(Circulation. 2001;103:45.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Prospective Study of Pathogen Burden and Risk of Myocardial Infarction or Death
From the Cardiovascular Research Institute (J.Z., S.E.E.), MedStar Research Institute, Washington Hospital Center, Washington, DC; Department of Epidemiology (F.J.N.), The Johns Hopkins University School of Public Health, Baltimore, Md; and LDS Hospital and University of Utah (B.D.H, J.L.A., J.B.M.), Salt Lake City.
Correspondence to Dr Stephen E. Epstein, CRI, Washington Hospital Center, 110 Irving St, NW, Suite 4B-1, Washington, DC 20010..
Background—We previously demonstrated that the risk of coronary artery disease (CAD) increased in relation to the number of pathogens (the "pathogen burden") in a cross-sectional study. In the present prospective study with a different patient cohort, we evaluated the effect of pathogen burden on the risk of myocardial infarction (MI) or death among CAD patients.
Methods and Results—IgG antibodies to cytomegalovirus (CMV), hepatitis A virus (HAV), herpes simplex virus type 1 (HSV1), HSV type 2 (HSV2), Chlamydia pneumoniae and Helicobacter pylori, and C-reactive protein (CRP) levels were tested in baseline blood samples from 890 patients who had significant CAD on angiography. The mean follow-up period was 3 years. The baseline prevalence of antibodies directed against CMV, HAV, HSV1, or HSV2, but not C pneumoniae and H pylori, was significantly higher among patients who subsequently developed MI or death than among control subjects. After adjustment for traditional risk factors, number of diseased vessels, and clinical presentation, relative hazards (95% confidence limits) for MI or death were 2.0 (1.4 to 3.2) for CMV, 1.6 (1.1 to 2.3) for HAV, and 1.5 (1.0 to 2.2) for HSV2. Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion. Adjusted relative hazards of MI or death associated with pathogen burden were significant among individuals with low or high CRP levels.
Conclusions—The results suggest that infection plays an important role in incident MI or death and that the risk posed by infection is independently related to the pathogen burden.
Key Words: pathogens • antibodies • coronary disease • myocardial infarction
This article has been cited by other articles:
 |
|
 |
|
  M. S. V. Elkind, P. Ramakrishnan, Y. P. Moon, B. Boden-Albala, K. M. Liu, S. L. Spitalnik, T. Rundek, R. L. Sacco, and M. C. Paik Infectious Burden and Risk of Stroke: The Northern Manhattan Study Arch Neurol, November 9, 2009; (2009) 2009.271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-H. Kang, J.-D. Ho, Y.-H. Chen, and H.-C. Lin Increased Risk of Stroke After a Herpes Zoster Attack: A Population-Based Follow-Up Study Stroke, November 1, 2009; 40(11): 3443 - 3448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Epstein, J. Zhu, A. H. Najafi, and M. S. Burnett Insights Into the Role of Infection in Atherogenesis and in Plaque Rupture Circulation, June 23, 2009; 119(24): 3133 - 3141. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M Simanek, J. B. Dowd, and A. E Aiello Persistent pathogens linking socioeconomic position and cardiovascular disease in the US Int. J. Epidemiol., June 1, 2009; 38(3): 775 - 787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F J. Nieto Commentary: Understanding the pathophysiology of poverty Int. J. Epidemiol., June 1, 2009; 38(3): 787 - 790. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Lamontagne MD MSc, M.-P. Garant PhD, J.-C. Carvalho MD, L. Lanthier MD MSc, M. Smieja MD PhD, and D. Pilon MD MSc Pneumococcal vaccination and risk of myocardial infarction Can. Med. Assoc. J., October 7, 2008; 179(8): 773 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R A Pollitt, J S Kaufman, K M Rose, A V Diez-Roux, D Zeng, and G Heiss Cumulative life course and adult socioeconomic status and markers of inflammation in adulthood J Epidemiol Community Health, June 1, 2008; 62(6): 484 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Steptoe, A Shamaei-Tousi, A Gylfe, B Henderson, S Bergstrom, and M Marmot Socioeconomic status, pathogen burden and cardiovascular disease risk Heart, December 1, 2007; 93(12): 1567 - 1570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. L. Baker and K. A. Couch Azithromycin for the secondary prevention of coronary artery disease: A meta-analysis Am. J. Health Syst. Pharm., April 15, 2007; 64(8): 830 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, V. Murthy, K. Schultz, J. B. Tatro, K. A. Fitzgerald, and D. Beasley Toll-like receptor 3 signaling evokes a proinflammatory and proliferative phenotype in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2334 - H2343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Fernandez-Real, A. Lopez-Bermejo, J. Vendrell, M.-J. Ferri, M. Recasens, and W. Ricart Burden of Infection and Insulin Resistance in Healthy Middle-Aged Men Diabetes Care, May 1, 2006; 29(5): 1058 - 1064. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Chen, G. Yang, M. Zhou, M. Smith, A. Offer, J. Ma, L. Wang, H. Pan, G. Whitlock, R. Collins, et al. Body mass index and mortality from ischaemic heart disease in a lean population: 10 year prospective study of 220 000 adult men Int. J. Epidemiol., February 1, 2006; 35(1): 141 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Reinhardt, T. Mertens, U. Mayr-Beyrle, H. Frank, A. Luske, K. Schierling, and J. Waltenberger HCMV infection of human vascular smooth muscle cells leads to enhanced expression of functionally intact PDGF {beta}-receptor Cardiovasc Res, July 1, 2005; 67(1): 151 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Andraws, J. S. Berger, and D. L. Brown Effects of Antibiotic Therapy on Outcomes of Patients With Coronary Artery Disease: A Meta-analysis of Randomized Controlled Trials JAMA, June 1, 2005; 293(21): 2641 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Oshima, R. Ozono, Y. Yano, Y. Oishi, H. Teragawa, Y. Higashi, M. Yoshizumi, and M. Kambe Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1219 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun, W. Pei, Y. Wu, and Y. Yang An Association of Herpes Simplex Virus Type 1 Infection With Type 2 Diabetes Diabetes Care, February 1, 2005; 28(2): 435 - 436. [Full Text] [PDF]
|
|
|
|
|
|
J. Ngeh and C. Goodbourn Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila in Elderly Patients With Stroke (C-PEPS, M-PEPS, L-PEPS): A Case-Control Study on the Infectious Burden of Atypical Respiratory Pathogens in Elderly Patients With Acute Cerebrovascular Disease Stroke, February 1, 2005; 36(2): 259 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Zibaeenezhad, A. Amanat, A. Alborzi, and A. Obudi Relation of Chlamydia Pneumoniae Infection to Documented Coronary Artery Disease in Shiraz, Southern Iran Angiology, January 1, 2005; 56(1): 43 - 48. [Abstract] [PDF]
|
|
|
|
|
|
J Sheehan, P M Kearney, S O Sullivan, C Mongan, E Kelly, and I J Perry Acute coronary syndrome and chronic infection in the Cork coronary care case-control study Heart, January 1, 2005; 91(1): 19 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kato, T. Takita, Y. Maruyama, and A. Hishida Chlamydial infection and progression of carotid atherosclerosis in patients on regular haemodialysis Nephrol. Dial. Transplant., October 1, 2004; 19(10): 2539 - 2546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Progression of Early Carotid Atherosclerosis Is Only Temporarily Reduced After Antibiotic Treatment of Chlamydia pneumoniae Seropositivity Circulation, March 2, 2004; 109(8): 1010 - 1015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Nerheim, J. L. Meier, M. A. Vasef, W.-G. Li, L. Hu, J. B. Rice, D. Gavrila, W. E. Richenbacher, and N. L. Weintraub Enhanced Cytomegalovirus Infection in Atherosclerotic Human Blood Vessels Am. J. Pathol., February 1, 2004; 164(2): 589 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Agmon, B. K. Khandheria, I. Meissner, T. M. Petterson, W. M. O'Fallon, T. J. H. Christianson, D. O. Wiebers, T. F. Smith, J. M. Steckelberg, and A. J. Tajik Lack of association between Chlamydia pneumoniae seropositivity and aortic atherosclerotic plaques: A Population-Based transesophageal echocardiographic study J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1482 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. van der Ven, R. van Diest, K. Hamulyak, M. Maes, C. Bruggeman, and A. Appels Herpes Viruses, Cytokines, and Altered Hemostasis in Vital Exhaustion Psychosom Med, March 1, 2003; 65(2): 194 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Higgins Chlamydia pneumoniae and Coronary Artery Disease: The Antibiotic Trials Mayo Clin. Proc., March 1, 2003; 78(3): 321 - 332. [Abstract] [PDF]
|
|
|
|
|
|
J. B. Muhlestein and J. L. Anderson Infectious Serology and Atherosclerosis: How Burdensome Is the Risk? Circulation, January 21, 2003; 107(2): 220 - 222. [Full Text] [PDF]
|
|
|
|
|
|
M. Smieja, J. Gnarpe, E. Lonn, H. Gnarpe, G. Olsson, Q. Yi, V. Dzavik, M. McQueen, S. Yusuf, and for the Heart Outcomes Prevention Evaluation (HOPE Multiple Infections and Subsequent Cardiovascular Events in the Heart Outcomes Prevention Evaluation (HOPE) Study Circulation, January 21, 2003; 107(2): 251 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Horne, J. B. Muhlestein, J. F. Carlquist, T. L. Bair, T. E. Madsen, N. I. Hart, J. L. Anderson, and for the Intermountain Heart Collaborative (IHC) St Statin Therapy Interacts With Cytomegalovirus Seropositivity and High C-Reactive Protein in Reducing Mortality Among Patients With Angiographically Significant Coronary Disease Circulation, January 21, 2003; 107(2): 258 - 263. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Kalayoglu, P. Libby, and G. I. Byrne Chlamydia pneumoniae as an Emerging Risk Factor in Cardiovascular Disease JAMA, December 4, 2002; 288(21): 2724 - 2731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Prager, Z. Turel, W. S. Speidl, G. Zorn, C. Kaun, A. Niessner, G. Heinze, I. Huk, G. Maurer, K. Huber, et al. Chlamydia pneumoniae in Carotid Artery Atherosclerosis: A Comparison of Its Presence in Atherosclerotic Plaque, Healthy Vessels, and Circulating Leukocytes From the Same Individuals Stroke, December 1, 2002; 33(12): 2756 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sander, K. Winbeck, J. Klingelhofer, T. Etgen, and B. Conrad Reduced Progression of Early Carotid Atherosclerosis After Antibiotic Treatment and Chlamydia pneumoniae Seropositivity Circulation, November 5, 2002; 106(19): 2428 - 2433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Espinola-Klein, H.-J. Rupprecht, S. Blankenberg, C. Bickel, H. Kopp, A. Victor, G. Hafner, W. Prellwitz, W. Schlumberger, and J. Meyer Impact of Infectious Burden on Progression of Carotid Atherosclerosis Stroke, November 1, 2002; 33(11): 2581 - 2586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gabrielli, L. Santarelli, A. Gasbarrini, C. Espinola-Klein, H. J. Rupprecht, S. Blankenberg, C. Bickel, H. Kopp, J. Meyer, G. Rippin, et al. Role for Chronic Infections in Atherosclerosis? * Response Circulation, August 13, 2002; 106 (7): e32 - e32. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Vita and J. Loscalzo Shouldering the Risk Factor Burden: Infection, Atherosclerosis, and the Vascular Endothelium Circulation, July 9, 2002; 106(2): 164 - 166. [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, J. Zhu, J. P.J. Halcox, M. A. Waclawiw, S. E. Epstein, and A. A. Quyyumi Predisposition to Atherosclerosis by Infections: Role of Endothelial Dysfunction Circulation, July 9, 2002; 106(2): 184 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Blankenberg, L. Tiret, C. Bickel, D. Peetz, F. Cambien, J. Meyer, H. J. Rupprecht, and for the AtheroGene Investigators Interleukin-18 Is a Strong Predictor of Cardiovascular Death in Stable and Unstable Angina Circulation, July 2, 2002; 106(1): 24 - 30. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R K Singh, A D McMahon, H Patel, C J Packard, B J Rathbone, and N J Samani Prospective analysis of the association of infection with CagA bearing strains of Helicobacter pylori and coronary heart disease Heart, July 1, 2002; 88(1): 43 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Stollberger and J. Finsterer Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis Clin. Vaccine Immunol., March 1, 2002; 9(2): 207 - 215. [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Epstein The Multiple Mechanisms by Which Infection May Contribute to Atherosclerosis Development and Course Circ. Res., January 11, 2002; 90(1): 2 - 4. [Full Text] [PDF]
|
|
|
|
|
|
H. J. Rupprecht, S. Blankenberg, C. Bickel, G. Rippin, G. Hafner, W. Prellwitz, W. Schlumberger, and J. Meyer Impact of Viral and Bacterial Infectious Burden on Long-Term Prognosis in Patients With Coronary Artery Disease Circulation, July 3, 2001; 104(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sinisalo, K. Mattila, V. Valtonen, O. Anttonen, J. Juvonen, J. Melin, H. Vuorinen-Markkola, M. S. Nieminen, and for the Clarithromycin in Acute Coronary Syndrome Effect of 3 Months of Antimicrobial Treatment With Clarithromycin in Acute Non-Q-Wave Coronary Syndrome Circulation, April 2, 2002; 105(13): 1555 - 1560. [Abstract] [Full Text] [PDF]
|
|