Microbial mechanisms in atherosclerosis: Revisiting the infectious hypothesis

Atherosclerosis is traditionally viewed as a lipid-driven inflammatory disease; however, this model does not fully explain acute coronary events arising from non-obstructive lesions or the persistence of residual cardiovascular risk despite lipid-lowering therapy. Emerging evidence implicates infectious agents as contributors to plaque instability rather than primary initiators of disease. Epidemiological studies demonstrate temporal associations between infections and myocardial infarction, while molecular analyses have identified bacterial components within atherosclerotic plaques. Recent findings suggest that microorganisms exist within plaques as biofilms, structured communities embedded in an extracellular matrix that permits immune evasion and long-term persistence. Under host-derived physiological triggers, including inflammatory surges and metabolic stress, biofilm dispersion may expose bacterial products that amplify inflammation and contribute to plaque destabilization. This biofilm-centered framework complements the lipid-centric model by identifying microbial factors as amplifiers of plaque vulnerability. It also highlights potential diagnostic and therapeutic targets aimed at reducing residual inflammatory cardiovascular risk.