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28 Current Pharmaceutical Design, 2016, 22, 28-51

Air Pollution Exposure and Blood Pressure: An Updated Review of the Literature

Paolo Giorginia*, Paolo Di Giosiaa, Davide Grassia, Melvyn Rubenfireb, Robert D. Brookb and Claudio Ferria

a
Department of Life, Health and Environmental Sciences, Division of Internal Medicine and Nephrology, Univer-
sity of L’Aquila, L’Aquila, Italy; bDivision of Cardiovascular Medicine, University of Michigan, Ann Arbor,
Michigan, USA

Abstract: Both high arterial blood pressure (BP) and elevated levels of fine particulate matter (PM2.5) air pollution
have been associated with an increased risk for several cardiovascular (CV) diseases, including stroke, heart failure,
and myocardial infarction. Given that PM2.5 and high BP are each independently leading risk factors for premature
mortality worldwide, a potential relationship between these factors would have tremendous public health repercus-
sions. Therefore, the aim of this review is to summarize recent evidence linking air pollution and BP. Epidemiol-
ogical findings demonstrate that particulate pollutants cause significant increases in BP parameters in relation to
both short and long-term exposures, with robust evidence for exposures to PM2.5. Moreover, recent epidemiological
studies suggest a positive association between residence within regions with higher levels of ambient PM and an
increased incidence and prevalence of overt hypertension. Studies provide consistent results that elevated concentrations of pollutants in-
crease hospital admissions and/or emergency visits for hypertensive disorders and also support that PM levels increases BP in vulnerable
subsets of individuals (pregnant women, high CV risk individuals). In this context, PM-mediated BP elevations may be an important
pathway which acts as a potential triggering factor for acute CV events. Mechanistic evidence illustrates plausible pathways by which
acute and chronic exposures to air pollutants might disrupt hemodynamic balance favoring vasoconstriction, including autonomic imbal-
ance and augmented release of various pro-oxidative, inflammatory and/or hemodynamically-active mediators. Together these responses
may underlie PM-induced BP elevations; however, full details regarding the responsible mechanisms require further studies. As a conse-
quence of the ubiquity of air pollution, even a small effect on raising BP and/or the prevalence of hypertension, i.e. the major risk factor
for mortality and morbidity worldwide, would have enormous global public health implications.

Keywords: Air pollution, particulate matter, blood pressure, hypertension, cardiovascular risk, public health, epidemiology, endothelial
dysfunction.

INTRODUCTION CV risk factors, BP is strongly and directly related to CV mortality

Air pollution is a major environment-related health threat. In
2010, household pollution and ambient particulate matter (PM)
were the 3rd and 9th leading risk factors for premature morbidity and
mortality worldwide, respectively [1]. A vast array of studies
strongly supports that PM2.5 air pollution is causally-related to car-
diovascular (CV) diseases [2]. Short-term exposures to high levels
of PM rapidly increase the risk for myocardial infarction, stroke,
heart failure exacerbation, arrhythmia and CV-related death. The
most recent meta-analysis demonstrates that a 10 g/m3 increase in
fine particulate matter (PM2.5, mean diameter < 2.5 m) leads to a
2.5% elevation in risk for myocardial infarctions over the following
few days [3]. The CV risks related to longer-term exposures are 5 to
10-fold larger [2, 4]. Several gaseous pollutants, including carbon
monoxide (CO), oxides of nitrogen (NOx) and ozone (O3), have
also been associated with increased morbidity or mortality from CV
causes [2-11]. The large literature linking air pollution with CV
disorders and exploring the underlying biological mechanisms in-
volved has been extensively reviewed during the past few years [2,
11-14].
From a mechanistic standpoint, the inhalation of several air
pollutants has proven capable of triggering acute autonomic imbal-
ance as well as promoting the release of a variety of pro-oxidative,
inflammatory and/or hemodynamically-active mediators into the
systemic circulation [2]. As a consequence, numerous adverse re-
sponses - including elevations in blood pressure (BP) - potentially
capable of instigating acute CV events among susceptible individu-
als have been observed following exposures [2]. In the context of
*Address correspondence to this author at the University of L’Aquila, De-
partment of Life, Health and Environmental Sciences - San Salvatore Hospi-
tal, Delta 6 Building - V.le San Salvatore, Coppito (L’Aquila), 67100. Italy;
Tel/Fax: +39 +862 368621; E-mail: pa.giorgini@gmail.com
[15] and ranked as the leading risk factor for global disease burden,
accounting for more than 9 million deaths in 2010 [1]. While higher
levels of both PM and BP are each individually linked to premature
morbidity and mortality, a biological inter-connection between
these 2 leading risk factors (i.e., air pollution actually causes higher
BP) could represent an unprecedented threat to global public health
[1].
The principal aim of this review is to summarize recent evi-
dence linking air pollution and BP among human studies. Given
limitations on size and the clinical perspective of this review, ani-
mal exposure and toxicological studies are not presented; nonethe-
less, there are numerous basic science experiments that support the
association between air pollution and BP. We are aware of a similar
prior review [16] published in 2009 discussing the relationship
between BP and air pollution and of two recent meta-analyses in-
vestigating the associations of air pollution with hypertensive dis-
orders in pregnancy [17] and of long-term traffic-related air pollu-
tion with BP and prevalent hypertension [18]. Moreover, we aim to
provide researchers and healthcare professionals with an updated
overview of the complex biological mechanisms interacting be-
tween air pollution, arterial dysfunction, BP, and global CV risk.
AIR POLLUTION
The International Air Quality Guidelines provide detailed
summaries of gaseous and PM air pollutants as well as their con-
centrations from a regulatory standpoint [19-21].
In brief, primary pollutants are directly emitted into the atmos-
phere principally during the process of fossil fuel combustion and
comprise various gases such as sulfur dioxide (SO2), carbon mon-
oxide (CO), volatile organic compounds, oxides of nitrogen (NOx)
[nitric oxide (NO) and nitrogen dioxide (NO2)], as well as carbona-
ceous and non-carbonaceous primary particles [e.g., ultrafine parti-

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Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 29

cles (UFP) <0.1m in aerodynamic diameter]. Secondary pollutants
are formed within the atmosphere as a result of chemical reactions
between primary pollutants and natural atmospheric compounds
and include tropospheric ozone (O3) and secondary particles of
complex characteristics including PM2.5 (PM < 2.5 m in aerody-
namic diameter) [14].
PM is composed by both solid and liquid components that vary
in chemistry and size from <0.1 m (i.e., UFP), through the PM2.5
size range, to larger coarse PM from 2.5 to 10 m. The sources of
outdoor PM vary depending upon the specific location and the par-
ticulate sizes and commonly include traffic-related emissions,
power generation (e.g., coal-fired plants), industrial processes (e.g.,
manufacturing, metal processing), construction activities, wind-
blown dust (e.g., roadways, agriculture), and wood-burning [22].
In the modern urban environment, air pollution is a mixture of
both gases and PM, the latter being comprised of thousands of dif-
ferent chemicals (e.g., organic carbon compounds, sulfates, and
nitrates). The principal sources of pollution faced by most individu-
als within contemporary North American and European societies
are regional pollutants impacting hundreds of square miles such as
tropospheric O3 and secondary PM aerosols derived from the proc-
ess of fossil fuel combustion (e.g., coal-fired power plants). On top
of these background pollutants, individuals face the added effects
from localized areas of heightened exposures from nearby sources
such diesel exhaust (DE) and other traffic-related pollutants (NOx)
which are at highest concentrations within a few hundred meters of
point sources such as major roadways [23]. Finally, household and
indoor air pollution (e.g., cooking, biomass/solid fuel burning) are
important sources throughout the developing world. More than 3
billion people are exposed to high levels of these pollutants causing
them to be the 3rd leading cause of morbidity and mortality world-
wide [1].
HYPERTENSION
Overall hypertension prevalence is estimated to be around 30 -
40% of the general population worldwide [24] and it is expected to
grow as the population ages [25]. Hypertension is the most impor-
tant preventable contributor to morbidity and mortality worldwide
[1] and a large number of epidemiological studies support the evi-
dence that BP levels are directly related to the risk of stroke, myo-
cardial infarction, sudden death, heart failure, and kidney disease,
with a continuous log-linear relationship [15, 26, 28]. Authoritative
guidelines [29-32] generally define office high BP as values  140
mm Hg for systolic BP (SBP) and/or  90 mm Hg for diastolic BP
(DBP), with specific differences among various classifications (Ta-
ble 1). Lower cut-offs are generally accepted for home and ambula-
tory values compared with clinic ones [29, 31]. International Guide-
lines [29-32] establish that hypertension diagnosis should be based
on standard measurements of office, home and ambulatory BP,
generally by rest repeated measurements, using auscultatory or
semiautomatic methods, and sized cuffs and bladders [33, 34].
Health professional societies recommend global assessment of total
CV risk, pharmacological treatment if BP values are  140/90 mm
Hg [29, 30, 32], and, first of all, strongly endorse non pharmacol-
ogical approach (i.e., lifestyle modification, dietary treatment,
weight reduction, exercise-based regimens, meditation, and other
alternative approaches) among overall population [29, 35]. Al-
though health care providers are intensely encouraged to combat
hypertension through different strategies, less attention is paid to
other possible CV risk factors, such as air pollution [36], supporting
the need for educational efforts targeting patients and health profes-
sionals in order to educate and, therefore, reduce the detrimental
effects of air pollution on BP.
RELATIONSHIP BETWEEN AIR POLLUTION AND
BLOOD PRESSURE: EPIDEMIOLOGICAL EVIDENCE
There is mounting evidence of published studies since the pre-
vious review [16] exploring the pro-hypertensive effects of various
air pollutants. Recent original epidemiologic studies linking air
pollution and BP published after the prior review [16] are presented
in Table 2.
Short-Term Exposure Studies
The available evidence demonstrates the existence of a consis-
tent association between increased CV mortality and short-term
elevations in particulate pollution [2].
Several studies have explored the short-term effects of ambient
air pollutants on the development of high BP, with generally consis-
tent findings. In fact, most studies have established some degree of
positive relationship between short-term (
7 days) ambient outdoor
air pollution exposure and higher clinic/home BP [37-52], even
though studies were conducted in different geographical regions
(North America, South America, Europe and Asia) with relevant
variations in population characteristics (healthy subjects and high
risk patients; young and old individuals), timing of exposure (hours

Table 1. Guidelines blood pressure classifications.

JNC 7 [31] ASH/ISH [30] ESH/ESC [29]

Category
SBP DBP SBP DBP SBP DBP

Optimal <120 and <80

Normal <120 and <80 120 to 129 and/or 80 to 84

High normal 130 to 139 and/or 85 to 89

Prehypertension 120 to 139 or 80 to 89 120 to 139 or 80 to 89

Grade 1 hypertension 140 to 159 or 90 to 99 140 to 159 or 90 to 99 140 to 159 and/or 90 to 99

Grade 2 hypertension 160 or 100 160 or 100 160 to 179 and/or 100 to 109

Grade 3 hypertension 180 and/or 110

Isolated systolic hypertension 140 And <90

All values are mm Hg
BP indicates blood pressure; JNC, Joint National Committee; ASH, American Society of Hypertension; ISH, International Society of Hypertension; ESH, European Society of Hyper-
tension; ESC European Society of Cardiology; SBP, Systolic BP; DBP, diastolic BP.
30 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

Table 2. Epidemiological studies linking air pollution and blood pressure.

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Short-term (6 days). TSP concentration was associated with  hyper-

Patients with hospi- tension-related hospital admissions (p < 0.001).
Arbex et al., Araraquar Local monitor, Mean TSP level: 46.9 ± 26.4
tal admission for After further stratification, such correlation was
2010 [105] Brazil outdoor biomass
g/m3
hypertension observed only during the biomass burning
burning period (p < 0.001)

Pollutants levels in office

60 office workers workers/ truck drivers: 3
Average of the 2nd and 3rd A 10 g/m  in 8-day ambient PM10 was asso-
(M 40, age 30.3 ± Personal PM2.5: 94.6 ± 64.9/ of 3 seated rest readings, ciated with  SBP (1.0 mm Hg, 95% CI: 0.3
Baccarelli Short-term (1 to 8 days).
8) and 60 truck Beijing, 126.8 ± 68.8 g/m3; on the right arm using a to1.6, p = 0.003),  DBP (0.7mm Hg, 95%CI:
et al., 2011 Ambient outdoor and
drivers China Personal EC: 13.0 ± 4.0/17.2 ± mercury sphygmoma- 0.18 to 1.24; p-value = 0.01) in all participants.
BTDAS [37] personal exposure
(M 40, age 33.5 ± 6.6 g/m3; nometer and appropriate No differences between the two groups, and no
5.6) cuff sizes. associations with personal PM2.5 and EC
Ambient PM10: 119.5 ± 23.0 /
120.2 ± 21.5 g/m3;

2 populations: City
of Augsburg
Long-term (1 year). In the population of City of Augsburg the
Babisch et al., (N 1893, M 942, PM2.5 City of Augsburg level: Average of the 2nd and 3rd
Estimates of modeled 3 adjusted OR for a 1-g/m3  in PM2.5 was 1.2
2014 age 49.0 ± 13.9) 13.6 ± 0.9g/m of 3 rest readings, using an
Germany annual average mass (95% CI: 1.0 to 1.3), and 1.11 (95% CI: 1.0, to
KORA and Greater PM2.5 Greater Augsburg level: automatic oscillometric 1.3) after additional adjustment for noise.
concentration of parti-
Study[60] Augsburg 13.7 ± 0.9 g/m3 device
cles No association in Greater Augsburg population
(N 2273, M 104,
age 49.4 ± 13.8)

Personal PM2.5 median: 52 3 seated rest readings on A 1-log-g/m3  in PM2.5 exposure was associ-
Baumgartner Short-term (24 hours).
280 non-smoking g/m3 in summer and 105 the supported right arm in ated with  in SBP (2.2 mm Hg, 95% CI: 0.8 to
et al., 2011 Rural China Personal (indoor) expo-
women, age 51.9 g/m3 in winter accordance with standard 3.7; p = 0.003) and  in DBP (0.5 mm Hg, 95%
[38] sure
recommendations CI: –0.4 to 1.3; p = 0.3)

Baumgartner Short-term (24 hours).

240 children, M Mean PM2.5 53 g/m3 Readings using an auto-
et al., 2012 Rural China Personal indoor expo- NO associations
53%, age 10.3 Mean BC: 3.2 g/m3 mated device
[101] sure

 in SBP was associated with a 1-ln (g/m3)  in

Personal mean summer/winter Home BP measurements BC (4.3 mm Hg, p < 0.001), PM2.5 mass (2.2
Baumgartner Short-term (24 hours).
280 women, age levels:: PM2.5: 55/117 g/m3 using an automated device mm Hg; p = 0.002) and WSOM (1.2 mmHg; p =
et al., 2014 Rural China Personal indoor expo- 0.06). The effect of BC on SBP was almost 3
51.9 BC: 4/6 g/m3 and following standard
[75] sure times greater in women living near the highway
WSOM: 12/33 g/m 3 recommendations
(6.2 mmHg; 95% CI, 3.6 to 8.9 vs. 2.6 mmHg;
95% CI, 0.1 to 5.2).

Median long-term air pollu-

tion:
NO2: 21.8
g/m3
Long-term exposure to NO2 and PM2.5 absor-
Bilenko et al., Short-term (1 day) PM2.5 absorbance: 1.2 10-5/m bance was associated with  DBP in children
Seated rest readings in the who lived at the same address since birth (0.83
2013 1432 children, M Nether
estimated from air PM2.5 16.5
g/m3; PM10 24.5
non-dominant arm, with mm Hg, 95% CI: 0.06 to 1.6, p < 0.05; 0.8 mm
PIAMA 49.1%, Age 12.7 ± monitoring data.
g/m3
-lands sized cuffs, using auto-
Substudy 0.4 Long-term using a land Hg, 95% CI:-0.08 to 1.6, p = 0.08, respectively).
Median Short-term air pollu- matic device.
[100] use regression model tion: No association of BP with short-term air pollu-
tion or noise exposure
NO2 16.6
g/m3; PM10 21.4

g/m ;
3

O3 39.6
g/m3

A 10 g/m3  in total personal-level PM2.5

Brook et al., Personal PM2.5 level: 21.9 ±
65 non-smoking Short-term (1 to 5 days). Average of the 2nd and 3rd exposure was associated with  in SBP (1.4 mm
2010 Michigan, 24.8 g/m3
subjects, M 15, age Personal and ambient of 3 rest supine readings Hg; lag day 1, 95% CI: 0.8 to 2.0, p<0.001).
DEARS USA Ambient PM2.5 level: 15.4 ±
44.6 ± 15.7 outdoor exposure using automated device. No associations between community PM2.5
substudy [39] 7.5 g/m3
levels and CV outcomes
Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 31

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Daily mean personal PM2.5

Brook et al., level:
51 non-smoking Short-term (5 days). Average of 2nd and 3rd rest
2011 Michigan, No consistent relationships between PM levels
subjects, M 17%, Personal and ambient 18.0 ± 10.4 g/m3 supine readings, using
DEARS USA and BP
age 45 ± 14.3 exposure Daily mean ambient PM2.5 : automated device
substudy [40]
15.8 ± 7.6 g/m3

An IQR  in O3 (17.0 ppb) was associated with

 in SBP (0.8 mm Hg, 95% CI: 0.2 to 1.4, p <
0.05) and  in DBP (0.4 mm Hg, 95% CI: 0.04
to 0.8, p<0.05).
Short-term (
24hour). O3 level: 34.1 ± 13.0 (1 h max Average of the last 5 of 6 An IQR  PM (4.5 g/m3) was associated with
2,5
Cakmak et al., ppb) rest seated readings on the
N 5011, M 49.8%, Ambient monitoring  in SBP (0.6 mm Hg, 95% CI:0.3 to 0.9, p <
2011 Canada right arm using an auto-
age 39.3 ± 21.9 stations PM2.5 level: 6.0 ± 4.8 g/m3 0.05) and  in DBP (0.5 mm Hg, 95% CI: 0.3 to
CHMS [41] mated device and sized
NO2 level: 12.6 ± 8.6 ppb 0.8, p < 0.05).
cuff
An IQR  NO2 (IQR 12.6 ppb) was associated
with an  in SBP (1.1 mm Hg, 95% CI: 0.2 to
2.0, p < 0.05) and with  in DBP (1.3 mm Hg,
95% CI: 0.7 to 2.0, p < 0.05)

24-h mean PM10 level: 41.8 to

63.9 g/m3
Seated rest morning
24-h mean SO2 level: 1.9 to 6.9 reading using electronic Exposure to all 5 air pollutants was associated
Short-term (1 to 3 days).
ppb sphygmomanometers and with  SBP, ranging from 0.6 to 3.1 mm Hg.
N 9238, M 2922, 6 townships Single general
Chen et al., 24-h mean NO2 level: 13.9 to sized cuff on right upper Exposure to SO2, NO2, and O3 at various lag
2012 [42] age: 51.5 to 61.5 in Taiwan ambient air quality 26.1 ppb arm. Further BP meas- times was associated to  in DBP, ranging from
monitoring station in
1-h maximum CO level: 0.8 to urement with a standard 0.4 to 1.1 mm Hg.
each township mercury sphygmoma-
1.5 ppm
nometer
1-h maximum O3 level: 52 to
77.6 ppb

Long-term
35303 non hyper-
tensive adults, (follow-up 7.3 years). A 10-g/m3  of PM2.5 was associated with a 1.1
Chen et al., Ontario, Mean PM2.5 level: 10.7 g/m3 Ontario Hypertension
Estimates of ground- (95% CI, 1.0–1.2) adjusted HR of incident
2014 [61] M 47%, age 50.3 ± Canada (range, 2.9–19.2) Database
level PM2.5 concentra- hypertension.
12.0
tions

Mean PM10 level: 55.3 ± 26.2

g/m3 An IQR (34 g/m3) in day 1 average PM10 was
Chuang et al., associated with  SBP (0.5 mm Hg, 95% CI: -
Short-term (1 to 5 days). Mean O3 level: 26.8 ± 9.7 ppb Average of 2 closest of 3
2010 N 7578, M 3694, 0.09 to 1.0, p < 0.1).
Taiwan Ambient monitoring Mean NO2 level: 22.4 ± 10.1 readings of seated rest
TWSHHH age 43.1 ± 17.2 An IQR (12.2 ppb)  in day 3 average O3 was
stations ppb readings on the right arm.
[43] associated with DBP (0.4 mm Hg, 0.04 to 0.7,
Mean SO2 level: 4.4 ± 3.3 ppb p < 0.05)
Mean CO level: 0.8 ± 0.5 ppm

An IQR (48.0 g/m3)  in PM10 was associated

Mean PM10 level: 67.8 ± 33.5 with  SBP (16.3 mm Hg,95% CI: 12.3 to 20.4)
g/m3 and  DBP (14.9 mm Hg, 95%CI: 12.7 to 17.0).

Mean PM2.5 level: 35.3 ± 15.9 An IQR (20.42 g/m3)  in PM2.5 was associated
g/m3 with  SBP (32.08 mm Hg, 95% CI: 21.6 to
Chuang et al., Long-term (1 year). Average of 2 seated
N 1023, M 590, 42.6) and  DBP (31.3 mm Hg, 25.4 to 37.1).
2011 Taiwan Ambient monitoring Mean O3 level: 23.0 ± 6.8 ppb readings using mercury
age 69.1 ± 8.7 An IQR (9.0 ppb)  in O3 was associated with 
SEBAS [62] stations Mean NO2 level: 24.5 ± 9.5 sphygmomanometer
SBP (21.5 mm Hg,95% CI: 16.9 to 26.1) and 
ppb
DBP (20.6 mm Hg, 95%CI: 18.1 to 23.0).
Mean SO2 level: 4.9 ± 3.6 ppb
An IQR (12.8 ppb)  NO2 was associated with 
Mean CO level: 0.9 ± 0.5ppm SBP (14.4 mm Hg, 95%CI: 11.0 to 17.8) and 
DBP (12.4 mm Hg, 95%CI: 10.6 to 14.2).
32 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Incident case of hyperten-

Long-term (follow-up 10 3
PM2.5 level: 20.7 ± 2.1 sion defined as self-report The IRR for hypertension for a 10 g/m  in PM2.5
Coogan et al., 4204 black women, Los Ange- years).
g/m3 of was 1.5 (95% CI: 1.0 to 2.3), and the IRR for an
2012 [63] age 21 to 69 les, USA Estimated regression IQR (12.4 ppb)  in NOx was 1.1 (95% CI, 1.0–
NOx level: 43.3 ± 11 ppb doctor-diagnosed hyper-
model 1.2).
tension

9 months median level of

Long-term An IQR  in PM2.5 during the entire pregnancy
Preeclampsia was defined
st nd rd
NOx: 107.5 g/m3 (5.1 g/m3) and the 3rd trimester (7.3 g/m3) was
(1 , 2 and 3 trimes- as resting BP readings
associated with preeclampsia: ORs of 1.3 (95% CI:
ter). NO2: 55.7g/m3; PM2.5: 16.5
140/90 mm Hg and prote- 1.0 to 1.7) and 1.5 (95% CI: 1.1 to 2.0), respec-
Dadvand et Barcelona g/m3
8398 pregnancies Spatiotemporal inuria
0.3 g/dL after the
al., 2013 [83] Spain tively.
PM2.5–10: 21.7g/m3; PM10: 20th week of gestation in
exposure based on a 3 –5
An IQR (2.1 10 /m) in PM2.5 absorbance was
39.0 g/m previously normotensive
land use regression associated with preeclampsia in the 3rd trimester,
PM2.5 absorbance: 3.2 10– women
modeling framework 5 OR of 1.4 (95% CI: 1.0 to 1.9).
/m

Mean level:
BC 1.7 ± 0.8 g/m3; OC 7.8 ABPM in 2 sessions of 5 Associations of  air pollutants with  SBP and 
Los Ange-
64 CAD subjects, ± 3.7 g/m3 consecutive days during a DBP. The stronger association with OC: an IQR 
Delfino et al., les, USA Short-term (10 days).
M 38, age > 65 PM2.5 21.1 ± 11.4 g/m3; warm period and 5 con- in 5-day average OC (5.2 g/m3) was associated
2010 [44] Home outdoor exposure
years NOx: 46.6 ± 31.4 ppb secutive days during a with 8.2 mm Hg (95% CI: 3.0 to 13.4)  SBP and
cooler period 5.8 mm Hg (95% CI: 3.0–8.6)  DBP.
CO: 0.5 ± 0.3 ppm; O3: 27.1
± 11.5 ppb

In M subjects, association between prevalence rate

of hypertension and an IQR  in PM10 (IQR 19
Mean PM10 level: 123.1 ± g/m3, OR 1.2, 95% CI: 1.1 to 1.3), SO2 (IQR 20
14.6 g/m3 g/m3, OR 1.2, 95% CI: 1.1–1.3), O3 (IQR 9
Long-term g/m3, OR 1.2, 95% CI: 1.0 to 1.4).
Mean SO2 level: 54.42 ± 3 seated rest readings,
Dong et al., N 24845, M 12661, (3 year average). 14.3 g/m3 using standardized mercu- In M subjects, an IQR  in PM10 was associated
China with  in SBP (1.0 mm Hg, 95% CI: 0.5 to 1.5) and
2013 [64] age 45.6 ± 13.3 Municipal air pollution Mean NO2 level: 35.3 ± 5.5 ric-column sphygmoma-
3 nometer  in DBP (0.4 mm Hg, 95% CI: 0.1–0.8). An IQR
monitoring stations g/m
 in SO2 was associated with  in SBP (1.1 mm
Mean O3 level: 49.4 ± 14.1 Hg, 95%CI: 0.7–1.6) and  DBP (0.5 mm Hg, 95%
g/m3 CI: 0.2 to 0.8). An IQR  in O3 was associated with
 SBP (1.01mm Hg, 95% CI: 0.5–1.6) and DBP
(0.6 mm Hg, 95% CI: 0.2 to 0.9)

High levels of PM10, SO 2, NO 2, O 3, and CO were

associated with BP and hypertension.
Mean PM10 level: 88.9 ±
Average of 3 seated rest OR for hypertension ranged from 1.12 per 46.3
21.3g/m3
readings performed by g/m3  for O3 (95% CI: 1.10 to 1.13) to 1.68 per
Mean SO2 level: 49.8 ± trained nurses using 30.6 g/m3  for PM10 (95% CI, 1.53 to 1.86).
16.0g/m3 standardized mercuric
Long term exposure. The  in DBP ranged from 0.58 mm Hg per 46.3
Dong et al., 9354 children (M
Mean NO2 level: 36.4 ± sphygmomanometer, with g/m3  for O3 (95% CI, 0.52 to 0.63 mm Hg) to
4771), age 10.9 ± China Municipal air pollution
2014 [103] 11.1g/m3 an appropriate cuff size. 2.89 mm Hg per 563.4 g/m3  for CO (95% CI:
2.59 monitoring stations
Mean O3 level: 106.9 ± Hypertension defined as 2.53 to 3.24 mm Hg).
165.8g/m average SBP and DBP The  in SBP ranged from 0.50 mm Hg per 46.3
that is
95th percentile for g/m3  for O (95% CI: 0.43 to 0.57mm Hg) to
Mean CO level: 1390.6 ± 3
gender, age and height. 2.10 mm Hg per 30.6 g/m3  for PM (95% CI,
597.3g/m3 10

1.73 to 2.47 mm Hg). Non-breastfed children

exhibited consistently stronger effects.

A 10-g/m3 in NO2 levels was associated with 

SBP (1.3 mm Hg, 95% CI: 0.1 to 2.6) in non-
Foraster et al., The last of 2 or 3 rest medicated individuals.
Long-term
2014 N 3836, M 1720, Annual average NO2 level: seated readings, using a Stronger associations in participants with CV
Spain (annual average).
REGICOR age 57.0 ± 20.0 26.6 ± 11.7 g/m3 calibrated automatic disease:  SBP (6.0 mm Hg; 95% CI to 1.9, 10.1)
Study [65] Estimated model device. and  DBP (2.7 mm Hg; 95% CI: 0.2 to 5.2).
Prevalence of hypertension was not associated with
annual average NO2 levels.
Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 33

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

An IQR
of exposure to PM2.5 (2.4 g/m3) was

associated with
in SBP (1.4 mm Hg, 95% CI:
0.5 to 2.3) and
in DBP (0.9 mm Hg , 95% CI:
0.4 to 1.4).
Fuks et al., Mean PM2.5 level: 16.7 ± 1.6
Long-term (1 year). An IQR
of long-term exposure to PM10 (3.9
2011 HEINZ g/m3, Average of the 2nd and 3rd
N 4291, M 2147, Ambient validated g/m3) was associated with
in SBP (1.1 mm
NIXDORF Germany Mean PM10 level: 20.7 ± 2.6 of 3 readings using auto-
age 59.7 ± 7.8 dispersion and chemistry Hg, 95% CI: 0.2 to 2.0) and
in DBP (0.8 mm
RECALL g/m3 mated oscillometric device
transport model Hg, 95% CI: 0.3 to 1.2).
STUDY [66]
Residential proximity to high traffic and traffic
noise were associated with
prevalence of
hypertension: ORs = 1.5 (95% CI: 1.0, 2.3) and
1.3 (95% CI: 1.0, 1.6), respectively.

Short-term (5 days). An
10 g/m3 in PM2.5 and PM10 was associ-

1491 patients with Mean PM2.5 level: 102.4 g/m3
Guo et al., Beijing, ated with emergency visits for hypertension
emergency visits Ambient monitoring
2010 [106] China Mean PM10 level: 149.3 g/m3 with (ORs 1.1, 95% CI: 1.0 to 1.1 and ORs
for hypertension sites
1.0,95% CI: 1.0 to 1.1 respectively).

10 g/m3
in SO2 and NO2 was associated with

emergency visits for hypertension.
The ORs were 1.0 (95% CI: 1.0 to 1.0) for SO2
1491 patients with Short-term (5 days). Mean SO2 level: 47.5 g/m3 at lag 0 day, and 1.1 (95% CI: 1.0 to 1.1) for
Guo et al., Beijing,
emergency visits Ambient monitoring Mean NO2 level: 66.6 g/m3 NO2 at lag 3 day.
2010 [107] China
for hypertension sites After controlling for PM10, the ORs associated
with SO2 and NO2 were 1.02 (95% CI: 0.98 to
1.06) and 1.11 (95% CI: 1.04 to1.20), respec-
tively.

in 7-day NO2 was associated with  SBP (-

0.4%, 95% CI: -0.7% to -0.2%).
Short-term (7 days).
in PM10 was associated with
in SBP (1.0%,
Hampel et al., 1500 pregnant Mean NO2 level: 21.1 g/m3
France Ambient air monitoring Averaged readings 95% CI: 0.5% to 1.5%) during the 1st trimester
2011 [84] women Mean PM10 level: 19.1 g/m3
stations and  in SBP (-0.3%, 95% CI,-0.6% to 0.0 %
and -0.2%, 95% CI: -0.6% to 0.2%) during the
2nd and 3rd trimesters.

An IQR
in 5 days mean PM2.5 (3.5 g/m3)

predicts
in SBP (1.1 %, 95% CI: 0.0 to 2.2)
Daily mean level: Average of the 2nd and 3rd and
in DBP (1.0 %, 95% CI: 0.1 to 1.9).
N 70, affected by Short-term (1 to 5 days). PM2.5 8.6 g/m3; SO42– 2.2 of 3 rest seated readings,
Hoffmann An IQR
BC (0.25 g/m3) predicts
in SBP
type 2 diabetes Boston, 3 from the dominant arm,
et al., 2012 Ambient outdoor air g/m (1.7 %, 95% CI: 0.3 to 3.1) and
in DBP (1.5
mellitus, M 33, age USA using an automated oscil-
[45] pollution monitoring BC 0.60 g/m3; OC 3.5 g/m3 %, 95% CI: 0.3 to 2.6).
64.4 lometric sphygmoma-
PNC 14.5 1000/cm3; O3 25 ppb nometer In contrast, an IQR
in the 5-day mean of O3
(13.3 ppb) was associated with  in SBP (4 %,
95% CI: –6.6 to –1.4)

Mean PM2.5 level: 64.2 to

112.5 g/m3 An IQR
in PM2.5 (56.9 g/m3) in prior 30-
3 minute exposure was associated to
SBP (5.7
Mean BC level: 21 to 4 g/m
mm Hg, 95% CI: 2.9 to 8.5) and DBP (4.6 mm
Mean SO2 level: 2.4 to 11.2 Hg, 95% CI: 2.2 to 7.0).
23 of 40 CV pa- Short-term.
Huang et al., Beijing, ppb
tients, M 16, age Ambient air monitoring 24 hours ABPM Prior 12-hour BC was associated with
in DBP (
2012 [79] China Mean NO2 level: 22.9 to 33.8
65.6 ± 5.8 station 3.1 mm Hg , 95% CI: 0.4 to 5.7).
ppb
Prior 12-hour exposure to CO was associated
Mean O3 level: 51.8 to 60.5 with
in SBP (3.3 mm Hg, 95% CI: 0.0 to 6.7)
ppb and
DBP (3.5 mm Hg, 95% CI: 0.9 to 6.1)
Mean CO level: 0.9 to 2.6 ppm
34 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

PM2.5 exposure was positively associated with 

pulse pressure for those categorized as obese
Short-term (1 to 5 lag Daily mean PM2.5 level: 15.0 Average of the 2nd and 3rd
across lags 2 (4.2 mm Hg, p < 0.05) and 3 days
Kannan et al., N 348, M 99, age Michigan, days). g/m3 of 3 rest seated readings (2.6 mm Hg, p<0.05).
2010 [46] 46.3 ± 1.1, USA Ambient air quality from the right arm, using a
Waist circumference similarly modified the
monitoring sites portable cuff device.
effect of exposure to PM2.5 on pulse pressure
(4.3 mm Hg, p = 0.003)

An IQR  (20.8
g/m3 ) in outdoor 24-hour

mean PM2.5 concentration was associated with
Mean Outdoor PM2.5 level:
Short-term (24 hours). The average of last 3 of 5 an  in SBP (4.7 mm Hg, 95% CI: 1.1 to 8.2)
Jacobs et al., N 81 elderly, M 27, 24.4 ± 19.0 g/m3; consecutively rest read- and in pulse pressure ( 4.0 mm Hg, 95% CI : 1.8
Belgium Home indoor and out-
2012 [47] mean age > 80 Mean Indoor PM2.5 level: ings with an automated to 6.2) in persons on antihypertensive medica-
door monitoring tion.
device
15.5 ± 9.6 g/m3
A subset of PM constituents was found to have
robust positive associations with BP

431 pregnancies, Seated BP readings on the In the 3rd trimester SBP  in a linear fashion
Jedrychowski non-smoking, non- Short-term (1 day).
Krakow, left arm using the standard
3 across a dosage of PM2.5 and on average aug-
et al., 2012 Mean PM2.5 level: 33.6 g/m
obese, Poland Personal exposure mercury sphygmoma- mented by 6.1 mm Hg (95% CI, 0.6 to 11.6)
[85]
age 27.7 nometer with log unit of PM2.5 concentration

Mean PM10 level: 26.1 ± 4.8

g/m3
In non-smokers woman, an IQR  in PM10 (7.3
Mean PM2.5 level: 16.5 ± 2.7
Middle-term g/m3) and O3 (15.3 ppb) levels was associated
1684 pregnant g/m3 Seated readings at heart
with  SBP of 1.9 (95% CI: 0.8 to 2.9) and 1.8
Lee et al., Pittsburg, (1st trimester). level taken by nursing
women, Mean O3 level: 22.7 ± 8.6 ppb mm Hg (95% CI:1.1 to 4.6) mm Hg, respec-
2012 [87] USA Space–time interpolation staff at multiple visits
age 24.9 ± 5.9 Mean NO2 level: 18.7 ± 2.9 tively, and  DBP of 0.6 mm Hg (95% CI: 0.27
method during pregnancy
ppb to 1.47) and 1.1 mm Hg (95% CI: 0.46 to 2.71)
respectively.
Mean SO2 level: 8.6 ± 2.4 ppb
Mean CO level: 0.5 ± 0.2 ppm

Gestational hypertension IQR  in PM2.5 (4 g/m3) and O3 (16.8 ppb)

Middle-term (1st trimes- 50Th Percentile level:
was defined as BP
were associated with preeclampsia (OR = 1.15,
Lee et al., 34705 pregnancies, Pittsburg, ter). PM10: 24.8g/m3 140/90 mm Hg, whereas 95 % CI = 0.96–1.4 and OR= 1.12, 95 % CI: 0.9
2013 [86] age 29.1 USA Space–time interpolation PM2.5: 15.6 g/m3 preeclampsia was defined to 1.4), and gestational hypertension (for PM2.5
method as gestational hyperten- OR = 1.11, 95 % CI = 1.0 to 1.2; for O3 OR =
O3: 21.7 ppb
sion + proteinuria 1.12, 95 % CI = 1.0–1.3)

904 emergency Mean level:

Lin et al., visits for hyperten- PM10 :66.9
g/m3
Taiwan Air monitoring stations No association between BP and PM levels.
2013 [108] sion,
PM10 pollution standards
M 49.1% index: 84.4

An IQR (7.1 g/m3)  in personal PM2.5 was

associated with  SBP (RC: 3.4 mm Hg, SE:
Mean personal PM2.5 level: 6.3 1.43, p < 0.05).
g/m3
An IQR (0.2 g/m3)  in indoor BC was associ-
Mean indoor BC level: 0.4 ated with  SBP (RC: 3.2 mm Hg, SE: 1.0, p <
Short-term (24 hours). g/m3 0.05) and  in DBP (RC: 3.2 mm Hg, SE: 0.8, p
28 non-smoking < 0.05).
Liu et al., Winsord, Personal and ambient Mean outdoor BC level: 0.7
seniors, M 11, age Standard procedures
2009 [48] Cananda indoor and outdoor g/m3 An IQR  in outdoor BC (0.5 g/m3) was asso-
64 to 96
exposure Mean indoor PM2.5 level: 6.8 ciated with  SBP (RC: 3.2 mm Hg, SE: 1.5, p <
g/m3 0.05) and  in DBP (RC: 4.3 mm Hg, SE: 1.3, p
< 0.05).
Mean outdoor PM2.5 level:
15.3 g/m3 An IQR (3.5 g/m3)  in indoor PM2.5 was
associated with  DBP (RC: 3.4 mm Hg, SE:
1.3, p < 0.05).
Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 35

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Annual mean level:

Liu et al., Average of 2 rest seated
2014 Long-term. NO2: 23.3 g/m3 readings, with relaxed NO2, PM 2.5, PM 10 and PM2.5absorbance were not
GINIplus 2368 children Germany Land use regression PM2.5:,14.9 g/m3 elbow at heart level, using associated with BP. Only noise was associated
LISAplus model exposure PM10: 22.1 g/m3 an automated monitor and with DBP.
studies [102] sized cuffs
PM2.5 absorbance: 1.5 g/m3

Preeclampsia defined

Long-term (pregnancy). as resting BP readings
The adjusted OR for acquiring preeclampsia

Malmqvist 140/90 mm Hg and
81110 pregnant Individual-level expo- Mean NO level : 16.4 g/m3 after exposure during the 3rd trimester was 1.5
et al., 2013 Sweden x proteinuria
0.3 g/dL
women sure estimates with high (95% CI: 1.3 to 1.7) in the highest quartile of
[88] after the 20th week of
spatial resolution. NOx compared with the lowest
gestation in previously
normotensive women

Pollutant levels at 0 to 4 hours:

OR of high BP at admission to labor/delivery 
PM10: 19.7 to 19.9
g/m3 in normotensive women after exposure to NOx
Short-term (<4 hours). PM2.5: 8.9 to 9
g/m3 Clinical BP was measured (by 0.2%/5 units), SO2 (by 0.3%/1 unit), CO and
Männistö upon admission using several air toxics (by 3%–4%/high exposure).
et al., 2014
151276 pregnant
USA Three-dimensional EC: 0.2
g/m3; OC: 0.6
g/m3
women multipollutant regional CO: 486 to 505 ppb; O : 28.5 standard equipment. Similar or stronger effects among women with
[89] 3
air quality model gestational hypertension and preeclampsia.
to 29.2 ppb
Exposure to PM10  OR high BP in women with
NOx 17.9 to 19.5 ppb; SO2: 2.5
preeclampsia by 3%/5 units.
to 2.6 ppb

Pollutant level at 1st, 2nd and 3rd In non-obese women, 2 SD  in PM2.5 (7
g/m3 )
trimester: and in CO (1 ppm) were associated with  OR
CO: 0.58 to 0.7 ppm; NO : 28 [9.1 (95% CI: 3.3 to 24.6) and 5.0 (95% CI:1.9
Mobasher Long-term (pregnancy). 2
Hypertensive disorders of to 13.3), respectively] of hypertensive disorders
298 pregnant California, to 30 ppb
et al., 2013 Spatially mapped ambi- pregnancy defines as BP
women USA during 1st trimester.
[90] ent air quality data O3: 18.2 to 21.5 ppb readings
140/90 mm Hg
Positive association between exposure to O3 in
PM10 34.5 to 35.1
g/m3
the 2nd trimester and hypertensive disorders (OR
PM2.5 17 to 18.1
g/m3 2.05, 95% CI:1.22–3.46)

Average of rest seated

2 populations: BC
Mordukhovich group (461, all M,
et al., 2009 age 71.2 ± 6.5), PM
[49] group (457, all M,
age 72.2 ± 6.7)
Mean BC level: 1.1 ± 0.4 readings from the right
Greater Short-term (7days). g/m3 1-SD  in BC (0.43- g/m3) was associated with
and left arm using a stan-
Boston,  in SBP (1.5 mm Hg, 95% CI: 0.1 to 2.8) and
Ambient monitoring site Mean PM2.5 level: 12.1 ± 4.9 dard mercury sphygmo-
USA  in DBP (0.9 mm Hg, 95% CI: 0.2 to 1.6)
g/m3 manometer with a 14 cm
cuff.

A 10 g/m3  in PM10 was associated with 11 to

Mean level: 13%  in risk of hospitalization due to hyperten-
Nascimento 606 hospital admis- São José Short-term (4 days).
PM10 : 24.1 ± 12.2 g/m3 sion. RR of hospital admission ranged between
et al., 2013 sions for hyperten- dos Cam- Single monitoring
SO2 : 2.96 ± 2.2 g/m3 1.018 and 1.021 for PM10 and between 1009 and
[109] sion pos, Brazil station 1013 for PM + SO2 + O 3.
O3 : 71.5 ± 39.6 g/m3

Orru et al., Long-term (annual). Mean PM exhaust level: 0.1 The associations between PM and hypertension
N 1684, M 48%, Self-reported prevalence
3
2009 RHINE Estonia Modeled mean levels of g/m ; Mean PM10 level: 0.8 was positive but non-significant (OR 1.4, 95%
age 35 of hypertension
[67] locally emitted PM g/m3; CI 0.9 to 2.1)

Middle term In the 1st trimester, 10 g/m3  in O3 was associ-

Olsson et al., Preeclampsia defined
120755 pregnancies Sweden (1st trimester) O3 and NOx ated with pre-eclampsia (OR 1.04, 95% CI 1.01
2013 [94] according ICD-10
Local monitoring station to 1.08). No association for NOx

Preeclampsia defined as
CO 0.80 (0.59–1.02) ppm sustained pregnancy-
Rudra et al., Mixed results for CO exposure in different
3509 pregnancies USA Estimated Model induced hypertension (

2011 [95] PM2.5:10.1 (8.7–11.4) g/m3 adjusted models. No association with PM2.5
140/90 mm Hg) and
proteinuria
36 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Associations between admissions for hyperten-

Mean long-term level: sion and levels of NO2 (IQR 12.8 ppb; OR, 1.06;
N 5365 hospital 95% CI, 1.0 to 1.1), SO2 (IQR 2.3 ppb; OR, 1.0;
Szyszkowicz CO: 0.7 ppm; NO2: 21.9 ppb
admissions for Edmonton Short-term (9 days). 95% CI, 1.0-1.1), and PM10 (IQR 15.0
g/m3;
et al., 2012 hypertension, SO2: 2.6 ppb; O3: 18.6 ppb
Canada OR, 1.06; 95% CI, 1.0-1.1) for lag day 3, as
[110]
M 2069 PM10: 22.6
g/m3; PM2.5 :8.5 well as for PM10 (IQR 15.0
g/m3; OR, 1.06;

g/m3 95% CI, 1.0-1.1) and PM2.5 (IQR 6.2
g/m3; OR,
1.07; 95% CI, 1.0-1.1) for lag day 6

Long-term (1 year). An IQR  in 1-year average BC exposure (0.3

Average of seated read-
Schwartz et 853 elderly men, Boston,
g/m3 ) was associated with  in SBP (2.6 mm
Ambient estimated Mean BC levels: 0.5
g/m 3
ings from right and left
al., 2012 [68] age 72.6 ± 7.4 USA Hg, 95% CI: 1.47 to 3.80) and with  in DBP
spatio-temporal model arm, using a standard cuff.
(2.4 mm Hg, 95% CI: 1.77 to 3.05)

An IQR  in the 5-h moving average of PM10

was associated with a  in SBP (2.5 mm Hg,
19 M traffic con- Short-term (
5 hour). 95%CI: 1.3 to 3.8) and an IQR in the 4-h
Sergio Chia- PM10 level: 41.9 ± 23.4
g/m3
troller, moving average of PM10 with an  in DBP (2.4
relli et al., Brazil Ambient outdoor 24-h ABPM
O3 level: 31.8 ± 33.2
g/m3 mm Hg, 95% CI: 1.4 to 3.4). An IQR in the O3
2011 [50] age 42.8 ± 5.2 exposure
5-h moving average was associated with a  in
SBP (1.2 mm Hg, 95% CI: 0.09 to 2.2) and in
DBP (1.6 mm Hg, 95%CI: 0.7 to 2.5)

Doubling of NOx exposure during 1- and 5-year

periods was associated with  in SBP (0.5 mm
1 or 2 readings in the Hg, 95% CI: –0.9 to –0.2 and  0.5 mm Hg,
Long-term (1 and 5
1 year median NOx level: 20.2 supine position after a 95% CI: –0.84 to –0.16), respectively.
years).
Sørensen et N 44436, M 21344,
g/m3 minimum of 5 min rest, Long-term exposure associated with a lower
Denmark Validated dispersion
al., 2012 [69] age 55.9 (median) 5 year median NOx level: 19.6 using automated oscillo- prevalence of baseline self-reported hyperten-
model to estimate metric sphygmoma-

g/m3 sion (per doubling of 5-year mean NOx, OR =
exposure nometers 0.96; 95% CI: 0.9 to 1.0), whereas long-term
NOx exposure not associated with incident self-
reported hypertension during follow-up.

Mean pollutants level at schools

with low/high pollution:
3
Short-term. Outdoor PM1: 7.3/58.2
g/m Mean of 5 seat BP read-
BP values were significantly (p < 0.005) in
166 children, in 2 Outdoor and indoor Outdoor PM2.5: 28.5/183.0
g/m3 ings using an automated
Sughis et al., Lahore, children living in the high pollution area
schools, M 55%, schools portable laser- instrument with a standard
2012 [99] Pakistan Outdoor PM10: 223.0/728.6
g/m3 (115.9/70.9 mm Hg) than children living in the
Age 9.9 operated aerosol mass cuff suitable for <33 cm
Indoor PM1: 8.4/52.7
g/m3 low pollution area (108.3/66.4 mm Hg)
analyzer arm circumference.
Indoor PM2.5: 29.1/163.0
g/m3
Indoor PM10: 222.9/590.7
g/m3

A 10
g/m3  in PM10 was associated with  of
night-time SBP at the same day (1.3 mm Hg,
Tsai et al., 95% CI: 0.06 to 2.58 mm Hg; p=0.04), at 1 day
Short-term (1-7 days).
2012 N 359, M 49% , ABPM on the left arm, prior (1.2 mm Hg, 95% CI: 0.02 to 2.44 mm Hg;
France Ambient monitoring PM10 level: 23.5 ± 13.6
g/m3
Hercules age 56.8±10.5 with appropriate size cuff p = 0.046).
station
Study [80] A 10
g/m3  in PM10 was associated with  of
DBP at 2 day prior (0.7 mm Hg, 95% CI: 0.03–
1.42 mm Hg; p = 0.04)

A 10
g/m3  PM10 was associated with a 1.1
Mean of 2 readings using
mm Hg (95 % CI: 0.43 to 1.79) and 2.1 mm Hg
an automated oscillomet-
(95% CI: 1.3 to 2.9)  in SBP in the 2nd and 3rd
Van Den Long-term (preg- ric sphygmanometer.
Rotterdam trimester, respectively.
Hooven 7006 pregnancies, nancy). Mean PM10 levels: 30.3
g/m3 Preeclampsia defined as
Nether A 10
g/m3  NO2 was associated with in SBP
et al., 2011 age 30.5 Spatiotemporal mod- Mean NO2 level : 39.8
g/m3 BP 140/90 mm Hg after
-lands (approximately 1 mm Hg) in all trimester
[91] eling techniques 20 weeks of gestation in
(p<0.05). 10
g/m3  in PM10 was associated
previously normotensive
with an  risk of pregnancy-induced hyperten-
women, plus proteinuria
sion, OR 1.72 (95% CI: 1.1 to 2.6)
Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 37

(Table 2) Contd….

Author Subjects Location Exposure assessment Pollutant levels BP evaluation Findings

Significant  in mean postpartum DBP (69.5 ±

9.8 mmHg) in women exposed to high CO
pregnancy hypertension (14.1 ppm) compared to women exposed to
2707 pregnancies, Mean CO levels defined as >140 mm Hg lower CO (1.8 ppm) levels (68.0 ± 8.3 mmHg, p
Vigeh et al., Local monitoring
non-smoking, age Iran Lower Group: 1.8 ppm SBP and/or >90 mmHg
2011 [96] station < 0.01).
26 Higher group: 14.1 ppm DBP after the 20th week
rate of pregnancy hypertension in the higher
of gestation
CO exposed than the lower exposed women
(adjusted OR 2.02, 95% CI 1.35–3.03).

Long-term (preg- Both PM10 and PM2.5 were associated with

Vinikoor- North gestational hypertension; the risk ratios for an
nancy). Mean PM10 level: 22.2
g/m3
Imler et al., 222775 pregnancies Carolina, IQR  in exposure were 1.07 (95% CI 1.0 to
Ambient monitoring Mean PM2.5: 14.5
g/m3
2012 [92] USA 1.1) for PM10 (IQR: 3.92
g/m3 ) and 1.11 (95%
stations
CI 1.0 to 1.1) for PM2.5 (IQR: 2.2
g/m3 )

An IQR  in 3 (3.1 g/m3) and 4 (2.9 g/m3)

week average PM2.5 was associated with  in
Wellenius et Middle-term (1-28 Rest supine and standing supine DBP (0.9 mm Hg, 95%CI: 0.1 to 1.8 and
747 elderly partici- repeated readings in the
al., 2012 Boston, days). 1 mm Hg, 95% CI: 0.1 to 1.9 respectively).
pants, M 276, Daily PM2.5 levels: 8.6 g/m3 dominant arm using an
MOBILIZE USA Ambient monitoring An IQR (0.2 g/m3)  in 3 and 4 week average
age 78.3 ± 5.3 aneroid sphygmomanome-
[70] station BC was associated with  in supine DBP ( 1.2
ter
mm Hg, 95% CI: 0.2 to 2.2 and1.4 mm Hg, 95%
CI: 0.3 to 2.5, respectively)

Means of rest seated

Short-term (7 days). readings from right and A 1-SD  in BC (0.4 g/m3) was associated with
Wilker et al., N 789 , all M, age Boston, Average BC level: 1.0 ± 0.4
Ambient monitoring left arm, using a standard  in SBP (3.0 mm Hg, 95% CI: 2.3 to 3.8) and 
2010 [51] 72.3 ± 7.5 USA g/m3
site mercury sphygmoma- in DBP (2.3 mm Hg, 95% CI: 1.88 to 2.67)
nometer with a 14-cm cuff

An IQR (51.2 g/m3)  in PM2.5 was associated

with  in SBP (1.1 mm Hg, 95% CI: 0.17 to
Daily Mean PM10 levels: 135.4
Short-term (1 day). g/m3 Average of 2nd and 3rd or 1.99) and  in DBP (1.0 mm Hg, 95% CI: 0.31
Wu et al., to 1.61).
Beijing, more rest seated readings,
2013 HVNR 39 M students Ambient monitoring Daily Mean PM2.5 levels: 82.0
China 3 using automated oscillo- A subset of PM2.5 constituents (carbonaceous
Study [52] site g/m
metric monitor fractions, ions and metals/metalloid elements)
were found to have robust positive associations
with BP

Wu et al., Long-term (preg- 1st, 2nd, 3rd trimester: Preeclampsia defined as at The risk of preeclampsia increased 33% (OR =
California, nancy). least the occurrence of BP 1.33; 95% CI, 1.18–1.49] and 42% (OR = 1.42;
2009 [97] 81186 pregnancies NOx: 7.1 to 7.5 ppb
USA Line-source dispersion > 140/90 mm Hg and 95% CI, 1.26–1.59) for the highest NOx and
PM2.5: 1.8 g/m3 proteinuria PM2.5 exposure quartiles, respectively.
model

Mean level in the monitoring

stations: Pollutants were associated with prevalence of
hypertensive disorders: NO2 (OR=1.21, 95% CI
NO2 level: 27.9 ppb; Hypertensive disorder was 1.1 to 1.4), PM (OR=1.24, 95% CI 1.1 to 1.4),
Long-term (preg- 2.5

nancy). PM10 level: 21.9 to 26.1
g/m3 defined as new arterial SO2 (OR=1.13, 95% CI 1.0 to 1.3) and CO
Xu et al., Florida,
22041 pregnancies hypertension in a pregnant
2014 [93] USA Ambient monitoring PM2.5 level: 10.0 to 10.4 g/m3 (OR=1.12, 95% CI 1.0 to 1.2) per IQR.
woman after 20 weeks of
stations SO2 level: 4.7 to 8.6 ppb Similar effects observed in 1st trimester expo-
gestation
sure to NO2, SO 2 and CO, and 2nd trimester
CO level: 0.5 to 0.9 ppm
exposures to PM2.5
O3 level: 0.03 to 0.04 ppm

Zhao et al., 1 g/m3  in BC during the previous 10 hours

2014 65 metabolic syn- Short-term (5 days). Daily BC level: 3.9 to 4.8 g/m3 was associated with  in SBP (0.5 mm Hg, 95%
drome subjects, 28 China ABPM
AIRCMD Personal exposure CI: 0.2 to 0.9) and  DBP (0..4 mm Hg, 95% CI:
M, age 61 ± 9
Study [74] 0.1 to –0.7)

Abbreviations: TSP, total suspended particles; M, male; PM, particulate matter; PM2.5, fine PM mean diameter
2.5 m; EC, Elemental Carbon; PM10 PM with mean diameter
10
m; SBP, systolic blood pressure; CI, confidence interval; DBP, diastolic blood pressure; BC, black carbon; O3, ozone; ppb, parts per billion; NO2 nitrogen dioxide; IQR, interquar-
tile range; NOx, oxides of nitrogen; SO2, sulfur dioxide; CO, carbon monoxide; OC, organic carbon; WSOM, water soluble organic mass; PM2.5-10, coarse PM mean diameter between
2.5 and 10 m; CV, cardiovascular; ABPM, ambulatory blood pressure monitor; CAD, coronary artery disease; OR, Odds Ratio, PNC, particle number concentration, SD, standard
deviation; IRR, incidence rate ratios; RC, regression coefficient; SE, standard error; RR, relative risk, ICD, international classification of diseases; HR, hazard ratio.
38 Current Pharmaceutical Design, 2016, Vol. 22, No. 1
to 7 days), concentrations (low to high levels), detection system
(ambient and personal levels; indoor and outdoor concentrations),
as well as BP measurements (clinic, home and 24 hours ambulatory
monitoring; automated device and mercury sphygmomanometer)
(Table 2). Among several studies reported in Table 2, a few of the
most noteworthy recent publications that best exemplify the major-
ity of findings have been selected for more detailed discussion.
In particular, the Canada Health Measures Survey (CHMS) [41]
tested the association between cardiopulmonary parameters and air
pollutants (PM2.5, O3 and NO2) detected on the same day of BP
measurement in a wide national population (5011 individuals).
Each daily PM2.5 increase of 4.5 g/m3 was significantly associated
with elevations in both SBP and DBP, by approximately 0.5 mm
Hg. Similarly, resting SBP and DBP were higher for an interquar-
tile range (IQR) increase in O3 and NO2 [41]. Likewise, a secondary
analysis from Taiwanese Survey on Prevalence of Hyperglycemia,
Hyperlipidemia, and Hypertension (TWSHHH) [43] collecting data
from 7578 individuals showed that an IQR (34 g/m3) increase in
1-day average PM10 (particles with an aerodynamic diameter
10)
was associated with higher SBP (0.47 mm Hg), as well as an IQR
(12.15 ppb) augment in 3-days average O3 was linked with higher
DBP (0.37 mm Hg). Several other studies have confirmed the hy-
pertensive effect on clinic/home BP from hours (
24 hours) [50,
52] to few days (
8 days) after ambient outdoor PM exposure [37,
45], despite different PM levels. Interestingly, Wu et al. [52] stud-
ied the relationship between various PM chemical constituents and
BP among students living in Beijing and found that subset of PM2.5
constituents - including carbonaceous fractions [organic carbon
(OC) and elemental carbon (EC)], ions (chloride and fluoride), and
metals/metalloid elements (nickel, zinc, magnesium, lead, and arse-
nic) - have robust positive associations with different BP variables.
On the other hand, concentrations of manganese, chromium, and
molybdenum were associated with lower BP. Similarly Jacobs et al.
[47] showed that vanadium, iron and nickel contents of PM2.5 were
significantly associated with SBP and pulse pressure in patients on
antihypertensive medication among a cohort of elderly subjects.
These findings suggest potential linkages between different pollu-
tion sources and PM-related CV effects. A previous study investi-
gating the hemodynamic effects of short-term variations in ambient
PM2.5 levels in three locations within the Detroit metropolitan area
among a cohort of 347 adults have drawn similar conclusions [57].
In fact, while in the whole population a 10
g/m3 elevation in PM2.5 support the unique previous study demonstrating higher SBP for
was associated with increases in SBP, similar PM2.5 levels caused
different BP effects in the three districts, suggesting that peculiar
chemicals or sources of PM2.5 play a relevant role in the subsequent
BP response [57].
Among other markers of particulate pollution, several groups of
authors reported higher BP after short-term exposure to black car-
bon (BC), a common indicator of traffic emissions, especially re-
lated to diesel fuel combustion and proximity to road traffic [45, 48,
49, 51].
On the other hand, findings from another Taiwanese study [42]
g/m3) increase of 1 year average BC in a cohort study of 853
conducted on 9238 adults indicated that short-term (1 to 3 lag days)
exposure to PM10, SO2, CO, and O3 consistently reduced SBP and
pulse pressure. Stronger relationship among men, elderly, patients
with hypertension, and those residents in an industrial township was
observed. However, in the same population DBP was increased by
gases (SO2, NO2, and O3). Few comparisons can be made between
the two Taiwanese studies [42, 43]. Although the average concen-
trations of air pollutants were all below the National Taiwanese
Ambient Air Quality Standards in both studies and BP measure-
ments methods were similar, there are several potentials explana-
tions for the contrasting findings. For instance, it is broadly estab-
lished that particulate pollution is an extreme complex of different
chemicals with high spatial and temporal variability in sources and
composition [53, 54] and, hence, differences in singular compounds
levels could explain these opposite findings. Moreover, the BP-
Giorgini et al.
lowering effect showed by Chen et al. [42] may also be due to
variations in the individual susceptibility: the population in this
study was constituted by adult (mean age: 51.5 to 61.5 years) non-
smokers from 6 townships in Taiwan, while TWSHHH [43] study
population was younger (mean age: 43.1 years) and included smok-
ers. Previous large studies among elderly subjects reported inverse
[55] or no association [56] between air pollutants and BP. In addi-
tion, smoking status could also contribute to the inconsistent asso-
ciations between air pollution and BP. Accordingly, Brook et al.
[39] demonstrated that secondhand smoke exposure could influence
the relationship between personal PM exposure and BP values.
Taken together, a large number of recent published epidemi-
ologic studies report small but statistically significant positive asso-
ciations between short-term PM exposure and BP parameters.
These observations confirm the harmful effect of PM exposure on
BP reported in previous studies [58, 59]. Hypertensive responses
have been generally also observed after short-term exposure to O3
and NO2 with stronger associations with DBP [41-43], even if there
are some conflicting findings [45], most likely due to differences in
population characteristics.
Long-Term Exposure Studies
Numerous epidemiological studies have consistently estab-
lished that long-term exposure to ambient air pollutants increases
CV morbidity and mortality rates [2]. Moreover, scientific proofs
also suggest that longer-term pollutants exposure confers higher
risks than shorter-term exposure [2, 4]. However, compared with
short-term effect of air pollution, the relationship between long-
term exposure and BP is less known. A comprehensive summary of
the recent epidemiologic findings regarding the long-term effects of
air pollutant exposures on BP is reported in Table 2 [60-69].
Various studies found positive associations between BP levels
and particulate pollution concentrations in the middle (3 and 4
weeks) [70] and in the long-term (1 to 3 years) exposure [62, 64,
66], reporting higher SBP ranging from 0.5 to 32 mm Hg per IQR
increase of PM2.5 and/or PM10. The wide range of PM effect on BP
in these studies may be explained by spatial and temporal variabil-
ity, differences of pollutant sources and components, of individual
characteristics, as well as of exposure assessment. However, all
published studies concordantly demonstrate harmful consequences
on BP levels after long-term exposure to PM. These recent findings
middle-term (30 days) exposure to PM2.5 [71].
In addition, BC - i.e. common marker of fossil fuel combustion
pollution - has been linked to increased BP levels [68, 70]. In par-
ticular, the Maintenance of Balance, Independent Living, Intellect,
and Zest in the
Elderly (MOBILIZE) Boston Study found roughly 1.3 mm Hg
increase in both SBP and DBP after 3 and 4 weeks of BC exposure
in a cohort of 747 US elderly individuals [70]. Similarly, Schwartz
et al. demonstrated higher augments (roughly 2.5 mm Hg) per IQR
(0.32
male living in Boston [68]. Accordingly, among studies investigat-
ing gases related to traffic pollution, both a secondary analysis of
Social Environment and Biomarkers of Aging Study (SEBAS) [62]
and the Registre Gironí del Cor (REGICOR) Study [65] observed
increased BP levels for long-term NO2 exposure, although other
authors failed to find an association [64] or reported inverse rela-
tionship [69] between NOx and BP in large cross-sectional analyses
with very long-term exposure (1 to 5 years). Otherwise, traffic is
also a source of noise, which has been related with BP [72] and
only some studies have adjusted for noise as a confounding factor
[60, 65, 66, 69].
Among gases, investigators reported that also long-term con-
centrations of O3 may negatively affect BP values, as demonstrated
Air Pollution and Blood Pressure
in the SEBAS cohort [62] and among male individuals in a Chinese
cross-sectional study [64].
The few available studies assessing the prevalence and inci-
dence of hypertension after air pollution exposure provide some
mixed results [60, 61, 63-66, 69].
To date, only a handful of published papers have discussed the
effect of air pollution on incident hypertension [61, 63, 69]. In a
study among more than 3000 black women living in Los Angeles
with a 10 years follow-up, authors reported an association between
NOx levels and increased risk of becoming hypertensive, although
the linkage was marginally significant controlling for PM2.5 [63].
On the other hand, PM2.5 has been associated with non-significant
increases in incident hypertension [63]. An aforementioned study of
44436 Danish individuals with a 5 years follow-up, showed that
NOX exposure was not associated with incident self-reported hyper-
tension [69]. However, Chen et al. [61] recently conducted a popu-
lation-based cohort study assembling a cohort of 35303 non-
hypertensive Canadian adults without history of CV disease, fol-
lowed for an average of 7.3 years. The study principally aimed to
determine whether exposure to ambient PM2.5 was associated with
incident hypertension, by using Ontario Hypertension Database and
estimates of ground-level PM2.5 concentrations derived from satel-
lite [61]. Authors observed that exposure to low ambient PM2.5
levels were robustly associated with an increased incidence of hy-
pertension after a mean follow-up of 7.3 years [61].
Few studies have explored the associations between BP preva-
lence and air pollution [60, 64, 66, 67]. Recently, the Kooperative
Gesundheitsforschung in der Region Augsburg (KORA) Study [60]
evaluated the effect of traffic noise and PM2.5 levels on hyperten-
sion prevalence in a population living in two German cities (total
participants 4166) and found a small positive association between
PM2.5 and the prevalence of hypertension only in one of the two
cities, no longer significant after adjustment for noise. In the Heinz
Nixdorf Recall Study [66], residential proximity to high traffic and
noise was associated with a somewhat higher prevalence in a com-
parable German population of 4291 individuals. A substudy of the
Respiratory Health in Northern Europe (RHINE) cohort [67] dem-
onstrated a positive but non-significant association between PM
exposure and self-reported prevalence of hypertension among a
cohort of 1684 Estonian subjects. Otherwise, in a larger cross-
sectional study among 24845 Chinese subjects, authors observed
robust associations between prevalence rate of hypertension and 3
years average concentrations of PM10, SO2 and O3 [64]. Overall, the
observed differences in hypertension prevalence could be most
likely due to the higher pollutant levels, the larger population and
the longer averaged levels (3 years) of pollutants analyzed by the
Chinese study [64] compared to the ones reported by European
studies [60, 66, 67]. These recent findings corroborate previous
results, demonstrating a relationship between increased PM2.5 levels
and small increase in prevalence of self-reported hypertension [73].
A recent meta-analytic study (not included in Table 2)- investi-
gating the cross-sectional association of long-term traffic-related air
pollution with BP and prevalent hypertension in 15 studies (almost
all aforementioned and included in Table 2) collecting data from
more >100, 000 European subjects [18]- have provided interesting
results. Findings have showed that traffic load was associated with
increases in SBP and DBP in non-medicated participants, with an
estimated odds ratio (OR) for prevalent hypertension of 1.05 [95%
confidence interval (CI): 0.99-1.11]. Particulate and gaseous traffic
related pollutants were not clearly associated with BP, though posi-
tive relationships with BP in medicated participants and in the sub-
group of studies with higher quality BP measurements were ob-
served.
In sum, epidemiologic studies demonstrate that long-term expo-
sure to particulate pollution significantly increases BP values, sup-
porting an association of higher ambient PM levels with incidence
Current Pharmaceutical Design, 2016, Vol. 22, No. 1 39
and prevalence of hypertension. Although a relationship between
other pollutants (O3, BC, NOx, SO2) and BP has been reported,
further research is required to make firm conclusions.
Personal Exposure Studies
Most published papers generally analyzed the association be-
tween BP changes and ambient levels of various air pollutants de-
tected by a regional monitoring site. Although this is a valid expo-
sure assessment as particulate pollutants concentrations are typi-
cally spatially homogenous [53], some degree of exposure misclas-
sifications could occur because of personal short-term exposure to
different sources (e.g., traffic, occupational, indoor pollutants, sec-
ond-hand tobacco smoke), with consequent relevant biological
effects [2]. Personal detecting systems have been designed to re-
produce the exposure of individuals to pollutants more appropri-
ately than do those measured at a fixed monitoring site.
Among the few studies with personal air pollutant measurement
(Table 2) [37-40, 48, 74, 75] the Beijing Truck Driver Air Pollution
Study (BTDAS) [37] found that personal PM2.5 and EC measured
during work hours did not show any significant association with BP
changes among both 60 office workers and 60 truck drivers. Simi-
larly, Brook et al.[40] observed no consistent relationships between
short-term exposure to total personal-level PM2.5 and BP values
among 51 nonsmoking subjects living in Michigan, suggesting that
relatively low PM2.5 (mean level 18.0 ± 10.4 g/m3) concentrations
may require a longer cumulative duration of exposure in order to
produce a significant effect.
On the other hand, the same group of authors observed that 24
hours total personal PM2.5 exposure was associated with a small
increase in SBP (1.4 mm Hg), while community PM2.5 levels de-
tected at local air quality monitoring site were not associated with
hemodynamic responses [39], confirming analogous results ob-
tained in a previous study [76]. Similarly Liu et al. [48] found a 3.4
mm Hg increase in SBP per a 7.1 g/m3 elevation in 24 hours per-
sonal PM2.5 exposure in non-smoking elderly subjects recruited
from three nursing homes located in Windsor (Canada). Interest-
ingly, BP levels were related to indoor and outdoor BC and indoor
PM2.5, but there was no relationship with outdoor PM2.5 levels de-
tected by monitors located close to the nurses homes [48], as ob-
served in studies of Brook et al. [39, 76].
In sum, it is possible that differences in pollutant concentra-
tions, constituents, or subject susceptibilities may have been re-
sponsible for discordant findings among personal exposure studies.
Moreover, it is hypothesizable that pollutant mixture within the
personal exposure differs substantially from the particles measured
by the community-based monitor, and that personal PM2.5 could
trigger a more robust or rapid pro-hypertensive response then ambi-
ent levels, accordingly with previous conclusions [16].
Indoor Exposure Studies
Household air pollution from solid fuels accounted for 3.5 mil-
lion deaths and 4.3% of global disability-adjusted life years in 2010
[1]. However, there is a lack of epidemiologic data on the hemody-
namic consequences of indoor air pollution.
A cross-sectional study [38] investigated the association be-
tween BP and personal exposure to PM2.5 among 280 adult non-
smoking women living in rural China households using biomass
fuels. Authors found that 1-log-g/m3 increase in PM2.5 exposure
was associated with 2.2 mm Hg higher SBP and 0.5 mm Hg higher
DBP among all women, with stronger association among women >
50 years of age. These findings are consistent with a previous ran-
domized intervention study among Guatemalan women exploring
the effect of indoor biomass smoke on BP levels [77], which ob-
served that use of improved cooking stoves - resulting in lower PM
exposure - was associated with lower BP values compared to the
use of a traditional open-fire cooking. Indoor PM and BC exposure
have been related to increased BP levels also independently from
40 Current Pharmaceutical Design, 2016, Vol. 22, No. 1
biomass smoke among Taiwanese students [78] and Canadian sen-
iors [48].
Although the role of indoor pollution on BP should be con-
firmed in longitudinal studies, available evidence suggests that
indoor PM2.5 exposure, particularly from biomass combustion, may
be a risk factor for elevated BP and, hence, for CV events.
Ambulatory Blood Pressure Monitoring Studies
Few studies have explored the hemodynamic effect of air pollu-
tion through ambulatory BP monitoring (Table 2) [44, 50, 74, 78-
80], and usually found increases in BP for averaging periods rang-
ing from 0 to 24 hours among most published papers [50, 44, 75,
78]. Delfino et al. [44] observed stronger magnitudes of association
in longer multiday averaging times of hourly home outdoor air
pollutant concentrations, showing an approximately linear BP in-
crease in 10 days of exposure among 64 elderly subjects with coro-
nary artery disease living in Los Angeles. Hercules Study [80] ana-
lyzed the association of exposure to PM10 measured by a local re-
gional monitoring station on the day of examination and 7 days
before with ambulatory BP monitoring in 359 French adults. A 10-
g/m3 increase in PM10 was associated with higher nighttime SBP
(1.32 mm Hg) and higher nighttime DBP (0.72 mm Hg). However,
the associations with BP rapidly diminished with increasing lag
days (0 to 5) [80]. It is possible that the discordant multiday trend
compared to Delfino et al. [44] findings could be due to differences
in exposure assessment (local regional monitoring versus home
outdoor monitoring).
Thus, the ambulatory BP monitoring may have provided a more
accurate evaluation within a shorter time period of exposure, show-
ing a BP effect in the very short term period of exposure, most
likely due to the larger number of observations recorded through
ambulatory devices.
Studies Among Subjects with Higher Cardiovascular Risk
It seems conceivable that the susceptibility of the individuals
plays an important role in determining the hemodynamic responses
to air pollution. Therefore, of special interest are several studies
evaluating the impact of air pollution among subjects with higher
CV risk (Table 2) [42-49, 51, 65, 68, 70, 75]. Among them, it is
well established that elderly represents a population with higher CV
risk: 42 million American adults  60 years of age have 1 or more
CV diseases, as well most cases of CV disease occur in individuals
aged 65 years or older [81]. Studies assessing BP consequences of
short-term exposure to air pollution among elderly individuals have
shown some discordant findings. In fact, whilst recent published
papers generally observed an hypertensive effect of particulate and
traffic related pollutants after
24 hour of exposure [47, 48] and 7
to 10 days [44, 49, 51] among elderly, findings of a large Taiwan-
ese report indicated that short-term (1 to 3 lag days) exposure to
PM10, SO2, CO, O3 consistently reduced SBP and pulse pressure,
with stronger relationship among men, elderly patients [42],
corroborating previous large studies results that reported inverse
[55] or no association [56] between air pollutants and BP in elderly
subjects.
Among studies exploring the effects on BP of middle- and long-
term air pollution exposure in elderly subjects, the overall evidence
demonstrates a consistent increase in BP after middle (21-28 days)
[70] and long-term (1 year) [62, 68] exposure to particulate and/or
gaseous pollutants.
Few studies have evaluated the hemodynamic impact of air
pollution in CV subjects [44, 45, 74] and observed that PM and
various markers of traffic-related air pollution (BC, OC) can rapidly
cause small BP augments in subjects affected by metabolic syn-
drome [74], type 2 diabetes [45] and coronary artery disease [44].
Moreover, a community-based study with a multiethnic sample
of adults demonstrates that obesity may confer susceptibility to
Giorgini et al.
acute CV effects of airborne particulate matter [46] and the REGI-
COR Study [65] reported increased BP levels for long-term near-
road traffic-related air pollution (NO2) exposure, with stronger as-
sociation in participants with CV disease.
We have recently estimated the influence of ambient regional
PM2.5 concentrations during the previous 1 to 7 days on arterial BP
among approximately 2, 000 patients enrolled in a cardiac rehabili-
tation program at the University of Michigan. Preliminary results
demonstrate that higher levels of outdoor fine particles were linked
to increases in rest BP parameters and to elevations in adjusted SBP
levels obtained during peak exercise test (unpublished observa-
tions). Similarly, authors have previously reported increases in rest
BP and some hypertensive effect during moderate exercise among
cardiac rehabilitation patients [58].
Taken together, these studies suggest that PM can increase BP
in high CV risk individuals and, therefore, act as a significant trig-
gering factor for acute CV events among vulnerable subjects.
Studies in Pregnancy and Childhood
Pregnant women can be considered a high risk population for
hypertensive disorders, since changes in pregnancy lead to in-
creased stress on the CV system [82]. Therefore, air pollution could
aggravate and/or trigger hemodynamic adverse response in this
vulnerable group of subjects. Several studies linking air pollution
with BP and/or hypertensive disturbs among pregnant women have
been recently published (Table 2) [17, 83-97].
The relationship between particles and higher BP has been ex-
plored in some studies [85, 87, 91]. Authors generally found in-
creases in SBP values across 1st trimester [87], 2nd trimester [91],
and 3rd trimester [84, 91]. Associations between higher BP and NOx
have been reported in studies evaluating short-term [89] and long-
term [91] exposure, although some authors demonstrated discordant
findings [84]. Some degree of increased BP levels for other gases
(O3 [87], SO2 [89], CO [89, 96]) has also been observed.
Larger number of published papers have evaluated the risk of
hypertensive disorders of pregnancy (gestational hypertension,
preeclampsia and eclampsia), usually defined - regarding BP values
- as at least SBP  140 mm Hg or DBP  90 mm Hg on two or
more occasions [29, 31]. Most studies consistently establish higher
risk of gestational hypertension and/or preeclampsia for particle
exposure during pregnancy [83, 86, 88-93-97]. Authors also ob-
served a relationship between hypertensive disorders of pregnancy
and exposure to NOx [88, 93, 97], CO [90, 93, 96], O3 [86, 90, 94]
and SO2 [93].
A very recent meta-analysis (not included in Table 2) of epide-
miological studies (in majority already aforementioned) investigat-
ing the association between exposure to ambient air pollution and
pregnancy-induced hypertensive disorders, identified 17 studies
published between 2009 and 2013, evaluating the impact of NO2,
NOX, PM10, PM2.5, CO, and O3. Results showed increased risks of
hypertensive disorders for all pollutants except CO. In particular, a
5g/m3 increase in PM2.5 was strongly associated with pregnancy-
induced hypertensive disorders (OR 1.47, 95% CI: 1.27-1.68) and
with preeclampsia (OR 1.30, 95% CI: 1.11-1.48) [17].
Childhood high BP is an important predictor of hypertension
and CV risk later in life [98]. Few studies have previously investi-
gated the association between air pollution and BP among children
(Table 2) [99-103]. A cross-sectional analysis [99] examined the
effect of particulate air pollution on BP among 179 Pakistan chil-
dren, attending two schools, one in a highly polluted area (100 indi-
viduals) and one in a low polluted area (79 individuals). Findings
observed that BP values were significantly higher in children living
in the high pollution area (115.9/70.9 mm Hg) than in the low pol-
lution area (108.3/66.4 mm Hg). Accordingly, a recent study on a
large population of Chinese children (9354 subjects) indicate that
high levels of PM10, SO2, NO2, O3, and CO are associated with
Air Pollution and Blood Pressure
increased arterial BP and hypertension and that breastfeeding may
reduce the risk [103]. A study conducted on 1432 children in Neth-
erlands concluded that long-term exposure to traffic-related air
pollution may increase DBP, whilst there was no association with
short-term air pollution or noise exposure [100]. However, a com-
parable study among more than 2000 German children reported that
long term exposure to NO2, PM2.5, PM10 and PM2.5 absorbance
were not associated with changes in BP [102]. Finally, among 240
children living in rural China exposed to air pollution from indoor
biomass combustion investigators found that increased PM2.5 and
BC exposures were not associated with hypertensive effects [101].
Taken together, while there is inadequate evidence to formulate
conclusions regarding the effects of pollutants during childhood,
available evidence demonstrates that both particles and gases cause
hypertensive effects during pregnancy. Since hypertensive disorders
of pregnancy represent a leading cause of maternal and neonatal
morbidity and mortality [104], these findings may have important
public health implications in promoting maternal and child health.
Air Pollution and Hospitalizations for Hypertension
Air pollution has been linked with elevations in CV deaths and
hospital admissions in several epidemiologic studies [2]. Neverthe-
less, few studies have explored the air pollution-mediated acute
hospital admission and/or emergency visits for hypertension (Table
2) [105-110].
Short-term exposure (< 10 days) to particle pollution has been
related to increased risk of admission and/or emergency visits for
hypertensive disorders [105, 106, 109, 110]. A large study assessing
emergency department visits (5365 admissions) for hypertension in
Edmonton, Canada, from April 1992 to March 2002 observed that
even low levels of gaseous and particulate ambient pollutants were
associated with hypertensive emergencies for lag day 3 and 6 [110].
Similar findings were reported for gaseous pollutants in a Chinese
time stratified case-crossover study [107], and for particles from
sugarcane biomass burning in a Brazilian time-series study [105].
Only a Taiwanese group of investigators found no association be-
tween air pollutants and hypertension emergency visits [108].
In sum, even short-term exposure to low level of air pollutants
may produce acute hypertensive effects and, in turn, play a relevant
role in precipitating CV events among vulnerable subjects.
NATURAL EXPERIMENT, INTERVENTION STUDIES AND
CONTROLLED EXPOSURE STUDIES
The biological plausibility suggested by epidemiological find-
ings between air pollution and BP, has been tested planning natural
experiments or intervention studies, and, furthermore, designing
humans randomized controlled pollutant exposure studies. These
studies have been comprehensively summarized in Table 3 [111-
126]. Previous papers already discussed in published review [16]
have not been included in Table 3.
First of all, we recognize several limitations that affect discus-
sion and comparison among these studies. In fact, since BP was
usually not the primary outcome of research, studies may have suf-
fered from methodological and experimental inadequacies, regard-
ing the sample size, BP measurement methods, pollutant detection,
as well as subject susceptibility. Nevertheless, overall evidence
allows formulating some firm conclusions.
Few reports have been designed to assess the hemodynamic
effects of natural exposure to different sources of pollutants, mainly
produced by industry or agriculture. Among 101 nonsmoking adult
volunteers living near industrial swine operations, PM10 and hydro-
gen sulfide exposure were weakly associated with increased BP
[126]. Similarly, elevations in 24 hour SBP have been reported in
28 healthy male workers exposed to pollutants from sugarcane
burning [111]. Camkak et al. [114] observed that an IQR change in
PM2.5 was associated with approximately 1 mm Hg increase of both
Current Pharmaceutical Design, 2016, Vol. 22, No. 1 41
SBP and DBP among students who spent 5 days close to a steel
plant, with peculiar effect of several chemicals. Surprisingly, in
similar exposure conditions, Liu et al. [120] found no association
for particles and opposite results for O3.
Interesting findings have been observed among intervention
experiments. Among studies examining the impact of a cleaner-
burning cookstove intervention, investigators observed substantial
reductions of SBP among obese and older subjects of a study popu-
lation composed by 74 Nicaraguan women [115], and higher preva-
lence of hypertension among 244 biomass fuel-using women com-
pared to 236 women who cooked with liquefied petroleum gas
[117]. These results confirm the previous findings collected in 120
women living in Guatemala [77]. Improvements of indoor air qual-
ity obtained installing indoor air filters [125] or, simply, by closing
windows in high polluted environment [78] have been linked with
healthy hemodynamic effects. In fact, air filters use significantly
reduced both SBP (7.9 mm Hg lower) and DBP (4.5 mm Hg lower)
in a small Canadian population (N 37) [125]. Finally, as previously
observed among healthy volunteers [127], wearing a facemask ab-
rogates the pro-hypertensive response also in coronary heart disease
patients during a 2-hour walk in highly-polluted environment of
Beijing [118].
Several controlled exposure studies have evaluated the effects
of particulate pollution on BP. Concentrated ambient particles
(CAPs) studies [112, 113] demonstrate augments in BP of ap-
proximately 1 mm Hg compared to filtered air (FA) among cohorts
of healthy adults. Brook et al. [113] reported linear increases of
arterial pressure per 10 min of exposure during the inhalation of
coarse CAP when compared with changes during FA. Similarly, DE
exposure has been generally related to some degree of higher BP in
published papers [116, 121, 123]. The largest of these studies
among 45 nonsmoking subjects exposed to 2 hours of DE with
PM2.5 levels maintained at 200 g/m3, demonstrates that SBP in-
creased at all of the points measured during and after (up to 24
hours) DE exposure compared to FA, with the mean effect peak 60
minutes after exposure initiation (5.1 mm Hg) [116]. The only
study reporting no effect on arterial pressure tested experimental
exposure to dilute wood smoke in a randomized double-blind
crossover study [124]. Differences in chemicals and/or concentra-
tions may explain these not significant findings.
Therefore, controlled exposure studies have provided additional
evidence that short-term exposure to particles directly acts on
hemodynamic balance. Interestingly, there is some evidence that
reductions in pollution exposure using air filters or efficient face-
masks cause decreases in arterial BP [118, 125].
BIOLOGICAL MECHANISMS
We do not aim to review all the animal and basic science
mechanistic studies exploring the biological pathways linking air
pollution and BP, but we will present a few of the most recent and
influential findings of major impact on the field that have been
published since the prior review.
Observational and experimental studies have proposed several
potential biological pathways to explain by which inhaled pollut-
ants may adversely affect CV system [2]. An overview of the
mechanistic evidence supports that there are some interacting broad
pathways (Fig. 1). First, pollutants may cause autonomic nervous
system (ANS) imbalance favoring sympathetic over parasympa-
thetic tone, and this effect may be prompted by lung irritant sensory
receptors and afferent nerve stimulation [128, 129]. Second, air
pollution breathing could mediate the generation and release of
endogenous proinflammatory mediators (e.g., cytokines, activated
immune cells or platelets) or vasculo-active molecules [i.e., endo-
thelin (ET), possibly histamine or microparticles] from various
sources (especially lung cells) that have been shown to “spill-over”
into the systemic circulation [128, 130]. Indeed, particles inhaled
into the lungs are supposed to trigger an inflammatory response
42 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

Table 3. Natural experiment, intervention studies and controlled exposure studies linking air pollution and blood pressure.

Author Subjects Pollutant exposure BP evaluation Findings

Barbosa 28 healthy M workers (age Median PM2.5 level during harvest / non- Work during burnt sugarcane harvest period was associated with
31.6 ± 6.3) during burnt harvest periods at the sugarcane field:
et al., ABPM  24-hour SBP compared to other period (120.2 ± 10.3 vs117.1 ±
sugarcane and during a
2012[111] 87.0/ 50.0 g/m3 10.0, RC: 3.7, 95% CI: 0.3; 7.1, p = 0.034)
control period

15 healthy adults (M 8, age

35.4 ± 15.4) exposed for 130 The target levels for the fine and coarse Both fine and coarse CAPs determined  SBP (2.5 mm Hg, p =
Bellavia et al., Rest seated readings using
minutes to fine CAPs, coarse CAP experiments were 250 and 200 g/m3, 0.001; 1.6 mm Hg, p = 0.03, respectively) and nonsignificantly
2013 [112] a standardized protocol
CAPs, or HEPA-filtered respectively. DBP (0.98 mm Hg, p = 0.1; 0.8 mm Hg, p = 0.11, respectively)
medical air

SBP (mean difference = 0.3 mm Hg; 95% CI: 0.05 to 0.6; p =

0.02) and DBP (0.3 mm Hg; 95% CI: 0.003 to 0.5; p = 0.05)
Average of 3 rest supine linearly  per 10 min of inhalation of coarse CAP when compared
32 healthy adults (M 16, age Coarse particle exposure (CAP 76.2 ±
Brook et al., right upper arm readings,
25.9 ± 6.6) exposed to coarse 51.5 g/m3) in a rural location and FA for with FA.
2014 [113] using an automated
particle and FA 2 hours SBP (0.7 mm Hg; 95% CI: –0.1 to 1.6; p = 0.09) and DBP (1.1
monitor
mm Hg; 95% CI: 0.3, 2.0; p = 0.01) were on average  throughout
coarse CAP exposure vs FA air exposure.

An IQR change in PM2.5 was associated with  in DBP (0.9 mm

Mean daily levels near steel plant/college
campus:
59 healthy subjects (M 46%, SO2:7.8 ± 13.2/1.6 ± 4.2 ppb
age 24.2 ± 5.8) who spent 5-
Cakmak et al., days near a steel plant and 5- NOx: 14.0 ± 10.4/ 6.0 ± 5.4 ppb
2014 [114] O3: 29.7 ± 8.6/ 32.6 ± 9.5ppb
days on a college campus
UFP :13054± 13106/ 5907 ± 3641 parti-
cles/cm3
PM2.5 : 12.8 ± 8.1/ 11.6 ± 7.2 g/m3
Hg, 95% CI: 0.2 to 1.5) and  in SBP (0.9 mm Hg, 95% CI: 0.1 to
1.7)
Association with several chemicals : Cd, associated with  in
Seated rest readings using DBP (0.2 mm Hg , 95% CI 0.04 to 0.3) and  in SBP (0.2 mm
an automated monitor Hg , 95% CI: 0.01 to 0.3).
Al (0.5 mm Hg, 95% CI: 0.1 to 0.9), Ca (0.6 mm Hg , 95% CI
0.02 to 1.2), and Mn (0.8 0mm Hg , 95% CI 0.1 to 1.5) associ-
ated with in DBP.
Pb associated with  in SBP (3.0 mm Hg , 95% CI: 2.1 to 3.9)

Mean 48-hour levels with open fire/ eco-

74 Nicaraguan women (age
Clark et al., 35.4) at baseline (using an
2013 [115] open fire) and after interven-
tion (using Eco-stoves)
stoves:
Mean of 2nd and 3rd rest Although substantial reductions in BP were not observed among
Indoor PM2.5: 1801 ± 1587 / 416 ± 523 seated readings using the entire population, a 5.9 mm Hg (95% CI:
11.3 to
0.4) in
g/m3 aneroid sphygmomanome- SBP observed among women 40 or more years of age and a 4.6
Indoor CO: 25.8 / 7.2 ppm ters. mm Hg  (95% CI:
10.0 to 0.8) among obese women

Personal CO: 2.1 / 0.8 ppm.

45 nonsmoking subjects (M
SBP  at all of the points measured during and after DE exposure;
Cosselman 30, age 18 to 49), exposed to
et al., PM2.5 maintained at 200 g/m3 during DE the mean effect peaked between 30 and 60 minutes after expo-
DE exhaust and FA for 2 ABPM
exposure sure initiation (3.8 mm Hg, 95% CI: -0.4 to 8.0; and 5.1 mm Hg,
2012 [116] hours on days separated by 2
95% CI: 0.7 to 9.5, respectively)
weeks

244 women biomass fuel- Particulate pollution in indoor air biomass 72 biomass-using women had hypertension and 96 had prehyper-
using (median age 34) and fuel/liquefied petroleum gas: 3 rest seated readings tension. In contrast, 26 gas-using women had hypertension and 45
Dutta et al.,
236 control women (median using digital sphygmoma- had prehypertension. (Chi-square test p < 0.001). Biomass users
2011 [117] PM10: 276 ± 108 / 97 ± 36 g/m3
age 33) cooking with lique- nometer had  prevalence of SBP, DBP, and SBP + DBP than gas-using
fied petroleum gas PM2.5: 156 ± 63 / 52 ± 27 g/m3 women (p < 0.05).

Personal PM2.5 exposure with mask 61/

98 patients (M 87%, age 62 ±
without mask 89 g/m3
Langrish 7) with EC walked in Beijing,
China, once while using a Background exposure with mask/without Lower mean BP (93 ± 10 vs. 96 ± 10 mm Hg, p = 0.025) wearing
et al., 2012 ABPM
highly efficient face mask, mask: face mask during the prescribed walk
[118] and once while not using the PM10: 92 /103 g/m3; SO2: 38 /54 ppb;
mask
NO2: 36 /36 ppb

Readings using a
Langrish 14 healthy nonsmokers semi-automatic sphygmo-
Mean airborne particle concentration of manometer at the upper Following exposure to DE, the nitric oxide synthase inhibitor
et al., 2013 subjects (M 8, age 26) ex-
313 ± 11 g/m3 arm of the dominant arm. caused a greater  in BP (p = 0.048)
[119] posed to DE or FA.
Air Pollution and Blood Pressure Current Pharmaceutical Design, 2016, Vol. 22, No. 1 43

(Table 2) Contd….

Author Subjects Pollutant exposure BP evaluation Findings

An IQR  in mean 1- to 4-h means (30.5, 29.8, 28.5, and 27.8

N 40, living in Taiwan,
Lin et al, male/female ratio 1:1, age 22
± 1.4. Participants were asked
2009 [78]
to keep their windows open
and closed in different visits.
g/m3) in PM10 levels predicts  by 1.9–2.6 mm Hg in SBP and
Mean Ambient Indoor level by 1.5–2.1 mm Hg in DBP.
PM10 (visits 1-4): 32.5 to 39 g/m3 An IQR  in mean 1- to 4-h means (21.5, 20.3, 19.6, and 18.8
48 hours ABPM
PM2.5 (visits 1-4): 22.7 to 27.3 g/m3 g/m3) in PM2.5 levels predicts  by 1.9–3.0 mm Hg in SBP and
by 1.5–2.4 mm Hg in DBP.
NO2 (visits 1-4): 18.8 to 19.9 ppb
Effects of indoor PM10 and PM2.5 on BP were greatest during the
visits with windows open.

Mean levels on college campus/ near steel

61 healthy, non-smoking plant: Resting SBP and DBP and pulse pressure, and post-exercise BP
Mean of the last 5 of 6
Liu et al., subjects (M 28, median age PM2.5: 9.4 / 11.1 g/m3 rate were not significantly different between two sites. After a 30-
readings, in a rest and
22) who spent 5-days near a minute exercise O3 concentration was significantly associated
2014 [120] Ultrafine PM: 4440 / 7174 count/cm3 sitting position, using an
steel plant and 5 days on a with a  in SBP (1 mm Hg, 95% CI: 1.8 to 0.1) and  DBP
SO2: 0.6 / 1.2 ppb; NO2: 3.9 / 5.8 ppb automated device
college campus (0.9 mm Hg, 95% CI:1.6, 0.1)
O3: 32.2 / 31.0 ppb; CO: 0.4 / 0.7 ppm

Mean pollutant level FA / diluite DE /

16 healthy men (age 18 to 32) filtered DE / pure carbon nanoparticulate: Supine BP readings using
Mills et al., exposed to, diluite DE, pure a semi-automated non- SBP after inhalation of DE (145 ± 4 vs. 133 ± 3 mm Hg, p <
PM: <1 / 348 ± 64 / 6 ± 16 / 70 ± 28 g/m3
2011 [121] carbon nanoparticulate, invasive oscillometric 0.05) compared with FA
filtered DE, or FA Particle number: <1 / 1198 ± 204 / 2 ± 4 / sphygmomanometer.
3865 ± 4241000/cm3

PM levels before, during and after Olym-

pics.
N 180 (77 M, age 20 to 65), Mean PM2.5 levels (g/m3): 83 ± 92.7 Rest seated readings, with
Mu et al., before, during and after before, 33 ± 48.7 during and 46 ± 57after supported backs, feet flat Unclear results. in DBP (4.1 mm Hg, 95% CI: 1.90 to 6.18)
2014 [122] Olympics 2008 in Beijing Olympics. on the floor and supported among males during the games (lowest PM2.5 level).
(China) Mean PM10 levels (g/m3): 128 ± 122 arms at the heart level.
before, 56 ± 60.4 during and 106 ± 96.7
after Olympics

6 healthy middle-aged par-

Tong et al., ticipants with glutathione-S- Exposure to the highest concentration of DE resulted in  5mm
100, 200, 300g/m3 whole DE
2014 [123] transferase-Mu 1 null geno- Hg in DBP
type exposed to DE

Wood smoke exposure mean levels:

Resting readings in a
Unosson N 14 (M 8, age 26) exposed to PM1 314 ± 38 g/m3 semirecumbent position,
dilute wood smoke or FA for
et al., 2013 CO 25 ± 6 ppm using a validated semiau- No effect on BP after wood smoke exposure compared to FA.
3 hours during intermittent
[124] NOx 0.41 ± 0.12 ppm tomated sphygmoma-
exercise
nometer
EC 0.72 ± 0.08

Indoor weekly mean level Filter/Placebo

N 37(M 43%, age 32) who
Weichenthal et received an electrostatic air
al., 2013 [125] filter and a placebo filter for 1
week.
PM10 :38.0 ± 35/ 69.8 ± 67 g/m3
PM2.5 :30.0 ± 30/ 61.0 ± 64 g/m3
PM1 :25.9 ± 27/ 54.6 ± 60 g/m3
NO2 :2.86 ± 3.3/ 3.46± 3.0 ppb
CO2 :1212 ± 408/ 1332± 540 ppm
Air filter use was associated with  in SBP (7.9 mm Hg,95% CI: -
17 to 0.82), and  in DBP (4.5 mm Hg, 95% CI: -11 to 2.4).
The average of the 2
closest of 3 readings, in An IQR in PM10 (35 g/m3) was associated with a  in SBP
sitting position, using an (crude 0.57 mm Hg, 95% CI: -3.1 to 4.2; adjusted 0.18 mm Hg,
automated device 95% CI: -5.0 o 5.4), whereas inverse associations observed for
PM1 and PM2.5

101 nonsmoking volunteers
Wing et al., (M 35, median age 53) living
2013 [126] near industrial swine opera-
tions sitting outdoors for 10
min twice daily for 2 weeks
1 ppb  in H2S was associated with  in SBP (0.29 ± 0.12 mm
Average of 2 seated rest Hg) and DBP (0.12 ± 0.08 mm Hg).
H2S and PM10 readings, self-measured,
Semivolatile PM10 had a small negative association with DBP (–
using an automated device
0.06 mm Hg ± 0.03).

M indicates male; ABPM, ambulatory blood pressure monitor; vs, versus; PM, particulate matter; PM2.5, fine PM, with mean diameter
2.5 m;RC, regression coefficient; CI,
confidence interval; SBP, systolic blood pressure; CAP, concentrated ambient particles; DBP, diastolic blood pressure; FA, filtered air; HEPA, High-Efficiency-Particulate-Air; SO2,
sulfur dioxide; EC, Elemental Carbon; O3, ozone; ppb, parts per billion; NO2 nitrogen dioxide; PM10 PM with mean diameter
10 m; IQR, interquartile range; CO, carbon monox-
ide; UFP, ultra-fine particle, with mean diameter
1 m; DE diesel exhaust; CAD, coronary artery disease; H2S, hydrogen sulfide;
44 Current Pharmaceutical Design, 2016, Vol. 22, No. 1 Giorgini et al.

PM

Activation of lungs
ANS reflex arcs PM and/or constituents
Pulmonary oxidative transmitted into blood
stress & inflammation

ANS imbalance
nSNS / ÈPSNS
UFP, soluble metals
' HRV Systemic Oxidative stress
Organic compounds
and Inflammation
uactivated WBCs, cytokines (IL-1, IL-6, TNF-), acute phase response (fibrinogen, CRP) ET1,
tissue RAS and Rho Kinase activation, Toll-like receptor-4 activation. Epigenetic mechanisms
Endothelial dysfunction

 ROS  Vasoconstriction
 BH4 Arterial Stiffness
 NO FMD

INCREASED BLOOD PRESSURE

Fig. (1). Mechanisms by which PM air pollution may affect vascular function and increase blood pressure.
Abbrevations: CRP, C-reactive protein; ET1, endothelin; HRV, heart rate variability; IL-1, interleukin 1; IL-6, interleukin 6; NO, nitric oxide; BH4, tetrahydro-
biopterin; PM, particulate matter; PSNS, parasympathetic nervous system; RAS, renin angiotensin system; ROS, reactive oxygen species; SNS, sympathetic
nervous system; TNF-a, tumor necrosis factor alpha; UFP, ultra-fine particles; WBC, white blood cells.

within the alveolae, with a subsequent systemic inflammation re-
sulting in detrimental vascular effects [2]. Third, soluble constitu-
ents (e.g., metals) and/or nano-sized particles may be capable of
translocating across the alveolar membrane gaining access to the
bloodstream and directly influencing the vascular endothelium
[131-134]. The relevance of each pathway may vary depending
upon time course of exposure, pollutant characteristics, susceptibil-
ity of the individuals, and likely overlap some degree in their ad-
verse actions [2]. In sum, air pollution can mediate increases of BP
in a biphasic manner consisting of an initial response within min-
utes-to-hours (due to acute ANS imbalance) and a subsequent BP
elevation owing to increased arterial vasoconstrictor responsiveness
(caused by endothelial dysfunction, oxidative stress, and inflamma-
tion).
Autonomic Nervous System Imbalance
A recent published review has broadly discussed the impacts of
air pollution exposure on the function of major pulmonary sensory
receptors, baroreceptors, and carotid body chemoreceptors [129].
Several studies demonstrated that acute increases in BP occurring in
conjunction with pollution exposure are probably triggered by rapid
changes in ANS balance favoring sympathetic nervous system-
mediated arterial vasoconstriction [135, 136]. For instance, small
and rapid increases in BP parameters have been reported after ex-
perimental exposure to particles and gases [112, 113, 116, 121, 123,
137]. These acute effects may be driven by autonomic reflexes and
changes in sympathetic nervous system activity.
Numerous studies have reported the adverse prognostic value of
a decrease in heart rate variability (HRV), a manifestation of an
imbalance of ANS [138]. Although data from controlled exposure
studies are limited and rather inconsistent, PM2.5 exposure is gener-
ally associated with a reduction in HRV, suggesting that autonomic
activity is altered by the exposure itself [2]. Some studies observed
reductions in HRV parameters following CAP exposure [139-142]
but not following diluted DE exposure [143], suggesting that the
molecular composition of the PM is critical for these effects.
Among studies assessing both BP and HRV parameters, Brook et
al. [113] have recently shown that 2 hour inhalation of coarse PM
from a rural location was associated with a rapid elevation in BP
and heart rate during exposure, probably due to autonomic imbal-
ance. The BP increase was rapid, transient and occurred in conjunc-
tion with an elevation in heart rate. Both changes were also dis-
played during concomitant alterations in HRV, supporting vagal
withdrawal and correlative sympathetic activation [113].
These findings suggest that the inhaled particles probably per-
turbed autonomic balance via the activation of afferent pulmonary
autonomic reflexes. In order to deeply investigate this hypothesis,
Robertson et al. induced myocardial ischemia and reperfusion in
anesthetised rats after intratracheal instillation of DE (6 h, 0.5 mg),
Air Pollution and Blood Pressure
founding increases in BP, arrhythmias, tissue edema and reperfu-
sion injury after DE exposure. Investigators subsequently tested the
inhibition of transient receptor potential vanilloid (TRPV1) - a lung
receptor involved in autonomic reflex arcs - and demonstrated that
intratracheal application of an antagonist of TRPV1 prevented in-
creases in BP, arrhythmia, as well as myocardial injury. Systemic
1 adrenoreceptor inhibition with metoprolol also attenuated in-
creases in myocardial oxidative stress and reperfusion injury [144].
With regard to long-term exposure pathways, investigators
explored the effect of 6 months CAPs exposure on BP in mice and
found higher BP levels and increased sympathetic activity (eleva-
tions in both low-frequency BP variability and urinary norepineph-
rine excretion). Moreover, pharmacologic inhibition with guan-
facine (central
2a receptor agonist) reduces the elevation in BP,
suggesting a role of increased sympathetic tone in CAPs exposure -
induced hypertension [145].
Concerning other pollutants, studies reported some degree of
reduction in HRV linked to ambient O3 and NO2 levels [146, 147].
Moreover, authors have demonstrated that reducing personal air
pollution exposure using a facemask during a walk in highly-
polluted environment of Beijing increased HRV among both
healthy individuals and patients affected by coronary heart disease
[119, 127]. Finally, it has been observed that altered autonomic
balance could also affect peripheral vasomotor tone (causing vaso-
constriction) via oxidative stress pathways [148].
Vascular Function
Several aforementioned studies have reported an association
between sub-acute/chronic air pollution exposure and increased BP.
PM-induced endothelial dysfunction driven by vascular inflamma-
tion and oxidative stress seems to play a relevant role in adverse
modulation of hemodynamic response.
The endothelium is an active biologic interface, modulating
tone, hemostasis, and inflammation through the CV system. The
production of nitric oxide (NO) in vascular endothelial cells plays
an important role in the regulation of vessel tone and structure,
protecting the vascular wall from atherosclerosis [149, 150]. Endo-
thelial dysfunction may contribute to increased systemic vascular
resistance, thus leading to the development of hypertension, proba-
bly due to impaired endothelium-dependent vasodilation [149-151].
Although the endothelial mechanisms underlying these impaired
responses are still the source of debate, some investigators explored
molecular pathways by which particle exposure could trigger altera-
tions in endothelial function, central aortic hemodynamics and their
relationships with peripheral BP changes.
Consistent with the hypothesis that changes in NO bioavailabil-
ity are responsible for the vascular vasomotor effects of air pollu-
tion exposure, recent studies have shown that rats exposed to DE
have increased expression of endothelial NO synthase along with an
increase in plasma nitrate and nitrite concentrations, suggesting a
disturbance of the NO pathway [152]. Accordingly, Langrish et al.
[118] studied the role of NO bioavailability after DE inhalation
among healthy volunteers, evaluating bilateral forearm blood flow,
BP and arterial stiffness, during intrabrachial infusions of acetyl-
choline, sodium nitroprusside, and a NO synthase inhibitor (NG-
monomethyl-L-arginine). NO plasma concentrations increased
following DE inhalation; in the presence of the NO clamp, acetyl-
choline and sodium nitroprusside caused a dose-dependent vaso-
dilatation, not affected by DE inhalation; following exposure to DE,
NO synthase inhibitor caused a greater increase in BP and central
arterial stiffness compared to filtered air. These findings demon-
strate that DE inhalation perturbs normal vascular homeostasis with
enhanced NO generation that is unable to counteract NO depletion
[118].
In this context, studies describing the effects of particles expo-
sure on flow mediated dilation (FMD) of the brachial artery are
Current Pharmaceutical Design, 2016, Vol. 22, No. 1 45
limited. Whilst studies assessing short-term exposure to air pollu-
tion among high CV risk patients (e.g., diabetic individuals) have
demonstrate that higher community level pollution is related to
lower FMD [153, 154], investigators have observed some mixed
results among healthy individuals [39, 154, 155]. With regard to
long-term exposure, MESA Air study firstly reported an association
between annual exposures to PM2.5 and impaired conduit artery
function as indicated by lower brachial artery FMD [156]. Accord-
ingly, Wilker et al. observed that residential proximity to a major
roadway and higher levels of spatially resolved estimates of PM2.5
were associated with impaired FMD and poor microvascular func-
tion among large community-based cohort of middle-aged and eld-
erly adults [157].
As regards the hypothesis that exposure to air pollution may
affect arterial stiffness, Lundback et al. demonstrated that DE in-
duced an increase in aortic augmentation pressure, 10 minutes post-
exposure in healthy adults, although minimal changes may have
occurred in peripheral brachial BP [158]. Similarly, in a small real-
world panel study of children living in Italy, central arterial stiff-
ness was found to be significantly higher in children living near
than in those living far from major roads [159].
In sum, overall evidence demonstrates that both short and long-
term exposure to particle pollution can impair vascular function,
most likely acting on endothelial function.
Oxidative Stress and Inflammation
A state of oxidative stress is characterized by a relative imbal-
ance between pro-oxidant and antioxidant molecules within bio-
logical tissues. Robust evidence demonstrates that exaggerate vas-
cular oxidative stress is a central characteristic in the pathogenesis
of atherosclerosis and endothelial dysfunction [149-151, 160, 161].
The large literature explaining the role of oxidative stress in the CV
actions of particulate air pollution has been extensively reviewed
[2, 130]. It is plausible that pulmonary oxidative stress and inflam-
mation following PM inhalation are partially responsible for the
activation of these observed systemic vascular responses. For in-
stance, it has been demonstrated that PM2.5 exposure disrupts nor-
mal vascular homeostasis and vasoactive mediator balance through
reactive oxygen species (ROS) dependent mechanisms [162]. Two
very detailed studies showed that PM inhalation increased BP in
angiotensin-II infused rats. The effect was associated with raised
levels of aortic O2 and endothelial NO synthase uncoupling, by a
mechanism that involved depletion of tetrahydrobiopterin (BH4; a
key cofactor for endothelial NO synthase), and stimulation of
NADPH oxidase and rho-mediated pathways [163, 164]. Investiga-
tor explored the hypothesis that central nervous system inflamma-
tion may be involved in chronic PM2.5 exposure-induced increases
in BP and sympathetic nervous system activation. In mice exposed
to CAPs for 6 months, higher BP levels and sympathetic activation
have been shown. Moreover, the elevation in sympathetic tone was
accompanied by an hypothalamic inflammation, evidenced by in-
creased expression of pro-inflammatory genes [E-selctin, tumor
necrosis factor (TNF
), intercellular adhesion molecule (ICAM)-1]
and activation of pro-inflammatory pathways [inhibitor kappaB
kinase (IKK)/nuclear factor-kappaB (NF-B)] in isolated hypotha-
lamic tissue [145].
It is reasonably well established that inhalation of air pollutants
induces pulmonary and systemic inflammation [2, 130, 165]. There
is evidence that exposure to ambient PM can be associated with
elevated systemic proinflammatory biomarkers [165]. Deposition of
PM in the lungs triggers activation of NADPH oxidase within the
lung itself, causing stimulation of the bone marrow by alveolar
macrophages and a subsequent systemic inflammatory response
[162]. Several reports have showed detailed association of air pollu-
tion exposure with day-to-day variation in acute-phase proteins,
such as C-reactive protein (CRP), interleukin (IL)-1b, IL-6, tumor
necrosis factor-alpha (TNF
), fibrinogen, white blood cell counts
46 Current Pharmaceutical Design, 2016, Vol. 22, No. 1
and circulating soluble adhesion molecules [166-168]. These pul-
monary and systemic inflammatory responses may then activate
vascular oxidative stress, with interdependent mechanisms, stimu-
lating local cytokine and superoxide generation via toll-like recep-
tor 4 and NADPH oxidase 2-dependent mechanisms and generating
ROS [169], which may, in turn, act within the blood vessels limit-
ing NO bioavailability [170]. Accordingly, observational and ex-
perimental studies demonstrated that exposure to air pollution is
associated with release of potent endogenous vasoconstrictor me-
diators (ET-1) into the circulation [171, 172].
Taken together, experimental studies offer plausible pathways
whereby interacting processes like oxidative stress and inflamma-
tion can affect vascular function and, therefore, influence hemody-
namic responses.
Direct Action of Pollutants on Cardiovascular Tissues
Some PM constituents (i.e., UFP, soluble metals) once inhaled
deep into the lungs may be able to pass through the alveolar capil-
lary membrane, reaching the systemic circulation, and directly act
on CV tissues [131-134]. Thereafter, certain compounds have
proven capable of directly stimulate angiotensin II subtype 1 recep-
tor and epidermal growth factor signaling (potentially by disrupting
phosphatase activities). Other chemicals (e.g., transition metals,
organic molecules, and semi-quinones) may influence redox cy-
cling of biological tissues, increase ROS levels in vascular tissue
and thereby disturb vasomotor balance [2, 172]
Epigenetic Pathways
Epigenetic studies examining gene-air pollution exposure inter-
actions may shed more light on the biological mechanisms by
which air pollution affects susceptibility to CV diseases. A new
hypothesis suggests that individual susceptibility to air pollution
may be linked with genomic polymorphism and reduced levels of
DNA methylation associated with oxidative stress [172]. Oxidative
stress from pollutants exposure can reduce the capacity of methyl-
transferases to interact with DNA or modify the expression of genes
implicated in the methylation process. In the New York City cohort
on fetal growth and health development of children, prenatal air
pollution exposure was significantly associated with genomic hy-
pomethylation in cord blood white cells DNA, suggesting a poten-
tial, but unexplored role for epigenetic modifications [173]. Re-
cently, in a controlled exposure study it has been reported that CAP
exposure caused rapid epigenetic mechanism of hypomethylation.
This epigenetic change was directly associated with hypertensive
responses providing the first experimental evidence of PM-induced
DNA hypomethylation correlated to BP [112]. The importance of
epigenetic changes triggered by PM exposure and their relation-
ships to peripheral BP changes remains unclear and should be fur-
ther investigated.
CONCLUSION
Our review provides consistent evidence whereby air pollution
can promote hypertensive hemodynamic responses. Similar conclu-
sions have been previously published by other reviewers [16].
Overall, epidemiological findings demonstrate that particulate pol-
lution cause small, yet significant increases in BP parameters both
in the short [37, 41, 43, 45, 47, 50, 52, 37-52] and in the long-term
[62, 64, 66, 70] exposure. Furthermore, recent large studies support
the idea that prolonged exposure to PM could increase both preva-
lence and incidence of hypertension [61, 64]. Although associations
with higher BP levels have been reported for several pollution
markers, studies detecting both short and long-term effects of PM2.5
air pollution have provided more robust results [38, 39, 41, 45-48,
52, 60-63, 66, 70]. In fact, fine particles substantially increase BP
despite numerous and different experimental and methodological
variables. On the other hand, some gaseous chemicals (O3, NO2,
SO2) have been linked with exaggerate BP reactions in the short
Giorgini et al.
[41, 43] and in the long-term [62-65] exposure, but further research
is needed to make firm conclusions. Epidemiological studies pro-
vide sufficient evidence that elevated concentrations of particles
[104, 106, 109, 110] and gaseous [107, 109, 110] pollutants in-
crease hospital admissions and/or emergency visits for hypertensive
disorders. At the same time, it is plausible that some vulnerable
categories of subjects, such as elderly [44, 47, 48, 49, 51, 62, 68,
70], pregnant women [17, 83-94, 96, 97], as well as patients af-
fected by metabolic syndrome [74], diabetes [45], and heart dis-
eases [44], may experience similar and/or more significant acute BP
elevations compared to healthy subjects, with potentially more dan-
gerous consequences (i.e. trigger of acute CV events) following
exposure.
Although the available evidence suggests a causal relationship
between PM2.5 and hypertension, we acknowledge the importance
of more research in areas of controversy and uncertainty to clarify
the full nature of this issue. However, we speculated that the reason
of discrepancies within discussed studies could be partially ex-
plained by differences among the several variables taken into ac-
count among studies. First, particulate pollution is a complex of
different chemicals with spatial and temporal variability in sources
and composition [2, 53], and, therefore, exposure misclassification
due for example to local sources, indoor exposure, as well peculiar
chemicals should be taken into account. Accordingly, measurement
of personal exposure seems to provide a more accurate assessment.
Moreover, it is plausible that several environmental factor (e.g.
temperature, noise, odors) or co-pollutant (gases) may have con-
founded the results. Second, patient susceptibility (e.g. age, comor-
bidity, pregnancy, medication status) might play important roles in
determining the hemodynamic responses to air pollution. Third, BP
measurements have been recorded using different devices (e.g.
manual and automated, as well as ambulatory monitoring) and con-
ditions (e.g. single or multiple measurements; seated, supine and
standing readings). Finally, different exposure methodologies have
been used and BP was usually not the primary outcome of research
in experimental studies.
Although consistent data examining both PM10 and PM2.5 ef-
fects exists, we believe that future evaluation exploring the effects
on BP of individual chemicals, coarse and ultrafine particles, gases,
as well as personal and mixed air pollution exposure are needed.
Mechanistic evidence shows broad pathways by which air pol-
lutants might act on hemodynamic balance in the short and in the
long-term exposure. In brief, existing evidence supports that air
pollution can generate acute autonomic imbalance, favoring sympa-
thetic over parasympathetic tone, and cause an innate and adaptive
immune responses triggered by pollutant deposition throughout the
lungs, that do not remain confined within the pulmonary tissue [2,
129]. Various pro-oxidative, inflammatory and/or hemodynami-
cally-active mediators (e.g., cytokines, activated leukocytes and
platelets, oxidized lipids) have been shown to “spill-over” into the
systemic circulation [2, 130]. Moreover, soluble constituents (e.g.,
metals) and/or nano-sized particles may prove to be capable of
translocating into the systemic CV system [2, 131-134]. The rele-
vance of each pathway may vary depending upon the time course of
exposure, the pollutant characteristics, the CV response or event
type observed, the susceptibility of the individuals, and likely over-
lap to some degree in their adverse actions [2]. Hence, numerous
adverse responses potentially capable of instigating acute CV
events among susceptible individuals have been observed following
exposures including vasoconstriction, endothelial dysfunction, pro-
thrombotic and coagulant propensities, plaque destabilization and
inflammation, enhanced arrhythmia potential, as well elevations in
heart rate and BP [2].
As a consequence of the role of hypertension as the major risk
factors for premature mortality worldwide, and of the global detri-
mental effects of air pollution, we believe that the findings summa-
rized in our review demonstrate an unequivocal relationship be-
Air Pollution and Blood Pressure
tween particulate pollutants and BP and these results have large
public health repercussions. In fact, it is well established that even
small changes in BP levels lead to consistent decreases in stroke,
coronary heart disease and overall mortality [172]. We speculate
that hypertensive consequences of PM2.5 exposure represent one of
the most important biological mechanisms explaining the role of
particulate pollution as a modifiable factor contributing to CV mor-
bidity and mortality. Similarly, unhealthy consequences of indoor
and outdoor air pollution act on worldwide population, with consid-
erable public health implications [1].
Therefore, we advise healthcare providers to educate their pa-
tients, in particular those at heightened CV risk, about the potential
adverse hemodynamic effects of air pollution, in order to reduce
individual exposure and subsequently moderate the effect of air
pollution on public health.
CONFLICT OF INTEREST
The authors confirm that this article content has no conflict of
interest.
ACKNOWLEDGEMENTS
Declared none.
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Received: July 19, 2015 Accepted: November 5, 2015
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