Ambient Air Pollution and Atherosclerosis: Insights Into Dose, Time, and Mechanisms

Ambient air pollution due to particulate matter ≤2.5 μ is the leading environmental risk factor contributing to global mortality, with a preponderant majority of these deaths attributable to atherosclerotic cardiovascular disease (ASCVD) causes such as stroke and myocardial infarction. Epidemiological studies in humans have provided refined estimates of exposure risk, with evidence suggesting that risk association with particulate matter ≤2.5 levels and ASCVD continues at levels well below air quality guidelines in North America and Europe. Mechanistic studies in animals and humans have provided a framework of understanding of the duration and pathways by which air pollution exposure may predispose to atherosclerosis. Although acute exposure to particulate matter ≤2.5 is associated with oxidative stress and inflammation, system transmission of signals from the lungs to extrapulmonary sites may involve direct translocation of components, biologic intermediates, and autonomic nervous system activation. End-organ effector pathways such as endothelial barrier disruption/dysfunction, thrombosis, vasoconstriction/increased blood pressure, and plaque instability, may contribute to ASCVD. The strength of the association of air pollution with ASCVD offers an opportunity to mitigate its consequences. Although elimination of anthropogenic sources of air pollution with a switch to clean energy provides the ultimate solution, this may not be possible in the interim and may require personal protection efforts and an integrated approach to managing risk posed by air pollution for ASCVD.