Evaluation of IFN- γ, Inflammatory Marker And Infectious Etiology As Risk Factors For Coronary Artery Disease
Keywords:
Coronary artery disease, Chlamydia pneumoniae, CMV, IFN- γAbstract
Background: We evaluated the role of Chlamydia pneumoniae (C. pneumoniae) and Cytomegalovirus (CMV) infection in coronary artery disease(CAD) patients. Interferon- γ (IFN-γ) levels in serum were assessed for ongoing inflammatory activity by these microorganisms.
Methods: Persistent and chronic infection of C. pneumoniae was assessed by the level of IgA and IgG antibodies as well as 16S rRNA gene of C.pneumoniae. Chronic CMV presence was detected by IgG antibodies. IFN-γ levels in serum were analysed by ELISA.
Results: Among the 63 CAD cases, C. pneumoniae IgG antibodies were present in 34(53.97%;95% CI: 41.66% to 66.28%) cases, C. pneumoniae IgA antibodies were detected in 42(66.67%; 95% CI :55.03% to78.31%) cases (p<0.05). PCR for detection of C. pneumoniae was done on 40 cases, among which 13 (32.5%; 95% CI: 17.99% to 47.01%) of cases were positive for 16SrRNA gene of C. pneumoniae. CMV IgG was positive in 41 (65.08%; 95% CI: 53.31% to 76.85%) cases. On assessing the patients of CAD for major traditional risk factors,35(55.55%) had past history of CAD, 20(31.75%) of dyslipidemia, 19 (30.16%) gave history of smoking and 18 (28.75%) were obese. On comparison of infectious etiology and traditional risk factors, it was clear that C. pneumoniae and CMV both were more (p<0.001) strongly associated with CAD than the traditional risk factors. Mean level of IFN-γ in these patients was 32.13pg/ml and that of controls was 11.32pg/ml. Raised IFN-γ was observed in 39 (61.9%) patients of which 14 (35.9%) were patients of primary hypertension, 7 (17.9%) were patients of angina and 18 (46.15%) were patients of MI.
Conclusions: C. pneumoniae and chronic CMV infection appear to have a role in the pathogenesis of CAD. Elevated IFN-γ levels suggests that these pathogens aggravate the inflammatory process of atherogenesis and hasten the disease process.
DOI:Â 10.21276/APALM.1551
References
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30. Javier NF, Aaron RF, Sorlie PD, Grayston JT, Wang SP, Lloyd P. Chlamydia pneumoniae infection and Incident Coronary Heart disease. The Atherosclerosis Risk in Communities Study. Am J Epidemiol 1999;150: 149-56.
31. Ridker PM. Inflammation, infection and cardiovascular risk: How good is the clinical evidence? Circulation 1998;97: 1671-4.
32. Danesh J, Wong Y, Ward M, Muir J. Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population-based study of coronary heart disease. Heart 1999;81:245-7.
33. Wong YK, Dawkins K, Ward ME. Detection of Chlamydia pneumoniae DNA circulating in the blood of patients attending for cardiac angiography: premilinary clinical and serological correlates. In : Chlamydial Infections (Stephens RS, Byme GI, Christiansen G et al., eds). International Chlamydial Symposium, San Francisco, USA,1998; 232-8.
34. Boman J, Soderberg S, Forsberg J, Birgander LS, Allard A, Persson K 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;178:274-7.
35. Yuk-ki Wong, Dawkins KD,Ward ME. Circulating Chlamydia pneumoniae DNA as a predictor of Coronary Artery Disease. J Am Coll Cardiol 1999; 34: 1435-9.
36. Danesh J, Collins R, Peto R. Chronic infection and coronary heart disease: is there a link? Lancet 1997; 350:430-6.
37. Grayston JT, Golubjatnikov R, Hagiwara T . Serologic tests for Chlamydia pneumoniae. Pediatr Infect dis J 1993;12:790-1.
38. VanDyke TE and VanWinkelhoff A J. Infection and inflammatory mechanisms,†Journal of Clinical Periodontology.2013;40:S1–S7.
39. Yusuf S and Anand S. Deciphering the causes of cardiovascular and other complex diseases in populations: achievements, challenges, opportunities, and approaches.Progress in Cardiovascular Diseases2010;53: 62–67.
40. Vaddi K, Nicolini FA, Mehta P, Mehta JL. Increase secretion of tumour Necrosis Factor-α and Interferon- γ by Mononuclear Leukocytes in patients with Ischemic Heart Disease Relevance in Superoxide Anion Generation. Circulation1994; 90:694-99.
41. Hem C J, Srivastava P, Sarkar R, Prasad J, Mittal AS. Association of Plasma Circulatory Markers, Chlamydia pneumoniae, and high sensitive C-Reactive protein in Coronary Artery Disease Patients of India. Mediators of Inflammation, Hindawi Publishing Corporation 2009;Volume 9.
2. Hansa G, Bhargava K, Bansal M, Tandon S, Kasliwal RR. Carotid intima-media thickness and coronary artery disease: An Indian perspective. Asian Cardiovasc Thorac Ann 2003;11:217-21.
3. Goyal P, Kalek SC, Chaudhry R, Chauhan S, Shah N. Association of common chronic infections with coronary artery disease in patients without any conventional risk factors. Indian J Med Res 2007;125:129-36.
4. Gupta R. Secondary prevention of coronary artery disease in urban Indian primary care. Int J Cardiol 2009;135:184-6.
5. Gayelos CA, Quinn TC. The role of Chlamydia pneumoniae in cardiovascular disease. Adv Intern Med 2000; 45:139-73.
6. Saikku, P, Mattila, Nieminen M S, J. K. Huttunen, M. Leinonen, M,et.al, Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet.1988; 2:983–986.
7. Yamashita, K., K. Ouchi, M. Shirai, T. Gondo, T. Nakazawa, and H. Ito.Distribution of Chlamydia pneumoniae infection in the atherosclerotic carotid artery. Stroke. 1998;29:773–778.
8. Campbell, L. A., E. R. O’Brien, A. L. Cappuccio, C.-C. Kuo, S.-P. Wang, D.Stewart, D. L. Patton, P. K. Cummings, and J. T. Grayston. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.J. Infect. Dis. 1995;172:585–588.
9. Bauriedel, G, Andrié R, Likungu J A, Welz A, Braun P, Welsch U, Lüderitz B. Persistenz von Chlamydia pneumoniae in koronarem Plaquegewebe. Ein Beitrag zur Infektions- und Immunhypothese bei instabiler Angina pectoris. Dtsch. Med. Wschr. 1999;124:1408–1413.
10. Mosorin, M., H.-M. Surcel, A. Laurila, M. Lehtinen, R. Karttunen, J. Juvonen, J. Paavonen, R. P. Morrison, P. Saikku, and T. Juvonen. 2000.Detection of Chlamydia pneumoniae-reactive T lymphocytes in human atherosclerotic plaques of carotid artery. Arterioscler. Thromb. Vasc. Biol.20:1061–1067.
11. Elkind MSV, Lin I F, Grayston J T, Sacco R L. Chlamydia pneumoniae and the risk of first ischemic stroke. The Northern Manhattan Stroke Study. Stroke 2000;31:1521–1525.
12. LaBiche R, Koziol D, Quinn T C, Gaydos C, Azhar S, Ketron G, Sood S, DeGraba TJ. Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque.Stroke.2001;32:855–860.
13. Glader CA, Boman J, Saikku P, Stenlund S, Weinehall L, Hallmanns G, Dahlén G H. The proatherogenic properties of lipoproteins may be enhanced through the formation of circulating immune complexes containing Chlamydia pneumoniae-specific IgG antibodies. Eur.Heart J. 2000;21:639–646.
14. Burian, K, Kis D Z, Virok V, Endresz Z, Prohaszka J. Duba K. Berencsi K. Boda L.et al. 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.
15. Epstein S E, Zhou Y F, Zhu J. Infection and atherosclerosis. Emerging mechanistic paradigms. Circulation. 1999;100:20–28.
16. Blankenberg S, Rupprecht H J, Bickel C, Espinola-Klein C, Rippin G, Hafner G, Ossendorf M, Steinhagen K, Meyer J. Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease. Circulation. 2001;103:2915–2921.
17. Zhu JA, Quyyumi A, Norman JE, Csako G, Epstein S E.Cytomegalovirus in the pathogenesis of atherosclerosis. The role of inflammation as reflected by elevated C-reactive protein levels. J. Am. Coll. Cardiol. 1999;34:1738–1743.
18. Zhu J, Shearer G M, Norman J E, Pinto LA, Marincola F M, Prasad A,et al. Host response to cytomegalovirus infection as a determinant of susceptibility to coronary artery disease. Sex-based differences in inflammation and type of immune response. Circulation. 2000; 102:2491–2496.
19. Adeyi O, Smith O, Robles S. Public policy and the challenge of chronic noncommunicable diseases. Washington, DC: The World Bank; 2007.
20. WHO. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008b.
21. WHO. World health statistics 2009. Geneva: World Health Organization; 2009e.
22. WHO Department of Child and Adolescent Health and Development. The current evidence for the burden of group a streptococcal diseases, Discussion papers on child health. Geneva: World Health Organization; 2005.
23. Goldberg RJ, Burchfiel CM, Benfante R, Chiu D, Reed DM, Yano K. Lifestyle and biologic factors associated with atherosclerotic disease in middle-aged men: 20 year findings from the Honolulu Heart Program. Arch intern med 1995; 155:686-94.
24. Braunwald E Shattuk Lecture- cardiovascular medicine at the turnoff the millennium:triumphs, concerns and oppurtunities. N Eng J Med 1997;337:1360-9.
25. Mohan V, Deepa R, Shanthirani S, Premlatha G.Prevalence of coronary artery disease and it’s relationship to lipids in a selected population in South India. The Chennai Urban Population Study (CUPS). J Am Coll Cardiol 2001; 38:682-687.
26. Satpathy G, Sharma A, Vaish S. Immunocomb Chlamydia bivalent assay to study Chlamydia species specific antibodies in patients with coronary heart disease. Indian J Med Res 2005; 121: 171-175.
27. Grayston JT,Campbell LA, Kuo CC, Mordhorst CH, Saikku P, Thom DH et al. A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 1990; 161: 618-25.
28. Elkind MSV, Lin I-F, Grayston JT, Sacco RL . Chlamydia pneumoniae and the risk of first ischemic stroke: the Northern Manhattan Stroke Study. Stroke 2000; 31:1521-5.
29. Roivainen M, Viik-Kajander M, Palosou T, Toivanen P, Leinonen M, Saikku P et al. Infections, inflammation and risk of coronary heart disease. Circulation 2000; 101: 252-8.
30. Javier NF, Aaron RF, Sorlie PD, Grayston JT, Wang SP, Lloyd P. Chlamydia pneumoniae infection and Incident Coronary Heart disease. The Atherosclerosis Risk in Communities Study. Am J Epidemiol 1999;150: 149-56.
31. Ridker PM. Inflammation, infection and cardiovascular risk: How good is the clinical evidence? Circulation 1998;97: 1671-4.
32. Danesh J, Wong Y, Ward M, Muir J. Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population-based study of coronary heart disease. Heart 1999;81:245-7.
33. Wong YK, Dawkins K, Ward ME. Detection of Chlamydia pneumoniae DNA circulating in the blood of patients attending for cardiac angiography: premilinary clinical and serological correlates. In : Chlamydial Infections (Stephens RS, Byme GI, Christiansen G et al., eds). International Chlamydial Symposium, San Francisco, USA,1998; 232-8.
34. Boman J, Soderberg S, Forsberg J, Birgander LS, Allard A, Persson K 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;178:274-7.
35. Yuk-ki Wong, Dawkins KD,Ward ME. Circulating Chlamydia pneumoniae DNA as a predictor of Coronary Artery Disease. J Am Coll Cardiol 1999; 34: 1435-9.
36. Danesh J, Collins R, Peto R. Chronic infection and coronary heart disease: is there a link? Lancet 1997; 350:430-6.
37. Grayston JT, Golubjatnikov R, Hagiwara T . Serologic tests for Chlamydia pneumoniae. Pediatr Infect dis J 1993;12:790-1.
38. VanDyke TE and VanWinkelhoff A J. Infection and inflammatory mechanisms,†Journal of Clinical Periodontology.2013;40:S1–S7.
39. Yusuf S and Anand S. Deciphering the causes of cardiovascular and other complex diseases in populations: achievements, challenges, opportunities, and approaches.Progress in Cardiovascular Diseases2010;53: 62–67.
40. Vaddi K, Nicolini FA, Mehta P, Mehta JL. Increase secretion of tumour Necrosis Factor-α and Interferon- γ by Mononuclear Leukocytes in patients with Ischemic Heart Disease Relevance in Superoxide Anion Generation. Circulation1994; 90:694-99.
41. Hem C J, Srivastava P, Sarkar R, Prasad J, Mittal AS. Association of Plasma Circulatory Markers, Chlamydia pneumoniae, and high sensitive C-Reactive protein in Coronary Artery Disease Patients of India. Mediators of Inflammation, Hindawi Publishing Corporation 2009;Volume 9.
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Rizvi M, Haider M, Gupta R, Azam M, Malik A, Rabbani MU. Evaluation of IFN- γ, Inflammatory Marker And Infectious Etiology As Risk Factors For Coronary Artery Disease. Ann of Pathol and Lab Med [Internet]. 2018 Jan. 27 [cited 2024 Oct. 30];5(1):A8-16. Available from: https://pacificejournals.com/journal/index.php/apalm/article/view/apalm1551
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