This editorial refers to ‘Long-term exposure to air pollution is associated with survival following acute coronary syndrome’, by C. Tonne and P. Wilkinson, on page 1306

The first well-known episode of air pollution causing a marked mortality peak developed in London during the great smog between 5 and 9 December 1952. In those days, air pollution—owing to a combination of high atmospheric pressure, absence of wind and rain, and intensive domestic heating with low-quality coal as fuel—caused as many as 12 000 deaths. To give an idea of the dramatic dimension of that episode, the number of London victims of German bombs was 30 000 during the Second World War.1 More recently, in 2008, the World Health Organization (WHO) estimated that urban outdoor air pollution caused 1.34 million premature deaths worldwide, an annual number that can be contrasted with the 4.8 million premature deaths attributable to smoking.2 According to WHO, the impressive number of deaths attributed to bad air had increased by 16% from 2004 to 2008, with little reason to imagine that the situation has improved in subsequent recent years.2

Air pollution affects the whole planet, particularly densely populated metropolitan areas of Eastern and Southern China, Northern India, and the emerging countries of South-East Asia. Europe is not spared, particularly Benelux and the South and East of the continent. The main pollutants are distinguished as primary—such as NOx and SO2 produced directly from car traffic, industrial emissions, and domestic heating—and secondary (typically ozone), that stem from primary pollutants as a consequence of chemical reactions taking place in the atmosphere. Particulate matter (PM) in the inhaled air, primary or secondary in origin, is considered more and more as the main culprit for the pollution-related increase in global mortality, particularly for the smaller particles of <2.5 µm in aerodynamic diameter (PM2.5) and the ultrafine particles (PM0.1) that penetrate not only the alveolar gas-exchange space but also the systemic blood circulation.3 Respiratory diseases, triggered by the acute and chronic inhalation of gaseous and corpuscular airborne substances, were originally considered to be the main cause for the pollution-associated increase in mortality and morbidity. More recently, cardiovascular diseases have emerged as a greater threat to human health caused by air pollution.4 A broad summary of the evidence stemming from an array of time-series, case-crossover, and cohort studies tells us that an ∼10% increase in cardiovascular mortality is determined by a relatively modest (and thus frequently occurring) increase of 10 µg/mm3 in terms of short- and long-term exposure to PM.4 Tonne and Wilkinson5 now add to this compelling evidence further epidemiological data stemming from a huge UK database, that included >150 00 patients who had previously developed acute coronary syndromes (ACS), with a 4-year follow-up and almost 40 000 incident deaths. Their main findings were higher mortality rates for post-ACS patients exposed to higher levels of pollution, with a 20% increased risk of deaths for any 10 µg/mm3 PM2.5 increase.5

With this background, what are the mechanistic links between inhaled PM and the development of cardiovascular disease? A multitude of experimental and clinical studies indicate that thrombosis, inflammation, atherosclerosis, and automatic dysregulation interplay in this multifactorial process (Figure 1). Rodents exposed to PM doses comparable with those to which people are exposed in metropolitan areas develop platelet function abnormalities and haemostatic changes, ultimately resulting in intravascular thrombus formation.6 Activation in the lung of inflammatory cells (endothelial cells, macrophages, and circulating neutrophils) leads to a marked local increase of cytokines such as interleukin-6 that may act as a stimulus for subsequent systemic inflammation, leading in turn to hypercoagulability and enhanced thrombogenesis.7 In humans, the most significant and comprehensive mechanistic insights stem from several studies carried out by Mills et al.,8–10 who demonstrated in healthy people and patients with coronary artery disease that the finest PM contained in diesel exhaust, inhaled under controlled experimental conditions by these volunteers, inhibited vasodilatation in response to agonists, and also induced prothrombotic changes in blood such as hypofibrinolysis. Evidence for a hypercoagulable state also comes from epidemiological studies carried out in Lombardy, the densely populated Italian region in the Po river plain characterized by a particularly high degree of airborne pollution. The degree of exposure to PM was positively associated with a shortening of a global coagulation test, the prothrombin time, and higher plasma concentrations of the prothrombotic amino acid homocysteine, particularly in smokers.11,12 Pertaining to atherogenesis, exposure of apo-E-deficient animals to PM enhanced the progression of atherosclerosis, that also depended upon a proinflammatory effect of PM.13 In particular, exposed animals display an overproduction of reactive oxygen species, which are implicated in the initiation and progression of atherosclerosis via several mechanisms including oxidation of LDLs and monocyte infiltration within the vessel wall.14

Figure 1

Mechanisms of action of the inhalation of particulate matter on cardiac functions and cardiovascular disease.

Figure 1

Mechanisms of action of the inhalation of particulate matter on cardiac functions and cardiovascular disease.

These experimental data were subsequently substantiated in humans. For instance, a biomarker of atherosclerosis such as carotid intima medial thickness becomes progressively more abnormal in proportion to the annual degree of exposure to ambient PM2.5 concentrations.15 Another biomarker of atherosclerosis, coronary artery calcium content, increased in proportion to the degree of proximity of residential exposure to car traffic.16 A further mechanism of the adverse effects of PM exposure on the cardiovascular system is related to autonomic dysregulation. A number of experimental and clinical studies indicate that PM exposure decreases heart rate variability, a well-established risk factor for arrhythmias and sudden cardiac death.17 The increased sympathetic drive may be due to the activation of pulmonary neurological reflex arcs and to direct effects of pollutants on cardiac ion channels, that are also thought to be the mechanisms and mediators of the hypertensive effects of air pollution.18

All in all, there is unequivocal evidence that mechanisms such as hypercoagulability, inflammation, atherosclerosis, and autonomic dysregulation interplay to increase cardiovascular mortality and morbidity in people exposed acutely and chronically to air pollution. The increased mortality related to long- and short-term exposure to pollutants occurs principally, but not exclusively, in susceptible individuals such as the elderly, the obese, and those with diabetes and pre-existing cardiovascular disease, as shown by Tonne and Wilkinson.5

What can be done in practice to control this important cause of cardiovascular morbidity and mortality, that in several countries is becoming more and more prominent? The most important message is that reduction in the amount of pollutants in metropolitan areas does indeed decrease cardiovascular mortality within a time interval as short as a few years,19 providing at the same time strong evidence for causality and stimulus towards adequate action by public health authorities. The impressively huge number of deaths worldwide due to air pollution would be substantially reduced—by ∼ 1 million annually from the current estimate of 1.34 million—if the WHO recommendations pertaining to the limits of PM2.5 concentrations were implemented.2 The responsibility for controlling air pollution rests on national governments of the planet, that are responsible for the implementation of an array of public health measures that would help to reduce pollution. Because this formidable goal is beyond the reach of individual interventions, what can be done by clinicians who take care of patients at increased risk of cardiovascular disease owing to their exposure to air pollution? First, and most importantly, we must make patients aware of the existence of this risk, and encourage them to be cognizant of the media alerts on air quality in their living areas. Moreover, Table 1 lists a number of simple and practically feasible recommendations that may be shared with patients at risk. Finally, the European Society of Cardiology should consider developing and producing scientific statements on air pollution and cardiovascular disease, similar to those prepared and published in 2004 and 2010 by the American Heart Association.4

Table 1

Practical recommendations in order to reduce exposure to airborne pollutants

Use cars and motorbikes as little as possible: always consider public transport alternatives 
Avoid walking and cycling in streets with high traffic intensity, particularly during the rush hour. On many websites there are applications that help in the choice of the most favourable routes 
Run and exercise in parks and gardens, but avoid major traffic roads. Choose rainy rather than sunny days, because air pollution is less 
Limit taking infants outdoors during highly polluted times (i.e. rush hour or in proximity to industrial sources or narrow streets with a high level of automobile traffic). Because pollutants are higher closer to the ground, try to keep infants in baby carriers (slings or pouches) rather than in prams/pushchairs 
A diet rich in fruits and vegetables containing antioxidants may help to counteract the effects of air pollution 
Use cars and motorbikes as little as possible: always consider public transport alternatives 
Avoid walking and cycling in streets with high traffic intensity, particularly during the rush hour. On many websites there are applications that help in the choice of the most favourable routes 
Run and exercise in parks and gardens, but avoid major traffic roads. Choose rainy rather than sunny days, because air pollution is less 
Limit taking infants outdoors during highly polluted times (i.e. rush hour or in proximity to industrial sources or narrow streets with a high level of automobile traffic). Because pollutants are higher closer to the ground, try to keep infants in baby carriers (slings or pouches) rather than in prams/pushchairs 
A diet rich in fruits and vegetables containing antioxidants may help to counteract the effects of air pollution 

Conflict of interest: none declared.

References

1
Bell
ML
Davis
DL
Fletcher
T
A retrospective assessment of mortality from the London smog episode of 1952: the role of influenza and pollution
Environ Health Perspect
 , 
2004
, vol. 
112
 (pg. 
6
-
8
)
2
WHO
 
Global Health Observatory Data Reporting 2001. http://www.who.int/phe/health_topics/outdoorair/databases/burden_disease/en/index.html (4 January 2013)
3
Mills
NL
Amin
N
Robinson
SD
Anand
A
Davies
J
Patel
D
de la Fuente
JM
Cassee
FR
Boon
NA
Macnee
W
Millar
AM
Donaldson
K
Newby
DE
Do inhaled carbon nanoparticles translocate directly into the circulation in humans?
Am J Respir Crit Care Med
 , 
2006
, vol. 
173
 (pg. 
426
-
431
)
4
Brook
RD
Rajagopalan
S
Pope
CA
III
Brook
JR
Bhatnagar
A
Diez-Roux
AV
Holguin
F
Hong
Y
Luepker
RV
Mittleman
MA
Peters
A
Siscovick
D
Smith
SC
Jr
Whitsel
L
Kaufman
JD
American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism
Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association
Circulation
 , 
2010
, vol. 
121
 (pg. 
2331
-
2378
)
5
Tonne
C
Wilkinson
P
Long-term exposure to air pollution is associated with survival following acute coronary syndrome
Eur Heart J
 , 
2013
, vol. 
34
 (pg. 
1306
-
1311
)
6
Nemmar
A
Hoet
PH
Dinsdale
D
Vermylen
J
Hoylaerts
MF
Nemery
B
Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis
Circulation
 , 
2003
, vol. 
107
 (pg. 
1202
-
1208
)
7
Mutlu
GM
Green
D
Bellmeyer
A
Baker
CM
Burgess
Z
Rajamannan
N
Christman
JW
Foiles
N
Kamp
DW
Ghio
AJ
Chandel
NS
Dean
DA
Sznajder
JI
Budinger
GR
Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway
J Clin Invest
 , 
2007
, vol. 
117
 (pg. 
2952
-
2961
)
8
Mills
NL
Tornqvist
H
Robinson
SD
Gonzalez
M
Darnley
K
Macnee
W
Boon
NA
Donaldson
K
Blomberg
A
Sandstrom
T
Newby
DE
Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis
Circulation
 , 
2005
, vol. 
112
 (pg. 
3930
-
3936
)
9
Mills
NL
Tornqvist
H
Gonzalez
MC
Vink
E
Robinson
SD
Soderberg
S
Boon
NA
Donaldson
K
Sandström
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
, vol. 
357
 (pg. 
1075
-
1082
)
10
Mills
NL
Miller
MR
Lucking
AJ
Beveridge
J
Flint
L
Boere
AJ
Fokkens
PH
Boon
NA
Sandstrom
T
Blomberg
A
Duffin
R
Donaldson
K
Hadoke
PW
Cassee
FR
Newby
DE
Combustion-derived nanoparticulate induces the adverse vascular effects of diesel exhaust inhalation
Eur Heart J
 , 
2011
, vol. 
32
 (pg. 
2660
-
2671
)
11
Baccarelli
A
Martinelli
I
Zanobetti
A
Grillo
P
Hou
LF
Bertazzi
PA
Bertazzi
PA
Mannucci
PM
Schwartz
J
Exposure to particulate air pollution and risk of deep vein thrombosis
Arch Intern Med
 , 
2008
, vol. 
168
 (pg. 
920
-
927
)
12
Baccarelli
A
Zanobetti
A
Martinelli
I
Grillo
P
Hou
L
Lanzani
G
Mannucci
PM
Bertazzi
PA
Schwartz
J
Air pollution, smoking, and plasma homocysteine
Environ Health Perspect
 , 
2007
, vol. 
115
 (pg. 
176
-
181
)
13
Sun
Q
Wang
A
Jin
X
Natanzon
A
Duquaine
D
Brook
RD
Aguinaldo
JG
Fayad
ZA
Fuster
V
Lippmann
M
Chen
LC
Rajagopalan
S
Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model
JAMA
 , 
2005
, vol. 
294
 (pg. 
3003
-
3010
)
14
Araujo
JA
Barajas
B
Kleinman
M
Wang
X
Bennett
BJ
Gong
KW
Navab
M
Harkema
J
Sioutas
C
Lusis
AJ
Nel
AE
Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress
Circ Res
 , 
2008
, vol. 
102
 (pg. 
589
-
596
)
15
Künzli
N
Jerrett
M
Garcia-Esteban
R
Basagaña
X
Beckermann
B
Gilliland
F
Medina
M
Peters
J
Hodis
HN
Mack
WJ
Ambient air pollution and the progression of atherosclerosis in adults
PLoS One
 , 
2010
, vol. 
5
  
e9096
16
Hoffmann
B
Moebus
S
Möhlenkamp
S
Stang
A
Lehmann
N
Dragano
N
Schmermund
A
Memmesheimer
M
Mann
K
Erbel
R
Jöckel
KH
Heinz Nixdorf Recall Study Investigative Group
Residential exposure to traffic is associated with coronary atherosclerosis
Circulation
 , 
2007
, vol. 
116
 (pg. 
489
-
496
)
17
Pope
CA
III
Verrier
RL
Lovett
EG
Larson
AC
Raizenne
ME
Kanner
RE
Schwartz
J
Villegas
GM
Gold
DR
Dockery
DW
Heart rate variability associated with particulate air pollution
Am Heart J
 , 
1999
, vol. 
138
 (pg. 
890
-
899
)
18
Dvonch
JT
Kannan
S
Schulz
AJ
Keeler
GJ
Mentz
G
House
J
Benjamin
A
Max
P
Bard
RL
Brook
RD
Acute effects of ambient particulate matter on blood pressure: differential effects across urban communities
Hypertension
 , 
2009
, vol. 
53
 (pg. 
853
-
859
)
19
Pope
CA
III
Ezzati
M
Dockery
DW
Fine-particulate air pollution and life expectancy in the United States
N Engl J Med
 , 
2009
, vol. 
360
 (pg. 
376
-
386
)

Author notes

The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.
doi:10.1093/eurheartj/ehs480.

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