|Year : 2002 | Volume
| Issue : 2 | Page : 83-87
Infectious aetiology in acute coronary syndromes
D Rajasekhar, G Subramanyam, S AA Latheef, V Vanajakshamma, A Srilatha, A Chaudhury
Dept. of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, India
Dept. of Cardiology, Sri Venkateswara Institute of Medical Sciences, Tirupati - 517 507, India
PURPOSE: To ascertain the relationship between seropositivity to chronic infections with Helicobacter pylori, Chlamydia pneumoniae and Cytomegalovirus (CMV) and acute coronary syndromes and association of each of these infective agent with biochemical parameters and cardiovascular risk factors. METHODS: The present study was a case-control study involving 117 patients [unstable angina (UA) n=101 and chronic stable angina (CSA) n = 16] attending cardiology clinic. The cases were aged 35-79 years and they were compared with age, sex and socio-economic status matched controls without evidence of coronary artery disease (CAD). RESULTS: Fifty seven (58%) patients with UA and 9(56%) patients with CSA were seropositive for H. pylori. Sixty seven (66%) subjects with UA and 15(94%) patients with CSA subjects were seropositive for C.pneumoniae. Two (2%) patients with USA were seropositive for Cytomegalovirus (CMV). Seropositivity in normal subjects for H. pylori, C. pneumoniae and CMV was 7(43.25%), 10(62.5%) and 1(6.25%) respectively. In linear regression analysis seropositivity of CMV showed positive association with HDL-C (P< 0.05). No significant association of infective agents and coronary syndromes was observed. CONCLUSIONS: Higher levels of lipids, lipoproteins, C-reactive protein and higher percentage of coronary risk factors in patients seropositive for H. pylori in UA suggests the role of infective agents in pathogenesis of atherosclerosis.
|How to cite this article:|
Rajasekhar D, Subramanyam G, Latheef S A, Vanajakshamma V, Srilatha A, Chaudhury A. Infectious aetiology in acute coronary syndromes. Indian J Med Microbiol 2002;20:83-7
|How to cite this URL:|
Rajasekhar D, Subramanyam G, Latheef S A, Vanajakshamma V, Srilatha A, Chaudhury A. Infectious aetiology in acute coronary syndromes. Indian J Med Microbiol [serial online] 2002 [cited 2017 Nov 17];20:83-7. Available from: http://www.ijmm.org/text.asp?2002/20/2/83/8353
Inoculation of chicken with avian herpes virus produced arterial disease that resembled human atherosclerosis. Several authors have reported association of coronary artery disease (CAD) with gram negative bacteria (Helicobacter pylori and Chlamydia pneumoniae) and with certain herpes viruses (Cytomegalovirus).,,,, Endothelial injury or dysfunction, smooth muscle proliferation, local inflammation,7 chronic inflammation, cross reactive antibodies or changes in cardiovascular risk factors12,13 are proposed mechanisms for the reported associations between infections and CAD. The possible mechanisms by which H. pylori, C. pneumoniae and Cytomegalovirus may influence cardiovascular risk are unknown. H. pylori and C. pneumoniae contain hsp 60 like sub units., These endothelial antigens might indirectly trigger atherogenesis via an auto immune reaction. CMV has been reported to inactivate P53, a protein that is directly involved in DNA repair and is associated with cellular proliferation that can lead to coronary restenosis. The possible relevance of CMV to arterial lesions is also supported by findings that neointimal proliferation of CMV infected rat is increased after vascular injury. A causal link between H. pylori, C. pneumoniae and Cytomegalovirus and coronary syndromes would be of major health importance in developing countries like India because the infection can be eradicated with a single course of antibiotics with little chance of reinfection. Bacterial infections in general lead to many changes in lipid, thrombic and other acute phase protein metabolism. Some of the changes occur with C. pneumoniae, H. pylori and Cytomegalovirus.
We conducted a case-control study to investigate the association between coronary syndromes with infective agents such as H. pylori, C. pneumoniae and CMV and association of each infective agent with lipid, lipoproteins, C - reactive protein levels and coronary risk factors.
| ~ Subjects and Methods|| |
Subjects were recruited from the patients attending cardiology clinic. The age of the subjects ranged from 35-79 years. The patients were categorized into different classes of coronary syndromes based on history, electrocardiogram, treadmill test and available angiogram reports. The distribution of subjects for various coronary syndromes was as follows: unstable angina (UA) n=117 and chronic stable angina (CSA) n=16. Subjects without evidence of CAD and matched for age, sex and socio-economic status were taken as control. Total cholesterol, triglycerides and HDL-C were analyzed using autoanalyzer. LDL-C and VLDL-C were calculated using Friedwald et al and Wilson and Spiger formulae. C-reactive protein was estimated by standard latex agglutination method (A vitex - CRP) Omega diagnostics, UK.
H. pylori specific IgG, C. pneumoniae IgG, CMV IgM were detected by ELISA techniques with kits obtained from Monobind Inc. USA, sero CP,(™) IgG Savyon, Israel, and Human diagnostics, Germany respectively. The procedures recommended by the kit manufacturers were followed. Readings were taken in automatic ELISA reader (Molecular Devices, USA). Data were analyzed using SPSS package version 6.0.
| ~ Results|| |
A total of 59(58%), 9(56%) and 7(43%) subjects were seropositive for H. pylori in UA, CSA and control group respectively. The number of subjects seropositive for C. pneumoniae in UA, CSA and control were 67(66%), 15(94%) and 10(62%) respectively. Only 2(2%) subjects with UA and 1(6%) in control group were seropositive for Cytomegalovirus. Significant difference between seropositivity to C.pneumoniae in UA and control group was observed (P<0.001) [Table - 1].
The prevalence of coronary risk factors and mean values of biochemical parameters is presented in [Table - 2]. No statistically significant difference between patients and controls was observed In patients with UA seropositivity to H. pylori higher levels of lipid and lipoproteins and higher percentage of risk factors were seen compared to patients who were seronegative for H. pylori.
Increased levels of lipids, lipoproteins and C - reactive protein and higher percentage of smoking (71%), alcoholism (43%), diabetes (85%) was observed in CSA patients seronegative for H. pylori than seropositive patients. However, in control group subjects seropositive for H. pylori showed higher levels of lipid and lipoproteins and higher percentage of smoking (86%), alcoholism (86%) and hypertension (71%) against subjects seronegative for H. pylori [Table - 3].
Patients seropositive for C. pneumoniae in UA showed lower levels of total cholesterol, triglycerides, LDL-C and higher percentage of smoking (57%), alcoholism (38%) than patients seronegative to C.pneumoniae, however, no significant difference was observed between the two groups. Subjects in control group seropositive to C. pneumoniae showed higher levels of total cholesterol, LDL-C and higher percentage of diabetes (20%) and alcoholism (40%) [Table - 4].
| ~ Discussion|| |
Almost one half of adults in developed countries are reported to have antibodies to H. pylori, C. pneumoniae and CMV. In the absence of specific treatment IgG antibodies to H. pylori persist indefinitely from early life and can be detected with greater than 90% accuracy. Antibody titres for C. pneumoniae are less reliable indicators of persistent respiratory infection. CMV antibody titers may fluctuate greatly owing to repeated reactivation of latent infection. These temporal variations make association of CAD and antibodies titers for C. pneumoniae, H. pylori and CMV difficult, if measured at one point.
In the present study, no significant association, either between infective agents and coronary syndromes or coronary heart disease taken together was observed when examined using logistic regression analysis. However, increased levels of total-C, triglycerides, LDL-C and VLDL-C was observed in patients seropositive for H. pylori in UA patients, whereas, decreased levels of lipids and lipoproteins in CSA shows the varying effect of H. pylori in different coronary syndromes. This also suggests that H. pylori influences lipid metabolism. In one study, increased triglyceride, total cholesterol and decreased HDL-C were observed in subjects seronegative to C. pneumoniae. In the present study, decreased levels of total cholesterol, triglycerides, HDL-C, LDL-C and VLDL-C were observed in subjects seropositive for C. pneumoniae in UA patients [Table - 4]. In contrast, in CSA, 15(94%) patients out of 16 were seropositive for C. pneumoniae. We are unable to explain this contradiction, hence the data is not presented in terms of coronary risk factors and biochemical parameters between seropositive and seronegative patients. Evidence shows that some herpes viruses can alter cholesterol metabolism in smooth muscle cells. In the present study seropositivity of CMV showed positive association with HDL-C (P<0.005) in linear regression analysis. This suggests that CMV may play a role in influencing individual risk factors.
Higher plasma concentration of C-reactive protein in individuals seropositive for H. pylori has been observed. In the present study higher levels of C-reactive protein in UA patients seropositive for C. pneumoniae was observed. This suggests the role of infection in causing coronary syndromes. Higher percentage of risk factors was observed in patients seropositive to H. pylori and C. pneumoniae in UA. Prevalence of diabetes has shown statistically significant difference between seropositive and seronegative patients in UA. This indicates that H. pylori may play a role in diabetes.
The results of the present study show no association of infective agent and coronary syndromes, however, higher levels of lipids, lipoproteins, C-reactive protein and higher percentage of coronary risk factors were observed in patients seropositive to H. pylori in unstable angina suggesting that H. pylori may influence coronary risk factors and may play a role in pathogenesis of atherosclerosis. This needs to be proved in studies involving larger samples with suitable adjustment for confounders. Limitations of the present study are small sample size and use of opportunistically recruited control group and dependence on only serological evidence for presence of infective agents.
| ~ References|| |
|1.||Fabricant CG, Fabricant J, Litrenta MM, Minick CR. Virus induced atherosclerosis. J Exp Med 1978; 148:335-340. |
|2.||Saikku P, Mattila K, Nieminen MS, Huttunen JK, Leinonen M, Eckman MR, 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. |
|3.||Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary heart disease. JAMA 1992; 268:68-72. [PUBMED] |
|4.||Saikku P, Leiononen M, Tenkanen L, Linnanmaki E, Ekman M, Manninen M, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Am Inter Med 1992;116:273-277. |
|5.||Mendall M, Carrington D, Stratchan D, Patel P, Molineaux N, Levy J, et al. Chlamydia pneumoniae: risk factors for sero positivity and association with coronary heart disease. J Infect 1995; 30:121-128. |
|6.||Mendall M, Goggin P, Levy J, Molineaux N, Strachan D, Camm A, et al. Relation of Helicobacter pylori infection as a risk factor for coronary heart disease. Br Heart J 1994;71:437 - 439. |
|7.||Gill EA, McIntyre TM, Prescott SM, Zimmerman GA. Mechanisms of vascular injury in the pathogenesis of infectious disease. Curr Opin Infect Dis 1992;5:381-88. |
|8.||Nallance P, collier J, Bhagat K. Infection, inflammation and infarction; Does acute endothelial dysfunction provide link? Lancet 1997; 349:1391-92. |
|9.||Epstein SE, Speir E, Zhou YF, Guetta E, Leon M, Finkel T. The role of infection in restenosis and atherosclerosis; focus on cytomegalovirus. Lancet 1996; 348 (suppl I):513-17. |
|10.||Patel P, Mendall MA, Carrington D, et al. Association of Helicobacter pylori and Chlamydia pneumoniae infection with coronary heart disease and cardiovascular risk factors. BMJ 1995; 311: 711-74. |
|11.||Leinonen M. Pathogenetic mechanisms and epidemiology of Chlamydia pneumoniae. Eur Heart J 1993; 14: (suppl K):57-61. |
|12.||Niemela S, Karttunen T, Korhonen T, et al. Could Helicobacter pylori infection increase the risk of coronary heart disease by modifying serum lipid concentrations? Heart 1996; 75:573 - 75. |
|13.||Cragg RKR, Fraser A, Metcaff PA. Helicobacter pylori seropositivity and cardiovascular risk factors in a multicultural work force. J Epidemol common Health1996; 50:573-579. |
|14.||Xu Q, Wick G. The role of heat shock proteins in protection and pathophysiology of the arterial wall. Mol Med Today 1996; 2:372-379. |
|15.||Speir E, Matali R, Huang ES, et al. Potential role of human cytomegalovirus and p53 interaction in coronary stenosis. Science 1994; 265:391-394. |
|16.||Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: Is there a link ? Lancet 1997; 350:430-436. |
|17.||Ellis RW. Infection and coronary heart disease. J Med Microbiol 1997; 46(7):535-539. |
|18.||Friedwald WT, Levy RJ, Fredrickson DS. Estimation of the concentration of LDL-C in plasma without use of the preparative ultracentrifuge. Clin Chem 1972; 18:499. |
|19.||Wilson DE, Spiger MJ. A dual precipatation method for quantitative plasma lipoprotein measurement without ultra centrifugation. J Lab Clin Med 1972; 82(3):473. |
|20.||Laurila A, Bloigu A, Nayha S, Hassi J, Leinonen M, Saikku P. Chronic Chlamydia pneumoniae infection is associated with a serum lipid profile known to be a risk factor for atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17(11):2910-2913. |