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

Abstract

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.

The Role of Viruses in Cardiac Allograft Vasculopathy

“…Exposure to a panel of five pathogens was found to be predictive of angiographic disease (30) and cardiovascular events (31). Similar results were reported in a study showing that exposure to increasing number of pathogens was associated with increased risk (32). Each of the factors were equally weighted, with 'pathogen burden' being defined as the aggregate number of positive serologies.…”

“…Bacterial infections were found to be predictive of outcome, only in the presence of elevated CRP, while the predictive effects of herpes infections were demonstrable independent of CRP levels. These observations have lead the investigators to propose the 'herpes Burden' (aggregate seropositivity to CMV, herpes simplex-1 and -2, and Epstein-Barr virus) as a more effective predictor of cardiovascular risk (32).…”

Dual role of infections as risk factors for coronary heart disease

“…These latent infections could be activated after the primary infection by a superinfection with an another agent [30]. Differences in host inflammatory response to infection comprise a potentially important factor modifying the inflammatory response of the host [31].…”

“…Pathogen burden with many infectious agents has been reported to increase additionally the risk of cardiovascular events [32,33,34]. A recent study found a positive correlation between the number of pathogens in CHD patients undergoing angiography and the impairment of coronary artery reactivity to acetylcholine, an endothelium-dependent vasodilator [35].…”

T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions

“…A pathogenetic role for infections in atherosclerosis is suggested by the detection of pathogens in the arterial vessels and by more or less strong association between atherosclerosis and serological responses to pathogens, such as cytomegalovirus, herpes simplex virus, Haemophilus influenzae, Chlamydia pneumoniae, or Helicobacter pylori, or between the extent of atherosclerosis and the infectious burden (2,(5)(6)(7)(8)(9)(10)(11)(12)(13). However, the role of cell-mediated immunity and the functional status of pathogenspecific T cells within atherosclerotic lesions remain poorly characterized.…”