The effects of hourly differences in air pollution on the risk of myocardial infarction: case crossover analysis of the MINAP databaseBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d5531 (Published 20 September 2011) Cite this as: BMJ 2011;343:d5531
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We are grateful for the thoughtful comments from Mills and Newby on
our study investigating the short-term associations between pollution
levels and risk of myocardial infarction (MI). We agree that our data
were consistent with some prothrombotic effect of air pollution, but we
concluded from the lack of any apparent net increase in short-term MI risk
associated with pollution increases that other, perhaps non-thrombotic,
mechanisms may be more important drivers of the pollution-associated net
mortality increases that have been observed previously.
The various valid points that Mills and Newby raise do not seem to
challenge this basic interpretation. They point out that the harvesting
phenomenon that we observed is consistent with an effect of traffic-
related pollution on coronary thrombosis, and we agree: were there no such
effect, we would not have expected to see any association between
pollution levels and MI risk at all. A number of experimental studies also
point to plausible pathways through which pollution might trigger MI.
Our findings were consistent with such a triggering effect, as we observed
a transiently increased risk of MI for up to 6 hours after exposure. This
is also consistent with the very short-term and transient observed effects
of diesel exposure on ST-segment changes in the correspondents' own
experimental work. However our data did not support an effect of
pollution on the overall MI risk over a 72-hour lag period; any pollution-
associated triggering of MIs appeared to result only in short-term
displacement (the bringing forward of MI events by a few hours or days).
In contrast with our observations for MI, short-term increases in broader
mortality outcomes after pollution peaks do not appear to be explained by
short-term displacement alone, hence our conclusion that other
mechanisms may be more important drivers of net mortality increases.
A number of important limitations of our data are raised by Mills and
Newby. As we discuss at some length in the manuscript, we used data from
central pollution monitors to capture pollution levels across
conurbations. Unpublished data from our group suggest that correlations
between pollution levels measured at different sites within a conurbation
remain high at several kilometres distance; nevertheless, this strategy is
likely to have led to some degree of measurement error, and may have
resulted in a bias towards the null in single pollutant models. Hales and
Edwards point out in their editorial accompanying our article that this
factor could explain a missed or underestimated effect, but not the
temporal (harvesting) pattern that we observed. In large-scale studies
of this type using routinely collected data, there is inevitably a trade-
off between study size and proximity of monitoring sites; restricting to
individuals living very close to a monitor would result in drastically
reduced study power. Predicted small-area pollution levels based on
spatial models may offer a solution to this dilemma in future studies, by
allowing a more personalised exposure without restrictive geographical
inclusion criteria; however, such modelled data would require careful
The MINAP dataset, which holds detailed timing data on acute coronary
events, offered an unprecedented opportunity to study associations at an
hourly temporal resolution in a large scale study. As Mills and Newby
point out, one disadvantage is that MIs resulting in death before hospital
admission are not recorded; MIs resulting in death at any time following
hospital admission would of course have been included. We find it
intuitively unlikely that pollution would be associated with a net
increase only in those MIs that resulted in death before hospital
admission, and yet no net increase at all in the remainder of MIs that
were admitted to hospital. However, we cannot exclude the possibility that
high levels of pollutants could exacerbate the severity of an MI and thus
the probability of early death by amplifying the thrombotic process. We
would therefore welcome future research clarifying this issue, using
alternative data sources which incorporate out-of-hospital deaths.
Finally, our study did not attempt to assess the impact of chronic
exposure to air pollution on MI risk. Whilst it is valid to consider acute
effects as a separate phenomenon, pollution policy must also be based on
an assessment of long-term risks. Unfortunately, the evidence base
regarding the long-term effects of air pollution exposure on MI risk
specifically is limited; only a handful of studies have been carried out,
and potential confounding by factors such as socioeconomic status and
occupation hampers many study designs. The development of methods and
strategies to clarify the long-term effects of pollution on specific
diseases should be a priority for future research in this area.
1. Bhaskaran K, Hajat S, Armstrong B, Haines A, Herrett E, Wilkinson
P, et al. The effects of hourly differences in air pollution on the risk
of myocardial infarction: case crossover analysis of the MINAP database.
BMJ. 2011; 343: d5531.
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4. Mills NL, ouml, rnqvist H, Gonzalez MC, Vink E, Robinson SD, et
al. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in
men with coronary heart disease. N Engl J Med 2007, Sep 13; 357(11):1075-
82 [The New England journal of medicine]; 2007.
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6. Hales S, Edwards R. Cardiovascular effects of exposure to air
pollution. Bmj. 2011; 343: d5814.
7. Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, Smeeth L.
Effects of ambient temperature on the incidence of myocardial infarction.
Heart. 2009; 95(21): 1760-9.
Competing interests: No competing interests
Bhaskaran and colleagues report findings from the Myocardial
Ischaemia National Audit Project (MINAP) in which they observed an
association between traffic-related air pollution and the onset of
symptoms in patients hospitalised for acute myocardial infarction (1). The
excess risk was only evident 1 to 6 hours after a 10 micrograms/m3
increase in particulate matter (PM10) or nitrogen dioxide with no overall
increase in hospitalisation for myocardial infarction over the 72-h period
after exposure. They conclude that exposure to traffic-related air
pollution results in displacement or harvesting with events brought
forward by a few hours that would have occurred anyway and suggest that
mechanisms other than thrombosis and myocardial infarction are responsible
for the excess in mortality associated with higher levels of air
We challenge the authors' interpretation of these findings and
suggest that an effect of traffic-related air pollution on coronary
thrombosis is entirely consistent with the harvesting phenomenon
described. We have previously demonstrated acute prothrombotic and
ischaemic effects of air pollution in healthy persons and patients with
coronary heart disease exposed under carefully controlled conditions to
diesel engine exhaust (2,3). Many patients with coronary atherosclerosis
have subclinical plaque rupture and intra-coronary thrombus is present in
15% of such patients (4). Most patients do not progress to acute
myocardial infarction, and many who do, have prodromal symptoms. Given
these observations, we have often wondered why previous studies of air
pollution have not shown a harvesting effect because a prothrombotic
mechanism would be predicted to cause both a harvesting effect and an
increase in the overall incidence of events. This is because of the high
prevalence of subclinical coronary thrombosis and the central role of
thrombosis in acutely triggering of myocardial infarction. What
alternative explanation do the authors propose to explain this harvesting
A number of limitations may have resulted in an underestimation of
the effect of air pollution on the incidence of myocardial infarction. The
strongest associations between short and long-term exposure to air
pollution and outcome are for cardiovascular death (5) and these patients
were not captured in the MINAP dataset. It is plausible that exposure to
traffic-related air pollution not only brings forward the onset of acute
myocardial infarction in vulnerable individuals, but that this in turn
increases cardiovascular death with the exclusion of patients not
surviving to reach hospital an important source of bias when using the
MINAP dataset. Exposure misclassification is likely to be an equally
important confounder with exposure estimates from 10 of the 15
conurbations studied based on a single fixed monitoring site within each
conurbation. Sensitivity analysis should include stratification based on
distance of residence from the central monitoring site. Given these
limitations and the observation that a majority of deaths from long-term
exposure to air pollution are due to coronary heart disease (6), it seems
counter-intuitive to conclude that the association between short-term
exposure to traffic-related air pollution and cardiovascular mortality is
not mediated through acute myocardial infarction. Moreover, associations
with the long-term risk of cardiovascular disease represent the
accumulation of acute events, principally myocardial infarction and sudden
cardiac death, and the short and long-term effects of air pollution are
NLM is supported by an Intermediate Clinical Research Fellowship from
the British Heart Foundation (FS/1/024/28266) and DEN is supported by the
British Heart Foundation Chair (CH/09/002). DEN and NLM hold a British
Heart Foundation Programme Grant into the cardiovascular effects of air
1. Bhaskaran K, Hajat S, Armstrong B, Haines A, Herrett E, Wilkinson
P, Smeeth L. The effects of hourly differences in air pollution on the
risk of myocardial infarction: case crossover analysis of the MINAP
database. BMJ 2011 343:d5531; doi:10.1136/bmj.d5531.
2. Lucking AJ, Lundback M, Mills NL, Faratian D, Barath SL, Pourazar
J, Cassee FR, Donaldson K, Boon NA, Badimon JJ, Sandstrom T, Blomberg A,
Newby DE. Diesel exhaust inhalation increases thrombus formation in man.
Eur Heart J. 2008;29(24):3043-51.
3. Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD,
Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE.
Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men
with coronary heart disease. N Engl J Med. 2007;357(11):1075-82.
4. Newby. Triggering of acute myocardial infarction. Heart
5. Pope CA 3rd, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski
D, Godleski JJ. Cardiovascular mortality and long-term exposure to
particulate air pollution. Epidemiological evidence of general
pathophysiological pathways of disease. Circulation. 2004;109(1):71-77.
6. Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH,
Anderson GL, Kaufman JD. Long-term exposure to air pollution and incidence
of cardiovascular events in women. N Engl J Med. 2007;356(5):447-458.
Competing interests: No competing interests
Higher rates of hospitalization and bigger mortality from cardiovascular illnesses have been observed during periods of greater environmental pollution.
In Santiago de Cuba, a Cuban province, a higher risk of death from cardiovascular diseases has also been demonstrated in relation
to the concentrations of PM, being highest for
fine particled material (FPM), especially in those aged 65 and over.
Recent epidemiological studies have discarded a simple association or false
relationship between the periods of more concentration of environmental
particles and the increment of deaths and hospitalizations for ischemic
Recently, in diabetic patients (who are highly sensitive to the effects of
cardiovascular diseases (CVD)) exposed to increments of FPM, it has
been observed that the risk of hospitalization for cardiac illness has
been twice as high as that in the general population and with an associated increase in mortality.
It has been observed that patients with chronic diseases, especially
lung infections, also have higher risk of hospitalizations for CVD when
they are exposed to atmospheric contamination.
Studies in humans have centred on the effects of FPM on the
variability of heart rate (HR) and in changes in
repolarization on electrocardiography (ECG). Normal people exposed in an intermittent and alternate form over 2 hours to
inhalation of air and of particles of coal of 10 to 25 ug/m3 during
exercise showed in continuous ECG parasympathetic attenuated post-exercise during exposure to fine
ultra particles. This diminished response didn't last more than 3 hours.
Also, in the same experiments ultrafine
particles altered ventricular repolarization. The increase in the QT interval induced
by exercise inhaling air was attenuated with exposure to FPM
and the effect persisted at least 21 hours later. Therefore, the
modification of the QT (corrected) was not explained by change in the
heart frequency. It is possible that the changes of the ventricular
repolarization can be due to an indirect effect, via the autonomous nervous
system, or to a direct effect on the ionic exchange in the ventricular
myocardium by unknown mechanisms. Also, these changes could
influence the appearance of cardiorespiratory arrest in people with
and without diagnosed cardiac illness.
The clinical studies in humans have extended to the implications of the
effect of FPM in patients with preexisting cardiac illness,
relating it to the variability of the heart rate of the repolarization
and of the enzymatic dysfunctions and proteins studied classically in
Diverse biological mechanisms have been studied to explain the significant
association between the concentration of atmospheric particled material and
excess of mortality and morbidity from CVD. Such mechanisms include the
alteration of the autonomous nervous system, inflammation,
immunity, free radicals and endothelial damage.
The polluting material is formed by particles in suspension and
toxic gases. The particulate material is classified as fine
particles, of less than 2,5 microns, and bigger particles, of 10 microns; the
small particles are associated more strongly with excess mortality.
The toxic gases are ozone (O3), SO2, NO2, CO2 and other volatile
On the basis mainly of experimental studies outlined by the investigators pathogenic mechanisms have been hypothesised. Particles enter the lung, where their interaction determines a series of effects, including those that
highlight changes in autonomous tone, inflammation, citoquinas action,
increase of free radicals or substances reactivate the O2 (also
denominated substances ROS or reactivate oxygen species), allergy and respiratory infection. These changes would cause diverse effects at
distance, as activation leucocitaria in the blood, alterations in
clotting, changes in the concentration of O2 and of the acid-base
mechanism and, in outstanding form, endothelial dysfunction at the level of
the cardiovascular system. Such changes can be due as much to the
particled material as to their reaction products.
Competing interests: No competing interests