Trained Immunity and Cardiovascular Risk: An Immunological Perspective

Systemic inflammation is a key driver of atherogenesis and its complications. While anti-inflammatory therapies targeting pathways such as IL-1β and IL-6 have shown promise in established atherosclerotic cardiovascular disease (ASCVD), potential systemic effects raise concerns about immune suppression and infection, underscoring the need for more precise immunomodulatory approaches. Trained immunity-a form of innate immune memory-has emerged as a potential contributor linking ASCVD risk factors to chronic inflammation and disease progression. In this review, we discuss the evidence for trained immunity in ASCVD, its induction by several known risk factors (e.g., hyperglycaemia, hypercholesterolemia, diet, chronic stress, inflammatory diseases, and infection), and its potential role in sustaining vascular inflammation. Advancing our understanding of the metabolic and epigenetic mechanisms underlying trained immunity, as well as defining shared and cumulative effects across risk factors, will be critical to guide the development of next-generation targeted therapies for ASCVD prevention and treatment.