Atherosclerotic cardiovascular disease in aging and the role of advanced cardiovascular imaging.

Aging and inflammation are key drivers in the pathogenesis of cardiovascular disease. Aging is characterized by chronic, systemic, dysregulated inflammation and dysfunctional immune responses - termed inflammaging - that give rise to cumulative cardiovascular damage. These noxious processes promote epithelial dysfunction, immune infiltration, foam cell deposition, and calcification, which result in atherosclerotic plaque formation. With aging, epithelial and vascular smooth muscle cell senescence further contribute to atherogenesis by the acquisition of the senescence-associated secretory phenotype, consequently secreting pro-inflammatory and pro-fibrotic factors that exert autocrine and paracrine effects to perpetuate a vicious cycle of tissue aging and eventual failure. Recent evidence has affirmed the use of anti-inflammatory therapy to reduce cardiovascular risk; however, the possibility of off-target adverse effects may limit the application. Moreover, systemic inflammatory markers are not sufficiently precise in localizing cardiovascular active inflammation, and conventional cardiovascular imaging methods can only detect structural changes in late-stage disease. Targeted molecular imaging offers imaging-guided precision theragnostic and early upstream preventive approaches by delineating the cellular biological mechanisms underpinning cardiovascular inflammaging and holds the potential to revolutionize the personalized treatment of early atherosclerotic disease. Here, we examine recent developments in molecular imaging in relation to the mechanisms underlying aging-related atherosclerotic cardiovascular disease. We highlight challenges facing the translation of molecular imaging into clinical practice and propose future directions of these novel diagnostic modalities.