COMMENTARIES

Chlamydia Pneumoniae and Associated Risk Factors in Coronary Artery Disease Patients in India

Aruna Mittal1, Hem C Jha1, and Jagdish Prasad2, 1Division of Microbiology/Tissue Culture, Institute of Pathology (ICMR), New Delhi, India, 2Department of Cardio-Thoracic & Vascular Surgery, Safdarjung Hospital, New Delhi, India

Please address correspondence to:
Dr. Aruna Mittal
Deputy Director (SG)
Institute of Pathology (ICMR)
Safdarjung Hospital Campus
Post Box no-4909
New Delhi, India, Pin-110029
Tel: (+91) 11-26198402-5
Fax: (+91) 11-26198401
Email: amittal_cp@rediffmail.com, amittal_iop@yahoo.com

Background: Coronary Artery Disease in India

 

Coronary artery disease (CAD) is a major cause of morbidity and mortality in humans and is predicted to be the leading cause of death in the world particularly in developing countries such as India [1,2]. It is reported that Asian Indians have the highest risk of CAD and the prevalence rate of CAD in India has been estimated to be 11% [3,4]. Chronic infection has been proposed as a possible causative agent in the development of acute coronary artery syndrome [5]. Infectious agents in particular Chlamydia pneumoniae (Cp) has been postulated to be the trigger for each of the major phases of atherosclerosis as it causes a chronic infectious state and upregulation of cytokines and adhesion molecules [6-8]. In addition, conventional risk factors among CAD patients such as sex, smoking, alcohol intake, genetic predisposition, hypertension, and diabetes mellitus impose additional risks for the severity of CAD. We reported high prevalence of Cp (29.6%) in CAD patients in India as revealed by nested PCR which is a matter of concern. Positive nested PCR findings in conjunction with Cp specific antibody prevalence may suggest an ongoing infection [9].

 

Chronic persistent infection of C.pneumoniae

 

Chronicity of persistent infection of Cp may be a major factor associated with the patho-physiological changes leading to CAD [10]. In our study seropositivity for Cp-specific IgA was detected significantly higher than the Cp IgG in CAD patients [9] and that CAD patients having IgA antibodies in their serum indicate a persistent or active infection while patients having both IgA and IgG may reveal chronicity of persistent active infection. It has been reported earlier that serum IgA antibody to Cp may be more predictive of coronary heart disease than IgG because IgA antibodies have different biological characteristics and may be better indicators of persistent chlamydial infection [11].

          Recently attention has been broadened to include the burden of infection hypothesis, the concept that it is not one specific infection per se but the cumulative burden of infection that increases a person’s risk of CAD [12]. These factors on compounding with pathogens like Cp, Helicobacter pylori (Hp) and Cytomegalovirus (CMV) intensifies the magnitude of risk impending towards CAD [13]. In our study seropositivity for C.pneumoniae-specific IgA and H. pylori IgA was significantly higher than the C.pneumoniae IgG and H.pylori IgG in CAD patients and that heavy smokers and non-alcoholics were more prone to these bacterial infections, which exacerbate the process of atherogenesis [14-16]. Further, presence of hsCRP and Cp specific immunoglobulins in occasional alcoholic group showed lower odds ratio than heavy and non-alcoholic groups, indicating that occasional alcoholics have lower risk of Cp infection as well as less chances of having CAD. Moreover, we detected the higher prevalence of Cp in CAD patients who had family history of diabetes and high blood pressure than controls showing thereby they are at higher risk of having CAD [9]. Thus our study revealed that seropositivity for specific IgA to Cp was significantly higher in CAD patients in association with higher hsCRP levels demonstrating the chronic persistence of Cp infection in CAD patients in India. This strongly suggests the role of burden of bacterial infection in progression of disease; however C.pneumoniae IgA remains the single independent atherosclerotic marker.

 

Risk for CAD First-Degree Relatives

 

Our study suggested that specific detection of Cp-IgA is significantly higher in CAD patients compared to CAD first-degree relatives (CAD-R), suggesting the major role of Cp in CAD progression [17]. In this context, our investigation adds to the strong evidence in association of Cp specific IgA and hsCRP with CAD. Furthermore, CAD-R is also at higher risk level for CAD progression compared to controls.

 

Cp and Pro-Inflammatory Cytokines

 

The role of various immuno-inflammatory mediators like cytokines in pathogenesis of atherosclerosis is gaining importance since these cytokines have a role in triggering the perpetuation of atherosclerosis and are potent inducer of reactive free radical, which can facilitate oxidation of low density lipoprotein, a key event in pathogenesis of atherosclerosis [18]. Kato et al. also suggested that elevated IgA antibody to Cp as a sign of a chronic and still active infection of a past exposure [19]. Further bacterial pathogen in particular Cp is reported to be a potent inducer of IL-6 which may induce plaque production and subsequently may cause elevation in serum CRP and IL-6 levels [20,21]. A putative relationship between IL-6 levels and Cp IgA titers has also been reported [22,23] which suggest a putative role of IL-6 in the initiation and progression of atherosclerosis. Our study for the first time revealed that positivity for IL-6 was higher in CAD patients with high Cp IgA positivity and hsCRP suggesting these patients may have more chronic disease condition. Additionally physiological characteristics of CAD were significantly higher in IL-6 positive CAD patients; however, IL-2 and TNF-α were not significantly detected in Cp IgA positive groups. Overall our data strongly hypothesizes the role of IL-6 in pathogenesis of CAD which may subsequently get accelerated through Cp infection [24].

References

  1.    John PH. 2003. Chlamydia pneumoniae and coronary artery disease: the Antibiotic Trials. Mayo Clin Proc 78: 321-32.
  2.    Dholpuria R, Raja S, Gupta BK, et al. 2007. Atherosclerotic risk factors in adolescents. Indian J Pediatr 74: 823-26.
  3.    Rissa HS, Kishor S, Trehan N. 2001. Coronary artery disease in young Indians - the missing link. J Indian Acad Clin Med 2(3): 128-32.
  4.    Enas AE, Annamalai SK. 2001. Coronary artery disease in Asian Indians: an update and review. Internet J Cardiol 1: Number 2.
  5.    Sheehan J, Kearney PM, Sullivan SO, Mongan C, Kelly E, Perry IJ. 2005. Acute coronary syndrome and chronic infection in the Cork coronary care case-control study. Heart 91(1): 19-22.
  6.    Tedgui A, Mallat Z. 2006. Cytokines in atherosclerosis: pathogenic and regulatory pathways. Physiol Rev 86: 515-81.
  7.    Østerud B, Bjørklid E. 2003. Role of monocytes in atherogenesis. Physiol Rev 83: 1069-12.
  8.    Jan H, Thüsen V, Kuiper J, Berkel TJCV, Biessen EAL. 2003. Interleukins in atherosclerosis: molecular pathways and therapeutic potential. Pharmacol Rev 55(1): 133-66.
  9.    Jha HC, Vardhan H, Gupta R, Varma R, Prasad J, Mittal A 2007. Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern. BMC Infect Dis 7:48.
  10.    Kosaka C, Hara K, Komiyama Y, Takahashi H. 2000. Possible role of chronic infection with Chlamydia pneumoniae in Japanese patients with acute myocardial infraction. Jpn Circ J 64: 819-24.
  11.    Linnanmak E, Leinonen M, Mattila K, Valtonen V, Saikku P. 1993. Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 87: 1130-34.
  12.    Sheehan J, Kearney PM, Sullivan SO, Mongan C, Kelly E, Perry IJ. 2005. Acute coronary syndrome and chronic infection in the Cork coronary care case-control study. Heart 91: 19-22.
  13.    Fong IW. 2000. Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. CMAJ 163(1): 49-56.
  14.    Jha HC, Prasad J, Mittal A. 2008. High IgA seropositivity for combined Chlamydia pneumoniae, Helicobacter pylori infection and high sensitive C-reactive protein in coronary artery disease patients in India can serve as atherosclerotic marker. Heart Vessels doi:10.1007/s00380-008-1062.9.
  15.    Kiechl S, Werner P, Egger G, et al. 2002. Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis. Stroke 33: 2170-76.
  16.    Kiechl S, Willeit J, Rungger G, Egger G, Oberhollenzer F, Bonora E.1998. Alcohol consumption and atherosclerosis: what is the relation? Stroke 29: 900-7.
  17.    Jha HC, Mittal A. 2008. Coronary artery disease patient's first degree relatives may be at higher risk for atherosclerosis. Int J Cardiol doi:10.1016/j.ijcard.2008.03.031.
  18.    Tesfamariam B, DeFelice AF. 2007. Endothelial injury in the initiation and progression of vascular disorders. Vascul Pharmacol 46: 229-37.
  19.    Kato A, Odamaki M, Takita T, Maruyama Y, Kumagai H, Hishida A. 2002. Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients. Kidney Int 61: 1143-52.
  20.    Kaukoranta-Tolvanen SS, Teppo AM, Laitinen K, Saikku P, Linnavuori K, Leinonen M. 1996. Growth of Chlamydia pneumoniae in cultured human peripheral blood mononuclear cells and induction of a cytokine response. Microb Pathog 21: 215-21.
  21.    Claiborne JS, Hui Z, Louis MM, Michael LT, Deborah D. 2005. Chlamydia pneumoniae burden in carotid arteries is associated with upregulation of plaque interleukin-6 and elevated C-reactive protein in serum. Arterioscler Thromb Vasc Biol 25: 2648-53.
  22.    Del JR, Woytas M, Groh A, et al. 2000. Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae. Infect Immun 68: 3635-41.
  23.    Mazzoli S, Tofani N, Semplici F, et al. 1998. Chlamydia pneumoniae antibody response in patients with acute myocardial infarction and their follow-up. Am Heart J 135:15-20.
  24.    Jha HC, Srivastava P, Sarkar R, Prasad J, Mittal A. 2008. Chlamydia pneumoniae IgA and elevated level of IL-6 may synergize to accelerate coronary artery disease outcome. J Cardiol doi:10.1016/j.jjcc.2008.07.001.

 

 

CLOSE THE WINDOW