Air pollution below US regulatory standards and cardiovascular diseases using a double negative control approach

Growing evidence suggests that long-term air pollution exposure is a risk factor for cardiovascular mortality and morbidity. However, few studies have investigated air pollution below current regulatory limits, and causal evidence is limited. We use a double negative control approach to examine the association between long-term exposure to air pollution at low concentration and cardiovascular hospitalizations among US Medicare beneficiaries aged ≥65 years between 2000 and 2016. The expected values of the negative outcome control (preceding-year hospitalizations) regressed on exposure and negative exposure control (subsequent-year exposure) are treated as a surrogate for omitted confounders. With analyses separately restricted to low-pollution areas (PM_2.5 < 9 μg/m³, NO₂ < 75.2 µg/m³ [40 ppb], warm-season O₃ < 88.2 μg/m³ [45 ppb]), we observed positive associations of the three pollutants with hospitalization rates of stroke, heart failure, and atrial fibrillation and flutter. The associations generally persisted in demographic subgroups. Stricter national air quality standards should be considered.