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Summary.

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

The effects of air pollution on health have been intensively studied in recent years. Acute exposure to environmental pollutants such as particulate and gaseous matters (carbon monoxide, nitrogen oxides, sulphur dioxide and ozone) was associated with an increased rate of events and mortality because of cardiovascular diseases. These effects were investigated in short-term studies, which related day-to-day variations in air pollution to disease, and in long-term studies, which have followed cohorts of exposed individuals over time. The evidence from the literature on the short-term cardiovascular effects of air pollutants is discussed from clinical and mechanistic points of view.


Introduction

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

Urban air pollution is considered a major health problem [1,2], because numerous epidemiological studies have shown an association between chronic exposure to pollutants, morbidity and mortality, especially for respiratory and cardiovascular diseases [3–5]. The first evidence of an association between acute exposure to increased air pollution and mortality dates back to the serious events that occurred in the Meuse Valley, Belgium (1930) [6], and in London (the ‘great smog’ of 1952) [7]. The London episode, characterized by 5 days of markedly elevated levels of air pollution, was followed by a dramatic increase in the short-term rate of general mortality and lung and heart diseases, which returned to normal rates after the acute episode had subsided. The London episode led to the introduction of air pollution control policies in the 1960s and 1970s. Following the introduction of these policies, the concentrations of pollutants decreased substantially in economically advanced countries. However, despite definite improvements in air quality achieved in many countries, the negative effects of air pollution are still an important public health problem [8–10].

Air pollution consists of gaseous and particulate-matter pollutants. The former include carbon monoxide (CO), nitrogen dioxide (NO2), sulphur dioxide (SO2) and ozone (O3). The latter include particulate matter (PM) with a cut-off of less than 10 μm in aerodynamic diameter (PM10), fine particles of less than 2.5 μm (PM2.5) and ultrafine particles of less than 0.1 μm (PM0.1) [11]. As compared with PM10 and PM2.5, ultrafine particles have a larger total surface area and hence a greater potential for carrying toxic substances, including metals, elemental and organic carbon and others. Because of their small size, ultrafine particles are deposited deep in the lung alveoli and can reach the blood stream. Particulate matter is the type of air pollutant that causes the most numerous and serious effects on human health, because of the broad range of different toxic substances that it contains; it may thus be considered the most relevant indicator of the impact on health of global air pollution [12,13].

In addition to the studies that investigated the effects on health of chronic exposure to air pollution in urban areas, a number of recent observations have shown that also acute exposure to air pollutants produces severe effects [14]. In these studies, the acute effects of air pollution were generally investigated by time-series analyses of changes in health outcomes (e.g. mortality, hospital admissions) in relation to short-term variations in ambient concentrations of pollutants.

Studies on short-term effects

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

After the epidemiologic studies that begun in the 1990s to examine the respiratory effects of air pollution, more recent studies based upon data from large metropolitan areas in North America and Europe focused on how acute peaks of pollution affect cardiovascular events [3].

Effects on mortality

The short-term effects of air pollution were quantified in two large studies conducted in the United States [15,16] (the National Morbidity, Mortality and Air Pollution Study [NMMAPS]) and in Europe (the Air Pollution and Health-European Approach [APHEA-2] project) [17,18]. The NMMAPS collected data on outcomes in 50 million people in the 20 largest cities. Average mortality rates were independently associated with particle concentrations on the day before death. Each 10-μg m–3 increase in PM10 was associated with an increase of 0.51% and 0.68% for daily all-cause and cardiopulmonary mortality [15]. A similar strong association between mortality and air pollution was demonstrated by the APHEA-2 study [17]. For 43 million people in 29 European cities, the estimated increase in daily mortality was 0.6% for each 10-μg m–3 increase in PM10, and cardiovascular deaths increased by 0.69%. Additional analyses of the APHEA-2 mortality data, based on lag periods of up to 40 days, found that the risk of adverse health effects associated with air pollution more than doubled (e.g. a 1.97% increase in mortality per 10-μg m–3 elevation in PM10) [18]. The APHEA project also examined the association between airborne particles and hospital admission for cardiac causes in eight European cities [19] and found that the percentage increases associated with a 10-μg m–3 elevation in PM10 were 0.5% for cardiac admissions in people of all ages and 0.7% for cardiac admissions in people older than 65 years.

A large number of smaller-scale, short-term studies on the acute effects of air pollution exposure have been published [20]. Typically, short-term mortality rates, hospital admissions and emergency room visits for exacerbations of existing symptoms did increase in relation to variations in air pollution (time-series studies). A recent update of the Meta-analysis of Italian Studies on the short-term effects of Air pollution [21], that considered data on 9 million people from 15 Italian cities for the period 1996–2002, showed that cardiorespiratory mortality increased with increasing concentrations of air pollutants (for NO2 0.40%, for CO 0.93%, for SO2 1.11% and for PM10 0.54%). Similar results were obtained in studies carried out in French and Spanish urban areas [22–24]. On the other hand, there is an association between reduction in fine particulate air pollution and decrease in mortality. In an update of the Harvard Six Cities Study [25], Laden et al. compared the results of an additional period of follow-up (1990–1998) with those previously collected (1974–1989) and observed that the decreased mean concentration of PM2.5 between the two periods was associated with a decreased mortality (relative risk, 0.73; 95% CI, 0.57–0.95).

Effects on cardiovascular events

Observations from across North America and Europe have demonstrated higher rates of hospitalizations for all cardiovascular causes and a direct association was also identified pertaining to the incidence of ischemic heart disease and heart failure [26]. For example, Wellenius et al. [27] analyzed particulate air pollution and hospital admissions for congestive heart failure in seven cities of the United States from 1986 to 1999 and found that a 10-μg m–3 increase in PM10 was associated with a 0.72% increase in the rate of admission for congestive heart failure on the same day. A pooled analysis [28] of studies based upon hospital admission showed increases in admission rates of 0.8% for heart failure and of 0.7% for ischemic heart disease for each 10-μg m–3 elevation in PM10. The acute effect of fine particulate air pollution on elderly people was analyzed by Dominici et al. [29], who studied a US population of 11.5 million individuals aged over 65 years and evaluated whether or not there was an association between daily concentrations of PM2.5 and hospital admissions for cardiovascular and respiratory diseases between 1999 and 2002. The largest association was found for heart failure, a 1.28% increase in risk per 10-μg m–3 elevation in same-day PM2.5.concentration.

In a case-crossover study, Peters et al. [30] correlated PM2.5 levels and onset of symptoms in 772 patients with myocardial infarction and found elevated odds ratios associated with an increase of 25 μg m–3 PM2.5 during a 2-h period before the event (1.48; 95% CI, 1.09–2.02) and an increase of 20 μg m–3 PM2.5 in the 24-h period before the event (1.69; 95% CI, 1.13–2.34). In a study on air pollution and emergency admissions in Boston, an association was found between NO2 (12.7% increase), PM2.5 (8.6% increase) and the risk of hospitalization for myocardial infarction [31]. In a crossover study conducted in the United States, Pope et al. [32] found that an increase in ambient particulate of 10 μg m–3 was associated with a 4.5% increased risk of acute coronary syndromes (unstable angina and myocardial infarction). The association between traffic-related air pollutants and acute myocardial infarction is also supported by the results of the European HEAPSS (Health Effects of Air Pollution among Susceptible Subpopulations) study [33]. Another study focused on patients with previous myocardial infarction and found that ambient air pollution was associated with an increased risk of hospital readmissions for cardiac causes [34].

The relationship between air pollution and stroke was evaluated by Wellenius et al. [35]. By analyzing the hospital admissions for ischemic and hemorrhagic stroke in nine US cities, an increase of 22 μg m–3 of PM10 was found to be associated with a 1.03% increase in hospital admissions for ischemic stroke in individuals aged 65 years or older.

In all, these findings, summarized in Table 1, indicate that short-term elevations in ambient particle levels are capable of worsening heart failure and triggering acute atherothrombotic cardiovascular events. These effects are particularly prominent in the elderly. Most importantly, an improvement of the conditions of air pollution is associated with a drastic decrease in the incidence of atherothrombotic cardiovascular events.

Table 1.   Summary of the most important studies on short-term cardiovascular effects of air pollution
Study [ref.]Air pollutantsResults
  1. NMMAPS, National Morbidity, Mortality and Air Pollution Study; APHEA, the Air Pollution and Health-European Approach; MISA, Meta-analysis of Italian Studies on the short-term effects of Air pollution; HSCS, Harvard Six Cities Study; HEAPSS, Health Effects of Air Pollution among Susceptible Subpopulations; PM, particulate matter; O3, ozone; SO2, sulfur dioxide; NO2, nitrogen dioxide; CO, carbon monoxide; PNC, particle number concentration.

(a) Short-term effects of air pollution on cardiovascular mortality
 NMMAPS [15]PM10, O3, SO2, NO2Increase of 0.68% (95% CI, 0.20–1.16) in the rate of cardiorespiratory deaths for each 10-μg m–3 elevation in PM10
 APHEA-2 [17]PM10, O3, SO2, NO2Increase of 0.6% (95% CI, 0.4–0.8) in the rate of cardiorespiratory deaths for each 10-μg m–3 elevation in PM10
 MISA [21]PM10, O3, SO2, NO2, COIncrease in the rate of cardiovascular deaths of 0.40% (95% CI, 0.46–1.05) for each 10-μg m–3 elevation in NO2, of 0.93% (95% CI, 0.10–1.77) for each 1-mg m–3 elevation in CO, of 1.11% (95% CI, 0.64–3.12) for each 10-μg m–3 elevation in SO2, and of 0.54% (95% CI, 0.02–1.02) for each 10-μg m–3 elevation in PM10
 HSCS [25]PM2.5Association between reduction in PM2.5 and overall mortality (relative risk, RR, 0.73; 95% CI, 0.57–0.95)
(b) Short-term effects of air pollution on cardiovascular events
 Wellenius [27]PM10Increase of 0.72% (95% CI, 0.35–1.10) in the rate of admission for congestive heart failure for each 10-μg m–3 elevation in PM10
 Dominici [29]PM2.5Increase of 1.28% (95% CI, 0.78–1.78) in the risk for congestive heart failure for each 10-μg m–3 elevation in PM2.5
 Peters [30]PM10, PM2.5Association between myocardial infarction and increase of 25 μg m–3 PM2.5 during a 2-h period before the event (OR, 1.48; 95% CI, 1.09–2.02) and an increase of 20 μg m–3 PM2.5 in the 24-h period before the event (OR, 1.69; 95% CI, 1.13–2.34)
 Pope [32]PM10, PM2.5Increase of 4.5% (95% CI, 1.1–8.0) in the risk of acute coronary syndrome for each 10-μg m–3 elevation in PM2.5
 HEAPSS [33]PM10, O3, NO2, CO, PNCAssociation between myocardial infarction and same day increase of 0.2 mg m–3 CO (RR, 1.005; 95% CI, 1.000–1.010) and of 10000 particles cm–3 PNC (RR, 1.005; 95% CI, 0.996–1.015)
 Wellenius [35]PM10Increase of 1.03% (95% CI, 0.04–2.04) in the rate of hospital admissions for ischemic stroke for each 22-μg m–3 elevation in PM10

Potential mechanisms

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

Our understanding of the biological mechanisms linking particulate air pollution and cardiovascular events is still in its infancy and warrants more experimental and clinical studies. Fig. 1 summarizes the potential mechanisms by which short-term exposure to air pollution may cause adverse cardiovascular effects. A possible mechanism, which has gained attention in the last few years, is that particulate matter alters the autonomic control of the heart [3]. Animal studies have shown that exposure to combustion particles can produce a reduction in heart rate variability, which reflects alterations in cardiac autonomic function that are considered a risk factor for sudden death and death from arrhythmia [36–38]. These data have been confirmed in humans. In the German MONICA (MONItoring of trends and determinants in CArdiovascular disease) study, heart rates increased in the presence of high concentrations of SO2 and CO [39]. Three studies conducted in the United States, including a total of 54 subjects, found a reduction in heart rate variability with the increases of PM10 or PM2.5 [40–42]. Of note, changes in heart rate variability occurred rapidly, within a few hours of exposure. Other studies confirmed these findings [43–46]. Thus, a deranged cardiac autonomic function may provide an important link between air pollution and cardiovascular mortality by triggering fatal tachyarrythmias. The occurrence of cardiac arrhythmias has been related to the degree of exposure to PM2.5 in high-risk individuals carrying an implanted cardioverter defibrillator. In 100 patients monitored for 3 years, NO2, CO and PM concentrations were most strongly related to discharges of defibrillators [47]. Two recent studies on the association between ambient air pollution and ventricular arrythmias further support this observation [48,49]. Extreme elevations in air pollution were also associated with hypertension during a prolonged period of air stagnation in Europe [50]. Another study found that exposure to abnormally elevated concentrations of PM2.5 and O3 rapidly increased diastolic blood pressure [51].

image

Figure 1.  Short-term air pollution exposure and cardiovascular adverse effects: possible mechanisms of action.

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In all, these data suggest a potential for adverse effects of PM and gaseous pollutants on cardiac autonomic balance. The underlying mechanisms responsible remain unclear but may involve activation of pulmonary neural reflex arcs, and direct effects of pollutants on cardiac ion channels and on the inflammatory system, which is activated in association with a rise in levels of air pollution [52–54]. The key role of inflammation in the pathogenesis of cardiovascular events induced by air pollution has been documented by animal studies, which showed a link between the degree of lung inflammation and the extent of thrombosis following vascular injury [55]. This mechanism is likely to involve the secretion of adhesion molecules by inflamed pulmonary endothelial cells, resulting in binding and activation of leukocytes and platelets, generation of hemostatically active microparticles and release of proinflammatory cytokines [56,57]. For instance, Nemmar et al. [58] showed that lung inflammation induced by particulate pollutant increases the risk for thrombosis via P-selectin exposure and systemic leukocyte activation. The effect of air pollution on platelets was confirmed by another study that found increased levels of soluble CD40L (a prothrombotic and proinflammatory marker of platelet activation) in response to high ambient concentrations of ultrafine PM [59]. On the other hand in vitro and ex vivo human and animal models have shown that the uptake in blood of ultrafine particles may also directly activate platelets [3].

With the aim of elucidating the mechanisms responsible for the atherothrombotic cardiovascular effects of air pollutants, some investigators have evaluated whether or not hemostatic changes occur in relation to the degree of air pollution [60]. In a double-blind, randomized, cross-over study [61], 30 healthy men volunteered to be exposed for 1 h during intermittent exercise either to diesel exhaust (300 μg m–3 particulate concentration), which is particularly rich in fine particulate pollutants (PM2.5), or to clean air. Forearm blood flow fibrinolysis and inflammation markers were measured before and during infusion of vasodilators 2 and 6 h after exposure to the diesel exhaust or clean air. Inhalation of diesel exhaust, at levels corresponding to those encountered in an urban environment, impaired vascular tone (impaired vasomotor response to vasodilators) and endogenous fibrinolysis (suppression of plasma tissue plasminogen activator). The authors hypothesized that the oxidative effects of diesel exhaust could lead to a reduction of nitric oxide bioavailability in the vessel wall, thus shifting the balance toward vasoconstriction, thereby providing a mechanistic link between air pollution, atherothrombosis and acute myocardial infarction. The short-term effects of concentrated ambient fine particles plus ozone on vascular function was studied in 25 healthy adults by Brook et al. [62], who found a significant correlation between the degree of fine particulate air pollution and arterial vasoconstriction, further supporting the key role of airborne pollutants in ischemic cardiovascular events [63].

The effects of exposure to air pollution on blood coagulation were investigated in a study conducted in the region of Lombardy in the north of Italy [64]. Global coagulation tests (prothrombin time and activated partial thromboplastin time), as well as plasma fibrinogen levels and naturally occurring anticoagulant proteins (antithrombin, protein C and protein S), were evaluated in 1218 healthy individuals and related to the degree of air pollution (PM10, CO, NO2, SO2 and O3) in the hours and days before blood sampling. A significant correlation was found between mild shortening of the prothrombin time and the degree of air pollution, both at the time of sampling or in the 30 days prior to sampling [64]. Short-term exposure to PM10 was also associated with increased homocysteine levels in smokers, but not in non-smokers [65]. Based on these results, it would appear that air pollution may determine short-term hypercoagulability, which in turn contributes to the increase in atherothrombotic cardiovascular events observed in the presence of high ambient concentrations of pollutants. The influence of ambient air pollution on inflammation, oxidative stress, blood coagulation and autonomic function was also investigated in 76 young healthy adults from Taiwan by Chuang et al. [66], who found that increases in PM10, PM2.5, sulfate, nitrate and O3 were associated with increases in C-reactive protein, 8-hydroxy-2′-deoxyguanosine (an oxidative stress marker), fibrinogen, plasminogen activator inhibitor-1 and decreased heart rate variability. The same author had previously found that urban air pollution increased plasma fibrinogen and plasminogen activator inhibitor-1 in patients with, or at risk of, cardiovascular disease [67].

Conclusions

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

An array of epidemiological data clearly demonstrates the existence of a relation between air pollution and adverse cardiovascular events. In particular, acute increases in air pollutants are paralleled by increases in cardiovascular mortality and emergency hospitalizations for cardiac and cerebrovascular events. Most importantly, a reduction of the same ambient air particles resulted in a decrease of such adverse events. Among the various types of air pollutants, fine and ultrafine PM contribute more strongly to these harmful effects. Despite the general improvement in air quality in urban areas attributable to strategies meant to control emission from cars and the use of cleaner fuels, it is not known whether or not this decrease also applies to those particulate matters that are currently not routinely measured, such as ultrafine particles.

The mechanisms linking inhalation of air pollutants to increased cardiovascular risk are not fully elucidated. However, several data indicate that exposure to particulate matter produces changes in the autonomic nervous system, activation of inflammatory pathways, endothelial dysfunction, arterial vasoconstriction and alterations in hemostasis responsible for the increased risk of atherothrombotic events (Fig. 1). Improving our understanding of the biological mechanisms underlying the acute cardiovascular effects of air pollution is essential to define the best prevention strategies.

Disclosure of Conflict of Interests

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References

The authors state that they have no conflict of interest.

References

  1. Top of page
  2. Summary.
  3. Introduction
  4. Studies on short-term effects
  5. Potential mechanisms
  6. Conclusions
  7. Disclosure of Conflict of Interests
  8. References
  • 1
    Brunekreef B, Holgate ST. Air pollution and health. Lancet 2002; 360: 123342.
  • 2
    Katsouyanni K. Ambient air pollution and health. Br Med Bull 2003; 68: 14356.
  • 3
    Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC Jr, Tager I. Expert Panel on Population and Prevention Science of the American Heart Association. 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 2004; 109: 265571.
  • 4
    Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, Kaufman JD. Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med 2007; 356: 44758.
  • 5
    Pope CA III, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 2004; 109: 717.
  • 6
    Nemery B, Hoet PH, Nemmar A. The Meuse Valley Fog of 1930: an air pollution disaster. Lancet 2001; 357: 7048.
  • 7
    Logan WP. Mortality in the London fog incident, 1952. Lancet 1953; 1: 3368.
  • 8
    Ozkaynak H, Thurston GD. Associations between 1980 U.S. mortality rates and alternative measures of airborne particle concentration. Risk Anal 1987; 7: 44961.
  • 9
    Pope CA, Schwartz J, Ransom MR. Daily mortality and PM10 pollution in Utah Valley. Arch Environ Health 1992; 47: 2117.
  • 10
    Schwartz J. Particulate air pollution and daily mortality in Detroit. Environ Res 1991; 56: 20413.
  • 11
    WHO Working Group. Health Aspects of Air Pollution with Particulate Matter, Ozone and Nitrogen Dioxide. Germany: Bonn, 2003. Available on the WHO website.
  • 12
    Schwarze PE, Ovrevik J, Lag M, Refsnes M, Nafstad P, Hetland RB, Dybing E. Particulate matter properties and health effects: consistency of epidemiological and toxicological studies. Hum Exp Toxicol 2006; 25: 55979.
  • 13
    Bathnagar A. Environmental cardiology. Studying mechanistic links between pollution and heart disease. Cir Res 2006; 99: 692705.
  • 14
    Peter A, Pope CA III. Cardiopulmonary mortality and air pollution. Lancet 2002; 360: 11845.
  • 15
    Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL. Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. N Engl J Med 2000; 343: 17429.
  • 16
    Dominici F, McDermott A, Daniels D. Mortality among residents of 90 cities. Special Report: Revised Analyses of Time-Series Studies of Air Pollution and Health. Boston: Health Effects Institute, 2003: 924.
  • 17
    Katsouyanni K, Touloumi G, Samoli E, Gryparis A, Le Tertre A, Monopolis Y, Rossi G, Zmirou D, Ballester F, Boumghar A, Anderson HR, Wojtyniak B, Paldy A, Braunstein R, Pekkanen J, Schindler C, Schwartz J. Confounding and effect modification in the short-term effects of ambient particles on total mortality: results from 29 European cities within the APHEA2 Project. Epidemiology 2001; 12: 52131.
  • 18
    Zanobetti A, Schwartz J, Samoli E, Gryparis A, Touloumi G, Peacock J, Anderson RH, Le Tertre A, Bobros J, Celko M, Goren A, Forsberg B, Michelozzi P, Rabczenko D, Hoyos SP, Wichmann HE, Katsouyanni K. The temporal pattern of respiratory and heart disease mortality in response to ait pollution. Environ Health Perspect 2003; 111: 118893.
  • 19
    Le Tertre A, Medina S, Samoli E, Forsberg B, Michelozzi P, Boumghar A, Vonk JM, Bellini A, Atkinson R, Ayres JG, Sunyer J, Schwartz J, Katsouyanni K. Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities. J Epidemiol Community Health 2002; 56: 7739.
  • 20
    Pope CA III. Epidemiology of fine particulate air pollution and human health: biologic mechanisms and who’s at risk? Environ Health Perspect 2000; 108: 71323.
  • 21
    Buggeri A, Bellini O, Terracini B. Meta-analysis of the Italian studies on short-term effects of air pollution MISA 1996-2002. Epidemiol Prev 2004; 5 (Suppl.): 4100.
  • 22
    Zenghnoun A, Czernichow P, Beaudeau P, Hautemaniere A, Froment L, Le Tertre A, Le Tertre A, Quenel P. Short-term effects of air pollution on mortality in the cities of Rouen and Le Havre, France, 1990-1995. Arch Environ Health 2001; 56: 32735.
  • 23
    Le Tertre A, Quenel P, Eilstein D, Medina S, Prouvost H, Pascal L, Boumghar A, Saviuc P, Zeghnoun A, Filleul L, Declercq C, Cassadou S, Le Goaster C. Short-term effects of air pollution on mortality in nine French cities: a quantitative summary. Arch Environ Health 2002; 57: 3119.
  • 24
    Ballester F, Rodriguez P, Iniguez C, Saez M, Daponte A, Galan I, Taracido M, Arribas F, Bellido J, Cirarda FB, Canada A, Guillen JJ, Guillen-Grima F, Lopez E, Perez-Hoyos S, Lertxundi A, Toro S. Air pollution and cardiovascular admissions association in Spain: results within the EMECAS project. J Epidemiol Community Health 2006; 60: 32836.
  • 25
    Laden F, Schwartz J, Speizer FE, Dockery DW. Reduction in fine particulate air pollution and mortality: extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med 2006; 173: 66772.
  • 26
    Hoek G, Brunekreef B, Fischer P, Van Wijnen J. The association between air pollution and heart failure, arrhythmia, embolism, thrombosis, and other cardiovascular causes of death in a time series study. Epidemiology 2001; 12: 3557.
  • 27
    Wellenius GA, Schwartz J, Mittleman MA. Particulate air pollution and hospital admissions for congestive heart failure in seven United States cities. Am J Cardiol 2006; 97: 4048.
  • 28
    Morris RD. Airborne particulates and hospital admissions for cardiovascular disease: a quantitative review of the evidence. Environ Healt Perspect 2001; 109 (Suppl. 4): 495500.
  • 29
    Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 2006; 295: 112734.
  • 30
    Peters A, Dockery DW, Muller JE, Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 2001; 103: 28105.
  • 31
    Zanobetti A, Schwartz J. Air pollution and emergency admissions in Boston, MA. J Epidemiol Community Health 2006; 60: 8905.
  • 32
    Pope CA III, Muhlestein JB, May HT, Renlund DG, Anderson JL, Horne BD. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 2006; 114: 24438.
  • 33
    Lanki T, Pekkanen J, Aalto P, Elosua R, Berglind N, D’Ippoliti D, Kulmala M, Nyberg F, Peters A, Picciotto S, Salomaa V, Sunyer J, Tiittanen P, Von Klot S, Forastiere F. Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction: the HEAPSS study. Occup Environ Med 2006; 63: 84451.
  • 34
    Von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D’Ippoliti D, Elosua R, Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer J, Forastiere F. Health Effects of Particles on Susceptible Subpopulations (HEAPSS) Study Group. Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities. Circulation 2005; 112: 30739.
  • 35
    Wellenius GA, Schwartz J, Mittleman MA. Air pollution and hospital admissions for ischemic and hemorrhagic stroke among medicare beneficiaries. Stroke 2005; 36: 254953.
  • 36
    Godleski JJ, Verrier RL, Koutrakis P, Catalano P, Coull B, Reinisch U, Lovett EG, Lawrence J, Murthy GG, Wolfson JM, Clarke RW, Nearing BD, Killingsworth C. Mechanisms of morbidity and mortality from exposure to ambient particles. Res Rep Health Eff Inst 2000; 91: 588.
  • 37
    Watkinson WP, Campen MJ, Costa DL. Cardiac arrhythmia after exposure to residual oil fly ash particles in a rodent model of pulmonary hypertension. Toxicol Sci 1998; 41: 20916.
  • 38
    Campen MJ, Costa DL, Watkinson WP. Cardiac and thermoregulatory toxicity of residual oil fly ash in cardiopulmonary-compromised rats. Inhal Toxicol 2000; 12 (Suppl. 2): 722.
  • 39
    Peters A, Perz S, Doring A, Stieber J, Koenig W, Wichmann HE. Increases in heart rate during an air pollution episode. Am J Epidemiol 1999; 150: 10948.
  • 40
    Pope CA, Verrier RL, Lovett EG, Larson AC, Raizenne ME, Kanner RE, Schwartz J, Villegas GM, Gold DR, Dockery DW. Heart rate variability associated with particulate air pollution. Am Heart J 1999; 138: 8909.
  • 41
    Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, Allen G, Verrier M, Cherry R, Verrier R. Ambient pollution and heart rate variability. Circulation 2000; 101: 126773.
  • 42
    Liao 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: 5215.
  • 43
    Luttman-Gibson H, Suh HH, Coull BA, Dockery DW, Sarnat SE, Schwartz J, Stone PH, Gold DR. Short-term effects of air pollution on heart rate variability in senior adults in Steubenville, Ohio. J Occup Environ Med 2006; 48: 7808.
  • 44
    Park SK, O’Neill MS, Vokonas PS, Sparrow D, Schwartz J. Effects of air pollution on heart rate variability: the VA normative aging study. Environ Health Perspect 2005; 113: 3049.
  • 45
    Schwartz J, Litonjua A, Suh H, Verrier M, Zanobetti A, Syring M, Nearing B, Verrier R, Stone P, MacCallum G, Speizer FE, Gold DR. Traffic related pollution and heart rate variability in a panel of elderly subjects. Thorax 2005; 60: 45561.
  • 46
    Adar SD, Gold DR, Coull BA, Schwartz J, Stone PH, Suh H. Focused exposures to airborne traffic particles and heart rate variability in the elderly. Epidemiology 2007; 18: 95103.
  • 47
    Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, Baliff J, Oh JA, Allen G, Monahan K, Dockery DW. Air pollution and incidence of cardiac arrhythmia. Epidemiology 2000; 11: 117.
  • 48
    Rich DQ, Schwartz J, Mittleman MA, Link M, Luttmann-Gibson H, Catalano PJ, Speizer FE, Dockery DW. Association of short-term ambient air pollution concentrations and ventricular arrhythmias. Am J Epidemiol 2005; 161: 112332.
  • 49
    Berger A, Zareba W, Schneider A, Ruckerl R, Ibald-Mulli A, Cyrys J, Wichmann HE, Peters A. Runs of ventricular and supraventricular tachycardia triggered by air pollution in patients with coronary heart disease. J Occup Environ Med 2006; 48: 114958.
  • 50
    Ibald-Mulli A, Stieber J, Wichmann HE, Koenig W, Peters A. Effects of air pollution on blood pressure: a population-based approach. Am J Pub Health 2001; 91: 5717.
  • 51
    Urch B, Silverman F, Corey P, Brook JR, Lukic KZ, Rajagopalan S, Brook RD. Acute blood pressure responses in healthy adults during controlled air pollution exposures. Environ Health Perspect 2005; 113: 10525.
  • 52
    Peters A, Frohlich M, Doring A, Immervoll T, Wichmann HE, Hutchinson WL, Pepys MG, Koenig W. Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study. Eur Heart J 2001; 22: 1198204.
  • 53
    Pope CA III, Hansen ML, Long RW, Nielsen KR, Eatough NL, Wilson WE, Eatough DJ. Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects. Environ Health Perspect 2004; 112: 33945.
  • 54
    Ruckerl R, Ibald-Mulli A, Koenig W, Schneider A, Woelke G, Cyrys J, Heinrich J, Marder V, Frampton M, Wichmann HE, Peters A. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Resp Care Med 2006; 173: 43241.
  • 55
    Nemmar A, Nemery B, Hoet PH, Vermylen J, Hoylaerts MF. Pulmonary inflammation and thrombogenicity caused by diesel particles in hamsters: role of histamine. Am J Respir Crit Care Med 2003; 168: 136672.
  • 56
    Hrachovinova I, Cambien B, Hafezi-Moghadam A, Kappelmayer J, Camphausen RT, Widom A, Xia L, Kazazian HH Jr, Schaub RG, McEver RP, Wagner DD. Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med 2003; 9: 10205.
  • 57
    Van Eeden SF, Tan WC, Suwa T, Mukae H, Terashima T, Fujii T, Qui D, Vincent R, Hogg JC. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)). Am J Respir Crit Care Med 2001; 164: 82630.
  • 58
    Nemmar A, Hoet PHM, Vandervoort P, Dinsdale D, Nemery B, Hoylaerts MF. Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation: role of P-selectin. J Thromb Haemost 2007; 5: 121726.
  • 59
    Ruckerl R, Phipps RP, Schneider A, Frampton M, Cyrys J, Oberdorster G, Wichmann HS, Peters A. Ultrafine particles and platelet activation in patients with coronary heart disease – results from a prospective panel study. Part Fibre Toxicol 2007; 4: 114.
  • 60
    Vermylen J, Hoylaerts MF. The procoagulant effects of air pollution. J Thromb Haemost 2007; 5: 2501.
  • 61
    Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation 2005; 112: 39306.
  • 62
    Brook RD, Brook JR, Urch B, Vincent R, Rajagopalan S, Silverman F. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation 2002; 105: 15346.
  • 63
    Vermylen J, Nemmar A, Nemery B, Hoylaerts MF. Ambient air pollution and acute myocardial infarction. J Thromb Haemost 2005; 3: 195561.
  • 64
    Baccarelli A, Zanobetti A, Martinelli I, Grillo P, Hou L, Giacomini S, Mannucci PM, Bertazzi PA, Schwartz J. Effects of exposure to air pollution on blood coagulation. J Thromb Haemost 2007; 5: 25260.
  • 65
    Baccarelli A, Zanobetti A, Martinelli I, Grillo P, Hou L, Lanzani G, Mannucci PM, Bertazzi PA, Schwartz J. Air pollution, smoking, and plasma homocysteine. Environ Health Perspect 2007; 115: 17681.
  • 66
    Chuang KJ, Chan CC, Su TC, Lee CT, Tang CS. Urban air pollution on inflammation, oxidative stress, coagulation and autonomic dysfunction in young adults. Am J Respir Crit Care Med 2007; 176: 3706.
  • 67
    Su TC, Chan CC, Liau CS, Lin LY, Kao HL, Chuang KJ. Urban air pollution increases plasma fibrinogen and plasminogen activator inhibitor-1 levels in susceptible patients. Eur J Cardiovasc Prev Rehabil 2006; 13: 84952.