Relationship between fine particulate air pollution and ischaemic heart disease morbidity and mortality

Abstract

Objective To assess the relationship between fine particulate matter (PM2.5) concentration and ischaemic heart disease (IHD) morbidity and mortality.
Methods A time-series study conducted in Beijing from 1 January 2010 to 31 December 2012. Data on 369 469 IHD cases and 53 247 IHD deaths were collected by the Beijing Monitoring System for Cardiovascular Diseases, which covers all hospital admissions and deaths from IHD from Beijing's population of 19.61 million.
Results The mean daily PM2.5 concentration was 96.2 μg/m3 with a range from 3.9 to 493.9 μg/m3. Only 15.3% of the daily PM2.5 concentrations achieved WHO Air Quality Guidelines target (25 μg/m3) in the study period. The dose–response relationships between PM2.5 and IHD morbidity and mortality were non-linear, with a steeper dose–response function at lower concentrations and a shallower response at higher concentrations. A 10 μg/m3 increase in PM2.5 was associated with a 0.27% (95% CI 0.21 to 0.33%, p<2.00×10−16) increase in IHD morbidity and a 0.25% (95% CI 0.10 to 0.40%, p=1.15×10−3) increase in mortality on the same day. During the 3 years, there were 7703 cases and 1475 deaths advanced by PM2.5 pollution over expected rates if daily levels had not exceeded the WHO target.
Conclusions PM2.5 concentration was significantly associated with IHD morbidity and mortality in Beijing. Our findings provide a rationale for the urgent need for stringent control of air pollution to reduce PM2.5 concentration.

Full text

ORIGINAL ARTICLE
Relationship between fine particulate air pollution
and ischaemic heart disease morbidity and mortality
Wuxiang Xie,
1
Gang Li,
2
Dong Zhao,
1
Xueqin Xie,
3
Zaihua Wei,
2
Wei Wang,
1
Miao Wang,
1
Guoxing Li,
4
Wanru Liu,
3
Jiayi Sun,
1
Zhangrong Jia,
1
Qian Zhang,
1
Jing Liu
1
▸Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
heartjnl-2014-306165).
1
Department of Epidemiology,
Beijing Anzhen Hospital,
Capital Medical University,
Beijing Institute of Heart, Lung
and Blood Vessel Diseases,
Beijing, China
2
Information Statistics Center,
Beijing Center for Diseases
Prevention and Control,
Beijing, China
3
Beijing Public Health
Information Center, Beijing,
China
4
Department of Occupational
and Environmental Health,
School of Public Health, Peking
University, Beijing, China
Correspondence to
Professor Jing Liu, Department
of Epidemiology, Beijing
Anzhen Hospital, Capital
Medical University, Beijing
Institute of Heart, Lung and
Blood Vessel Diseases, No. 2
Anzhen Street, Chaoyang
District, Beijing, China;
ejingliu@163.com
Received 6 May 2014
Revised 16 September 2014
Accepted 3 October 2014
Published Online First
23 October 2014
▸http://dx.doi.org/10.1136/
heartjnl-2014-306379
▸http://dx.doi.org/10.1136/
heartjnl-2014-306800
To cite: Xie W, Li G,
Zhao D, et al.Heart
2015;101:257–263.
ABSTRACT
Objective To assess the relationship between fine
particulate matter (PM
2.5
) concentration and ischaemic
heart disease (IHD) morbidity and mortality.
Methods A time-series study conducted in Beijing from
1 January 2010 to 31 December 2012. Data on
369 469 IHD cases and 53 247 IHD deaths were
collected by the Beijing Monitoring System for
Cardiovascular Diseases, which covers all hospital
admissions and deaths from IHD from Beijing’s
population of 19.61 million.
Results The mean daily PM
2.5
concentration was
96.2 μg/m
3
with a range from 3.9 to 493.9 μg/m
3
. Only
15.3% of the daily PM
2.5
concentrations achieved WHO
Air Quality Guidelines target (25 μg/m
3
) in the study
period. The dose–response relationships between PM
2.5
and IHD morbidity and mortality were non-linear, with a
steeper dose–response function at lower concentrations
and a shallower response at higher concentrations.
A10μg/m
3
increase in PM
2.5
was associated with a
0.27% (95% CI 0.21 to 0.33%, p<2.00×10
−16
)
increase in IHD morbidity and a 0.25% (95% CI 0.10 to
0.40%, p=1.15×10
−3
) increase in mortality on the
same day. During the 3 years, there were 7703 cases
and 1475 deaths advanced by PM
2.5
pollution over
expected rates if daily levels had not exceeded the WHO
target.
Conclusions PM
2.5
concentration was significantly
associated with IHD morbidity and mortality in Beijing.
Our findings provide a rationale for the urgent need for
stringent control of air pollution to reduce PM
2.5
concentration.
INTRODUCTION
Industrialisation has historically been accompanied
by air pollution.
1
With spectacular economic
growth during the past three decades, China has
become the largest energy consumer and the
second-largest economy in the world. Meanwhile,
air pollution has become a serious issue in China.
2
From 21 February 2014 to 26 February 2014,
heavy smog lingered over Beijing, and the govern-
ment raised the city’s smog alert to the second
highest level for the very first time and maintained
it for 132 h because the concentration of fine par-
ticulate matter (PM
2.5
)—that which is ≤2.5 mmin
aerodynamic diameter—measured over 400 μg/m
3
.
3
A meta-analysis that combined the results from
13 studies solely using either mortality or admis-
sion data reported that PM
2.5
pollution was
significantly associated with the risk of myocardial
infarction.
4
However, to fully reflect the association
between PM
2.5
and ischaemic heart disease (IHD),
both non-fatal and fatal cases and both in-hospital
and out-of-hospital deaths, should be considered.
Moreover, this meta-analysis did not include
studies from developing countries where PM
2.5
pollution is more severe, so the association between
PM
2.5
and IHD at very high levels of pollution is
still unclear.
A cohort study explored the exposure–response
relationship for cardiovascular mortality in relation
to PM
2.5
from active smoking, second-hand smoke
and ambient air pollution, and found that the
exposure–response function is extremely steep at
very low estimated PM
2.5
exposure levels and flat-
tens out at high levels.
5
However, the shape of the
dose–response relationship between PM
2.5
and car-
diovascular risk in a real and severe air pollution
environment is still unclear.
Therefore, we conducted this study in Beijing to
explore the short-term dose–response relationship
between PM
2.5
and IHD morbidity and mortality
at city level. Such information is crucial for
evidence-based policy making regarding clinical
practice, public health, air pollution and even eco-
nomic development.
METHODS
PM
2.5
and weather data
The US embassy Beijing Air Quality Monitor is
atop the embassy building located in Chaoyang dis-
trict, reporting hourly PM
2.5
concentrations using
an automatic Met One BAM-1020 βattenuation
monitor (Met One Instruments, Grants Pass,
Oregon, USA).
67
A previous study has demon-
strated that the data from the monitor exhibited
approximately the same trend as citywide PM
2.5
concentrations.
8
In online supplementary figure S1,
the station is at the centre of the red circle, with a
radius of 40 km defined as previous studies.
9
Coverage includes 79.2% of Beijing’s total popula-
tion and all areas of high population density
(>5000 people/km
2
). The area also covers 97.8%
(44/45) of the tertiary hospitals and 79.3% (69/87)
of the secondary hospitals in Beijing that admit
IHD cases. If the cumulative time of missing hourly
PM
2.5
data was <12 h during a day, that day was
considered as qualified and the daily averaged
PM
2.5
concentration was calculated directly
Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165 257
Cardiac risk factors and prevention

(1060 days). Otherwise, daily averages were calculated using
linear interpolation (36 days).
Meteorological data on daily mean temperature, relative
humidity and dew-point temperature were obtained from the
China Meteorological Data Sharing Service System.
10
Health data
The resident population of Beijing was 19.61 million, according
to data from the 2010 National Population Census. IHD cases
were identified by the Beijing Monitoring System for
Cardiovascular Diseases which links the routinely collected
records in the Beijing Hospital Discharge Information System
and the Beijing Vital Registration Monitoring System.
11
The
Hospital Discharge Information System is operated by the
Beijing Public Health Information Center and covers discharges
from all government and private hospitals at secondary or ter-
tiary level in Beijing.
12
Hospital discharges of IHD were identi-
fied according to the primary discharge diagnosis with the
International Classification of Diseases Tenth Revision (ICD-10)
codes of I20-I25. The Vital Registration Monitoring System is
managed by Beijing Center for Disease Control and Prevention
and covers all deaths in Beijing.
13
Deaths due to IHD, including
both those in and out of hospital, were identified according to
the underlying causes of death, with ICD-10 codes of I20–I25
and I46.
Cases of IHD were identified by linking records of hospital
admissions and deaths. A total of 340 819 IHD admissions and
53 247 IHD deaths were collected by our monitoring systems
during the 1096 days. Any hospital admissions or death records
for the same patient that occurred within 28 days (n=24 597)
were assumed to relate to one case and were excluded.
14 15
Finally, 369 469cases of IHD morbidity were analysed. These
included 199 209 cases of acute IHD (I20.0 and I21–I22), 111
851cases of chronic IHD (I25) and 58 409 cases of other types
of IHD (I20.1, I20.8, I20.9 and I23–I24). Mortality outcomes
included 53 247 IHD deaths, among which 13 867 and 39 380
deaths occurred in and out of hospital, respectively.
Statistical analyses
Daily data of IHD cases or deaths, PM
2.5
concentration and
weather variables were linked by date and, therefore, can be
analysed with a time-series design. Because morbidity and mor-
tality from IHD were rare, we fit the following generalised addi-
tive Poisson model to explore the association between PM
2.5
and IHD:
Log[E(Yt)]¼intercept + day of week + ps(calendar time, 10)
þpsðtemperature;6)
þps(dew-point temperature, 3) +
b
PM2:5
where E(Y
t
) represents the number of IHD cases or deaths at
day t; the day of week was controlled for as a categorical vari-
able; ps represents penalised spline function and βrepresents
the log-relative risk of IHD morbidity or mortality associated
with a unit increase of PM
2.5
. Relative risks of IHD morbidity
and mortality with a 10 μg/m
3
increase in PM
2.5
concentration
were calculated. Percentage change equals relative risk minus 1
and then multiplies by 100. The Z test was used to compare the
two relative risks derived from subgroup analysis.
16
Degrees of freedom (df ) for calendar time, temperature and
dew-point temperature were selected based on the parameters
used in the previous studies,
17 18
and were further tested by sen-
sitivity analyses.
We used the smoothing function to graphically analyse the
dose–response relationship between the log-relative risk of mor-
bidity or mortality and PM
2.5
concentration. To estimate the
associations between PM
2.5
concentration and IHD morbidity
and mortality, we fitted the models with different lag structures
from lag 0 day to lag 4 days. Considering that single-day lag
models might underestimate the associations,
19
we used the
3-day and 5-day moving averages of PM
2.5
concentrations (lag
0–2 days and lag 0–4 days, respectively). We adjusted for tem-
perature and dew-point temperature on the day when the cases
or deaths occurred in the single-day lag models, and adjusted
for the 3-day means of the two meteorological variables in the
lag 0–2 days model, or the 5-day means in the lag 0–4days
model.
Potential autocorrelations in the case and death data were
accessed by the plots of autocorrelation functions for the resi-
duals from the current-day models, and no clear evidence of
autocorrelation was found (see online supplementary figure S2).
The IHD cases and deaths advanced by PM
2.5
pollution was
estimated based on the population-attributable risk fraction
(PARF), which was calculated as (relative risk–1)/relative risk,
assuming that the prevalence of exposure to air pollution was
100%.
The following equations were used to calculate the IHD cases
and deaths advanced by PM
2.5
pollution over expected rates if
daily levels had not exceeded the target:
IHD cases advanced by PM
2.5
pollution=
P
1096
t¼1
PMtTarget
100 PARFlag0 337

;
IHD deaths advanced by PM
2.5
pollution=
P
1096
t¼1
PMtTarget
100 PARFlag0 49

;
where PM
t
is the PM
2.5
concentration at day t. PARF
lag0
is the
PARF for lag 0 day; 337 and 49 is the average number of daily
cases and deaths, respectively. When (PM
t
–Target) <0, the
number of cases or deaths advanced by PM
2.5
pollution at day t
was set to 0.
All statistical analyses were performed using R Programming
Language (V.3.0.2, R Development Core Team) using the
NLME, MGCV and TSMODEL packages.
RESULTS
IHD morbidity and mortality
Of the 369 469 IHD cases that occurred during the study
period, 59.9% of the data were male cases and 44.6% were
under 65 years of age. Among 53 247 IHD deaths, 74.0%
occurred out of hospital (table 1). On average, 337 IHD cases
(range: 111 to 743) and 49 IHD deaths (range: 21 to 92)
occurred per day.
PM
2.5
concentration and weather conditions
During the 1096 days, the mean daily PM
2.5
concentration was
96.2 μg/m
3
, with a range from 3.9 to 493.9 μg/m
3
(table 2). Only
47.4% (519 days) of the daily PM
2.5
concentrations achieved the
target of Chinese Ministry of Environmental Protection 2010
(75 μg/m
3
), 22.2% (243 days) achieved the target of the US National
Ambient Air Quality Standards (35 μg/m
3
) and 15.3% (168 days)
258 Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165
Cardiac risk factors and prevention

achieved the target of WHO Air Quality Guidelines (25 μg/m
3
).
Weather conditions are also shown in table 2.
Associations between PM
2.5
concentration and IHD risk
There were clear dose–response relationships of PM
2.5
concen-
tration with IHD morbidity and mortality ( figure 1). These rela-
tionships are non-linear with a steeper dose–response function
at lower concentrations (0–75 μg/m
3
) and a shallower response
at higher concentrations.
As shown in table 3, after adjusting for day of the week, sea-
sonality and other time-varying influences and weather condi-
tions, a 10 μg/m
3
increase in PM
2.5
was associated with a 0.27%
(95% CI 0.21 to 0.33%, p<2.00×10
−16
) increase in IHD mor-
bidity and a 0.25% (95% CI 0.10 to 0.40%, p=1.15×10
−3
)
increase in IHD mortality on the same day. Significant lag asso-
ciations of PM
2.5
with IHD morbidity were observed at lag 1, 2
and 3 days, whereas, no significant lag association with IHD
mortality was noted. Both 3-day and 5-day average concentra-
tions significantly associated with IHD morbidity and mortality.
The current day and lag 0–2 days associations of PM
2.5
with
different types of IHD were all significant (figure 2). A signifi-
cantly stronger lag association was found for chronic IHD cases
versus acute cases (lag 3 days) and for non-fatal cases versus
fatal cases (lag 1, 2, 3 and 4 days), while no significant differ-
ence was observed for the associations of PM
2.5
with in-hospital
deaths versus out-of-hospital deaths.
The associations of PM
2.5
with IHD by age and gender
Among people aged ≥65 years, current-day, 3-day and 5-day
average of PM
2.5
were significantly associated with both IHD
morbidity and mortality (figure 3). However, for those aged
<65 years, significant associations were only found with IHD
morbidity. A significantly stronger association of PM
2.5
with
IHD morbidity on the same day was found for people aged
≥65 years than for those aged <65 years (p=0.028). The
Table 1 Number of cases and deaths from ischaemic heart disease (IHD) in Beijing from 2010 to 2012 by sex and age groups
Men Women
<45 years 45–64 years ≥65 years <45 years 45–64 years ≥65 years
IHD cases 13 971 105 553 101 902 1 653 43 723 102 667
Acute 7526 56 738 55 354 765 22 194 56 632
Chronic 3423 25 911 33 210 547 13 435 35 325
Others 3022 22 904 13 338 341 8 094 10 710
IHD deaths 959 6 335 21 317 190 2 035 22 411
In-hospital 83 961 6 360 29 423 6 011
Out-of-hospital 876 5 374 14 957 161 1 612 16 400
Table 2 Distribution of daily data on fine particulate matter
(PM
2.5
) and weather conditions in Beijing from 2010 to 2012
Days
Mean
±SE Min 25th 50th 75th Max
PM
2.5
(μg/m
3
) 1096 96.2±2.2 3.9 39.6 78.2 130.3 493.9
Temperature (°C) 1096 13.0±0.4 –13 2 15 24 35
Relative humility
(%)
1096 50.4±0.6 9 33 52 67 97
Dew-point
temperature (°C)
1096 1.9±0.4 –28.4 –9.7 2.4 15.0 25.9
Figure 1 Smoothed plots of concentration of fine particles (degree of
freedom=3) against the risk of morbidity (A) and mortality (B) from
ischaemic heart disease (IHD). The X-axis is the current-day (lag 0 day)
fine particulate matter (PM
2.5
) concentrations (mg/m
3
). Y-axis is the
predicted log (relative risk (RR)), after adjusting for calendar time, day
of the week, current-day temperature, and dew-point temperature, is
shown by the solid line, and the dotted lines represent the 95% CI.
Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165 259
Cardiac risk factors and prevention

associations of 3-day or 5-day average concentration with both
IHD morbidity and mortality were significantly stronger among
the older people (p<0.05).
The associations of current-day, 3-day and 5-day average of
PM
2.5
with IHD morbidity and mortality were all significant
among men and women (figure 3). The current-day association
with IHD morbidity was stronger in women than in men
(p=0.019). However, no gender difference was observed for
IHD mortality.
IHD cases and deaths advanced by PM
2.5
pollution
As shown in table 4, there were 4099 cases and 855 deaths
advanced by PM
2.5
pollution over expected rates if daily levels
had not exceeded the Chinese target (75 μg/m
3
) during the
study period. The corresponding numbers were 6860 cases and
1312 deaths for the US target (35 μg/m
3
) and 7703 cases and
1475 deaths for WHO target (25 μg/m
3
).
Results of sensitivity analyses
Online supplementary figure S3 presents the percentage change
in IHD morbidity and mortality associated with a 10 μg/m
3
increase in PM
2.5
, under different df for calendar time, tempera-
ture and dew temperature. The estimate became stable when df
for calendar time is closer to 10, while increasing df has little
effect on the estimates for temperature and dew temperature,
suggesting that the findings on the associations of PM
2.5
concen-
tration with IHD morbidity and mortality are robust.
To evaluate the potential effect of excluding the 24 597 cases
reported within 28 days for the same patient, sensitivity analyses
were conducted by including these cases. As shown in online
supplementary table S1, similar results have been found.
DISCUSSION
This study provides strong evidence of the associations of PM
2.5
with IHD morbidity and mortality in Beijing. These dose–response
relationships are non-linear with a steeper dose–response function
at lower concentrations and a shallower response at higher
concentrations.
The exploration of the dose–response relationship between
PM
2.5
concentration and IHD risk is crucial to determine the
pattern and scope of the adverse response. A cohort study con-
ducted in 1.2 million American adults evaluated the exposure–
response relationship for cardiovascular mortality in relation to
PM
2.5
from active cigarette smoking, second-hand smoke and
ambient air pollution.
5
The results suggested a relatively steep
dose–response function at very low levels of PM
2.5
and a flatten-
ing out at high levels, which is consistent with our results. To
the best of our knowledge, our study provides the first city-level
investigation of the dose–response relationship between PM
2.5
pollution and IHD risk in a real and severe air pollution envir-
onment. The finding that an increase in PM
2.5
at very low levels
was sufficient to induce a significant adverse response on IHD
morbidity and mortality implies that there is no threshold for
safety of PM
2.5
pollution. This result is supported by other
time-series studies conducted in the USA
17 20
and also sup-
ported by a recent cohort study conducted in Europe, which
indicated that even in concentration ranges well below the
present European annual mean limit value (<25 mg/m
3
), PM
2.5
concentration is associated with natural-cause mortality and inci-
dence of acute coronary events.
21 22
These findings strongly
support that policymakers would be justified in reducing targets
for PM
2.5
concentration. Although at higher PM
2.5
concentra-
tions the slope of the curve became shallower, the risk contin-
ued to rise as PM
2.5
concentration was higher, implying that
there is no saturation effect for the risk of IHD at a level of
PM
2.5
concentration as high as 500 mg/m
3
.
Several time-series studies conducted in Western countries
have evaluated the association of PM
2.5
and cardiovascular
admissions, and the results are inconsistent. The Medicare
Cohort Air Pollution Study (MCAPS) using Medicare files with
11.5 million individuals older than 65 years of age, reported
that a 10 μg/m
3
increase in PM
2.5
concentration was related to
0.44% (95% CI 0.02% to 0.86%) increase in IHD admission,
17
an association close to the finding for patients at the same age
group in our study. However, the study conducted in Finland,
including 20 007 admissions for coronary heart disease, found
no association between PM
2.5
and coronary heart disease admis-
sions, probably due to the extremely low level of air pollution
in that study.
23
Possibly because of the higher level of PM
2.5
pollution in
Beijing, a longer lag association was noted in our study than the
previous results, which reported a lag of 1–2days.
17 24
Interestingly, we found a significantly stronger lag association
for chronic IHD cases versus acute cases and for non-fatal cases
versus fatal cases, a difference which has not been reported pre-
viously as far as we know. A possible reason for this difference
is that the time lag between symptoms onset and the hospitalisa-
tion in chronic IHD or non-fatal IHD cases was longer. Besides,
the findings from a recent study may partly explain the differ-
ence from the perspective of underlying biological mechanisms.
The study revealed that exposure to higher levels of air pollu-
tion lead to acute inflammatory and prothrombotic responses in
the early lag period, followed by a gradual decrease in effect
estimates to often negative effects due to compensatory
mechanisms.
25
The updated American Heart Association scientific statement
on Particulate Matter Air Pollution and Cardiovascular Disease
suggested that the elderly are a susceptible population; however,
the evidence is limited, especially for morbidity.
26
The MCAPS
study found the association of PM
2.5
with IHD admission rate
was stronger among the population aged ≥75 years than among
those aged 65–74 years, but that the difference was not
Table 3 Percentage change and 95% CI in morbidity and
mortality from ischaemic heart disease associated with a 10 μg/m
3
increase in fine particulate matter (PM
2.5
) concentration for different
lag days
Percentage change (95% CI) p Value
Morbidity
Lag 0 days 0.27 (0.21 to 0.33) <2.00×10
−16
Lag 1 days 0.16 (0.11 to 0.21) 5.56×10
−10
Lag 2 days 0.15 (0.10 to 0.19) 7.76×10
−11
Lag 3 days 0.07 (0.03 to 0.12) 9.18×10
−4
Lag 4 days 0.02 (–0.02 to 0.07) 3.00×10
−1
Lag 0–2 days 0.35 (0.28 to 0.43) <2.00×10
−16
Lag 0–4 days 0.25 (0.16 to 0.34) 2.43×10
−8
Mortality
Lag 0 days 0.25 (0.10 to 0.40) 1.15×10
−3
Lag 1 days 0.00 (–0.13 to 0.13) 9.67×10
−1
Lag 2 days –0.11 (–0.23 to 0.00) 5.72×10
−2
Lag 3 days –0.17 (–0.28 to –0.05) 3.95×10
−3
Lag 4 days –0.11 (–0.22 to 0.01) 6.25×10
−2
Lag 0–2 days 0.34 (0.14 to 0.53) 7.12×10
−4
Lag 0–4 days 0.26 (0.03 to 0.49) 2.94×10
−2
260 Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165
Cardiac risk factors and prevention

significant.
17
In this study, we provide clear evidence to support
that people older than 65 years are more sensitive to PM
2.5
pol-
lution. These findings indicate that older persons are more sensi-
tive to the elevated PM
2.5
and should stay at home when PM
2.5
concentration is extremely high. Using a face mask may also be
considered, given the evidence that it could reduce symptoms
and improve a range of cardiovascular health measures in
patients with IHD.
27
Furthermore, we found a stronger associ-
ation of PM
2.5
with IHD morbidity on the same day in women
than in men. This is supported by the previous systematic
review which reported that more studies of adults report stron-
ger associations among women, possibly because of increased
deposition of fine particles, higher airway hyper-responsiveness
to oxidants or relatively lower socioeconomic status.
28
Compared with previous studies, our study has several
strengths. First, morbidity and mortality data were collected
from an established monitoring system which covers all deaths
and all hospital admissions of IHD in Beijing. The large number
of patients allowed us to examine the associations at high levels
of validity and reliability. Second, all hospital admissions and
death records for the same patient that occurred within 28 days
were excluded, so the potential dilution of the effect from inter-
hospital transfers and rehospitalisations related to the same
event was reduced as much as possible. Third, given the high
Figure 2 Percentage change and 95% CI in morbidity and mortality from ischaemic heart disease (IHD) associated with per 10 μg/m
3
increase in
fine particulate matter (PM
2.5
) concentration by types of IHD: acute versus chronic cases, fatal versus non-fatal cases and in-hospital versus
out-of-hospital deaths. *p Value obtained from Z test for the difference between the two relative risks derived from subgroup analysis.
Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165 261
Cardiac risk factors and prevention

level of pollution in Beijing, we were able to evaluate the dose–
response relationship in a very wide range of PM
2.5
concentrations.
This study also has some limitations. First, multiple compari-
sons have been conducted to evaluate the associations of PM
2.5
with IHD among several subgroups. Therefore, false positive
associations would likely have occurred simply by chance.
Second, because public data from other stations were not avail-
able until 2013,
29
our assessment of PM
2.5
was derived entirely
from the single monitoring station in the US embassy, Beijing.
This station covers all areas with high density of population, but
not some remote areas in Beijing. The inclusion of patients
Figure 3 Percentage change and 95% CI in morbidity and mortality from ischaemic heart disease associated with per 10 μg/m
3
increase in fine
particulate matter (PM
2.5
) concentration by age or sex. *p Value obtained from Z test for the difference between the two relative risks derived from
subgroup analysis.
262 Xie W, et al.Heart 2015;101:257–263. doi:10.1136/heartjnl-2014-306165
Cardiac risk factors and prevention

residing farther than 40 km from the monitoring station may
result in exposure misclassification.
In conclusion, our results have demonstrated that PM
2.5
con-
centration significantly associated IHD morbidity and mortality
in Beijing. The dose–response relationships between PM
2.5
and
IHD morbidity and mortality were non-linear, with a steeper
dose–response function at lower concentrations and a shallower
response at higher concentrations. Stringent control of air pollu-
tion to reduce PM
2.5
concentration is urgently needed.
Key messages
What is already known on this subject?
Air pollution with particulate matter (PM
2.5
)≤2.5 mmin
aerodynamic diameter increases cardiovascular risk and is a
serious problem in Beijing, China. However, most particle–
outcome relationship studies in China focused solely on mortality.
What might this study add?
This study adds to the literature that a non-linear dose–response
association exists between PM
2.5
and ischaemic heart disease
(IHD) morbidity and mortality, with a steeper dose–response
function at lower concentrations and a shallower response at
higher concentrations in an environment with high
concentration of PM
2.5
, and provides a better understanding of
the upper ranges of the dose–response curve.
How might this impact on clinical practice?
These findings indicate that measures should be taken by
patients with IHD to prevent the harm of PM
2.5
pollution.
Patients with IHD, especially those older patients, should be
advised to stay indoors or use a mask on days with unusually
high air pollution levels.
Contributors JL had full access to all the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis. Study concept
and design: W.X, GL, DZ, JL. Acquisition of data: WX, GL, XX, ZW, WL, GL, JL.
Analysis and interpretation of data: WX, MW, JS, ZJ, QZ, JL. Drafting of the
manuscript: WX, DZ, JL. Critical revision of the manuscript for important intellectual
content: WX, GL, DZ, WW, JL. Statistical analysis: WX, JL. Administrative, technical,
or material support: WX, GL, DZ, JL. Study supervision: JL.
Funding This work was supported by Capital Health Research and Development of
Special (contract No. 2011-1005-01), the National Natural Science Foundation of China
(contract No. 81302503), and the National Science & Technology Pillar Program During
the Twelfth Five-Year Plan Period of China (contract No. 2011BAI08B01).
Competing interests None.
Ethics approval Our project ‘Morbidity and Mortality from Cardiovascular Disease
in Beijing: a Surveillance Study’(contract No. 2011-1005-01), has been approved by
the Anzhen Hospital Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
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Table 4 The ischaemic heart disease cases and deaths advanced
by fine particulate matter (PM
2.5
) pollution over expected rates if
daily PM
2.5
levels had not exceeded the standard targets from 2010
to 2012
Standard Targets (μg/m³) Non-attainment days Cases Deaths
China 75 577 4 099 855
USA 35 853 6 860 1 312
WHO 25 928 7 703 1 475
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