Clinical and Experimental Nephrology

, Volume 10, Issue 1, pp 55–62

Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients

  • Krista L. Lentine
  • Julie Parsonnet
  • Isabella Taylor
  • Elizabeth M. Wrone
  • Richard A. Lafayette
ORIGINAL ARTICLE

Abstract

Background

Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients.

Methods

We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01.

Results

Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome.

Conclusions

Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.

Key words

Cardiovascular disease Chlamydia pneumoniae C-reactive protein Helicobacter pylori Hemodialysis Mortality 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Stenvinkel, P, Heimburger, O, Paultre, F, Diczfalusy, U, Wang, T, Berglund, L,  et al. 1999Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failureKidney Int551899911CrossRefPubMedGoogle Scholar
  2. 2.
    Zimmermann, J, Herrlinger, S, Pruy, A, Metzger, T, Wanner, C 1999Inflammation enhances cardiovascular risk and mortality in hemodialysis patientsKidney Int5564858CrossRefPubMedGoogle Scholar
  3. 3.
    Saikku, P, Leinonen, M, Mattila, K,  et al. 1988Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarctionLancetII9836Google Scholar
  4. 4.
    Kuo, CC, Coulson, AS, Campbell, LA, Cappuccio, AL, Lawrence, RD, Wang, SP,  et al. 1997Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of arteries of lower extremities from patients undergoing bypass operation for arterial obstructionJ Vasc Surg262931CrossRefPubMedGoogle Scholar
  5. 5.
    Moazed, TC, Campbell, LA, Rosenfeld, ME, Grayston, JT, Kuo, CC 1999Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient miceJ Infect Dis18023841CrossRefPubMedGoogle Scholar
  6. 6.
    Danesh, J, Youngman, L, Clark, S, Parish, S, Peto, R, Collins, R 1999Helicobacter pylori infection and early onset myocardial infarction: case-control and sibling pairs studyBMJ319115762PubMedGoogle Scholar
  7. 7.
    Zoccali, C, Benedetto, FA, Mallamaci, F, Tripepi, G, Fermo, I, Foca, A,  et al. 2000Inflammation is associated with carotid atherosclerosis in dialysis patients. CREED Investigators. Cardiovascular Risk Extended Evaluation in Dialysis PatientsJ Hypertens18120713CrossRefPubMedGoogle Scholar
  8. 8.
    Stenvinkel, P, Heimburger, O, Jogestrand, T 2002Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivityAm J Kidney Dis3927482PubMedGoogle Scholar
  9. 9.
    Zoccali, C 1998CREED Investigators. C-reactive protein and atherosclerosis in dialysis patientsNephrol Dial Transplant1327101Google Scholar
  10. 10.
    Haubitz, M, Brunkhorst, R 2001C-reactive protein and chronic Chlamydia pneumoniae infection – long-term predictors for cardiovascular disease and survival in patients on peritoneal dialysisNephrol Dial Transplant1680915PubMedGoogle Scholar
  11. 11.
    Wolf, SC, Mayer, O, Jurgens, S, Vonthein, R, Schultze, G, Risler, T,  et al. 2003Chlamydia pneumoniae IgA seropositivity is associated with increased risk for atherosclerotic vascular disease, myocardial infarction and stroke in dialysis patientsClin Nephrol592739PubMedGoogle Scholar
  12. 12.
    Bellomo, G, Lippi, G, Saronio, P, Reboldi, G, Verdura, C, Timio, F,  et al. 2003Inflammation, infection and cardiovascular events in chronic hemodialysis patients: a prospective studyJ Nephrol1624551PubMedGoogle Scholar
  13. 13.
    Haubitz, M, Votsch, K, Woywodt, A, Nashan, B, Groh, A, Haller, H,  et al. 2004Serologic evidence of Chlamydia pneumoniae infection as a long-term predictor of cardiovascular death in renal transplant recipientsTransplantation77151721PubMedGoogle Scholar
  14. 14.
    Zoccali, C, Mallamaci, F, Tripepi, G, Parlongo, S, Cutrupi, S, Benedetto, FA,  et al. 2003Chlamydia pneumoniae, overall and cardiovascular mortality in end-stage renal disease (ESRD)Kidney Int6457984CrossRefPubMedGoogle Scholar
  15. 15.
    Naidu, BR, Ngeow, YF, Pang, T 2003Ethnic distribution of Chlamydophila pneumoniae antibodies in a Malaysian population and possible correlation with coronary heart diseaseEur J Epidemiol181357PubMedGoogle Scholar
  16. 16.
    Fabrizi, F, Martin, P, Dixit, V, Quan, S, Brezina, M, Abbey, H,  et al. 1999Epidemiology of Helicobacter pylori in chronic haemodialysis patients using the new RIBA H. pylori SIANephrol Dial Transplant14192933PubMedGoogle Scholar
  17. 17.
    Dowell, SF, Peeling, RW, Boman, J, Carlone, GM, Fileds, BA, Guarner, J,  et al. 2001Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada)Clin Infect Dis33492503PubMedGoogle Scholar
  18. 18.
    Verkooyen, RP, Willemse, D, Hiep-van Casteren, SC, Mousavi Joulandan, SA, Shnijder, RJ, Van Den Bosch, JM,  et al. 1998Evaluation of PCR, culture, and serology for diagnosis of Chlamydia pneumoniae respiratory infectionsJ Clin Microbiol3623017PubMedGoogle Scholar
  19. 19.
    Hoymans, VY, Bosmans, JM, Van Renterghem, L, Mak, R, Ursi, D, Wuyts, F,  et al. 2003Importance of methodology in determination of Chlamydia pneumoniae seropositivity in healthy subjects and in patients with coronary atherosclerosisJ Clin Microbiol41404953CrossRefPubMedGoogle Scholar
  20. 20.
    Replogle, ML, Glaser, SL, Hiatt, RA, Parsonnet, J 1995Biologic sex as a risk factor for Helicobacter pylori infection in healthy young adultsAm J Epidemiol14285663PubMedGoogle Scholar
  21. 21.
    Tozawa, M, Iseki, K, Iseki, C, Takishita, S 2002Pulse pressure and risk of total mortality and cardiovascular events in patients on chronic hemodialysisKidney Int6171726CrossRefPubMedGoogle Scholar
  22. 22.
    Haider, AW, Wilson, PW, Larson, MG, Evans, JC, Michelson, EL, Wolf, PA,  et al. 2002The association of seropositivity to Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus with risk of cardiovascular disease: a prospective studyJ Am Coll Cardiol40140813CrossRefPubMedGoogle Scholar
  23. 23.
    Kato, A, Odamaki, M, Takita, T, Maruyama, Y, Kumagai, H, Hishida, A 2002Association between interleukin-6 and carotid atherosclerosis in hemodialysis patientsKidney Int61114352CrossRefPubMedGoogle Scholar
  24. 24.
    Muller, J, Nyvad, O, Larsen, NA, Lokkegaard, N, Pedersen, RS, Solling, J,  et al. 2002Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis patients, renal transplant recipients and healthy controlsScand J Clin Lab Invest625039PubMedGoogle Scholar
  25. 25.
    Nakajima, F, Sakaguchi, M, Oka, H, Kawase, Y, Shibahara, N, Inoue, T,  et al. 2004Prevalence of Helicobacter pylori antibodies in long-term dialysis patientsNephrology (Carlton)9736Google Scholar
  26. 26.
    Jaspersen, D, Fassbinder, W, Heinkele, P, Kronsbein, H, Schorr, W, Raschka, C,  et al. 1995Significantly lower prevalence of Helicobacter pylori in uremic patients than in patients with normal renal functionJ Gastroenterol305858PubMedGoogle Scholar
  27. 27.
    Nakajima, F, Sakaguchi, M, Amemoto, K, Oka, H, Kubo, M, Shibahara, N,  et al. 2002Helicobacter pylori in patients receiving long-term dialysisAm J Nephrol2246872CrossRefPubMedGoogle Scholar
  28. 28.
    Gasbarrini, A, Cremonini, F, Armuzzi, A, Ojetti, V, Candelli, M, Di Campli, C,  et al. 1999The role of Helicobacter pylori in cardiovascular and cerebrovascular diseasesJ Physiol Pharmacol5073542PubMedGoogle Scholar
  29. 29.
    Jones, DW, Chambless, LE, Folsom, AR, Heiss, G, Hutchinson, RG, Sharrett, AR,  et al. 2002Risk factors for coronary heart disease in African Americans: the Atherosclerosis Risk in Communities study, 1987–1997Arch Intern Med162256571CrossRefPubMedGoogle Scholar
  30. 30.
    Duranti, E, Imperiali, P, Sasdelli, M 1996Is hypertension a mortality risk factor in dialysis?Kidney Int Suppl55S1734PubMedGoogle Scholar
  31. 31.
    Cheung, AK, Sarnak, MJ, Yan, G, Dwyer, JT, Heyka, RJ, Rocco, MV,  et al. 2000Atherosclerotic cardiovascular disease risks in chronic hemodialysis patientsKidney Int5835362CrossRefPubMedGoogle Scholar
  32. 32.
    Foley, RN, Herzog, CA, Collins, AJ 2003Smoking and cardiovascular outcomes in dialysis patients: the United States Renal Data System Wave 2 studyKidney Int6314627CrossRefPubMedGoogle Scholar
  33. 33.
    Kalantar-Zadeh, K, Stenvinkel, P, Pillon, L, Kopple, JD 2003Inflammation and nutrition in renal insufficiencyAdv Ren Replace Ther1015569PubMedGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2006

Authors and Affiliations

  • Krista L. Lentine
    • 1
    • 2
  • Julie Parsonnet
    • 3
    • 4
  • Isabella Taylor
    • 5
  • Elizabeth M. Wrone
    • 6
  • Richard A. Lafayette
    • 5
  1. 1.Saint Louis University Center for Outcomes Research Salus CenterSt. LouisUSA
  2. 2.Division of Nephrology, Department of MedicineSaint Louis University School of MedicineSt. LouisUSA
  3. 3.Division of Infectious Diseases and Geographic Medicine, Department of MedicineStanford University School of MedicineStanfordUSA
  4. 4.Division of Epidemiology, Department of Health Research and PolicyStanford University School of MedicineStanfordUSA
  5. 5.Division of Nephrology, Department of MedicineStanford University School of MedicineStanfordUSA
  6. 6.Diablo Nephrology Medical GroupWalnut CreekUSA

Personalised recommendations