Long-Term Exposure to Air Pollution and Survival After ACS
Long-Term Exposure to Air Pollution and Survival After ACS
In this study of a large population of patients with advanced ischaemic heart disease, long-term exposure to air pollution was associated with all-cause mortality. The association was strongest for PM2.5 concentrations; there was no evidence of an association for the other pollutants. Whereas small-area income deprivation explained a substantial amount of the association between PM2.5 and mortality, exposure to PM2.5 explained little of the large socioeconomic gradient in mortality rate. The association between PM2.5 and mortality was not sensitive to adjustment for other measures of socioeconomic deprivation, including a random intercept for admitting hospital, or more flexibility in our model of time trends.
The primary strengths of our study are its large size, including a patient population from all of England and Wales, and detailed data on in-hospital treatments, discharge drugs, and patient characteristics which allowed for comprehensive confounder adjustment. One of the main limitations was the lack of cause-specific death, which limited our ability to analyse mortality outcomes in more detail. The majority of deaths among these ACS survivors is likely to be due to cardiovascular causes, although we cannot rule out that deaths influenced by air pollution were due to non-cardiovascular causes. The spatial resolution of the exposure model was fairly modest and corresponded to background concentrations, limiting our ability to investigate the role of local sources such as traffic. Exposure was assigned to individuals based on their postcode of residence at time of first admission. Complete data on residential history were not available; however, we explored the stability of residential postcodes over time among individuals who were re-admitted to hospital. There was no change in postcode for 75% of patients who were re-admitted, and the postcode centroid changed by ≤300 m for 90%. Although individual-level deprivation data were unavailable, we adjusted for area-level deprivation as well as for individual-level smoking and clinical history, which are likely to be important mediators of the relationship between an individual's socioeconomic position and prognosis. Several studies have shown that area-level measures of deprivation are more correlated with air pollution exposure, and comprehensive adjustment using area-level measures can essentially remove the correlation between individual-level deprivation and air pollution exposure. Although we adjusted for drugs prescribed at discharge, no data were available on drugs taken during the follow-up or for secondary prevention measures, which may have resulted in some residual confounding.
This study advances the field in several ways. First, our study provides the most comprehensive accounting for important differences in case management across hospitals through a combination of using detailed clinical data on treatments within the MINAP database and allowing each hospital to have its own baseline hazard. Differences across hospitals and potential clustering of patients within hospitals have not been accounted for in similar studies. Second, the most comparable study in terms of size assigned exposure at the county level using ambient monitors and was consequently restricted to urban areas. Third, the detailed data within MINAP allowed for comprehensive adjustment for confounding, particularly for smoking and discharge drugs which were not available for previous studies. Finally, our study provides evidence that particulate air pollution exposure does not contribute substantially to socioeconomic inequalities in post-MI prognosis. This hypothesis has been discussed in the literature, but not tested.
Our results for PM2.5 are consistent with a broad body of evidence indicating that PM in this size range is especially relevant for cardiovascular mortality. The biological plausibility of our findings is supported by accumulating evidence that pulmonary oxidative stress and inflammation in response to inhaled particles lead to systemic oxidative damage and inflammation as well as consequent endothelial dysfunction, increased thrombosis, and plaque vulnerability. Brief exposure to combustion-related particles among MI survivors has been shown to promote myocardial ischaemia and inhibit fibrinolytic capacity. Evidence from both human and animal studies suggests that long-term exposure to particulate air pollution enhances the progression and instability of underlying atherosclerosis via inflammatory processes, thereby promoting further ischaemic events. This evidence is supported by epidemiological findings of an association with the occurrence of MI as well as cardiovascular mortality. Our findings of a positive association between long-term exposure to air pollution and mortality were specific to PM2.5, which was somewhat unexpected given that exposure to PM2.5 was highly correlated with PM10. The confidence intervals for the PM10 association were wider than those of NO2 and NOx, for which the evidence of a null association was clearer.
Studies with large numbers of events among the general population are required to answer the question of whether MI survivors are more susceptible to the effects of air pollution compared with the general population. We were not able to address this question in this study. If MI survivors are found to be more susceptible, this could have important public health implications. Thirty-day mortality for ACS has fallen year on year in England and Wales, leading to a growing number of MI survivors for whom air pollution may pose an elevated risk that receives relatively little attention in clinical settings.
In conclusion, we observed an association between long-term exposure to PM2.5 and all-cause mortality among patients with a previous ACS event. Exposure to air pollution explained relatively little of the large socioeconomic gradient in survival. The extent to which this population is at higher risk of death compared with the general population and implications for secondary prevention in this population requires further investigation.
Discussion
In this study of a large population of patients with advanced ischaemic heart disease, long-term exposure to air pollution was associated with all-cause mortality. The association was strongest for PM2.5 concentrations; there was no evidence of an association for the other pollutants. Whereas small-area income deprivation explained a substantial amount of the association between PM2.5 and mortality, exposure to PM2.5 explained little of the large socioeconomic gradient in mortality rate. The association between PM2.5 and mortality was not sensitive to adjustment for other measures of socioeconomic deprivation, including a random intercept for admitting hospital, or more flexibility in our model of time trends.
The primary strengths of our study are its large size, including a patient population from all of England and Wales, and detailed data on in-hospital treatments, discharge drugs, and patient characteristics which allowed for comprehensive confounder adjustment. One of the main limitations was the lack of cause-specific death, which limited our ability to analyse mortality outcomes in more detail. The majority of deaths among these ACS survivors is likely to be due to cardiovascular causes, although we cannot rule out that deaths influenced by air pollution were due to non-cardiovascular causes. The spatial resolution of the exposure model was fairly modest and corresponded to background concentrations, limiting our ability to investigate the role of local sources such as traffic. Exposure was assigned to individuals based on their postcode of residence at time of first admission. Complete data on residential history were not available; however, we explored the stability of residential postcodes over time among individuals who were re-admitted to hospital. There was no change in postcode for 75% of patients who were re-admitted, and the postcode centroid changed by ≤300 m for 90%. Although individual-level deprivation data were unavailable, we adjusted for area-level deprivation as well as for individual-level smoking and clinical history, which are likely to be important mediators of the relationship between an individual's socioeconomic position and prognosis. Several studies have shown that area-level measures of deprivation are more correlated with air pollution exposure, and comprehensive adjustment using area-level measures can essentially remove the correlation between individual-level deprivation and air pollution exposure. Although we adjusted for drugs prescribed at discharge, no data were available on drugs taken during the follow-up or for secondary prevention measures, which may have resulted in some residual confounding.
This study advances the field in several ways. First, our study provides the most comprehensive accounting for important differences in case management across hospitals through a combination of using detailed clinical data on treatments within the MINAP database and allowing each hospital to have its own baseline hazard. Differences across hospitals and potential clustering of patients within hospitals have not been accounted for in similar studies. Second, the most comparable study in terms of size assigned exposure at the county level using ambient monitors and was consequently restricted to urban areas. Third, the detailed data within MINAP allowed for comprehensive adjustment for confounding, particularly for smoking and discharge drugs which were not available for previous studies. Finally, our study provides evidence that particulate air pollution exposure does not contribute substantially to socioeconomic inequalities in post-MI prognosis. This hypothesis has been discussed in the literature, but not tested.
Our results for PM2.5 are consistent with a broad body of evidence indicating that PM in this size range is especially relevant for cardiovascular mortality. The biological plausibility of our findings is supported by accumulating evidence that pulmonary oxidative stress and inflammation in response to inhaled particles lead to systemic oxidative damage and inflammation as well as consequent endothelial dysfunction, increased thrombosis, and plaque vulnerability. Brief exposure to combustion-related particles among MI survivors has been shown to promote myocardial ischaemia and inhibit fibrinolytic capacity. Evidence from both human and animal studies suggests that long-term exposure to particulate air pollution enhances the progression and instability of underlying atherosclerosis via inflammatory processes, thereby promoting further ischaemic events. This evidence is supported by epidemiological findings of an association with the occurrence of MI as well as cardiovascular mortality. Our findings of a positive association between long-term exposure to air pollution and mortality were specific to PM2.5, which was somewhat unexpected given that exposure to PM2.5 was highly correlated with PM10. The confidence intervals for the PM10 association were wider than those of NO2 and NOx, for which the evidence of a null association was clearer.
Studies with large numbers of events among the general population are required to answer the question of whether MI survivors are more susceptible to the effects of air pollution compared with the general population. We were not able to address this question in this study. If MI survivors are found to be more susceptible, this could have important public health implications. Thirty-day mortality for ACS has fallen year on year in England and Wales, leading to a growing number of MI survivors for whom air pollution may pose an elevated risk that receives relatively little attention in clinical settings.
In conclusion, we observed an association between long-term exposure to PM2.5 and all-cause mortality among patients with a previous ACS event. Exposure to air pollution explained relatively little of the large socioeconomic gradient in survival. The extent to which this population is at higher risk of death compared with the general population and implications for secondary prevention in this population requires further investigation.