"...reports suggest that much of PM toxicity is related to the transition metal content of the particles..."
"...show that environmental exposure to these metals results in their
deposition in the heart and blood vessels, and that the cardiovascular
tissues are significant targets of metal toxicity. Moreover, the
cardiotoxicity of transition metals, heavy metals, and metalloids is
well known...."
"...there are approximately 350,000 sudden cardiac deaths each year in
the United States alone, of which as many as 60,000 deaths could be
related to particulate air pollution (82)...."
[Quotes above are from the articles below. Tires aren't what you zinc they are...]
IMPACT OF TIRE-DERIVED FUEL ON THE CHEMICAL COMPOSITION OF COAL-COMBUSTION PRODUCTS
LAFREE, Sara T.1, GIERÉ, Reto1, CARLETON, Loran E.1, ZINGG, Anatol1,
and TISHMACK, Jody K.2, (1) Earth & Atmospheric Sciences, Purdue
Univ, West Lafayette, IN 47907-1397, , (2) Building
Services & Grounds, Purdue Univ, West Lafayette, IN 47907-1661
Every year in the U.S., millions of scrap tires are discarded.
Conventionally, these tires are disposed of in landfills. However, this
disposal method not only contributes to landfill crowding, but also
poses a potential threat to human safety and health. Tires are buoyant
when buried underground, so over time, whole tires migrate upwards
through landfill piles, thus harming landfill covers. If tires are not
buried, they are often stockpiled or illegally dumped. These piles
provide a breeding ground for mosquitoes and rodents, and are also
prone to fire due to their tendency to retain heat.
To help alleviate our nation’s current scrap tire problem, various
solutions for reusing tires have been, and are currently being,
developed. Today, approximately 20 percent of tires are reused. One use
of scrap tires involves burning tire chips as a source of energy.
Tire-derived fuel (TDF) is being explored as a means of reducing fossil
fuel use. TDF produces more energy through combustion than coal
incineration, so, for this reason, it is considered a favorable
option. *** However, the potentially harmful effects of burning
these tires are yet to be fully discovered.
The Purdue University power plant conducted an experiment with two
different sets of fuel combusted at the same conditions (»1500 °C):
pure coal and a mixture of 95 wt% coal plus 5 wt% TDF. Compared to pure
coal, the TDF-coal mixture is considerably richer in Zn (133±34 vs.
32±43 ppm), and also has a higher S content (1.76±0.91 vs. 0.57±0.55
wt%). The bulk Zn concentrations in combustion products derived from
TDF are 238, 3850, and 61500 ppm in bottom ash, mechanical separator
ash, and electrostatic precipitator ash, respectively. These
concentrations are high when compared to the pure coal values of 68,
106, and 3450 ppm. This increase may lead to higher Zn concentrations
in both atmospheric emissions and leachates from ash disposal sites.
---------------------------------------
Press release Feb 18 2003.
The study, conducted in collaboration with Harvard University School of
Public Health and the National Institute of Environmental Health
Sciences, sheds light on how air pollutants may cause illness or death
from heart disease and is part of a major research initiative by the
EPA to better understand the health effects from particulate matter on
susceptible populations such as the elderly and young.
The metal composition of combustion particles used in the study
resembled those collected outside in polluted areas. Also, the
calculated average daily exposure of particulate matter over the study
period was comparable to exposures associated with highly polluted
urban environments. Animals prone to heart disease in the study showed
heart muscle inflammation, degeneration and scarring when exposed to
particulate matter, but no changes when exposed to filtered air. Metals
have been suggested as a cause of observed cardiovascular effects in
humans from air pollution. Because zinc was the predominant metal in
these particles, this study suggests that particle-associated zinc may
play a role in heart muscle damage. Additional research is under way to
provide further information about the possible health effects of
breathing particles containing metals.
-------------------
Study Shows Metals in Air Aggravate Asthma and Allergies
May 30, 2003
Marla Cone
Los Angeles Times
Microscopic pieces of metals in air pollution aggravate asthma and
allergies, according to research by the U.S. Environmental Protection
Agency and German scientists published this week.
The researchers concluded that people who live in areas with airborne
soot that contains a lot of metals are prone to more severe bouts of
asthma and allergic symptoms.
Evidence has been mounting in recent years that soot -- ultra-fine
particles of pollution -- aggravates asthma and allergies. The new
study implicates a specific ingredient of the soot -- metals, such as
zinc, copper, tin and cadmium. The metals are most often found in
emissions from factories and coal-burning plants.
Asthma is considered an epidemic in the U.S., afflicting an estimated 15 million people, including 5 million children.
Apparently, tiny pieces of metals cause airways to become inflamed,
restricting the flow of air that reaches the lungs. Such symptoms can
lead to asthma attacks. The metals also increased the animals'
sensitivity to common allergens -- substances such as dust or pollen
that cause allergic symptoms.
Scientists have been trying to figure out why deaths from respiratory
and heart diseases increase on days when particle pollution worsens.
The phenomenon occurs around the world. Some researchers have suspected
that metals in the air are responsible, and the new findings, published
in the journal Environmental
Health Perspectives, bolster that theory.
-----------------------------------------------
Am J Physiol Heart Circ Physiol 286: H479-H485, 2004; 10.1152/ajpheart.00817.2003
0363-6135/04 $5.00
SPECIAL MEDICAL EDITORIALS
Cardiovascular pathophysiology of environmental pollutants
Aruni Bhatnagar
Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky 40202
CARDIOVASCULAR DISEASE (CVD) is the leading cause of mortality in the
industrialized world. In the United States alone, it kills 1 million
people per year; accounting for over 40% of all deaths (50). Despite
significant medical advances, the decline in CVD mortality in the
United States that began in the 1960s has leveled off, and recent
estimates suggest that it may be even beginning to rise again (33).
More alarmingly, CVD is rapidly becoming a major cause of death
worldwide, and current projections indicate that between 1990 and 2020,
the proportion of worldwide deaths from CVD will increase from 28.9% to
36.3% (58). With the ominous increase in the incidence of diabetes and
obesity, both of which profoundly affect cardiovascular health (6), the
total burden of CVD in the future may be even greater. Although
intensively studied, the reasons underlying the high incidence of CVD
remain unclear. Several "risk factors" have been associated with the
development of CVD, but it is sobering to consider that many patients
suffering from heart disease have no established risk (32), suggesting
that quantitatively important determinants of CVD are currently unknown
(33).
The development of CVD is a result of a chronic and complex interplay
between genetic and environmental factors. Whereas genetic makeup is a
critical determinant (related to a set of nonmodifiable risk factors
such as age, sex, family history, height, and postmenopausal status in
women), large changes in the incidence of CVD over the last century
indicate that environmental influences are also as important. Multiple
studies show that nongenetic factors such as diet, smoking, physical
activity, and alcohol intake significantly modify CVD risk (50). In
addition, it has been reported that migration of genetically similar
populations to new environments alters CVD risk (33), indicating that
heart disease is not an inevitable fate of an aging population, but
that its development is profoundly modified by the environment. Other
contributors of risk, e.g., elevated low-density lipoprotein (LDL)
cholesterol, hypertension, diabetes, obesity, reduced high-density
lipoprotein (HDL), lipoprotein a, fibrinogen, homocysteine, plasminogen
activator inhibitor, and left ventricular hypertrophy are a combination
of environmental and genetic factors. Indeed, the term "risk factor"
was coined by the Framingham group investigating the epidemiology of
CVD (50). Since then there have been extensive and ongoing efforts to
establish that environmental factors contribute to the induction,
progression, and severity of CVD; although a clear role of
environmental pollutants in affecting heart disease is only now
beginning to emerge.
There are multiple reasons for the delayed appreciation of
cardiovascular toxicity as a significant outcome of pollutant exposure.
Whereas some of these reasons relate to historical chance or bias,
others may be related to the difficulty in demonstrating small changes
in CVD risk over the high background levels of the disease. Added to
this is the experimental difficulty in demonstrating the effects of
pollutants on CVD because only the severity and progression, rather
than induction, of the disease are likely to be affected. Such
demonstrations require well-established animal models of ongoing CVD,
some of which have become available only in the last few years [e.g.,
the apolipoprotein E-knockout (apoE)- or the LDL-receptor null mice] or
are still under development (such as those for studying the
cardiovascular complications of effect of Type 2 diabetes on CVD).
Finally, because the heart and blood vessels are neither the site of
primary exposure (as lung, gut, or skin) nor of metabolism and
detoxification (e.g., kidney or liver), it has been tacitly assumed
that cardiovascular tissues suffer less from exposure to environmental
toxins. This assumption is, however, not supported by extensive data
demonstrating robust cardiovascular effects of environmental
pollutants. The most dramatic example of these is provided by the
studies on the cardiovascular effects from smoking, which have
consistently demonstrated over the past 30 years that smoking
dramatically exacerbates CVD (50). More than 400,000 deaths in the
United States per year are due to tobacco smoke-related illness,
roughly half of which could be attributed to cardiovascular causes (3).
The untoward cardiovascular effects of tobacco smoke and its
constituents such as butadiene are graded and appear on exposure to
concentrations that are much lower than those that lead to cancer (50,
65). In animal models, exposure to cigarette smoke has been directly
shown to increase atherogenesis (25) and myocardial infarct size (99).
Moreover, exposure to second-hand cigarette smoke exacerbates
atherosclerotic lesion formation and mitochondrial DNA damage in the
aorta of apoE-null mice (42), indicating that passive smoking could
affect CVD progression synergistically with hypercholesterolemia.
The high vulnerability of cardiovascular tissues to environmental
pollutants is dramatically underscored by a recent report showing that
the hearts of rats exposed to environmental tobacco smoke accumulate as
many DNA adducts as the lung (36). When the exposure was stopped, the
number of DNA lesions in lung and the tracheal epithelium was
diminished, but no significant DNA repair was observed in the
myocardium, indicating a relatively high vulnerability of the heart to
chronic and cumulative injury caused by environmental toxins (36). In
addition to tobacco smoke, other pollutants have also been reported to
affect cardiovascular tissues (vide infra). However, the most
persuasive data to emerge from such studies relate to the effects of
ambient particulate matter on heart disease and CVD mortality. These
data point toward a link between the levels of air particulates and CVD
and lend support to the notion that pollutants can adversely affect
cardiovascular health.
LINK BETWEEN AIR POLLUTION AND HEART DISEASE
Extensive epidemiological studies suggest a link between particulate
air pollution and daily mortality rates as well as between overall
mortality and long-term exposure. Consistent associations have been
demonstrated (21, 46, 69, 76) with both respirable particles (<10 µm
in diameter; PM10) and fine particles that reach the deep lung (<2.5
µm; PM2.5). Depending on the method of analysis and the specific urban
populations examined, it has been estimated that each 10 µg/m3
elevation in the PM10 level increases the relative rate of death from
all causes by 0.4–1% (21,46,69,76) and each 10 µg/m3 increase in
long-term average PM2.5 is associated with a 4% increased risk of all
cause mortality and a 6% increased risk of cardiopulmonary mortality
(11).
A potential link between air particulates and CVD in particular is
suggested by several time series studies showing that elevated PM10 and
PM2.5 levels are associated with an increase in cardiovascular hospital
admissions (20, 68, 78, 79). Stratification by diagnosis suggests
specific associations with ischemic heart disease and congestive heart
failure (35). Heart failure deaths, which make up 10% of all
cardiovascular deaths, accounted for 30% of cardiovascular deaths
related to PM (35). Elevated PM2.5 concentrations have also been
associated with a transient risk of acute myocardial infarction within
a few hours and 1 day after exposure (66).
Although the relationship between PM exposure and cardiopulmonary
mortality appears causal, specific mechanisms by which exposure to air
particulates affects cardiovascular health remain unclear (82, 90).
Both PM10 and PM2.5 can penetrate the airways and alveoli of the lung,
and the ultrafine particles (<0.1 µm in diameter) have been shown to
also pass into systemic circulation (59, 60) and cause extrapulmonary
toxicity. The observations that air pollution accelerates heart rate,
diminishes heart rate variability (HRV), and increases the incidence of
arrhythmias suggest primary effects on myocardial excitability or
autonomic regulation of the heart or both (82, 90). In a small and
heterogeneous cohort of elderly subjects, a negative association
between HRV and mean heart rate and PM10 levels has been reported (70),
suggesting perturbations in the cardiac autonomic function. A similar
association was found in two other cohort studies (28, 51) as well as
in a linear study on an occupational cohort that was continuously
monitored for PM2.5 exposures (52). Both long-acting and short-acting
components were reported, indicating acute as well as cumulative
effects that could be related to changes in sympathetic tone and
cytokines. Most recently, decreased HRV has been demonstrated in
elderly people exposed to concentrated ambient particles (19).
Autonomic changes have also been observed in animal studies. Dogs
exposed to concentrated ambient particles show increasing sympathetic
influences with increasing cumulative exposure dose (27). Normal rats
exposed to residual oil fly ash (ROFA) or its metal constituents
display bradycardia and arrhythmia (12), whereas rats with myocardial
infarction and preexisting premature ventricular complexes exposed to
ROFA show increased arrhythmia frequency (95). Nonetheless, specific
mediators of PM-induced changes in autonomic regulation, sinus rhythm,
conduction disturbances, and susceptibility to arrhythmia remain
unidentified. Whereas PM exposure has been shown to increase systemic
(87) and local cytokine release in the lung and lung cells (14, 22, 38)
and to stimulate irritant receptors (89), it remains unclear to what
extent these changes contribute to its cardiovascular toxicity,
although direct irritant disturbance of cardiovascular function during
PM inhalation has been demonstrated in spontaneously hypertensive rats
(44).
Increases in markers of vascular inflammation such as endothelins and
C-reactive protein have been reported in rats or humans exposed to
particulates (67,86), but no unifying concepts have emerged. The
observations that PM exposures lead to an elevation of blood pressure
and endothelins in the absence of lung injury and without changing
blood oxygenation levels (91) does however suggest that hypoxia is
unlikely to be a significant cause of cardiovascular changes caused by
PM exposure. The hypoxemia hypothesis is also inconsistent with the
lack of correlation between blood oxygen saturation and PM10levels in
high-altitude dwellers (20). Therefore, a likely scenario may be a
cumulative multifactorial effect on hemostatic, vasoconstrictive, and
autonomic factors leading to increased electrical instability and
triggering myocardial infarction in a susceptible population. The
recent observations that concentrated ambient particle exposures
enhance ischemia in a dog model of acute coronary occlusion (94) and
increase conduit artery vasoconstriction in healthy adults (9) provide
one plausible mechanism by which PM exposure could precipitate sudden
coronary vasoconstriction in flow-limited occlusive arteries or rupture
unstable plaques, but the underlying cellular and molecular mechanisms
remain unclear.
In addition to precipitous events, PM exposure could also induce
chronic and pervasive cardiovascular injury. Such effects are suggested
by studies on rats showing PM-induced increases in cardiac
chemiluminescence after acute exposures (31), increases in fibrinogen
and blood viscosity after 7 days of exposure (86), and low-grade
inflammatory injury to the myocardium (45) as well as coronary and
renal arteries in mice (57) after chronic exposures. In addition, a
4-wk exposure to PM10 has also been shown to accelerate atherosclerotic
lesion progression in Watanabe heritable hyperlipidemic rabbits (83).
This increase in atherosclerotic lesions was correlated with the number
of alveolar macrophages, suggesting that PM exposure increases
vulnerability to plaque rupture. Hence, further studies are clearly
warranted to determine how chronic exposures to low levels of PM affect
atherogenesis and the formation of arterial lesions. Moreover, because
lipid peroxidation and oxidative stress are key elements in arterial
accumulation of cholesterol and plaque progression (26), vascular
deposition of redox active PM particles (particularly their metal
constituents) could exacerbate cholesterol oxidation and the formation
of lipid-laden cells. These effects of PM are likely to depend
critically on the nature of the airborne particulates, their size,
composition, reactivity, and their ability to penetrate cardiovascular
tissues and elicit detrimental responses.
PM COMPOSITION AND METAL TOXICITY
The composition of air particulates is highly heterogeneous and varies
with geographic location and local climate, season, industry, and
traffic. The particulates are made up of combustive products,
resuspended crustal and biological materials (pollen, bacteria,
viruses, and endotoxins), metals (e.g., Fe, V, Ni, Cu, Zn, Pb, Mn),
inorganic compounds (oxides, nitrates, and sulfates), polyaromatic
hydrocarbons, ethers, amines, and nitriles as well as carboxylic acids
and aldehydes (56, 98). With such a heterogenous composition, systemic
identification of toxicity due to individual components is a daunting
task and represents a major challenge to the field. However, several
reports suggest that much of PM toxicity is related to the transition
metal content of the particles. For instance, in rats subjected to
intratracheal PM instillation, the lung dose of bioavailable transition
metals, but not instilled PM mass, was the primary determinant of the
acute inflammatory response (18). In agreement, some investigators
studying the direct effects of PM on cells in culture have reported
that PM-generated oxidants and toxicity are prevented by removing
metals or by metal-chelating agents (29, 39, 41, 71). Collectively,
these studies are consistent with the view that PM exposures result in
the delivery of metals to multiple extrapulmonary sites where they form
reactive centers that continually catalyze the generation of reactive
oxygen species and induce oxidative stress.
Whereas PM-associated metals in general may be toxic, the role of
specific metals is less well understood. Several PM-associated metals
have been tested for their contribution to toxicity. Universally high
toxicity has been attributed to vanadium, although the Ni, Cu, Fe, and
Zn content of PM has also been linked to selective measures of toxicity
in a tissue-specific manner (1, 14, 43). For cardiovascular exposures
in particular, Ni has been linked to the cardiodepressant effects of
ROFA exposure (72, 96), and changes in HRV have been correlated with V
and Pb content in broiler workers (53). Clearly, further work is
warranted, not only to elucidate the role of metals in PM toxicity, but
also to study the effects of environmental transition metals on CVD in
general. To date little is known in regard to mechanisms by which
nonparticulate exposure to environmental metals affects cardiovascular
health. Basics of metal delivery and deposition in cardiovascular
tissues remain largely unknown, although studies with Ni (62), Cr (24),
Hg (13), and Cd (40) show that environmental exposure to these metals
results in their deposition in the heart and blood vessels, and that
the cardiovascular tissues are significant targets of metal toxicity.
Moreover, the cardiotoxicity of transition metals, heavy metals, and
metalloids is well known. Long-term arsensic exposure is associated
with peripheral vascular disease and with an increase in the incidence
of ischemic heart disease (93). Exposures to cadmium are associated
with arterial hypertension in men (77) and young monkeys (2) and
increases aortic resistance in rabbits (85). Interestingly, large
increases in myocardial trace element concentration have been observed
in cases of idiopathic dilated cardiomyopathy (24). Furthermore, an
increase in the incidence of heart failure in Japanese inhabitants of
an area polluted by cadmium has been reported (61). These observations
underscore the relevance of metal pollutants (in air particulates or
drinking water) to CVD risk while at the same time point toward a
greater need for understanding the metabolism of exogenous as well as
endogenous trace metals (particularly Fe and Cu) and how they affect
CVD.
GASEOUS POLLUTANTS
In addition to metals, the effects of PM could be mediated or modified
by other gaseous pollutants. Atmospheric CO and NO2 levels have been
shown to be associated with hospital admissions for ischemic heart
disease (48) and with an increased risk of ST-segment depression during
repeated exercise tests performed by patients with stable coronary
artery disease (63). Increased risk of cardiovascular morbidity and
mortality on CO exposure has been documented by several epidemiological
studies (10, 54, 97). Ozone is an additional copollutant, which is very
effective in inducing pulmonary inflammation and edema (15), and animal
studies demonstrate a direct bradycardiac effect of ozone exposure (5).
Moreover, chronic (1 parts/million for 2 wk) exposure to ozone has been
reported to increase total blood cholesterol levels in guinea pigs and
rats (88), but the observations were not followed up by more
mechanistic studies. Even though human ozone exposures have been
associated with a decrease in heart rate variability (28), no firm data
have emerged linking environmental ozone exposure to increased
cardiovascular morbidity and mortality. In general, the effects of
gaseous pollutants on CVD have not been systematically examined, and
the mechanisms by which they could affect CV health remain speculative.
ENVIRONMENTAL ALDEHYDES
Because aldehydes increase in the air in parallel with PM, and several
aldehydes such as crotonaldehyde, glyoxal, glycoaldehyde, and
hydroxybenzaldehdye are important constituents of PM2.5 (56, 74), it
appears likely that they could mediate, at least in part, the
cardiotoxic effects of PM exposure. Moreover, several volatile
aldehydes may be PM copollutants. Aldehydes are present in high
concentrations in automobile exhaust and smog and are generated during
combustion of organic material in any form (coal, wood, paper, or
cotton). They constitute 1 to 2% of the volatiles generated from
automobile exhaust and the burning of fossil fuels (23). Cigarette
smoke contains 50–70 parts/million acrolein, and 0.04–2.2 parts/million
acrolein has been detected near petrochemical plants (23). In addition,
acrolein and related aldehydes are also present in high abundance in
several food substances, and their concentration is particularly high
in fried foods and reheated oils (17, 23). With the exception of
metals, aldehydes are the major toxicants in drinking water. Over 36
different aldehydes are found in drinking water, of which acrolein and
endrin have been classified as the two highest priority pollutants
(23).
Extensive epidemiological and experimental data suggest that aldehydes
affect cardiovascular health. Direct exposure to high concentrations of
unsaturated aldehydes is cardiotoxic. They induce contractile arrest of
the perfused heart (80) and arrhythmogenic changes in the myocyte
excitability (7). Even the less reactive saturated aldehydes, when
delivered intravenously, cause prolongation of the Q-T interval,
arrhythmogenesis, and ventricular fibrillation in dogs (37). Low doses
of acrolein and formaldehyde (0.05–0.1 mg/kg iv) elicit vasopressor
effects (23), suggesting that increased systolic blood pressure may be
one of the main symptoms of acute aldehyde exposure. Chronic changes in
cardiovascular tissues on aldehyde exposure have also been documented.
Repeated exposure to
-ethylacrolein for 13 wk has been found to cause cardiac hypertrophy
(4). Additionally, exposure to low concentrations of acrolein leads to
an increased deposition of the aldehyde in the aorta in cockerels (64)
and increases hypercholesterolemia and plaque formation in the
atherosclerosis-prone apoE-null mice (8). Occupational exposure to
aldehydes could also induce cardiovascular changes. The increased risk
of atherosclerotic heart disease in plant workers producing
formaldehyde (81) and the higher incidence of heart disease in
undertakers (49), embalmers (92), and perfumery workers (30) has been
linked to aldehyde exposure. Finally, the high concentration of
aldehydes in cigarette smoke (17) raises the possibility that some of
the adverse cardiovascular effects of smoking are related to aldehyde
toxicity.
In addition to direct exposure to aldehydes, exposure to industrial
pollutants that generate aldehydes has also been linked to an increased
risk of cardiovascular disease. Exposure to 1,3-butadiene (which is
metabolized to crotonaldehyde, 75) is associated with an increased
incidence of atherosclerosis, particularly in African-American workers
exposed to butadiene in styrene-butadiene rubber polymer manufacturing
plants (55). The atherogenic potential of butadiene has also been
substantiated in studies on experimental animals. Exposure to 20
parts/million butadiene has been shown to accelerate atherogenesis in
cockerels (65), supporting the idea that butadiene exposure is a
significant risk factor for atherosclerosis. This is particularly
significant given that butadiene is a ubiquitous pollutant abundant in
urban air (34). Similar increases in CVD risk have been suggested for
workers exposed to vinyl chloride, which is metabolized via cytochrome
P450 to its active constituent, chloroaldehyde (84). The increased
incidence of cardiovascular disease in vinyl chloride-exposed
populations is evinced by a 7-year study of 1,100 workers exposed to
vinyl chloride monomer (47). This study showed a significant increase
in cardiovascular diseases, including hypertension, myocardial
infarction, and other circulatory disorders in vinyl chloride-exposed
workers.
POLLUTION MAY BE A NEW RISK FACTOR FOR HEART DISEASE
The totality of evidence discussed above strongly supports the view
that exposure to environmental toxins significantly increases CVD risk,
which contributes to the overall health burden of air pollution. The
World Health Organization (WHO) has ranked air pollution as one of the
top ten contributors to preventable deaths (16). In 1995, the WHO
estimated that 460,000 avoidable deaths occur annually as a result of
outdoor urban exposures, and in 1997, it was estimated that annually
nearly 700,000 deaths are related to air pollution and that about 8
million avoidable deaths will occur per annum worldwide by 2020 (16).
In a recent European assessment (46), outdoor air pollution (PM10) was
found to be responsible for 6% of total mortality, half of which was
attributed to automobile emissions. Because excess mortality associated
with PM is largely related to cardiopulmonary deaths, the contribution
of CVD to the overall health burden of pollution is likely to be
numerically significant. For instance, there are approximately 350,000
sudden cardiac deaths each year in the United States alone, of which as
many as 60,000 deaths could be related to particulate air pollution
(82).
Additional, less readily quantifiable, cardiovascular burden of
pollution may be related to pervasive changes such as hypertension or
dyslipidemia that have been shown to be caused by exposure to
aldehydes, particulates, insecticides, and metals. Collectively, these
data raise the possibility of an etiologic relationship between chronic
pollutant exposure and hypertension or hypercholesterolemia and could
partially account for the endemism of CVD in the industrialized world.
Not only could pollutants exacerbate and accelerate CVD, risk factors
associated with CVD could predispose and sensitize for pollutant
toxicity. Thus preexisting CVD in itself could be a risk factor of
environmental toxicity. Chronic hypercholesterolemia, for instance,
could significantly affect xenobiotic metabolism and disposition by
either altering the expression of detoxification enzymes in liver and
peripheral tissues or by providing additional circulating nucleophilic
binding sites (e.g., lysine residues of apolipoprotein and ethanolamine
phospholipids). Moreover, interaction with lipoprotein nucleophiles
could decrease xenobiotic clearance and deliver xenobiotics to
otherwise inaccessible vascular sites, prevent receptor-mediated
lipoprotein clearance, and dysregulate lipoprotein metabolism. Binding
to reactive electrophiles could also in turn activate the lipoprotein,
facilitating the formation of the prothrombinase complex leading to
increased blood coagulability (cf, 100). Such interactions have the
potential of setting up positive feedback cycles in which environmental
pollutants could prevent lipoprotein clearance and increase their
thromobogenecity, which in turn would diminish xenobiotic clearance and
metabolism and facilitate xenobiotic delivery to sites not accessible
to detoxification enzymes (e.g., the vascular intima). Additionally,
xenobiotic-induced dysregulation of redox-activated trans-acting
factors could initiate chemical atherogenesis (73). Such scenarios are
currently speculative, however, that they are likely and supported
indirectly by multiple lines of evidence points to an urgent need for
further study.
Realizing the need for studying the cardiotoxicity as a significant
consequence of exposure to environmental pollutants, the National
Institute of Environmental Health Sciences, the National Heart, Lung,
and Blood Institute, and the Environmental Protection Agency
collaboratively organized a workshop on the "Role of Environmental
Agents in Cardiovascular Disease." This workshop stressed the need for
systematic elucidation of environmental causes of cardiovascular
toxicity and for more extensive epidemiological and screening
strategies for identifying cardiotoxin pollutants ("heart
disease-causing" akin to "cancer-causing" chemicals). It was
recommended that such identifications be followed by elucidation of
toxin-specific metabolism and of the molecular, cellular, and systemic
mechanisms that mediate the cardiotoxic effects of common environmental
pollutants. Finally, because not all exposed individuals are likely to
be equally sensitive, identification of specific susceptibility factors
(old-age, diabetes, hypercholesterolemia) was suggested. It was
expected that together these studies will lead to the identification of
environmental pollutants as heretofore unrecognized CVD risk factors
and spur the development of the new discipline of "Environmental
Cardiology."
ACKNOWLEDGMENTS
The author thanks Dr. John Godleski and Dr. Pat Mastin for critical reading of the paper and insightful comments.
GRANTS
The author also thanks the National Institute of Environmental Health
Sciences for support through Grants R01 ES-12062 and P01 ES-11860.
FOOTNOTES
Address for reprint requests and other correspondence: A. Bhatnagar,
Division of Cardiology, Dept. of Medicine, Room 421, Delia Baxter
Bldg., 580 S. Preston St., Louisville, KY 40202 (E-mail:
).
FOOTNOTES
The costs of publication of this article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section 1734 solely to
indicate this fact.
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Air Pollutants 
