1997 Aug 9;350(9075):430–436. [PubMed]
  • Karvonen M, Tuomilehto J, Pitkäniemi J, Naukkarinen A, Saikku P. Importance of smoking for Chlamydia pneumoniae seropositivity. Int J Epidemiol. 1994 Dec;23(6):1315–1321. [PubMed]
  • O'Neill C, Murray LJ, Ong GM, O'Reilly DP, Evans AE, Bamford KB. Epidemiology of Chlamydia pneumoniae infection in a randomly selected population in a developed country. Epidemiol Infect. 1999 Feb;122(1):111–116. [PubMed]
  • Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Wong Y, Bernardes-Silva M, Ward M. Chlamydia pneumoniae IgG titres and coronary heart disease: prospective study and meta-analysis. BMJ. 2000 Jul 22;321(7255):208–213. [PMC free article] [PubMed]
  • West R. Commentary: adjustment for potential confounders may have been taken too far. BMJ. 2000 Jul 22;321(7255):213–213. [PubMed]
  • Ridker PM, Kundsin RB, Stampfer MJ, Poulin S, Hennekens CH. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation. 1999 Mar 9;99(9):1161–1164. [PubMed]
  • Ridker PM, Hennekens CH, Buring JE, 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 Oct 19;131(8):573–577. [PubMed]
  • Nieto FJ, Folsom AR, Sorlie PD, Grayston JT, Wang SP, Chambless LE. Chlamydia pneumoniae infection and incident coronary heart disease: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 1999 Jul 15;150(2):149–156. [PubMed]
  • Maass M, Bartels C, Krüger S, Krause E, Engel PM, Dalhoff K. Endovascular presence of Chlamydia pneumoniae DNA is a generalized phenomenon in atherosclerotic vascular disease. Atherosclerosis. 1998 Oct;140 (Suppl 1):S25–S30. [PubMed]
  • Davidson M, Kuo CC, Middaugh JP, Campbell LA, Wang SP, Newman WP, 3rd, Finley JC, Grayston JT. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Circulation. 1998 Aug 18;98(7):628–633. [PubMed]
  • Ericson K, Saldeen TG, Lindquist O, Pâhlson C, Mehta JL. Relationship of Chlamydia pneumoniae infection to severity of human coronary atherosclerosis. Circulation. 2000 Jun 6;101(22):2568–2571. [PubMed]
  • Thomas M, Wong Y, Thomas D, Ajaz M, Tsang V, Gallagher PJ, Ward ME. Relation between direct detection of Chlamydia pneumoniae DNA in human coronary arteries at postmortem examination and histological severity (Stary grading) of associated atherosclerotic plaque. Circulation. 1999 Jun 1;99(21):2733–2736. [PubMed]
  • Boman J, Söderberg S, Forsberg J, Birgander LS, Allard A, Persson K, Jidell E, Kumlin U, Juto P, Waldenström A, et al. High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors. J Infect Dis. 1998 Jul;178(1):274–277. [PubMed]
  • Wong YK, Dawkins KD, Ward ME. Circulating Chlamydia pneumoniae DNA as a predictor of coronary artery disease. J Am Coll Cardiol. 1999 Nov 1;34(5):1435–1439. [PubMed]
  • Blasi F, Boman J, Esposito G, Melissano G, Chiesa R, Cosentini R, Tarsia P, Tshomba Y, Betti M, Alessi M, et al. Chlamydia pneumoniae DNA detection in peripheral blood mononuclear cells is predictive of vascular infection. J Infect Dis. 1999 Dec;180(6):2074–2076. [PubMed]
  • Molestina RE, Miller RD, Ramirez JA, Summersgill JT. Infection of human endothelial cells with Chlamydia pneumoniae stimulates transendothelial migration of neutrophils and monocytes. Infect Immun. 1999 Mar;67(3):1323–1330. [PMC free article] [PubMed]
  • Gaydos CA, Summersgill JT, Sahney NN, Ramirez JA, Quinn TC. Replication of Chlamydia pneumoniae in vitro in human macrophages, endothelial cells, and aortic artery smooth muscle cells. Infect Immun. 1996 May;64(5):1614–1620. [PMC free article] [PubMed]
  • Kalayoglu MV, Hoerneman B, LaVerda D, Morrison SG, Morrison RP, Byrne GI. Cellular oxidation of low-density lipoprotein by Chlamydia pneumoniae. J Infect Dis. 1999 Sep;180(3):780–790. [PubMed]
  • 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 Feb;103(4):571–577. [PMC free article] [PubMed]
  • Laitinen K, Laurila A, Pyhälä L, Leinonen M, Saikku P. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infect Immun. 1997 Nov;65(11):4832–4835. [PMC free article] [PubMed]
  • Muhlestein JB, Anderson JL, Hammond EH, Zhao L, Trehan S, Schwobe EP, Carlquist JF. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation. 1998 Feb 24;97(7):633–636. [PubMed]
  • Blessing E, Lin TM, Campbell LA, Rosenfeld ME, Lloyd D, Kuo C. Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice. Infect Immun. 2000 Aug;68(8):4765–4768. [PMC free article] [PubMed]
  • Moazed TC, Campbell LA, Rosenfeld ME, Grayston JT, Kuo CC. Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. J Infect Dis. 1999 Jul;180(1):238–241. [PubMed]
  • Hu H, Pierce GN, Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest. 1999 Mar;103(5):747–753. [PMC free article] [PubMed]
  • 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 Jul 15;96(2):404–407. [PubMed]
  • 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 Jan;20(2):121–127. [PubMed]
  • Muhlestein JB, Anderson JL, Carlquist JF, Salunkhe K, Horne BD, Pearson RR, Bunch TJ, Allen A, Trehan S, Nielson C. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. Circulation. 2000 Oct 10;102(15):1755–1760. [PubMed]
  • Anderson JL, Muhlestein JB, Carlquist J, Allen A, Trehan S, Nielson C, Hall S, Brady J, Egger M, Horne B, 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 Mar 30;99(12):1540–1547. [PubMed]
  • Nieto FJ. Viruses and atherosclerosis: a critical review of the epidemiologic evidence. Am Heart J. 1999 Nov;138(5 Pt 2):S453–S460. [PubMed]
  • 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 Dec 2;96(11):4095–4103. [PubMed]
  • Ridker PM, Hennekens CH, Stampfer MJ, Wang F. Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation. 1998 Dec 22;98(25):2796–2799. [PubMed]
  • Sorlie PD, Nieto FJ, Adam E, Folsom AR, 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 Jul 10;160(13):2027–2032. [PubMed]
  • Adler SP, Hur JK, Wang JB, Vetrovec GW. Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis. J Infect Dis. 1998 Jan;177(1):209–212. [PubMed]
  • Siscovick DS, Schwartz SM, Corey L, Grayston JT, Ashley R, Wang SP, Psaty BM, Tracy RP, Kuller LH, Kronmal RA. 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 Nov 7;102(19):2335–2340. [PubMed]
  • Zhou YF, Leon MB, Waclawiw MA, Popma JJ, Yu ZX, Finkel T, Epstein SE. Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med. 1996 Aug 29;335(9):624–630. [PubMed]
  • Smith K, Parsonnet J. Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. N Engl J Med. 1997 Feb 20;336(8):587–588. [PubMed]
  • Hosenpud JD. Coronary artery disease after heart transplantation and its relation to cytomegalovirus. Am Heart J. 1999 Nov;138(5 Pt 2):S469–S472. [PubMed]
  • Weis M, von Scheidt W. Cardiac allograft vasculopathy: a review. Circulation. 1997 Sep 16;96(6):2069–2077. [PubMed]
  • Koskinen P, Lemstrøm K, Mattila S, Häyry P, Nieminen MS. Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft. Clin Transplant. 1996 Dec;10(6 Pt 1):487–493. [PubMed]
  • Bartels C, Maass M, Bein G, Brill N, Bechtel JF, Leyh R, Sievers HH. Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease. Circulation. 2000 Jan 18;101(2):137–141. [PubMed]
  • Wu TC, Hruban RH, Ambinder RF, Pizzorno M, Cameron DE, Baumgartner WA, Reitz BA, Hayward GS, Hutchins GM. Demonstration of cytomegalovirus nucleic acids in the coronary arteries of transplanted hearts. Am J Pathol. 1992 Mar;140(3):739–747. [PubMed]
  • Gulizia JM, Kandolf R, Kendall TJ, Thieszen SL, Wilson JE, Radio SJ, Costanzo MR, Winters GL, Miller LL, McManus BM. Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart allografts. Am J Pathol. 1995 Aug;147(2):461–475. [PubMed]
  • Streblow DN, Soderberg-Naucler C, Vieira J, Smith P, Wakabayashi E, Ruchti F, Mattison K, Altschuler Y, Nelson JA. The human cytomegalovirus chemokine receptor US28 mediates vascular smooth muscle cell migration. Cell. 1999 Nov 24;99(5):511–520. [PubMed]
  • Speir E, Modali R, Huang ES, Leon MB, Shawl F, Finkel T, Epstein SE. Potential role of human cytomegalovirus and p53 interaction in coronary restenosis. Science. 1994 Jul 15;265(5170):391–394. [PubMed]
  • Zhou YF, Shou M, Guetta E, Guzman R, Unger EF, Yu ZX, Zhang J, Finkel T, Epstein SE. Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall. Circulation. 1999 Oct 5;100(14):1569–1575. [PubMed]
  • Persoons MC, Daemen MJ, van Kleef EM, Grauls GE, Wijers E, Bruggeman CA. Neointimal smooth muscle cell phenotype is important in its susceptibility to cytomegalovirus (CMV) infection: a study in rat. Cardiovasc Res. 1997 Nov;36(2):282–288. [PubMed]
  • Lemström K, Sihvola R, Bruggeman C, Häyry P, Koskinen P. Cytomegalovirus infection-enhanced cardiac allograft vasculopathy is abolished by DHPG prophylaxis in the rat. Circulation. 1997 Jun 17;95(12):2614–2616. [PubMed]
  • Joshipura KJ, Douglass CW, Willett WC. Possible explanations for the tooth loss and cardiovascular disease relationship. Ann Periodontol. 1998 Jul;3(1):175–183. [PubMed]
  • Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol. 2000 Oct;71(10):1554–1560. [PubMed]
  • Whincup P, Danesh J, Walker M, Lennon L, Thomson A, Appleby P, Hawkey C, Atherton J. Prospective study of potentially virulent strains of Helicobacter pylori and coronary heart disease in middle-aged men. Circulation. 2000 Apr 11;101(14):1647–1652. [PubMed]
  • Nicholson AC, Hajjar DP. Herpesvirus in atherosclerosis and thrombosis: etiologic agents or ubiquitous bystanders? Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):339–348. [PubMed]
  • Zhu J, Nieto FJ, Horne BD, Anderson JL, Muhlestein JB, Epstein SE. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation. 2001 Jan 2;103(1):45–51. [PubMed]
  • Wanishsawad C, Zhou YF, Epstein SE. Chlamydia pneumoniae-induced transactivation of the major immediate early promoter of cytomegalovirus: potential synergy of infectious agents in the pathogenesis of atherosclerosis. J Infect Dis. 2000 Feb;181(2):787–790. [PubMed]
  • Strong JP, Malcom GT, McMahan CA, Tracy RE, Newman WP, 3rd, Herderick EE, Cornhill JF. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA. 1999 Feb 24;281(8):727–735. [PubMed]
  • Williams KJ, Rodrigueza WV. Atherosclerosis: cell biology and lipoproteins. Curr Opin Lipidol. 1998 Oct;9(5):511–513. [PubMed]
  • Barber DA, Burnett JC, Jr, Fitzpatrick LA, Sieck GC, Miller VM. Gender and relaxation to C-type natriuretic peptide in porcine coronary arteries. J Cardiovasc Pharmacol. 1998 Jul;32(1):5–11. [PubMed]
  • Meydani M, Lipman RD, Han SN, Wu D, Beharka A, Martin KR, Bronson R, Cao G, Smith D, Meydani SN. The effect of long-term dietary supplementation with antioxidants. Ann N Y Acad Sci. 1998 Nov 20;854:352–360. [PubMed]
  • Hoogwerf BJ, Young JB. The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not. Cleve Clin J Med. 2000 Apr;67(4):287–293. [PubMed]
  • Seppälä H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H, Lager K, Huovinen P. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med. 1997 Aug 14;337(7):441–446. [PubMed]
  • Arason VA, Kristinsson KG, Sigurdsson JA, Stefánsdóttir G, Mölstad S, Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ. 1996 Aug 17;313(7054):387–391. [PMC free article] [PubMed]
  • Leach AJ, Shelby-James TM, Mayo M, Gratten M, Laming AC, Currie BJ, Mathews JD. A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae. Clin Infect Dis. 1997 Mar;24(3):356–362. [PubMed]
  • Dagan R, Leibovitz E, Greenberg D, Yagupsky P, Fliss DM, Leiberman A. Dynamics of pneumococcal nasopharyngeal colonization during the first days of antibiotic treatment in pediatric patients. Pediatr Infect Dis J. 1998 Oct;17(10):880–885. [PubMed]
  • Craighead JE. Report of a workshop: disease accentuation after immunization with inactivated microbial vaccines. J Infect Dis. 1975 Jun;131(6):749–754. [PubMed]
  • Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM. Chlamydia infections and heart disease linked through antigenic mimicry. Science. 1999 Feb 26;283(5406):1335–1339. [PubMed]
  • Gilbert DN. Preface. J Infect Dis. 2000 Jun;181(Suppl 3):S393–S393. [PubMed]

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