Cardiovascular Effects of Ambient Particulate Air Pollution Exposure
2010; Lippincott Williams & Wilkins; Volume: 121; Issue: 25 Linguagem: Inglês
10.1161/circulationaha.109.893461
ISSN1524-4539
AutoresQinghua Sun, Xinru Hong, Loren E. Wold,
Tópico(s)Energy, Environment, and Transportation Policies
ResumoHomeCirculationVol. 121, No. 25Cardiovascular Effects of Ambient Particulate Air Pollution Exposure Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBCardiovascular Effects of Ambient Particulate Air Pollution Exposure Qinghua Sun, MD, PhD, Xinru Hong, MD, PhD and Loren E. Wold, PhD Qinghua SunQinghua Sun From the Division of Environmental Health Sciences, College of Public Health (Q.S.), Division of Cardiovascular Medicine (Q.S.), and Davis Heart and Lung Research Institute, Department of Internal Medicine (Q.S., L.E.W.), College of Medicine, Ohio State University, Columbus; Fuzhou General Hospital, Fujian, China (X.H.); and Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital (L.E.W.), Department of Pediatrics (L.E.W.), and Department of Physiology and Cell Biology (L.E.W.), Ohio State University, Columbus. , Xinru HongXinru Hong From the Division of Environmental Health Sciences, College of Public Health (Q.S.), Division of Cardiovascular Medicine (Q.S.), and Davis Heart and Lung Research Institute, Department of Internal Medicine (Q.S., L.E.W.), College of Medicine, Ohio State University, Columbus; Fuzhou General Hospital, Fujian, China (X.H.); and Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital (L.E.W.), Department of Pediatrics (L.E.W.), and Department of Physiology and Cell Biology (L.E.W.), Ohio State University, Columbus. and Loren E. WoldLoren E. Wold From the Division of Environmental Health Sciences, College of Public Health (Q.S.), Division of Cardiovascular Medicine (Q.S.), and Davis Heart and Lung Research Institute, Department of Internal Medicine (Q.S., L.E.W.), College of Medicine, Ohio State University, Columbus; Fuzhou General Hospital, Fujian, China (X.H.); and Center for Cardiovascular and Pulmonary Research, The Research Institute at Nationwide Children's Hospital (L.E.W.), Department of Pediatrics (L.E.W.), and Department of Physiology and Cell Biology (L.E.W.), Ohio State University, Columbus. Originally published29 Jun 2010https://doi.org/10.1161/CIRCULATIONAHA.109.893461Circulation. 2010;121:2755–2765An association between high levels of air pollutants and human disease has been known for more than half a century. Air pollution is composed of a heterogeneous mixture of compounds including ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen oxides (NOx), liquids, and particulate matter (PM). Substantial epidemiological evidence implicates air pollution, particularly PM, as a major risk factor with serious consequences on human health.1–3 Of particular interest in PM are the particles that are ≤10 μm in diameter (PM10) because they are the PM that ultimately enters the lungs.4 PM is further divided into coarse (10 to 2.5 μm; PM10–2.5), fine (<2.5 μm; PM2.5), and ultrafine ( 65 y of age1999–2002204 US counties27Wellenius et alExposure associated with increased hospital admission for CHFCHFPM10≥65 y of age1986–19997 US cities30Bell et alStrong relationship between PM2.5 and hospitalization for respiratory and cardiovascular diseases, especially in the Northeast region, with a 1.49% increase in hospitalizations of cardiovascular diseases per 10-μg/m3 increase in same-day PM2.5Respiratory and cardiovascular diseasesPM2.5≥65 y of age1999–2005202 US counties31Bell et alHigher PM2.5 content of nickel, vanadium, and elemental carbon associated with higher risk of cardiovascular and respiratory hospitalizationsCardiovascular and respiratory diseasesPM2.5 and chemical composition≥65 y of age1999–2005106 US counties32Morgan et alExposure associated with increased hospitalization for respiratory and heart disease, with increase in daily maximum 1-h particulate concentration associated with an increase of 3.01% in COPD and 2.82% in heart disease admissionsRespiratory and heart diseasePM2.5, O3, NO2, PM10All ages1990–1994Sydney, Australia34Schwartz et alExposure associated with hospital admissions for heart disease, with daily variation in PM10 associated with 2.48% increase and daily variation in CO associated with 2.79% increaseHeart diseasePM10, CO≥65 y of age1988–19908 US counties35Prescott et alExposure associated with emergency hospital admission for cardiac and respiratory disease, positive association with PM10, and negative association with O3Cardiac and respiratory diseasePM10, CO, NO2, O3All ages1981–1995UK36Linn et alExposure associated with increased hospitalization for cardiopulmonary illness, with a 25th to 75th percentile increase in CO predicting an increase of 4% in cardiovascular admission; NO2 and PM10 but not O3 showed similar increases in cardiovascular diseaseCardiopulmonary diseasePM10, CO, NO2, O3Adults1992–1995Los Angeles, US37Janssen et alPM10 associated with hospital admissions, especially for cardiovascular disease, in 14 cities in summer and winterCardiovascular diseasePM10Not specific199314 US cities38Wong et alAir pollution similarly associated with daily cardiorespiratory admissions in both cities, with significant positive association observed with PM10, NO2, SO2, and O3 in both citiesCardiorespiratory diseasePM10, O3, SO2, NO2All ages1992–1997Hong Kong, London39McGowan et alPM10 exposure associated with cardiorespiratory admission, with 3.37% increase in respiratory admissions and 1.26% rise in cardiac admissions for each interquartile rise in PM10Cardiorespiratory diseasePM10, CO, SO2, NOxAll ages1988–1998New Zealand40Mann et alExposure associated with hospital admission for myocardial infarction, with a 1-ppm increase in CO associated with a 3.60% increase in same-day IHD admissions with a secondary diagnosis of CHF, a 2.99% increase in persons with a secondary diagnosis of ARR, and a 1.62% increase in IHD admissions in persons without either secondary diagnosisMyocardial infarctionPM10, NO2, CO≥40 y of age1988–1995California41Koken et alExposure associated with increased hospitalization for cardiovascular disease, with O3 associated with an increase in the risk of hospitalization for acute myocardial infarction, coronary atherosclerosis, and pulmonary heart disease; SO2 for cardiac dysrhythmias; and CO for congestive heart failureCardiovascular diseasePM10, CO, SO2, O3, NO2>65 y of age1993–1997Colorado42Fung et alExposure to SO2 associated with daily cardiac hospital admission, with a percentage increase in daily admission of 2.6% for current-day SO2, 4.0% for 2-d mean level, and 5.6% for 3-d mean level for an increase in interquartile range of 19.3 ppb; the contributing effect of SO2 remained significant for all 3 levels when PM10 was includedCardiac diseaseSO2, PM10≥65 y of age1995–2000Ontario, Canada43(Continued)Table 1. ContinuedAuthorsKey FindingsDiseasesPollutantsSubjectsYearLocationReferenceCHF indicates chronic heart failure; BC, black carbon; OC, organic carbon; IHD, ischemic heart disease; and ARR, arrhythmia.Chang et alExposure, especially to PM10, associated with increased hospital admissions for cardiovascular diseaseCardiovascular diseasePM10, O3, NO2, CONot specific1997–2001Taiwan44Hosseinpoor et alCO exposure associated with increased hospitalization for angina pectoris, with each unit increase in CO causing a 1.00 increase in the number of admissionsAngina pectorisNO2, CO, O3, SO2, PM10Not specific1996–2001Iran45Maheswaran et alExposure associated with coronary heart disease mortality and hospital admission, with admission rate ratios of 1.00, 1.01, and 0.88 for the lowest NOx, PM10, and CO quintiles, respectivelyCoronary heart diseaseNOx, PM10, CO≥45 y of age1994–1998UK46Wellenius et alExposure associated with transiently increased ischemia but not hemorrhagic stroke, with an interquartile range increase in PM10 associated with a 1.03% increase in admissions for ischemic stroke on the same dayCardiac ischemiaPM10≥65 y of age19909 US cities47Low et alExposure associated with stroke hospital admission, with statistically significant, independent exacerbating effects of SO2 and PM10StrokeO3, NO2, SO2, CO, PM10Adults1995–2005New York, NY48Barnett et alExposure associated with adult cardiovascular hospital admissions, with all pollutants except O3 significantly associated with 5 categories of cardiovascular disease admissions in the elderlyCardiovascular diseaseNO2, CO, PM2.5, PM10, O3All ages1998–2001Australia, New Zealand49Johnston et alPM10 exposure positively associated with respiratory disease and ischemic heart disease admissions, especially in indigenous peopleRespiratory diseasePM10All ages2000–2005Australia50Migliaretti et alSignificant association between the increase in emergency hospital admission for respiratory causes and exposure, with a mean increase in emergency hospital attendance of 2.20% and 2.55% per 10-μg/m3 increase in exposure to SO2 and TSP, respectively, and a mean increase of 5.30% per 1-mg/m3 increase in exposure to CORespiratory diseaseSO2, CO, TSPAdults1997–1999Italy51Peng et alSignificant associations between PM10–2.5 and hospital admissions for cardiovascular and respiratory diseases, with a 10-μg/m3 increase in PM10–2.5 associated with a 0.36% increase in cardiovascular disease admissions on the same dayCardiovascular and respiratory diseasesPM2.5, PM10, PM10–2.5>65 y of age1999–2005US52Yang et alCHF admission associated with air pollutants on warm days in the single-pollutant model of PM10, NO2, CO, or O3CHFPM10, NO2, CO, O3Adults1996–2004Taiwan53Middleton et alIncreased risk of hospitalization with PM10 and O3, with every 10 μg/m3 increase in daily average PM10 associated with a 0.9% increase in all-cause and 1.2% increase in cardiovascular admissionsAll-cause, especially cardiovascular diseasePM10, O3All ages1999–2004Cyprus54Lin et alPositive association between respiratory hospital admissions and ambient O3 level 2 d before admission in 5 of the 11 regionsRespiratory diseaseO30–17 y of age1999–2001New York55Changes in Heart Rate and Cardiac FunctionIn an attempt to investigate associations between ambient PM and cardiovascular function in a repeated-measures study in Boston residents, exposure to PM2.5 with an average concentration of 15.5 μg/m3 was associated with decreased vagal tone, resulting in reduced heart rate variability.56 In another study that evaluated changes in mean heart rate and heart rate variability in humans, there was an association between exposure to PM10 on a previous day of 100 μg/m3 and significantly increased heart rate by 5 to 10 bpm, suggesting that changes in cardiac autonomic function, reflected by changes in mean heart rate and heart rate variability, may be part of the pathophysiological mechanism linking cardiovascular mortality and PM.57 In the Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) study,58 elevations in PM predicted risk for exercise-induced ST-segment depression in subjects with coronary artery disease. Another study in 3827 participants who underwent cardiac magnetic resonance imaging between 2000 and 2002 found that participants living within 50 miles of a major roadway had a higher cardiac function-left ventricular mass index associated with PM2.5 elevation, indicating chronic vascular end-organ damage from traffic-related environmental exposure.59 Several other studies have demonstrated a link between changes in heart rate and PM levels in mice60 and elderly humans.61 The possible mechanisms involved in these events include disturbances in cardiac autonomic control,62 reduction in cardiac vagal control,63 decreases in parasympathetic tone,64 and an imbalance in cardiac autonomic control.65Thrombosis and Other Changes in HemostasisPM has been associated with transient increases in plasma viscosity, acute-phase reactants, and endothelial dysfunction, as well as altered autonomic control of the heart. The effect of intravenous or intratracheal administration of ultrafine polystyrene particles, diesel exhaust particles, or PM2.5 on thrombus formation was investigated, indicating the effects of circulating particles on changes in hemostasis.66–71 In 3256 randomly selected men and women 25 to 64 years of age, high concentrations of SO2, CO, and TSP were associated with increased plasma viscosity.72 The Holland group studied ≈330 deaths during 1986 to 1994 and found that embolisms and thrombotic changes were increased after exposure to CO, O3, and SO2.73 In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust and filtered air in the United Kingdom and Sweden; postexposure thrombus formation, coagulation, platelet activation, and inflammatory markers were measured. These investigators found that diesel exhaust inhalation increased thrombus formation and platelet-neutrophil and platelet-monocyte aggregates.74Other epidemiological data link PM exposure to an augmentation of systemic inflammation as measured by C-reactive protein,26 an acute-phase protein associated with adverse outcomes in patients with unstable ischemic syndromes. In this prospective cohort survey in 1984 to 1985 with a 3-year follow-up of 631 randomly selected men 45 to 64 years of age who were free of cardiovascular disease at entry, the odds of observing C-reactive protein concentrations >5.7 mg/L (>90th percentile) tripled at normal ambient PM concentrations, and increases of 26 μg/m3 total suspended particles (mean of 5 days) raised the odds of having a C-reactive protein level 50% greater than the 90th percentile.26 Increased levels of fibrinogen, platelets, and white blood cell counts were also associated with exposure to TSP.75,76The regulation of fibrinolysis is another important aspect of endothelial function. Small areas of endothelial denudation and thrombus deposition are a common finding on the surface of atheromas and are usually subclinical. Therefore, endogenous fibrinolysis of the lesion might prevent thrombus propagation and vessel occlusion.77 Nevertheless, under adverse proinflammatory states or imbalances in the fibrinolytic system, microthrombi may propagate and ultimately lead to arterial occlusion and tissue infarction.78 In a series of double-blind, randomized crossover studies, both healthy men and patients with stable coronary artery disease were exposed to dilute diesel exhaust (PM, 300 μg/m3) for 1 hour while performing intermittent exercise79–81 and were then challenged by intrabrachial bradykinin, acetylcholine, sodium nitroprusside, and verapamil. Although there was a dose-dependent increase in blood flow with each vasodilator, this response was attenuated with bradykinin, acetylcholine, and sodium nitroprusside infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator that was suppressed 6 hours after exposure to diesel.79 In a double-blind, randomized crossover study, 20 men with a prior myocardial infarction were exposed in 2 separate sessions to dilute diesel exhaust (300 μg/m3) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. Exercise-induced ST-segment depression was found in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust. Exposure to diesel exhaust reduced the acute release of endothelial tissue plasminogen activator other than aggravating preexisting vasomotor dysfunction.81 In these studies, the acute release of tissue plasminogen activator, which is a key regulator of endogenous fibrinolytic capacity, was reduced after diesel exhaust inhalation. This effect persisted for 6 hours after the initial exposure,79 with the magnitude of this reduction comparable to that seen in cigarette smokers.82 This antifibrinolytic effect further underscores the prothrombotic potential of air pollution, especially under circumstances of vascular injury.Baccarelli et al83 performed several studies of air pollution exposure and changes in blood homeostasis. To investigate the association between pollution levels (PM10, CO, NO2, SO2, and O3) and changes in global coagulation tests such as prothrombin time and activated partial thromboplastin time, 1218 normal subjects from the Lombardia region in Italy were tested. Results showed that air pollution is associated with changes in global coagulation function, suggesting a tendency toward hypercoagulability after short-term exposure to air pollution. The effects of exposure to PM10 on the risk of developing deep vein thrombosis in 870 patients and 1210 control subjects from the Lombardy region in Italy between 1995 and 2005 were then tested, with findings suggesting that long-term exposure to PM10 is associated with altered coagulation function and deep vein thrombosis risk.84 Using distance from roads as a proxy for traffic exposure to further investigate whether living near major traffic roads increased the risk of deep vein thrombosis, they examined 663 patients with deep vein thrombosis of the lower limbs and 859 age-matched control subjects from cities with populations of >15 000 inhabitants in the Lombardia region in Italy from 1995 through 2005. They found that the risk of developing deep vein thrombosis was increased for subjects living near a major traffic road compared with those living farther away, which was approximately linear over the observed distance range and was not modified after adjustment for background levels of PM, indicating that living near major traffic roads is associated with an increased risk of developing deep vein thrombosis.85 A summary of these effects is presented in Table 2. Table 2. Effect of Air Pollution on Changes in Blood HomeostasisAuthorsKey FindingsPollutantsSubjectsYearLocationReferenceDVT indicates deep venous thrombosis; MFI, mean fluorescence intensity; PMN, polymorphonuclear leukocytes; and PT, prothrombin time.Peters et alExposure associated with increased plasma viscosity, with an odds ratio of 3.6 for plasma viscosity above the 95th percentile of the distribution comparing measurements during the air pollution episode with nonepisode measurements in men and an odds ratio of 2.3 for womenTSP, SO2, CO25–64 y1984–1985Augsburg, Germany72Hoek et alExposure associated with increased embolism, thrombosis, and mortality, with heart failure deaths responsible for ≈30% of the cardiovascular deaths related to PM10, SO2, CO, and NO2PM10, CO, SO2, NO2All ages1986–1994The Netherlands73Lucking et alExposure associated with increased ex vivo thrombus formation and in vivo platelet activation, with thrombus formation under low- and high-shear conditions increased by 24% and 19%, respectivelyDiesel exhaust21–44 y2008UK, Sweden74Mills et alExposure associated with inhibition of endogenous fibrinolytic capacity, with a greater increase in the ischemic burden during exposure to diesel exhaustDiesel exhaust59–61 y2007UK81Baccarelli et alExposure associated with changes in global coagulation function, with PT shorter with higher PM10 and NO2PM10, NO2, SO2, CO, O311–84 y1995–2005Italy83Baccarelli et alExposure associated with altered coagulation function and DVT risk, with each increase of 10 μg/m3 in PM10 associated with a 70% increase in DVT riskPM1018–84 y1995–2005Italy84Baccarelli et alLiving near major traffic roads associated with increased risk of DVT, with the increase in DVT risk approximately linear over the observed distance range from 718 to 0 mNot specific (distance from major roads)18–84 y1995–2005Italy85Ray et alExposure associated with activated circulating platelets and increased leukocyte-platelet aggregates, with the MFI of CD11b on the surface of circulating monocytes and PMN of biomass users increased by 50% and 68%, respectively, and a 62% and 48% increase in MFI observed in CD18 expression on the surface of these cells in biomass usersPM2.5, PM1021–60 y2003–2004India86AtherosclerosisThe main pathway by which PM contributes to increased cardiac risk is by initiating and promoting atherosclerotic progression, the underlying cause of most cardiovascular diseases.87–89 Atherosclerotic lesions can lead to ischemia of the heart, brain, or extremities. The disruption of a vulnerable but not necessarily stenotic atherosclerotic plaque in response to hemodynamic stress has been suggested as a mechanism that can trigger a myocardial infarction. Air pollution may induce atherosclerosis in the peripheral arteries, coronary arteries, and aorta. Short-term exposure to elevated PM has been associated with increased acute cardiovascular mortality, especially with an at-risk subset of the population, whereas prolonged exposure has been considered a causative factor for atherosclerosis.1 In an epidemiological study, Pope et al7 reported that PM2.5 exposure is a risk factor for cause-specific cardiovascular disease mortality via mechanisms that likely include pulmonary and systemic inflammation, accelerated atherosclerosis, and altered cardiac autonomic function.The precise pathway through which PM induces the initiation and progression of atherosclerosis has not been determined, but 2 hypotheses have been proposed and assessed experimentally. The original hypothesis proposed that inhaled particles provoke an inflammatory response in the lungs, with consequent release of prothrombotic and inflammatory cytokines into the circulation.90 The alternative pathway proposed that inhaled, insoluble PM2.5 or PM0.1 could rapidly translocate into the circulation, with the potential for direct effects on homeostasis and cardiovascular integrity.91 The ability of PM0.1 to cross the lung-blood barrier is likely to be influenced by a number of factors, including particle size and charge, chemical composition, and propensity to form aggregates.3 Once in the circulation, PM0.1 can interact with the vascular endothelium or have direct effects on atherosclerotic plaques, causing local oxidative stress and proinflammatory effects similar to those seen in the lungs. Through either direct translocation into the circulation or secondary pulmonary-derived mediators, PM augments atherogenesis and causes acute adverse thrombotic and vascular effects.In a series of animal models, mice fed high-fat chow and exposed to ambient PM2.5 demonstrated marked increases in plaque area, macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine, indicating that exposure to low concentrations of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.92,93 Consistently, Chen and Nadziejko94 exposed apolipoprotein E-knockout mice and apolipoprotein E-, low-density lipoprotein receptor-deficient mice to ambient PM2.5 and demonstrated that subchronic exposure to ambient PM in these mice had a significant impact on the size, severity, and composition of aortic plaque. The PM0.1 component could have a greater atherogenic effect than the PM2.5 fraction. Araujo et al95 compared the proatherogen
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