Abstract
Atherosclerosis and prothrombotic vascular states are complex pathologies of the tightly coupled immune and cardiovascular systems that, when dysregulated, synergistically act to elevate risk of acute cerebral ischemic events. Infectious exposures are atypical cardiovascular risk factors requiring methodological and paradigmatic departures from traditional risk factor investigation approaches. Several parameters of pathogen activity have been mechanistically mapped to immune and vascular processes that induce and aggravate atherosclerosis and can upregulate physiological states that are directly linked to triggering ischemic events. Elevated specific antibody titers in serum samples have been exploited to create objective measures of historical exposures to pathogens. This chapter reviews the following domains supporting Infectious Burden (IB) [or synonymously pathogen burden (PB)] and its association with stroke risk: (1) vascular, immune, and infectious dynamic frameworks for research; (2) hypothesized pathogen mechanisms influencing stroke risk, and important individual characteristics that may biologically interact with infection; (3) molecular exposure measurement tools and single pathogen association with stroke; (4) statistical measurement approaches to IB and selected evidence that evaluates IB associates with stroke; and (5) the current state in public health and clinical intervention strategies.