North American Journal of Medical Sciences

: 2013  |  Volume : 5  |  Issue : 8  |  Page : 445--453

The emerging role of outdoor and indoor air pollution in cardiovascular disease

Jacinta C Uzoigwe, Thavaleak Prum, Eric Bresnahan, Mahdi Garelnabi 
 Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, MA, USA

Correspondence Address:
Mahdi Garelnabi
Department of Clinical Laboratory and Nutritional Sciences, School of Health and Environment, University of Massachusetts Lowell, 3 Solomont Way, Lowell, MA 01854, Suite 4, Lowell, MA 01854


Outdoor and indoor air pollution poses a significant cardiovascular risk, and has been associated with atherosclerosis, the main underlying pathology in many cardiovascular diseases. Although, it is well known that exposure to air pollution causes pulmonary disease, recent studies have shown that cardiovascular health consequences of air pollution generally equal or exceed those due to pulmonary diseases. The objective of this article is to evaluate the current evidence on the emerging role of environmental air pollutions in cardiovascular disease, with specific focus on the types of air pollutants and mechanisms of air pollution-induced cardiotoxicity. Published literature on pollution was systematically reviewed and cited in this article. It is hoped that this review will provide a better understanding of the harmful cardiovascular effects induced by air pollution exposure. This will help to bring a better understanding on the possible preventive health measures and will also serve regulatory agencies and researchers. In addition, elucidating the biological mechanisms underlying the link between air pollution and cardiovascular disease is an essential target in developing novel pharmacological strategies aimed at decreasing adverse effects of air pollution on cardiovascular system.

How to cite this article:
Uzoigwe JC, Prum T, Bresnahan E, Garelnabi M. The emerging role of outdoor and indoor air pollution in cardiovascular disease.North Am J Med Sci 2013;5:445-453

How to cite this URL:
Uzoigwe JC, Prum T, Bresnahan E, Garelnabi M. The emerging role of outdoor and indoor air pollution in cardiovascular disease. North Am J Med Sci [serial online] 2013 [cited 2021 Nov 30 ];5:445-453
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Air pollution exposure is a major problem worldwide and has been linked to cardiovascular diseases (CVDs). Outdoor and indoor air pollution, which consists of a complex mixture of particulate matter (PM), gases (e.g., carbon monoxide [CO], ozone [O 3 ] , nitrogen dioxide [NO 2 ], sulfur dioxide [SO 2 ]), is increasingly recognized as an important determinant of CVDs. [1],[2],[3] PM is described as a mixture of suspended particles that vary in chemical composition and size. [1] There is increasing evidence that exposure to air pollution is not only linked to pulmonary diseases, but also mainly to CVDs. [2],[3],[4]

Many conditions predispose to death from CVDs, particularly coronary artery disease (CAD), and include hypercholesterolemia, [5] hypertension, [6] a thrombotic tendency, [7] the postmenopausal state, [8] and ventricular arrhythmias. [9] It is reported that sudden death is usually the first and only manifestation in about 20% of patients who present with CAD [10] and about 75% of patients with myocardial infarction die outside the hospital. [11] This suggests that treatment is not available for many patients, and the focus should be to prevent the development and progression of CVDs.

Previous research have shown that gaseous pollutants (e.g., CO, NO 2 ) and toxic substances present in fine PM (e.g., black carbon, primary and secondary aerosols, metals) can cross epithelium of airway following inhalation, reaching the vasculature, and induce the production of proinflammatory cytokines and reactive oxygen species. [12] The effects produced by these air pollutants might subsequently lead to hypertensive responses and changes in autonomic cardiac control. [13]

The objective of this article is to consider a number of different air pollutants found either outdoor or indoor, such as gaseous pollutants and PM, associated with detrimental cardiovascular effects. Specifically, this study would review the current information on the effects of pollution exposure on cardiovascular system and the different mechanisms of air pollution-induced cardiotoxicity. It is expected that this review would provide a better understanding of the harmful cardiovascular effect induced by air pollution exposure, as well as their mechanisms of actions, and such information would be of use to researchers, healthcare providers and regulatory agencies, and could also be used by policy makers to determine acceptable levels of air pollution and to design ways to minimize the harmful cardiovascular effects of air pollutants on the body. In addition, elucidation of the physiological and molecular mechanisms of air pollution-induced cardiotoxicity might become an essential target in developing the novel pharmacological strategies aimed at decreasing the adverse effects of air pollution on cardiovascular system.

 Outdoor/Indoor Air Pollutants and Associated Cardiovascular Effects

Certain environmental air pollutants are of special interest since they are associated with increased morbidity, hospitalization, [14] and mortality due to CVD. [2],[3] In the United States, the six commonly found air pollutants are particle pollution (often referred to as PM), ground-level O 3 , CO, SO 2 , NO 2 , and lead. [1] Worldwide, the air pollutants of concern include PM ("fine particles" [PM 2.5 < 2.5 μm], and "coarse particles" [PM 10 to 2.5 ]), ground-level O 3 , CO, SO 2 , NO 2 , lead, cigarette smoke, and carbon disulfide (CS 2 ).

 Particulate Matter Air Pollution

PM is a mixture of particles that can adversely affect human health and includes dust, dirt, soot, smoke, and liquid droplets directly emitted into the air by sources such as factories, power plants, cars, construction activity, fires, and natural windblown dust. It is reported that the size of PM is directly linked to their potential for causing health-related problems. The United States Environmental Protection Agency (EPA) is mainly concerned about particles that are 10 μm in diameter or smaller because those are the particles that generally pass through the throat and nose and enter the lungs. Once inhaled, these particles can cause harmful effects on the lungs and heart. EPA groups particle pollution into two categories: fine PM and coarse PM. [1]

Fine particulate matter (PM 2.5 )

Sources of PM 2.5

There are both outdoor and indoor sources of fine particulates (PM with an aerodynamic diameter less than 2.5 μm [PM 2.5 ]). Particles in the PM 2.5 size range are commonly found in smoke and haze and are of particular health concern since they are able to travel deeply into the respiratory tract, reaching the lungs and can also affect the heart. Throughout the world, the major sources of fine particles primarily are from human combustion of fossil fuels from different outdoor activities, such as from car, truck, bus, and off-road vehicle (e.g., construction equipment, snowmobile, locomotive) exhausts, other operations that involve the burning of fuels such as wood, heating oil, or coal, as well as natural sources such as forest and grass fires. PM 2.5 is also produced by common indoor activities, and such indoor sources of fine particles include tobacco smoke, cooking (e.g., frying, sautéing, and broiling), burning candles or oil lamps, and operating fireplaces and fuel-burning space heaters (e.g., kerosene heaters). Fine particles can also be emitted from the reaction of gases or droplets in the atmosphere from sources such as power generation plants. [1]

Cardiovascular effects of PM 2.5

Particles in the PM 2.5 size range are of particular health concern because they can reach the smaller airways and alveoli. [1] Scientific studies have linked increases in daily PM 2.5 exposure with increased cardiovascular morbidity and mortality. Exposure to ambient air-borne PM of < 2.5 μm (PM 2.5 ) is associated with increased incidences of specific acute CVDs, such as myocardial infarction, ischemic stroke, heart failure, cardiac arrhythmia, atrial fibrillation, [15] as well as peripheral arterial and venous diseases. [16] It is reported that constituents of ambient particulates from traffic emissions were more toxic than those from other sources. [17] Multiple studies have found associations between decreased heart rate variability (HRV) and elevated blood pressure and exposure to fine particulates (PM 2.5 ). [18] It is reported that short-term exposure to traffic-derived fine particulate air pollution is associated with acute cardiovascular events. [19]

Mechanism of action of PM 2.5 in cardiovascular disease

Several mechanisms have been reported for PM air pollution-associated cardiovascular effects, including inducing systemic inflammation, oxidative stress, increased blood coagulability, and autonomic and vascular imbalance. [20]

Kampfrath et al.[20] investigated the molecular mechanisms by which PM 2.5 mediates inflammatory responses in a mouse model of chronic exposure. Their findings suggest that PM 2.5 triggers an increase in oxidized phospholipids in lungs that then mediates a systemic cellular inflammatory response through Toll-like receptor 4 (TLR4)/NADPH oxidase-dependent mechanisms.

Coarse particulate matter (PM 10-2.5 )

Sources of PM 10-2.5

In contrast to fine particles which typically originate from combustion and photo-chemical processes, coarse particles [PM with aerodynamic diameter between 2.5 and 10 μm (PM 10-2.5 )] are mainly derived from processes such as mechanical grinding in industry and transportation, windblown dust, and agricultural activities; PM deposit preferentially in the upper and larger airways. [1]

Cardiovascular effects of PM 10-2.5

The findings from research on the health effects of coarse particles (PM 10-2.5 ) have been mixed. [21] Previous research has found associations between daily PM 10 concentrations and cardiovascular mortality in the Coachella Valley, a desert resort and retirement area east of Los Angeles, California. [22] Another study [23] concluded that after adjustment for PM 2.5 , there were no statistically significant associations between coarse particulates and hospital admissions for cardiovascular and respiratory diseases.

Mechanism of action of PM 10-2.5 in cardiovascular disease

One of the plausible mechanisms providing explanations for associations between exposure to airborne PM and increased risks of cardiovascular mortality is the alterations in cardiac autonomic control, assessed by changes in HRV. The relationship between. PM 10-2.5 and CVD is still controversial. Previous studies [24] found no relationship between PM 10-2.5 and changes in HRV; however, it was reported that those investigations took place in urban areas with low PM 10-2.5 levels. In a separate study, Lipsett et al.[25] examined the impact of PM on HRV in an area where PM 10-2.5 predominates, and found that elevated levels of ambient coarse particles (PM 10-2.5 ) may adversely affect HRV in older subjects with CAD.

 Ground-Level Ozone Pollution (or Smog)

Sources of ground-level ozone

O 3 is described as a colorless gas molecule consisting of three atoms of oxygen, highly reactive and with a high oxidizing power. Where O 3 forms determines whether it is beneficial or harmful to health. In nature, O 3 forms at high altitude layers, that is, the ­so-called "ozonosphere" (15-60 km) forming a protective layer and is regarded as good O 3 . This protective layer shields from the sun's harmful ultraviolet rays. Unfortunately, human-created chemicals are destroying this beneficial protective layer of O 3 . In contrast to good O 3 layer, O 3 near ground level is a harmful pollutant and is called bad O 3 . In lower atmosphere layers known as troposphere (<15 km high from the ground), O 3 formation is induced, especially during the summer when ultraviolet light in sun radiations triggers a chemical reaction with precursor chemical pollutants emitted by motor vehicles, thermoelectric plants, and industrial sources. These precursor pollutants are composed of nitro compounds like NO 2 and volatile organic hydrocarbons (VOC) like terpenes. [26]

Cardiovascular effects of ground-level ozone

Ground-level O 3 , a major component of urban smog, is one of six air pollutants that the United States EPA have determined as likely to cause human health problems. Breathing ground-level O 3 can result in a number of harmful health effects. Many epidemiologic studies have shown that there is an association between PM and O 3 and the increased incidence of cardiovascular morbidity and mortality. [27] Data on the cardiovascular effects of ground-level O 3 is mixed. Although a positive association between O 3 and ischemic heart disease was found in Helsinki, Finland, [28] no associations were found in studies conducted in Tucson, Arizona, [29] London, UK, [30] and Edinburgh, Scotland. [31]

Mechanism of action of ground-level ozone in cardiovascular disease

O 3 has a high oxidizing power, and reacts with biomolecules to form ozonides and free radicals. In the body, this reaction triggers an inflammatory response that conveys increased systemic oxidative stress, which has both pulmonary and cardiovascular effects. According to Srebot et al., [26] there is a possibility that pulmonary oxidant stress mediated by PM and/or O 3 exposure can result in downstream perturbations in the cardiovasculature, as the pulmonary and cardiovascular systems are intricately associated. Several mechanisms of cardiotoxicity have been observed and associated to ground-level O 3 exposure including modification of endothelial function and vascular vasomotricity, and alterations in autonomic control of cardiac frequency, activation of systemic inflammatory response mediated by cytokines and, increase of oxidative stress. [32],[33],[34],[35] In a randomized, double-blind, crossover chamber study by Brook et al., [27] it was found that O 3 can influence macrovascular diameter and tone. These researchers showed that inhalation of fine particulate air pollution and O 3 causes acute arterial vasoconstriction in healthy adults. [27] In one study conducted in the nursing home in Mexico, it was found that ambient levels of PM 2.5 and O 3 can reduce the high-frequency component of HRV and that patients with underlying arterial hypertension are particularly susceptible to this effect. [31] In another study, Gold et al. [36] suggested that both particulate and O 3 pollution may lead to short-term autonomic imbalance, reflected by changes in heart rate and HRV. It is reported that O 3 exposure mediates an inflammation response and increased oxidative stress in the cardiovascular system. In vitro studies [33] using peripheral human blood mononuclear cells have shown that a significant relationship exists between O 3 and increased lipid peroxidation and protein thiol group content. Studies using an animal model found that O 3 exposure causes increased systemic oxidative stress. [37]

 Nitrogen Dioxide Air Pollution

Sources of nitrogen dioxide

NO 2 , a suffocating, brownish gas, is predominantly derived from the oxidation of NO, the major outdoor source of which is combustion emissions, mainly from motor vehicles and stationary combustion sources such as electric utility and industrial boilers. NO 2 exposure indoors is from sources such as unvented combustion appliances. [1]

Cardiovascular effects of nitrogen dioxide

Harmful health effects from NO 2 may potentially result from NO 2 itself or its reaction products such as O 3 . NO 2 , an important air pollutant in the developed countries is positively associated with cardiovascular morbidity, hospitalization, and mortality. Research has shown that the concentration of NO 2 is associated with daily hospital emergency transports for ischemic heart diseases such as angina pectoris and myocardial infarction, [38] as well as for subsequent cardiac insufficiency and arrhythmia. Previous studies have shown that an interquartile range increase in NO 2 is associated with an increase of 6.1% of cardiovascular mortality. [39] It is reported that the cardiovascular effects of NO 2 are mainly observed in patients with CVDs aged 65 years or older who have high risks of atherogenesis. [40]

Mechanism of action of nitrogen dioxide in cardiovascular disease

Takano et al. demonstrated that daily exposure to NO 2 air pollution near ambient levels (0.16 ppm) enhances atherogenic lipid metabolisms primarily in the otsuka long-evans tokushima fatty (OLETF) rats, but less in the long-evans tokushima otsuka (LETO) rats. These researchers concluded that NO 2 air pollution near ambient levels is an atherogenic risk primarily in obese subjects. [41]

 Sulfur Dioxide Air Pollution

Sources of sulfur dioxide air pollution

SO 2 is considered a toxic gas in air pollution and is described as a highly irritating, colorless, soluble gas with a pungent odor and taste. SO 2 is generally found at considerably lower concentrations in indoors compared with outdoor. Indoor sources of SO 2 include the use of kerosene space heaters. [42] Outdoor sources of SO 2 include burning of fossil fuels (coal and oil), combustion of sulfur-containing fuels, especially in power plants and diesel engines, and smelting of mineral ores (aluminum, copper, zinc, lead, and iron) that contain sulfur. Oxidation of SO 2 results in formation of sulfur trioxide, which, as a result of its strong affinity for water, can be rapidly hydrated to form sulfuric acid. [43]

Cardiovascular effects of sulfur dioxide air pollution

Sunyer et al.[44] reported the association of daily SO 2 air pollution levels with hospital admissions for CVDs in Europe. Their results suggest that SO 2 pollution may play an independent role in triggering ischemic cardiac events. [44]

Mechanism of action of sulfur dioxide in cardiovascular disease

Blood viscosity has been linked to severity of CVD [45] and has been found to increase in association with increased levels of ambient total suspended particles and SO 2 . [46] Although SO 2 is considered to be toxic and detrimental to human health, recent studies suggest that SO 2 might be an endogenous gaseous signaling molecule involved in the regulation of cardiovascular functions. [47]

 Lead Air Pollution

Sources of lead air pollution

Lead enters the body when a person inhales particles of lead that are suspended in the air. Lead is a naturally occurring element and it does not go away over time, unlike most pollutants. It is reported that the United States eliminated lead from gasoline and paints, a change that significantly reduced lead in air pollution in the United States, cutting it by 98% by 2002. [48] However, most of the lead that entered the air in the past remains in the environment, especially in the soil near major roadways. [49] A major indoor source of lead is old paint found in homes built before 1978. [50] Additionally, lead-contaminated soil and dust tracked indoors from outside also contribute to indoor lead pollution. [48]

Cardiovascular effects of lead air pollution

The cardiovascular effects of lead exposure includes elevation of blood pressure and hypertension [51] Other impacts of lead exposure on CVD include an increased incidence of clinical cardiovascular end points such as coronary heart disease (CHD), stroke, and peripheral arterial disease, [52] as well as other cardiovascular function abnormalities including left ventricular hypertrophy and alterations in cardiac rhythm. [53] Studies have shown that the effects of lead poisoning may continue after the source of exposure has been eliminated. [53]

Mechanism of action of lead air pollution in cardiovascular disease

It is reported that chronic exposure to low lead levels results in arterial hypertension that persists long after the cessation of lead exposure. [54],[55] The potential mechanisms explaining a link between cardiovascular effect and environmental lead exposure include enhanced oxidative stress, [56] stimulation of the renin-angiotensin system, [57] and down-regulation of nitric oxide [58] and soluble guanylate cyclase. [59] These biological mechanisms could lead to increased vascular tone and peripheral vascular resistance. [54] Research has shown that chronic lead exposure promotes atherosclerosis in experimental animals. [60] Among US adults, increased blood lead levels were associated with an increased prevalence of left ventricular hypertrophy. [61]

 Carbon Monoxide Air Pollution

Sources of carbon monoxide pollution

CO is a colorless, tasteless, odorless, and highly toxic gas produced by incomplete burning of hydrocarbons in fuels. [62]

Poisoning with CO is an important cause of accidental and intentional injury throughout the world. There are many indoor sources of CO including poorly installed and maintained heating systems, charcoal grills and hibachi pots that are used indoors, gas kitchen stoves that are used for heating, water heaters, and automobile exhaust. [63]

The principal outdoor source of CO pollution in most large urban areas are automobiles. Other sources of CO include cigarette smoke, human and animal respiration, industrial processes, and burning of fossil fuels. [64]

Cardiovascular effects of carbon dioxide pollution

Exposure to CO has been implicated in the process of atherosclerosis. Evidence from human studies has shown that CO can exacerbate ischemic heart disease.

Mechanism of action of carbon monoxide pollution in cardiovascular disease

The predominant mechanism by which CO causes heart disease is through production of hypoxia. CO typically affects oxygenation of tissue due to carboxyhemoglobin (COHb) production, with consequent adverse to cardiovascular effects. The harmful effects of CO are more profound in the myocardium than in peripheral tissues because of very high oxygen extraction by the myocardium at rest. [65]

 Cigarette Smoke

Sources of cigarette smoke pollution

Cigarette smoke consists of many chemicals, including nicotine, the addictive substance of cigarette smoke, [66] tar or particulate phase with its many carcinogens, and gaseous compounds including CO. [67]

Cardiovascular effects of cigarette smoke pollution

Cigarette smoking is a well-established risk factor for CVD in both men and women. There are a number of clinical atherosclerotic syndromes that are associated with cigarette smoking, including stable angina, acute coronary syndromes, sudden death, and stroke. It is reported that smokers who inhale deeply are likely to have an increased risk of both symptomatic peripheral arterial disease and abdominal aortic aneurysm. [68] Epidemiological evidences have clearly shown that cigarette smoking in both men and women increases the incidence of myocardial infarction and CAD. [69]

Mechanism of action of cigarette smoke in cardiovascular disease

It is reported that specific environmental toxins (such as tobacco smoke) introduced through the lungs can initiate and/or accelerate CVD development. [70] Although there is clear evidence linking cigarette smoke exposure with CVD, the exact components of cigarette smoke and the mechanisms involved in cigarette smoking-related cardiovascular dysfunction have not been clearly elucidated. [71] The effect of CO in cigarette smoke on athero-thrombotic disease has been controversial. In one study, it was reported that CO could be responsible for smoking-related cardiovascular alterations. [72] In another study, it was found that CO from cigarette smoke was an unlikely cause for atherosclerosis or thrombus. [73] In studies using experimental models, it was demonstrated that polycyclic aromatic hydrocarbons (PAHs) present in the tar fraction of cigarette smoke have accelerated atherosclerosis. [74] It is reported that although the contribution of nicotine in cardiovascular morbidity and mortality induced by cigarette smoking is uncertain, nicotine has a well-established acute and chronic cardiovascular effects, principally through sympathetic activation. [75]

 Biomass Smoke

Sources of biomass smoke pollution

Indoor air pollution resulting from solid fuels, principally biomass and coal, has been ranked as one of top 10 environmental risk factors of global burden of disease by the World Health Organization. [76] Studies have shown that biomass burning, especially wood, contribute to outdoor pollution. [77] In the developing countries, organic materials such as wood, dung, or charcoal (biomass fuel) are burned and used for cooking, home heating, and lighting. [78] It is reported that cooking or heating with biomass fuels in stoves or fireplaces vented to the outdoors (airtight stoves) produces high indoor air pollution. Studies from China showed that solid fuel use for cooking and heating are important activities contributing to indoor air pollution. [79]

Cardiovascular effects of biomass smoke pollution

Biomass fuel-combustion smoke have been associated with adverse health effects. [80] It is reported that biomass fuel represents a considerable risk to cardiovascular health. The burning of solid fuels in the homes release several pollutants including respirable PM, PAHs, heavy metals, and many other organic pollutants, [81] which have been linked to CVDs. Studies have shown that exposure to PM can trigger acute cardiovascular events and accelerate chronic CVDs. [82] Studies conducted in China have shown that CVDs are expected to increase considerably in China, and the future trends in blood pressure, diabetes, total cholesterol, and body mass index may drive the CVD epidemic for the next 20 years. [83] Research has shown that biomass smoke in Guatemalan women increase diastolic blood pressure. [75]

Mechanism of action of biomass smoke air pollution in cardiovascular disease

The biological mechanisms associated with the toxic effects of in-home solid fuel exposure-related cardiovascular system are not completely understood, but the principal mechanisms may be linked to inflammation through the generation of reactive oxygen species and oxidative stress. It is reported that the potential biological mechanisms of action of biomass smoke include oxidative stress, promotion of inflammation with a systemic release of cytokines, and blood coagulation. In another study in China, it was shown that the use of biomass for cooking greatly increases exposure to PM, especially for the person performing the cooking. The PM released from biomass burning contains prooxidative organic hydrocarbons, such as PAHs, particularly in particle phase, that may cause oxidative damage to DNA and secretion of proinflammatory cytokines and chemokines that can result in detrimental cardiovascular effects. Exposure to PAH from cooking using biomass fuel is associated with oxidative damage to DNA, assessed by 8-hydroxy-2′-deoxyguanosine (8-OHdG), among workers in a Chinese restaurant. [84] Research has shown that chronic exposure to biomass smoke causes an increase in the number of leukocyte-platelet aggregates among Indian women, [85] and is recognized as a risk factor for thrombotic disease such as unstable angina, [86] myocardial infarction, [87] and stroke. [88]

 Carbon Disulfide Air Pollution

Sources of carbon disulfide air pollution

CS 2 is described as a colorless, volatile, inflammable, and odorant liquid with a sweet aromatic odor. CS 2 is used mainly as an industrial chemical for the manufacture of rayon, cellophane, and carbon tetrachloride, as well as production of rubber chemicals and pesticides. [55] This implies that exposure to CS 2 occurs predominantly in the workplace. It is reported that workers in industrial plants that utilize CS 2 in their manufacturing processes have a high degree of exposure potential. [56] The release of CS 2 from industrial processes are almost exclusively to the air, and individuals in proximity to these sites may be exposed. [55] Inhalation by humans is regarded as the main route of CS 2 absorption in both occupational and environmental exposure.

Cardiovascular effects of carbon disulfide air pollution

A study by Hernberg et al.[89] suggested that workers exposed for at least 5 years to CS 2 showed an excess of deaths due to CHD. Previous studies reported the enhancing effects of CS 2 on atherosclerosis, including elevated serum cholesterol, phospholipids, and triglycerides in experimental animals, which was confirmed by biochemical studies. [90] Epidemiological studies have shown that chronic exposure to high concentrations of CS 2 may increase the risk of accelerated atherosclerosis and CHD. [91] In many studies, it is reported that there is increased prevalence of high blood pressure, electrocardiographic (ECG) abnormalities, clinical CHD, and lipid metabolism disturbances in workers exposed to CS 2 in varying degrees. [92] Multiple studies have shown an association between occupational exposure to CS 2 and CHD, even at lower exposures (30-120 mg/m 3 ). [93] However, in many other studies, there was no significant increase of the risk for CHD, especially at lower levels of exposure. [94] At low concentrations (under 30 mg/m 3 ) of CS 2 the question of CHD risk is still a controversial issue. [89] Ethnic differences were suggested to play a role. Research conducted in Japan, the Netherlands, and Yugoslavia found that that there was no evidence that CS 2 exposure affected CHD incidence. [89] These contradictory results suggest that CS 2 has coronary effects when predisposing factors to the development of CHD are present.

Mechanism of action of carbon disulfide air pollution in cardiovascular disease

In a study by Kotseva and De Bacquer, [95] it was shown that occupational exposure to CS 2 may increase total cholesterol and the risk of CHD. Their results also showed that there is a dose-response relationship between the level and duration of exposure and the prevalence of CHD. While the risk for CHD is increased in workers exposed to high CS 2 concentration for many years (CS 2 index ≥300), even a relatively modest exposure (CS 2 index <300) may increase serum cholesterol. The results imply that CS 2 may act by inducing disturbances in the lipid metabolism and acceleration of the atherosclerosis. [95]

 Conclusion and Future Directions

Research linking air pollution to CVDs has grown substantially. This article has discussed the emerging role of outdoor and indoor air pollutions in CVD. Previous research has shown associations between increased ambient air pollution and increased mortality, morbidity, hospitalization, and emergency department visits from CVD. Air pollution is a modifiable risk factor and understanding the harmful cardiovascular effects linked to it would enable preventive health measures to be taken, in order to reduce air pollution levels and associated diseases, and would be of further use to healthcare providers, regulatory agencies, and researchers. In addition, a better understanding of the biological mechanisms linking indoor/outdoor air pollution and CVD might become a vital target in developing novel pharmacological strategies focused on decreasing adverse effects of air pollution on cardiovascular system.


1U.S. Environmental Protection Agency (EPA). Air Quality Criteria for Particulate Matter. Research Triangle Park, NC: US Environmental Protection Agency, National Center for Environmental Assessment. EPA 600/P-99/002aF-bF; 2004.
2Pope CA 3 rd , Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002;287:1132-41.
3Pope CA 3 rd , Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, et al. Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004;109:71-7.
4Garelnabi M. Emerging Evidences from the contribution of the traditional and new risk factors to the atherosclerosis pathogenesis. J Med Sci 2010;10:136-44.
5Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-7.
6Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, et al. Blood pressure, strokes and coronary heart disease. Part 2, short term reductions in blood pressure: Overview of randomised drug trials in their epidemiological context. Lancet 1990;335:827-38.
7Parthasarathy S, Litvinov D, Selvarajan K, Garelnabi M. Lipid peroxidation and decomposition--conflicting roles in plaque vulnerability and stability. Biochim Biophys Acta 2008;1781:221-31.
8Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 1996;334:1156-62.
9Karjalainen J, Kujala UM, Kaprio J, Sarna S, Viitasalo M. Lone atrial fibrillation in vigorously exercising middle aged men: Case-control study. BMJ 1998;316:1784-5.
10Kannel WB, McGee DL, Schatzkin A. An epidemiological perspective of sudden death 26 year follow up in the Framingham Study. Drugs 1984;28:1-16.
11Ruston A, Clayton J, Calnan M. Patients' action during their cardiac event: Qualitative study exploring differences and modifiable factors. BMJ 1998;316:1060-4.
12O'Toole TE, Zheng YT, Hellmann J, Conklin DJ, Barski O, Bhatnagar A. Acrolein activates matrix metalloproteinases by increasing reactive oxygen species in macrophages. Toxicol Appl Pharmacol 2009;236:194-201.
13Sun Q, Yue P, Deiuliis JA, Lumeng CN, Kampfrath T, Mikolaj MB, et al. Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 2009;119:538-46.
14Poloniecki JD, Atkinson RW, de Leon AP, Anderson HR. Daily time series for cardiovascular hospital admissions and previous day's air pollution in London, UK. Occup Environ Med 1997;54:534-40.
15Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, et al. Air pollution and incidence of cardiac arrhythmia. Epidemiology 2000;11:11-7.
16Baccarelli A, Martinelli I, Zanobetti A, Grillo P, Hou LF, Bertazzi PA, et al. Exposure to particulate air pollution and risk of deep vein thrombosis. Arch Intern Med 2008;168:920-7.
17Grahame TJ. Does improved exposure information for PM 2.5 constituents explain differing results among epidemiological studies? Inhal Toxicol 2009;21:381-93.
18Brook RD, Rajagopalan S. Particulate matter air pollution blood pressure. J Am Soc Hypertens 2009;3:332-50.
19Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, Smeeth L. Effects of air pollution on the incidence of myocardial infarction. Heart 2009;95:1746-59.
20Kampfrath T, Maiseyeu A, Ying Z, Shah Z, Deiuliis JA, Xu X, et al. Chronic fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ Res 2011;108:716-26.
21Brunekreef B, Forsberg B. Epidemiological evidence of effects of coarse airborne particles on health. Eur Respir J 2005;26:309-18.
22Ostro BD, Hurley S, Lipsett MJ. Air pollution and daily mortality in the Coachella Valley, California: A study of PM 10 dominated by coarse particles. Environ Res 1999;81:231-8.
23Peng RD, Chang HH, Bell ML, McDermott A, Zeger SL, Samet JM, et al. Coarse particulate matter air pollution and hospital admissions for cardiovascular and respiratory diseases among medicare patients. JAMA 2008;299:2172-9.
24Liao D, Creason J, Shy C, Williams R, Watts R, Zweidinger R. Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly. Environ Health Perspect 1999;107:521-5.
25Lipsett MJ, Tsai FC, Roger L, Woo M, Ostro BD. Coarse particles and heart rate variability among older adults with coronary artery disease in the coachella valley, California. Environ Health Perspect 2006;114:1215-20.
26Srebot V, Gianicolo EA, Rainaldi G, Trivella MG, Sicari R. Ozone and cardiovascular injury. Cardiovasc Ultrasound 2009;7:30.
27Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, et al. Air pollution and cardiovascular disease: A statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 2002;109:2655-71.
28Ponka A, Virtanen M. Low-level air pollution and hospital admissions for cardiac and cerebrovascular diseases in Helsinki. Am J Public Health 1996;86:1273-80.
29Schwartz J. Air pollution and hospital admissions for cardiovascular disease in Tucson. Epidemiology 1997;8:371-7.
30Prescott GJ, Cohen GR, Elton RA, Fowkes FG, Agius RM. Urban air pollution and cardiopulmonary ill health--a 14.5 year time series study. Occup Environ Med 1998;55:697-704.
31Holguín F, Téllez-Rojo MM, Hernández M, Cortez M, Chow JC, Watson JG, et al. Air pollution and heart rate variability among the elderly in Mexico City. Epidemiology 2003;14:521-7.
32Bocci V, Paulesu, L. Studies on the biological effects of ozone: 1. Induction of interferon gamma on human leucocytes. Haematologica 1990;75:510-5.
33Larini A, Bocci V. Effects of ozone on isolated peripheral blood mononuclear cells. Toxicol In Vitro 2005;19:55-61.
34Ye F, Piver WT, Ando M, Portier CJ. Effects of temperature and air pollutants on cardiovascular and respiratory diseases for males and females older than 65 years of age in Tokyo, July and August 1980-1995. Environ Health Perspect 2001;109:355-9.
35Zeghnoun A, Czernichow P, Beaudeau P, Hautemanière A, Froment L, Le Tertre A, et al. Short-term effects of air pollution on mortality in the cities of Rouen and Le Havre, France, 1990-1995. Arch Environ Health 2001;56:327-35.
36Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, et al. Ambient pollution and heart rate variability. Circulation 2000;101:1267-73.
37Kodavanti UP, Schladweiler MC, Ledbetter AD, Watkinson WP, Campen MJ, Winsett DW, et al. The spontaneously hypertensive rat as a model of human cardiovascular disease: Evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Toxicol Appl Pharmacol 2000;164:250-63.
38Ye F, Piver WT, Ando M, Portier CJ. Effects of temperature and air pollutants on cardiovascular and respiratory diseases for males and females older than 65 years of age in Tokyo, July and August 1980-1995. Environ Health Perspect 2001;109:355-9.
39Mar TF, Norris GA, Koenig JQ, Larson TV. Associations between air pollution and mortality in Phoenix, 1995-1997. Environ Health Perspect 2000;108:347-53.
40Wong TW, Lau TS, Yu TS, Neller A, Wong SL, Tam W, et al. Air pollution and hospital admissions for respiratory and cardiovascular diseases in Hong Kong. Occup Environ Med 1999;56:679-83.
41Takano H, Yanagisawa R, Inoue K, Shimada A, Ichinose T, Sadakane K, et al. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: A brief communication. Exp Biol Med 2004;229:361-4.
42Leaderer BP. Air pollutant emissions from kerosene space heaters. Science 1982;218:1113-5.
43World Health Organization (WHO). Air quality guidelines for Europe. WHO Regional Publications, European Series No. 23. Copenhagen, Denmark: World Health Organization; 1987. p. 23.
44Sunyer J, Ballester F, Tertre AL, Atkinson R, Ayres JG, Forastiere F, et al. The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (The Aphea-II study). Eur Heart J 2003;24:752-60.
45Junker R, Heinrich J, Ulbrich H, Schulte H, Schönfeld R, Köhler E, et al. Relationship between plasma viscosity and the severity of coronary heart disease. Arterioscler Thromb Vasc Biol 1998;18:870-5.
46Peters A, Döring A, Wichmann HE, Koenig W. Increased plasma viscosity during an air pollution episode: A link to mortality? Lancet 1997;349:1582-7.
47Chen SS, Tang CS, Jin HF, DU JB. Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the cardiovascular system. Chin Med J 2011;124:1901-5.
48California Air Resources Board (CARB). Report to the California legislature: Indoor aiir pollution in California. Sacramento, CA: California Environmental Protection Agency; 2005.
49U.S. Environmental Protection Agency (EPA). 2010 Lead-based paint. (Accessed May 18, 2013, at
50Dulskiene V. Environmental pollution with lead and myocardial infarction morbidity. Medicina (Kaunas) 2003;39:884-8.
51Glenn BS, Stewart WF, Links JM, Todd AC, Schwartz BS. The longitudinal association of lead with blood pressure. Epidemiology 2003;14:30-6.
52Weiss ST, Muñoz A, Stein A, Sparrow D, Speizer FE. The relationship of blood lead to blood pressure in a longitudinal study of working men. Am J Epidemiol 1986;123:800-8.
53Centers for Disease Control and Prevention (CDC). Blood lead levels - United States, 1999 -2002. MMWR Morb Mortal Wkly Rep 2005;54:513-6.
54U.S. Environmental Protection Agency (EPA). Air quality criteria for lead (final). 2006. (Accessed May 18, 2013, at
55Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Carbon disulfide (Update). Atlanta: Public Health Service, U.S. Department of Health and Human Services; 1996.
56Carmignani M, Boscolo P, Poma A, Volpe AR. Kininergic system and arterial hypertension following chronic exposure to inorganic lead. Immunopharmacology 1999;44:105-10.
57Rodríguez-Iturbe B, Sindhu RK, Quiroz Y, Vaziri ND. Chronic exposure to low doses of lead results in renal infiltration of immune cells, NF-kappaB activation, and overexpression of tubulointerstitial angiotensin II. Antioxid Redox Signal 2005;7:1269-74.
58Ding Y, Vaziri ND, Gonick HC. Lead-induced hypertension. II. Response to sequential infusions of l-arginine, superoxide dismutase, and nitroprusside. Environ Res 1998;76:107-13.
59Farmand F, Ehdaie A, Roberts CK, Sindhu RK. Lead-induced dysregulation of superoxide dismutases, catalase, glutathione peroxidase, and guanylate cyclase. Environ Res 2005;98:33-9.
60Revis NW, Zinsmeister AR, Bull R. Atherosclerosis and hypertension induction by lead and cadmium ions: An effect prevented by calcium ion. Proc Natl Acad Sci U S A 1981;78:6494-8.
61Schwartz J. Lead, blood pressure, and cardiovascular disease in men and women. Environ Health Perspect 1991;9:71-5.
62U.S. Environmental Protection Agency (EPA). Measuring Air Quality: The Pollutant Standards Index; Office of Air Quality Planning and Standards, US EPA; EPA 451/K-94-001; 1994. (Accessed May 18, 2013, at
63Linn R. Carbon monoxide and you. MT 8315. Montana, United States: Montana State University Extension; 1983. (Accessed May 18, 2013, at
64Greiner T. Indoor Air Quality: Carbon monoxide and carbon dioxide, ISU Extension Pub # AEN-125, Iowa, United States: Iowa State University; 1991. (Accessed May 18, 2013, at
65Ayres SM, Giannelli S Jr, Mueller H. Myocardial and systemic responses to carboxyhemoglobin. Ann N Y Acad Sci 1970;174:268-93.
66Powell JT. Vascular damage from smoking. Disease mechanisms at the arterial wall. Vasc Med 1998;3:21-8.
67Pryor WA, Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann N Y Acad Sci 1993;686:12-28.
68Reddy A, Williams R, Johansson T, editors. Energy after Rio. Prospects and Challenges. New York: United Nations Development Programme; 1996.
69Jin Y, Zhou Z, He G, Wei H, Liu J, Liu F, et al. Geographical, spatial, and temporal distributions of multiple indoor air pollutants in four Chinese provinces. Environ Sci Technol 2005;39:9431-9.
70Viegi G, Simoni M, Scognamiglio A, Baldacci S, Pistelli F, Carrozzi L, et al. Indoor air pollution and airway disease. Int J Tuberc Lung Dis 2004;8:1401-15.
71Zhang JJ, Smith KR. Household air pollution from coal and biomass fuels in China: Measurements, health impacts, and interventions. Environ Health Perspect 2007;115:848-55.
72Brook RD, Rajagopalan S, Pope CA 3 rd , Brook JR, Bhatnagar A, Diez-Roux AV, et al. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 2010;121:2331-78.
73Moran A, Gu D, Zhao D, Coxson P, Wang YC, Chen CS, et al. Future cardiovascular disease in china: Markov model and risk factor scenario projections from the coronary heart disease policy model-china. Circ Cardiovasc Qual Outcomes 2010;3:243-52.
74McCracken JP, Smith KR, Diaz A, Mittleman MA, Schwartz J. Chimney stove intervention to reduce long-term wood smoke exposure lowers blood pressure among Guatemalan women. Environ Health Perspect 2007;115:996-1001.
75Kjeldsen K, Thomsen HK, Astrup P. Effects of carbon monoxide on myocardium. Ultrastructural changes in rabbits after moderate, chronic exposure. Circ Res 1974;34:339-48.
76Zevin S, Saunders S, Gourlay SG, Jacob P, Benowitz NL. Cardiovascular effects of carbon monoxide and cigarette smoking. J Am Coll Cardiol 2001;38:1633-8.
77Penn A, Currie J, Snyder C. Inhalation of carbon monoxide does not accelerate arteriosclerosis in cockerels. Eur J Pharmacol 1992;228:155-64.
78Penn A, Snyder C. Arteriosclerotic plaque development is promoted by polynuclear aromatic hydrocarbons. Carcinogenesis 1988;9:2185-9.
79Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: Implications for nicotine replacement therapy. J Am Coll Cardiol 1997;29:1422-31.
80World Health Organization (WHO). World Health Report: Reducing risks, promoting healthy life. Geneva: WHO; 2002.
81Naeher LP, Brauer M, Lipsett M, Zelikoff JT, Simpson CD, Koenig JQ, et al. Woodsmoke health effects: A review. Inhal Toxicol 2007;19:67-106.
82Bailis R, Ezzati M, Kammen DM. Greenhouse gas implications of household energy technology in Kenya. Environ Sci Technol 2003;37:2051-9.
83Ostro B. Outdoor air pollution: Assessing the environmental burden of disease at national and local levels. Geneva, Switzerland: World Health Organization; 2004.
84Pan CH, Chan CC, Wu KY. Effects on Chinese restaurant workers of exposure to cooking oil fumes: A cautionary note on urinary 8-hydroxy-2'-deoxyguanosine. Cancer Epidemiol Biomarkers Prev 2008;17:3351-7.
85Ray MR, Mukherjee S, Roychoudhury S, Bhattacharya P, Banerjee M, Siddique S, et al. Platelet activation, upregulation of CD11b/CD18 expression on leukocytes and increase in circulating leukocyte-platelet aggregates in Indian women chronically exposed to biomass smoke. Hum Exp Toxicol 2006;25:627-35.
86Entman ML, Ballantyne CM. Association of neutrophils with platelet aggregates in unstable angina. Should we alter therapy? Circulation 1996;94:1206-8.
87Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: Studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 2001;104:1533-7.
88Konstantopoulos K, Grotta JC, Sills C, Wu KK, Hellums JD. Shear-induced platelet aggregation in normal subjects and stroke patients. Thromb Haemost 1995;74:1329-34.
89Beauchamp RO Jr, Bus JS, Popp JA, Boreiko, C. J., Golberg, L., et al. A critical review of the literature on carbon disulfide toxicity. Crit Rev Toxicol 1983;11:169-278.
90Zanettini R, Kotseva K, Agostini O, Cesana G. Occupational exposure to chemical and physical factors and cardiovascular diseases. Arch Science Lav 1989;5:347-58.
91Oliver LC, Weber RP. Chest pain in rubber chemical workers exposed to carbon disulphide and methaemoglobin formers. Br J Ind Med 1984;41:296-304.
92Vanhoorne M, De Bacquer D, De Backer G. Epidemiological study on the cardiovascular effects of carbon disulphide. Int J Epidemiol 1992;21:745-52.
93Drexler H, Ulm K, Hubmann M, Hardt R, Goen T, Mondorf W, et al. Carbon disulphide. III. Risk factors for coronary heart diseasees in workers in the viscose industry. Int Arch Occup Environ Health 1995;67:243-52.
94Omae K, Takebayashi T, Nomiyama T, Ishizuka C, Nakashima H, Uemura T, et al. Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers. Occup Environ Med 1998;55:468-72.
95Kotseva KP, De Bacquer D. Cardiovascular effects of occupational exposure to carbon disulphide. Occup Med 2000;50:43-7.