Skip to main content

Association of hyperhomocysteinemia and Chlamydia pneumoniae infection with carotid atherosclerosis and coronary artery disease in Japanese patients

Abstract

An elevated plasma level of homocysteine (Hcy) and infection by Chlamydia pneumoniae (C. pneumoniae) have been suggested as independent risk factors for carotid atherosclerosis (CA) and coronary artery disease (CAD), but the mechanisms involved are unclear. We investigated the correlation between positivity for antibody to C. pneumonia (anti-C. pneumoniae) and the Hcy level in patients with CA and CAD. The total plasma homocysteine (tHcy) concentration was determined in 99 patients with CA and 31 patients with CAD, as well as 119 controls with matched risk factors for atherosclerosis. The tHcy level was measured with a Bio-Rad microplate enzyme immunoassay. In the CAD group, the tHcy level (13.67 μmol/l) was significantly higher than that in other groups (CA group, 10.96 μmol/l; control group, 9.95 μmol/l; ANOVA, P = 0.0006). Positivity for anti-C. pneumoniae IgG was significantly more common in the CAD group (77.4%) than in the other groups (CA group, 53.5%; control group, 54.6%; ANOVA, P = 0.0490). There was no association between anti-C. pneumoniae IgA positivity or tHcy and conventional risk factors. However, anti-C. pneumoniae IgG positivity was significantly more common in subjects with higher tHcy levels than in those with low tHcy levels from each of the 3 groups. The CAD group had significantly higher tHcy levels, and tHcy was significantly associated with anti-C. pneumoniae IgG positivity. These findings indicate that elevation of tHcy is related to positivity for anti-C. pneumoniae IgG in patients with CAD.

This is a preview of subscription content, access via your institution.

References

  1. Salonen R, Salonen JT. Progression of carotid atherosclerosis and its determinants: a population-based ultrasonography study. Atherosclerosis 1999;81:33–40.

    Article  Google Scholar 

  2. Bots ML, Hofman A, Grobbee DE. Increased common carotid intima-media thickness. Adaptive response or a reflection of atherosclerosis? Findings from the Rotterdam Study. Stroke 1997;28:2442–2447.

    PubMed  CAS  Google Scholar 

  3. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997;96:1432–1437.

    PubMed  CAS  Google Scholar 

  4. Sawayama Y, Shimizu C, Maeda N, Tatsukawa M, Kinukawa N, Koyanagi S, et al. Effect of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST). JACC 2002;39:610–616.

    PubMed  CAS  Google Scholar 

  5. McCully KS. Vascular pathology of hyperhomocysteinemia: implications for the pathogenesis of atherosclerosis. Am J Pathol 1969;56:111–122.

    PubMed  CAS  Google Scholar 

  6. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149–1155.

    PubMed  CAS  Google Scholar 

  7. Perry IJ, Refsum H, Morris RW, Ebrahim SB, Ueland PM, Shaper AG. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995;346:1395–1398.

    PubMed  Article  CAS  Google Scholar 

  8. McQuillan BM, Beilby JP, Nidorf M, Thompson PL, Hung J. Hyperhomocysteinemia but not the C677T mutation of methylenetetrahydrofolate reductase is an independent risk determinant of carotid wall thickening. Circulation 1999;99:2383–2388.

    PubMed  CAS  Google Scholar 

  9. Willinek WA, Ludwig M, Lennarz M, Holler T, Stumpe KO. Highnormal serum homocysteine concentrations are associated with an increased risk of early atherosclerotic carotid artery wall lesions in healthy subjects. J Hypertens 2000;18:425–430.

    PubMed  Article  CAS  Google Scholar 

  10. Folsom AR, Neito FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, et al. Prospective study of coronary heart diseases incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation 1998;98:204–210.

    PubMed  CAS  Google Scholar 

  11. 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;161:618–625.

    PubMed  CAS  Google Scholar 

  12. Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet 1997;350:430–436.

    PubMed  Article  CAS  Google Scholar 

  13. Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary disease. JAMA 1992;268:68–72.

    PubMed  Article  CAS  Google Scholar 

  14. Linnanmaki E, Leinonen M, Mattila K, Nieminen MS, Valtonen V, Saikku P. Chlamydia pneumoniae: specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 1993;87:1130–1134.

    PubMed  CAS  Google Scholar 

  15. Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Mäkelä PH, 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.

    PubMed  Article  CAS  Google Scholar 

  16. Campbell LA, O’Brien ER, Cappuccio AL, Kuo CC, Wang SP, Stewart D, et al. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissue. J Infect Dis 1995;172:585–588.

    PubMed  CAS  Google Scholar 

  17. Davidson M, Kuo CC, Middaugh JP, Campbell LA, Wang SP, Newman WP 3rd, et al. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Circulation 1998;98:628–633.

    PubMed  CAS  Google Scholar 

  18. 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;64:1614–1620.

    PubMed  CAS  Google Scholar 

  19. Kaukoranta-Tolvanen SS, Teppo AM, 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 Pathol 1996;21:215–221.

    Article  CAS  Google Scholar 

  20. Maeda N, Sawayama Y, Tatsukawa M, Shimizu C, Kashiwagi S, Hayashi J. Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a suburban Japanese population. Atherosclerosis 2002;164:313–319.

    PubMed  Article  CAS  Google Scholar 

  21. Blann AD. Endothelial cell damage and homocysteine. Atherosclerosis 1992;94:89–91.

    PubMed  Article  CAS  Google Scholar 

  22. Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. Am J Cardiol 1999;83:821–825.

    PubMed  Article  CAS  Google Scholar 

  23. Sawayama Y, Tatsukawa M, Okada K, Maeda N, Shimizu C, Kikuchi K, et al. Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect of statins. Atherosclerosis 2003;171:281–285.

    PubMed  Article  CAS  Google Scholar 

  24. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993;362:801–809.

    PubMed  Article  CAS  Google Scholar 

  25. Stanger OH, Semmelrock HJ, Rehak P, Tiran B, Meinitzer A, Rigler B, et al. Hyperhomocyst(e)inemia and Chlamydia pneumoniae IgG seropositivity in patients with coronary artery disease. Atherosclerosis 2003;166:409.

    Article  Google Scholar 

  26. Donnelly JG, Pronovost C. Evaluation of the Abbott Imx fluorescence polarization immunoassay and the Bio-Rad enzyme immunoassay for homocysteine: comparison with high-performance liquid chromatography. Ann Clin Biochem 2000;37:194–198.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jun Hayashi.

About this article

Cite this article

Sawayama, Y., Tatsukawa, M., Maeda, S. et al. Association of hyperhomocysteinemia and Chlamydia pneumoniae infection with carotid atherosclerosis and coronary artery disease in Japanese patients. J Infect Chemother 14, 232–237 (2008). https://doi.org/10.1007/s10156-008-0607-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10156-008-0607-2

Key words

  • Homocysteine
  • Chlamydia pneumoniae
  • Atherosclerosis
  • Cardiovascular disease
  • Case-control study