Atherosclerosis is a systemic inflammatory disease leading to lipid-laden inflammatory lesions in the
arterial walls that may destabilize and rupture. It is becoming clear that addressing the “classical” risk factors for
atherosclerosis does not entirely reduce the risk of cardiovascular events. Novel biomarkers to be used in highthroughput
assays are necessary for diagnosis, for determination of the residual risk and for monitoring the effects
of the therapy. Since inflammation is a hallmark of atherosclerosis, tests for pro-inflammatory biomarkers have
been introduced such as for hsCRP, fibrinogen and IL-6, with many more at different stages of development.
There has been a dearth of novel approaches for the diagnosis and management of atherosclerosis, reflected in a continuous reliance on
LDL cholesterol as a proven target of investigations. To bring another perspective, here we briefly overview the accumulated epidemiological
and sero-epidemiological evidence suggesting systemic infections as a component of atherosclerotic inflammations. We have
shown that different individuals’ plaques are colonized with different bacterial species (atherosclerosis microbiota). Most of the time the
pathogens are likely in an intracellular state, shielded from the host immune responses. There are controlled clinical trials and metaanalyses
that corroborate the infections, specifically periodontal disease as a contributing risk factor of atherosclerosis. Infection-related
markers, including transcriptome signatures, may identify latent infection patients with sub-clinical disease. Thus, the emerging infection-
associated markers of inflammation could complement the existing ones and their use as companion diagnostics for atherosclerosis
should stimulate the growing field of personalized medicine within cardiovascular diseases.