Associations between ambient air pollution and daily mortality in a cohort of congestive heart failure: Case-crossover and nested case-control analyses using a distributed lag nonlinear model

Background: Persons with congestive heart failure may be at higher risk of the acute effects related to daily fluctuations in ambient air pollution. To meet some of the limitations of previous studies using grouped-analysis, we developed a cohort study of persons with congestive heart failure to estimate whether daily non-accidental mortality were associated with spatially-resolved, daily exposures to ambient nitrogen dioxide (NO₂) and ozone (O₃), and whether these associations were modified according to a series of indicators potentially reflecting complications or worsening of health.

Methods: We constructed the cohort from the linkage of administrative health databases. Daily exposure was assigned from different methods we developed previously to predict spatially-resolved, time-dependent concentrations of ambient NO₂ (all year) and O₃ (warm season) at participants' residences. We performed two distinct types of analyses: a case-crossover that contrasts the same person at different times, and a nested case-control that contrasts different persons at similar times. We modelled the effects of air pollution and weather (case-crossover only) on mortality using distributed lag nonlinear models over lags 0 to 3 days. We developed from administrative health data a series of indicators that may reflect the underlying construct of "declining health", and used interactions between these indicators and the cross-basis function for air pollutant to assess potential effect modification.

Results: The magnitude of the cumulative as well as the lag-specific estimates of association differed in many instances according to the metric of exposure. Using the back-extrapolation method, which is our preferred exposure model, we found for the case-crossover design a cumulative mean percentage changes (MPC) in daily mortality per interquartile increment in NO₂ (8.8 ppb) of 3.0% (95% CI: -0.4, 6.6%) and for O₃ (16.5 ppb) 3.5% (95% CI: -4.5, 12.1). For O₃ there was strong confounding by weather (unadjusted MPC = 7.1%; 95% CI: 1.7, 12.7%). For the nested case-control approach the cumulative MPC for NO₂ in daily mortality was 2.9% (95% CI: -0.9, 6.9%) and for O₃ 7.3% (95% CI: 3.0, 11.9%). We found evidence of effect modification between daily mortality and cumulative NO₂ and O₃ according to the prescribed dose of furosemide in the nested case-control analysis, but not in the case-crossover analysis.

Conclusions: Mortality in congestive heart failure was associated with exposure to daily ambient NO₂ and O₃ predicted from a back-extrapolation method using a land use regression model from dense sampling surveys. The methods used to assess exposure can have considerable influence on the estimated acute health effects of the two air pollutants.