Our study did not show associations between two-hour or 24-hour air pollution levels and the onset of myocardial infarction. This is in conflict with the first study from Boston [13
] but in line with the findings from Augsburg [16
] and Seattle [17
]. Analyses of possible effect modifiers used in previous studies, as well as of others not previously examined, did not show any associations for any of the air pollutants in any subgroup and none of the interactions between air pollutants and the covariates was statistically significant at the 0.05 level. This is remarkable in light of the fact that we estimated a total of 168 odds ratios and performed 80 interaction tests without any correction for multiplicity. The pollutants are correlated with each other and so are some of the modifiers, reducing the number of truly independent estimates. Even so, it would not have been surprising had we found a few estimates where the 95% confidence interval excluded unity.
As mentioned earlier, there are three previously reported studies that used similar temporal precision as we did when investigating the relationship between air pollution exposure and the onset of myocardial infarction. In order to compare our study in more detail with the other three, we provide a comparison of background characteristics in and air pollution levels and main results in . The adjusted odds ratios presented in are scaled to show the OR for an increase of the same unit increase across all four studies. There are several differences between the four studies. In comparing the effect estimates the Boston study stands out when it comes to the particle exposure even though showing levels similar to other studies. For the other pollutants all four studies report similar effect estimates. In contrast to the other investigated cities, Boston is in an area in which fine PM is dominated by sulfate. The sulfates are formed from sulfur dioxide emitted mainly from coal-burning power plants and other industrial sources, such as smelters, industrial boilers, and oil refineries. Although sulfates are regarded as relatively harmless in themselves, they may function as an indicator of a harmful mixture of air pollutants. The largest difference between the present study and the previously reported studies was that we chose to focus solely on persons experiencing their first myocardial infarction. Roughly a third of patients in Boston and Seattle had previously experienced a myocardial infarction and 14% of patients in Augsburg. We also had a larger proportion of current smokers and lower proportions of patients who had previously experienced angina pectoris or had been diagnosed with diabetes or hypertension. Peters et al.
argued that the larger proportion of hypertensive patients in Augsburg might diminish the association between air pollution and myocardial infarction; however no mechanism for this was suggested. Our study population was slightly healthier than those of the other studies in terms of previous heart disease and diabetes, and one could speculate that this makes them less sensitive to air pollution as a trigger for myocardial infarction. A distinction in susceptibility for air pollution with respect to severity of myocardial infarction has been seen for long term and short-term exposure to air pollution where exposure seems to be more strongly associated to fatal myocardial infarction, especially occurring out of hospital [19
]. All cases in our study were non-fatal.
Characteristics of myocardial infarction cases: a comparison of four studies.
Air pollution profiles and effect estimates for air pollution on onset of myocardial infarction. A comparison of four studies.
This study offered the opportunity of a well-defined study population with detailed information characterizing the onset of myocardial infarction collected within a few days after diagnosis. Air pollution data was collected continuously and retrieved retrospectively, blinded to the outcome. Some limitations need to be acknowledged. The main limitation is the lack of particulate air pollution data. Only PM10
was available and only for less than half of the study period. It would have been desirable to have data for finer particles like PM2.5
and particle number concentrations in order to better compare our results with the other studies and also to address the concern that these particles are particularly important for the cardiovascular effects of air pollution. In a previous analysis from Stockholm regarding the onset of ventricular arrhythmias in response to two-hour increases in air pollution [11
], the distance between where the event occurred and the air pollution monitor influenced the observed association. This raises the concern over the influence of misclassification of exposure when using fixed monitors in collecting air pollution exposure data. In an effort to examine this we performed interaction analyses based on the location of the admitting hospital, under the assumption that a subject who was admitted to a hospital in central Stockholm was in the city when the MI occurred, and hence the exposure information from the centrally located monitors may be more representative of the actual exposure compared to a subject who was admitted to a hospital farther away from the monitors. This interaction analysis did not provide any evidence that the potential misclassification of exposure due to distance from the air pollution monitors is responsible for the lack of a positive association. The Stockholm Onset study has previously been used to analyze several other triggers for myocardial infarction and associations have been observed for episodes of anger, heavy physical exertion, sexual activity, and work related stressful life events [22
]. It is not likely that any one of these factors would act as a confounder for the association between exposure to air pollution and acute onset of myocardial infarction. In addition, although this study was comparable in size to both the Boston and Augsburg studies, it was small in comparison to the Seattle study and the possibility of false negative results remains a concern.
In summarizing the evidence from all four studies, there appears to be weak support of a rapid effect of air pollution in triggering the onset of myocardial infarction. However, evidence from other studies showing specific ischemic associations must be considered in the overall interpretation. A meta-analysis of 19 time-series studies [32
] showed a 0.8% increased risk (95% CI 0.6, 1.1) of hospital admissions for ischemic heart disease with a 10 μg/m3
short-term increase of PM10
. Animal models have demonstrated effects of air pollution on inflammation [33
], oxidative stress [34
] and endothelial dysfunction [35
] including plaque progression and destabilization in an animal model of atherosclerosis [36
]. In double-blind randomized crossover studies performed on humans in exposure chamber, ST-segment depression [37
] as well as thrombus formation and platelet activation [38
] have been demonstrated after 1–2-hour exposures to diesel exhaust. ST-segment depressions have also been shown in a panel study in the presence of ambient levels of PM2.5
and black soot [39
]. Short-term increases in air pollution were associated with unstable angina or acute myocardial infarction in patients undergoing cardiac catherization with stronger associations seen in multi-vessel coronary disease [40
]. With the exception of the meta-analysis of time-series studies, all of the above mentioned human studies investigated patients with established coronary artery disease, suggesting that this may be an important factor modifying the ischemic response to air pollution. Therefore, total absence of a real association between air pollution and myocardial infarction seems unlikely, although it may be restricted to some extent to subgroups. Future efforts might explore air pollution as a trigger for myocardial infarction in patients with established coronary disease and perhaps focus on fatal events occurring out of hospital which seem to be particularly susceptible to air pollution increases.