Association of Sulfur, Transition Metals, and the Oxidative Potential of Outdoor [Formula: see text] with Acute Cardiovascular Events: A Case-Crossover Study of Canadian Adults

BACKGROUND: We do not currently understand how spatiotemporal variations in the composition of fine particulate air pollution [fine particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text])] affects population health risks. However, recent evidence suggests that joint concentrations of transition metals and sulfate may influence the oxidative potential (OP) of [Formula: see text] and associated health impacts. OBJECTIVES: The purpose of the study was to evaluate how combinations of transition metals/OP and sulfur content in outdoor [Formula: see text] influence associations with acute cardiovascular events. METHODS: We conducted a national case-crossover study of outdoor [Formula: see text] and acute cardiovascular events in Canada between 2016 and 2017 (93,344 adult cases). Monthly mean transition metal and sulfur (S) concentrations in [Formula: see text] were determined prospectively along with estimates of OP using acellular assays for glutathione ([Formula: see text]), ascorbate ([Formula: see text]), and dithiothreitol depletion ([Formula: see text]). Conditional logistic regression models were used to estimate odds ratios (OR) [95% confidence intervals (CI)] for [Formula: see text] across strata of transition metals/OP and sulfur. RESULTS: Among men, the magnitudes of observed associations were strongest when both transition metal and sulfur content were elevated. For example, an OR of 1.078 (95% CI: 1.049, 1.108) (per [Formula: see text]) was observed for cardiovascular events in men when both copper and S were above the median, whereas a weaker association was observed when both elements were below median values ([Formula: see text] , 95% CI: 1.007, 1.031). A similar pattern was observed for OP metrics. [Formula: see text] was not associated with acute cardiovascular events in women. DISCUSSION: The combined transition metal and sulfur content of outdoor [Formula: see text] influences the strength of association with acute cardiovascular events in men. Regions with elevated concentrations of both sulfur and transition metals in [Formula: see text] should be examined as priority areas for regulatory interventions. https://doi.org/10.1289/EHP9449