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  1. 1. Editorial Slides VP Watch, January 29, 2003, Volume 4, Issue 4 What is the link between infection and cardiovascular events?
  2. 2.  A possible role for infections in atherosclerosis has been intensely investigated since the landmark demonstration of herpes virus-induced atherosclerosis in chickens by Fabricant in 19781 .
  3. 3.  Human atherosclerotic disease has been associated with previous exposure to several microorganisms including Chlamydia pneumoniae, Porphyromonas gingivalis, CMV, HSV-1, HSV-2, hepatitis A virus, influenza virus, enterovirus, etc. Prospective studies are, however, limited.
  4. 4. A relatively recent approach suggests that the total pathologic burden is a stronger predictor of cardiovascular events than any particular infection2,3,4 .  Large randomized trials of antibiotic for secondary prevention of cardiovascular disease have been performed or are ongoing5,6 but even failure of those treatments should not be construed as evidence that the infectious theories are incorrect.
  5. 5.  As highlighted in VP Watch of this week, Smieja et al7 , for the Heart Outcomes Prevention Evaluation (HOPE) study, analyzed sera from 3168 patients for antibodies to Chlamydia pneumonia, H. Pylori, CMV and hepatitis A and followed the patients over 4.5 years of follow-up.
  6. 6. (Figure 1)
  7. 7. Figure 1 depicts a Kaplan- Meier plot for cumulative cardiovascular events by titer levels of C. pneumoniae IgG (A) and IgA(B). No statistical significance was found.
  8. 8. (Figure 2)
  9. 9. Figure 2 depicts a Kaplan- Meier plot for cumulative cardiovascular events by presence or absence of antibody to H. pylori, CMV, and HAV. Serology for CMV shows a mild predictive correlation with cardiovascular events with a hazard ratio (HR) of 1.24.
  10. 10. (Figure 3)
  11. 11.  Figure 3 depicts a Kaplan-Meier plot for cumulative cardiovascular events by total pathogen score (C pneumoniae IgG 512 or IgA 64; H pylori >40 AU; CMV >0.4 mIU/mL; and HAV >20 IU/mL). HR compares total pathogen score of 4 versus 0 or 1 combined. A score of 4 had an adjusted HR of 1.41 versus 0 or 1.
  12. 12.  Exposure to CMV but not C. pneumoniae, H. pylori or HAV was associated with a slight excess risk of subsequent cardiovascular events (myocardial infarction, stroke, cardiovascular death) Conclusion
  13. 13.  Total pathogen score based on these 4 infections predicted an increase hazard of cardiovascular events compared to the presence of none or only one of these infections. Con’t
  14. 14. ReferencesReferences 1. Fabricant CG, Fabricant J, Litrenta MM, et al. Virus- induced atherosclerosis. J Exp Med. 1978; 148: 335–340. 2. Zhu J, Nieto FJ, Horne BD, et al. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation. 2001; 103: 45–51. 3. Zhu J, Quyyumi AA, Norman JE, et al. Effects of total pathogen burden on coronary artery disease risk and C- reactive protein levels. Am J Cardiol. 2000; 85: 140–146 4. Rupprecht HJ, Blankenberg S, Bickel C, et al. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation. 2001; 104: 25–31.
  15. 15. References 5. Dunne MW. Rationale, and design of a secondary prevention trial of antibiotic use in patients after myocardial infarction: the WIZARD (Weekly Intervention with Zithromax [Azithromycin] for Atherosclerosis and Its Related Disorders) Trial. J Infect Dis. 2000; 181 (suppl 3): S572–S578. 6. Jackson LA. Description and status of the Azithromycin and Coronary Events Study (ACES). J Infect Dis. 2000; 181 (suppl 3): S579–S581. 7. Smieja M, Gnarpe J, Lonn E, Gnarpe H, Olsson G, Yi Q, Dzavik V, McQueen M, Yusuf S. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Circulation 2003;107:251-7