Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly.

SIGNIFICANCE: The incidence of cardiovascular events (CVEs) increases with age, representing the main cause of death in an elderly population. Aging is associated with overproduction of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function, thus predisposing elderly patients to thrombotic complications. Recent Advances: There is increasing evidence to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, upregulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with downregulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occurs during aging. This imbalance may predispose to thrombosis by enhancing platelet and clotting activation and eliciting endothelial dysfunction. Recently, gut-derived products, such as trimethylamine N-oxide (TMAO) and lipopolysaccharide, are emerging as novel atherosclerotic risk factors, and gut microbiota composition has been shown to change by aging, and may concur with the increased cardiovascular risk in the elderly. CRITICAL ISSUES: Antioxidant treatment is ineffective in patients at risk or with cardiovascular disease. Further, anti-thrombotic treatment seems to work less in the elderly population. FUTURE DIRECTIONS: Interventional trials with antioxidants targeting enzymes implicated in aging-related atherothrombosis are warranted to explore whether modulation of redox status is effective in lowering CVEs in the elderly. Antioxid. Redox Signal. 27, 1083-1124.