Infectious Burden and Atherosclerosis
March 1, 2002 4 minutes read
Infectious Burden and Atherosclerosis
Abstract & Commentary
Synopsis: This study and others support the view that infections are related to the development of atherosclerosis, the extent of vascular disease, and perhaps that specific types of pathogen (eg, bacterial vs viral) may influence plaque stability.
Source: Espinda-Klein C, et al. Circulation. 2002;105: 15-21.
With the recognition that atherosclerosis is in part an inflammatory phenomenon, has come a strong interest in whether individual common bacterial or viral pathogens may initiate and/or perpetuate a chronic inflammatory milieu in arteries, exacerbating or even initiating the complex pathobiology of atherothrombosis. A group from Mainz, Germany, has carefully examined this issue with a unique cross-sectional study attempting to correlate infectious burden with the extent of atherosclerosis in various arteries. This report, part of the Athero Gene project, established the total atherosclerotic burden in 570 patients referred for coronary angiography and correlated detectable vascular disease with a host of bacterial and viral pathogens. The goals were to see if total pathogen burden and an active inflammatory state (assessed by hs-CRP), and vascular disease burden, are related and whether these correlate with mortality over several years follow-up.
Five hundred seventy-two subjects were randomly chosen from a cohort of patients referred for coronary angiography between 1996 and 1998 in University Clinic, Mainz, Germany. Cerebral and peripheral vascular disease was assessed in each subject by clinical diagnosis, carotid ultrasound (duplex imaging), and ankle-brachial index. Three groups were identified and followed for an average of 3.2 years (range, 1.4-4.1): 1) no obvious vascular disease (n = 61); 2) CAD only (n = 265); and 3) coronary artery disease (CAD) and carotid and/or peripheral artery disease. A large panel of serologies for various organisms were obtained at baseline to assess infectious burden. These included lg G and lg A antibodies against CMV, Epstein-Barr, HSV-1, HSV-2, Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Helicobactor pylori. High sensitivity CRP was measured in all subjects. Espinda-Klein and colleagues asked 3 questions: 1) does atherosclerosis correlate with persistent bacterial or viral infections; 2) is there a relationship between atherosclerotic extent and number of pathogens; and 3) does prior infection with multiple pathogens influence clinical outcomes in patients with atherosclerosis?
Results: Seropositivity to C pneumoniae, H pylori, CMV and HSV-2 was independently correlated with advanced atherosclerosis. Increasing pathogen burden was significantly associated with atherosclerosis extent (odds ratio of 2.5 for 6-8 pathogen exposure vs 0-3). This relationship was only true for bacterial pathogens, not viral, and greater in subjects with CRP levels over 0.5. Cardiovascular (CV) mortality was associated with atherosclerotic burden; no disease = no mortality, CAD only = 3.5%, and 13.9% in subjects with disease in 2 or more vascular beds (P = 0.0001). CV mortality correlated with the number of seropositivities (risk increase of 2-3 fold in subjects with 4-8 pathogens; P = 0.02). Furthermore, within each of the 2 groups of atherosclerotic burden, the total number of seropositivities were associated with mortality with a risk of 11 fold with the highest pathogen burden in those who had advanced atherosclerosis.
Espinda-Klein et al concluded that "increasing numbers of infectious pathogens were significantly related to the extent of atherosclerosis and adverse long-term outcome." They believe that this study and others support the view that infections are related to the development of atherosclerosis, the extent of vascular disease, and perhaps that specific types of pathogens (eg, bacterial vs viral) may influence plaque stability.
Comment by Jonathan Abrams, MD
This is a sophisticated cross sectional analysis of infectious burden as it relates to atherosclerosis. Given our recent knowledge that inflammation is intimately related to the development and progression of atherosclerosis, these results are provocative but not surprising. The idea that a single pathogen (eg, C pneumoniae, H pylori, etc) "causes" vascular disease seems somewhat unlikely, as is the likelihood that an antibiotic will "cure" atherosclerosis. Stephen Epstein has promoted the concept of total pathogen exposure correlating with vascular inflammation. The recent explosion in hs-CRP studies linking this inflammatory marker with vascular risk fits in with the German data. It must be pointed out that not all reports are concordant with these data, particularly those assessing only one pathogen in a prospective fashion. However, reports from Epstein and the NHLBI are supportive. The hypothesis that vascular disease is related to chronic inflammation possibly modulated by autoimmune phenomena, seems reasonable, and cumulating pathogen burden appears to be a plausible mechanism for accelerated atherosclerosis. The robust data with hs-CRP in various population studies is supportive of the infection hypothesis.
In an accompanying editorial (Circulation. 2002;105:2-4), Ridker expresses caution in assuming that pathogen burden is causally related to clinical atherosclerosis. He points out that cross-sectional reports, such as this, have the possibility of confounding variables, mandating caution until more data (and the ongoing large antibiotic trials) become available. Nevertheless, bugs may turn out to be as hazardous to vascular health as cigarettes, cheeseburgers, and high cholesterol! v
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