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Circulation. 2001;104:25-31
doi: 10.1161/hc2601.091703
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(Circulation. 2001;104:25.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Impact of Viral and Bacterial Infectious Burden on Long-Term Prognosis in Patients With Coronary Artery Disease

Hans J. Rupprecht, MD; Stefan Blankenberg, MD; Christoph Bickel, MD; Gerd Rippin, PhD; Gerd Hafner, MD; Wilfried Prellwitz, MD; Wolfgang Schlumberger, PhD; Jürgen Meyer, MD, FACC; , for the AtheroGene Investigators1

From the Department of Medicine II (H.J.R., S.B., C.B., J.M.), the Department of Medical Statistics and Documentation (G.R.), and the Department of Clinical Chemistry (G.H., W.P.), Johannes Gutenberg University Mainz, Mainz, Germany, and EUROIMMUN (W.S.), Lübeck, Germany.

Correspondence to Hans-Jürgen Rupprecht, MD, University Clinic Mainz, Department of Medicine II, Langenbeckstr. 1, 55101 Mainz, Germany. E-mail rupprecht{at}2-med.klinik.uni-mainz.de

Background—The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD.

Methods and Results—In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level.

Conclusions—These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.


Key Words: infection • inflammation • prognosis • atherosclerosis • coronary disease




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