Two journal articles on Infection and coronary heart disease. with/

CDC Morbidity 2004

Number of noninstitutionalized adults with diagnosed heart disease: 24.7 million

Percent of noninstitutionalized adults with diagnosed heart disease: 11.5


Number of deaths:  654,092          [a middle class funeral/w/plot $10,000.00)

Deaths per 100,000 population: 222.7

Cause of death rank: 1

Source:  Deaths: Preliminary Data for 2004, table 7

The Journal of Medical Microbiology, Vol 46, Issue 7 535-539, Copyright © 1997 by Society for
General Microbiology


nfection and coronary heart disease
R. W. Ellis
Department of Clinical Bacteriology, University Hospital NHS Trust, Queen Elizabeth Medical Centre, Edgbaston,

A large body of evidence exists that implicates a number of microbial agents in the pathogenesis of coronary heart
disease (CHD). This, if proven, may have far-reaching implications for the prevention and treatment of CHD and other
atherosclerotic disease. The histopathology of atherosclerosis and its natural history suggest infectious causation at
many points along the progression of disease, particularly with regard to CHD, and a number of pathogens have been
the focus of study. Viral agents implicated include Coxsackie B4 virus, for which tenuous sero-epidemiological
associations exist, and the Herpesviridae. The animal herpesvirus causing Marek's disease in chickens causes
atherosclerotic lesions in these animals. Herpes simplex virus I and II have been found in aortic smooth muscle and
produce changes in vitro in smooth muscle that are similar to those seen at the beginning of atherosclerosis and which
may also explain some of the features of atherosclerotic complications. Cytomegalovirus is implicated more strongly
sero-epidemiologically by in-vivo detection in atherosclerotic lesions and by its links with post-cardiac transplant
vasculopathya syndrome similar to atherosclerosis. Bacteria have also been shown to have links with CHD. Chlamydia
pneumoniae and Helicobacter pylori have both been associated sero-epidemiologically with CHD, and these findings
have been consolidated by recent work showing their presence in atherosclerotic lesions in adults. Bacterial infections in
general lead to many changes in lipid, thrombic and other acute-phase protein metabolism, and some of these changes
occur with both C. pneumoniae and H. pylori infections. The ubiquity and similar epidemiological features to CHD of all
these microbial pathogens make the resolution of the causative issue impossible by retrospective means. All that can be
shown at present are a variety of weak and strong links, the significance of which can only be determined by large and
perhaps lifetime prospective studies.

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
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 [email protected]

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

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