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Infection and atherosclerosis. An alternative view on an outdated hypothesis
Frank R Stassen1, Tryfon Vainas, Cathrien A Bruggeman
1Department of Medical Microbiology and Maastricht Infection Center, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. F.Stassen@medmic.unimaas.nl
Abstract:
Already at the beginning of the 20th century, a potential role for microbes in vascular diseases was suggested. However, until the late '70 of that century, not much attention has been paid to this infection hypothesis. Then, predominantly based on the pioneering work of Fabricant et al., evidence for a contributing or even initiating role for microbes in atherosclerosis, as well as other vascular diseases, was accumulating. Also, the seminal paper by Saikku and co-workers, demonstrating serological evidence of an association of Chlamydia pneumoniae, an obligate intracellular respiratory gram-negative bacterium, with chronic coronary heart disease and acute myocardial infarction, significantly boosted the research on the infection hypothesis. Since then, numerous papers have been published demonstrating associations between a large variety of pathogens and atherosclerotic disease. Furthermore, many molecular mechanisms have been suggested by which microbes may affect atherogenesis. Nevertheless, in recent large randomised prospective trials, evaluating the efficacy of antibiotic treatment for the secondary prevention of coronary events, no reduction in the rate of cardiovascular events was observed, thereby seriously challenging the validity of the infection hypothesis. Nevertheless, the large body of supporting evidence, which has accumulate over the past decades, should not be ignored and maybe we should look at the hypothesis, and in particular the mechanisms by which microbes affect the disease, from a different angle.
Insights
The infection hypothesis suggests microbes contribute to vascular diseases like atherosclerosis. However, recent antibiotic trials failed to show benefits, challenging this theory despite accumulated evidence.
Area of Science:
- Microbiology
- Cardiovascular Disease Research
- Infectious Disease Epidemiology
Background:
- Early 20th-century suggestions of microbial involvement in vascular diseases were largely unexplored until the late 1970s.
- Pioneering work and the association of Chlamydia pneumoniae with coronary heart disease significantly advanced research into the infection hypothesis.
- Numerous studies have since explored links between various pathogens and atherosclerosis, proposing molecular mechanisms.
Observation:
- A substantial body of evidence suggests a role for microbes in the development and progression of atherosclerosis.
- Molecular mechanisms explaining how pathogens might influence atherogenesis have been proposed.
- Recent large-scale randomized trials evaluating antibiotic treatment for secondary prevention of coronary events yielded no significant reduction in cardiovascular events.
Findings:
- Despite extensive research and proposed mechanisms, recent clinical trials challenge the direct causal role of microbial infections in atherosclerosis.
- The efficacy of antibiotic therapy in preventing cardiovascular events has not been demonstrated in large prospective trials.
- The validity of the infection hypothesis as a primary driver of atherosclerosis is seriously questioned by current clinical evidence.
Implications:
- The accumulated evidence supporting a microbial link to vascular disease should not be disregarded.
- Future research may need to explore alternative angles or mechanisms by which microbes influence atherogenesis.
- Re-evaluating the infection hypothesis may lead to novel therapeutic strategies beyond conventional antibiotic treatments.
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