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New Insights Into Pollution and the Cardiovascular System

2013; Lippincott Williams & Wilkins; Volume: 127; Issue: 18 Linguagem: Inglês

10.1161/circulationaha.111.064337

1524-4539

Diane R. Gold, Murray A. Mittleman,

Global Health Care Issues

HomeCirculationVol. 127, No. 18New Insights Into Pollution and the Cardiovascular System Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBNew Insights Into Pollution and the Cardiovascular System2010 to 2012 Diane R. Gold, MD, MPH, DTM&H and Murray A. Mittleman, MD, DrPH Diane R. GoldDiane R. Gold From the Channing Laboratory, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School (D.R.G.); Department of Environmental Health (D.R.G.) and Epidemiology (M.A.M.), Harvard School of Public Health; and Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School (M.A.M.), Boston, MA. and Murray A. MittlemanMurray A. Mittleman From the Channing Laboratory, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School (D.R.G.); Department of Environmental Health (D.R.G.) and Epidemiology (M.A.M.), Harvard School of Public Health; and Cardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School (M.A.M.), Boston, MA. Originally published7 May 2013https://doi.org/10.1161/CIRCULATIONAHA.111.064337Circulation. 2013;127:1903–1913IntroductionAs cited in the recent 2010 American Heart Association scientific statement, the World Health Organization estimated that mass of fine particles <2.5 μm in aerodynamic diameter (PM2.5) contributed to ≈800000 premature deaths per year, ranking PM2.5 as the 13th leading cause of worldwide mortality.1 After an extensive review of studies on the cardiovascular effects of PM2.5, designed as a follow-up to a 2004 AHA scientific statement, the 2010 AHA report reached several new conclusions:Exposure to elevated levels of PM2.5 over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events. The evidence is strongest for ischemic heart disease (IHD) events, including myocardial infarction and heart failure hospitalizations.Longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposure over a few days and reduces life expectancy in more highly exposed populations by several months to a few years.Reductions in particulate matter (PM) levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years.Many credible pathological mechanisms have been elucidated that support the biological plausibility of these findings. These include systemic inflammation, systemic oxidative stress, thrombosis and coagulation, systemic and pulmonary arterial blood pressure responses, vascular (including endothelial) dysfunction, cardiac ischemia, and heart rate variability/autonomic dysfunction.The 2010 AHA document and the subsequent review by Sun et al2 focused on the literature on the mechanisms for cardiovascular effects of pollution and pointed out that there were fewer human studies and less consistency in study results concerning the following:Effects of fine particle mass on cerebrovascular and cardiac arrhythmia outcomes.Cardiovascular effects of the coarse (PM10-2.5) or ultrafine ( 1 pollutant and observational epidemiological studies that put >1 pollutant (particle mass and gases) into their predictive models. However, the definition of clusters of particle constituents and pollution mixtures and the ascertainment of their health effects are beyond the scope of this review. These are currently being actively investigated, in part through currently funded EPA Clean Air Act Centers (www.epa/oar/caa). We also acknowledge that there is a large complementary growing literature that uses in vitro and animal models to evaluate pollution effects; for the most part, that literature is beyond the scope of our review.Our review includes an update on sources of vulnerability and susceptibility. According to the EPA (2009 Particle Matter EPA Integrated Science Assessment, Chapter 8 [http://www.epa.gov/ncea/isa]),…the National Air Quality Standards are intended to provide an adequate margin of safety for both general populations and sensitive subgroups…to facilitate the identification of populations at the greatest risk for PM-related health effects, studies have evaluated factors that contribute to the susceptibility and//or vulnerability of an individual to PM. The definition for both of these terms has been found to vary across studies, but in most instances susceptibility refers to biological or intrinsic factors (eg, lifestage, gender) while vulnerability refers to nonbiological or extrinsic factors.In this review, vulnerability refers to factors that increase the potential for exposure, and susceptibility refers to individual factors that increase risk at any given level of exposure. Susceptibility implies a greater response at any given level of exposure.Our literature review is based primarily on 2010 to 2012 PubMed searches using combinations of the following key words: pollution; cerebrovascular, arrhythmia; atherosclerosis; coarse particles; ultrafine particles; OC, ozone, nitrogen dioxides, carbon monoxide, chronic effects; wild fires, biomass; and temperature, susceptibility, vulnerability.Update, 2010 to 2012: Cerebrovascular Effects of PollutionThe retina affords a view into microvascular changes that may be affected by pollution. After adjustment for multiple potential confounders, the Multi-Ethnic Study of Atherosclerosis (MESA) demonstrated an association between living in a region with higher with increased PM2.5 and reduced retinal vessel diameter.3 Cerebrovascular imaging is needed to evaluate the specific effects of pollution on macrovascular and microvascular disease leading to ischemic stroke and vascular dementia. Because of methodological or technological challenges, including the need for neuroimaging to identify the presence of subclinical disease and the difficulty of assessing the timing of stroke onset in studies based on administrative data,4 the relation of air pollution exposures to the risk of acute or chronic cerebrovascular outcomes has been less thoroughly examined than the relation of pollution to other cardiovascular outcomes. Many studies have used administrative data sets that are subject to misclassification of specific outcome diagnosis and the timing of stroke onset4 and do not lend themselves to the evaluation of biological mechanisms for the relation of pollution or pollutant components to cerebrovascular outcomes. These studies have been reviewed recently in a new report showing that the estimated odds ratio of ischemic stroke onset was 1.34 (P<0.001) after a 24-hour period classified as moderate (PM2.5, 15-10 µg/m3) by the US EPA's Air Quality Index compared with a 24-hour period classified as good (PM2.5 <15-10 µg/m3; the Figure).5 The increased risk was greatest within 12 to 14 hours of exposure.Download figureDownload PowerPointFigure. Odds ratio of ischemic stroke onset for US Environmental Protection Agency categories (good and moderate) of mean ambient fine particulate matter air pollution (PM2.5) levels in the 24 hours preceding stroke onset. Error bars indicate 95% confidence interval. Reproduced from Wellenius et al5 with permission from the publisher.Update, 2010 to 2012: Cardiac Arrhythmia, Arrhythmia Precursors, and PollutionEvidence continues to be mixed for associations between pollution and documented cardiac arrhythmias or electrophysiological changes such as repolarization abnormalities that may increase the risk of arrhythmias. Even more so than studies of stroke, ascertainment of the timing of the onset of the outcome and the specific electrophysiological nature of the outcome can be challenging to ascertain without personal monitoring, which is absent in studies of administrative data sets, which often report null findings.6 In their recent review, Link and Dockery7 concluded that "the incremental risk of air pollution in triggering arrhythmias…is greatest for patients with underlying cardiac disease." A London study examined associations of 11 pollutants with activation of implanted cardioverter-defibrillators, finding mostly weak associations with the elevation of a number of secondary regional pollutants, the strongest of which was the nontraffic particle component sulfate.8 Increases in premature ventricular counts, atrial fibrillation/flutter, and its precedent, P-wave complexity, were associated with increased PM2.5 in the previous 1 to 2 hours in a Pennsylvania study of 105 middle-aged healthy nonsmokers with 24-hour ECG and personal particle monitoring.9,10 Ghio et al11 presented a case report of new-onset atrial fibrillation that occurred 20 minutes into a controlled exposure to concentrated ambient particles and resolved within 2 hours with no sequella. In studies of vulnerable populations who have personal electrophysiological monitoring, ozone has also been considered a risk factor for arrhythmias. An increase in the maximum ozone level predicted increases in bradycardia and apnea in high-risk infants on home monitors.12Controlled human exposure to 1-hour exposures of diesel exhaust did not influence heart rhythm or variability in a UK study.13 Increased spatial dispersion of myocardial repolarization, but not T-wave alternans, was seen after controlled human exposures to concentrated ambient particles, ozone, or a combination of the 2 exposures.14 Increases in long-term estimated residential PM2.5 predicted increased odds of QT prolongation without overt ventricular abnormalities in the Multi-Ethnic Study of Atherosclerosis (MESA).15 Two recent studies (the Table) also suggest acute effects of O3 on repolarization abnormalities in sensitive subjects.16,17Update, 2010 to 2012: Cardiovascular Effects of the Coarse (PM10-2.5) or Ultrafine ( 1 pollutant at a time, associations of short-term increases in ambient gases and particles have been predictive of cardiovascular mortality or morbidity in the Po Valley of northern Italy (O3, NO2, PM2.5)21 and Seoul, South Korea (NO2, CO, SO2, PM10; weaker associations with O3).22 When a maximum 8-hour average was used, an interquartile range increase of 2-day average O3 predicted an increased risk of cardiovascular mortality of 4.5% (95% confidence interval, 1.4–7.5) that was more evident in the cool than in the warm season in Suzhou, China.23 After adjustment for PM, short-term elevations in O3 or NO2 were associated with increased cardiovascular mortality or morbidity in studies from Prague (O3),24 the Pearl River Delta of southern China (O3, NO2),25 and Lisbon, Portugal (O3)26; a study of 10 Italian cities (NO2)27; and the Public Health and Air Pollution in Asia Study, which evaluated health effects across large urban populations in 4 Asian countries (O3, NO2).28Short-term exposures to particle pollution (including black carbon and OC) were associated with increases in blood pressure, whereas increases in O3 were linked to blood pressure decreases in a repeated measures study of patients with type 2 diabetes mellitus.18 In elderly subjects with coronary artery disease from the Los Angeles, CA, basin, exposure to primary components of fossil fuel combustion (eg, OC) was associated with ST-segment depression39 and with elevated ambulatory blood pressure.40 Associations of OC with higher blood pressure were of greatest magnitude among obese participants.Long-term Exposures/Chronic EffectsSeveral recent large longitudinal cohort studies support the 2010 AHA conclusion that long-term particle mass exposures of traffic and nontraffic origin increase the risk of cardiovascular disease. Despite longitudinal decreases in PM2.5 levels, in the Harvard Six Cities Study, investigators found a linear dose-response association of mortality with annual average PM2.5 down to concentrations of 8 μg/m3. Exposures to PM constituents or other ambient pollutants were not considered.41 Long-term exposures to estimated residential PM2.5 predicted increased blood pressure in a study in Germany.42Recent studies also support the hypothesis that in real-world ambient pollution mixtures, both gases and particles contribute to long-term adverse cardiac effects. In the California Teachers Study, long-term exposure to PM10 was associated with elevated risks for IHD and incident stroke; exposure to nitrogen oxides was associated with elevated risk of IHD.29 In a metropolitan Vancouver population of 45- to 85-year-old adults followed up for 5 years, increased long-term exposures to black carbon, a marker for traffic, predicted increased cardiovascular hospitalization after PM2.5 and NO2 were controlled for.30 A study of long-haul truck drivers found that long-term exposures to elevated levels of ambient NO2 predicted increased cardiovascular mortality, but associations were attenuated and not significant (P 4000 adults found an association of increased carotid intima-media thickness and increased blood pressure with increased exposures to estimated long-term PM2.5 and distance to high traffic.42,53 A Danish study showed that living in city centers was associated with increased coronary artery calcification, but whether this association is due to increased pollution exposure is not known.54 Studies supporting a role for particles in increasing the risk of thrombus formation have recently been reviewed.55 In healthy volunteers, particle traps were shown to reduce thrombogenicity of diesel exhaust.56Update, 2010 to 2012: Susceptibility and VulnerabilityThe literature on susceptibility or vulnerability to particulate pollution has been summarized recently.57–60 Sources of susceptibility considered in our review include genetics, life stage or age, sex, preexisting chronic conditions (diabetes mellitus, obesity, cardiovascular disease, chronic obstructive pulmonary disease), adverse weather conditions, and acute infections (eg, influenza).61 As stated by the EPA (2009 Particle Matter EPA Integrated Science Assessment, Chapter 8 [http://www.epa.gov/ncea/isa]), lower socioeconomic position can be viewed both as a source of vulnerability (with increased absolute exposure to higher levels of pollution) and as a source of susceptibility (with increased disease at a given exposure because of susceptibility cofactors such as stress or lack of access to health care).GeneticsEvaluation of genetic susceptibility to air pollution has been used as a tool for exploring mechanisms and pathways for cardiovascular effects and may contribute to understanding the distribution of risk. In a recent systematic review, Zanobetti and colleagues62 found 16 articles evaluating gene–air pollution interaction and cardiovascular disease. These articles were based on 3 study populations: the Normative Aging Study (NAS),63–75 the Air Pollution and Inflammatory Response in Myocardial Infarction Survivors: Gene-Environment Interaction in a High Risk Group (AIRGENE),76,77 and MESA.78 These studies have focused o