Victor C. Van Hee

Exposure to traffic and left ventricular mass and function: the Multi-Ethnic Study of Atherosclerosis.

RATIONALE Ambient air pollution has been associated with heart failure morbidity and mortality. The mechanisms responsible for these associations are unknown but may include the effects of traffic-related pollutants on vascular or autonomic function. OBJECTIVES We assessed the cross-sectional relation between long-term air pollution, traffic exposures, and important end-organ measures of alterations in cardiac function-left ventricular mass index (LVMI) and ejection fraction-in the Multi-Ethnic Study of Atherosclerosis, a multicenter study of adults without previous clinical cardiovascular disease. METHODS A total of 3,827 eligible participants (aged 45-84 yr) underwent cardiac magnetic resonance imaging between 2000 and 2002. We estimated air pollution exposures using residential proximity to major roadways and interpolated concentrations of fine particulate matter (less than 2.5 microns in diameter). We examined adjusted associations between these exposures and left ventricular mass and function. MEASUREMENTS AND MAIN RESULTS Relative to participants living more than 150 m from a major roadway, participants living within 50 m of a major roadway showed an adjusted 1.4 g/m(2) (95% CI, 0.3-2.5) higher LVMI, a difference in mass corresponding to a 5.6 mm Hg greater systolic blood pressure. Ejection fraction was not associated with proximity to major roadways. Limited variability in estimates of fine particulate matter was observed within cities, and no associations with particulate matter were found for either outcome after adjustment for center. CONCLUSIONS Living in close proximity to major roadways is associated with higher LVMI, suggesting chronic vascular end-organ damage from a traffic-related environmental exposure. Air pollutants or another component of roadway proximity, such as noise, could be responsible.

Vascular Responses to Long- and Short-Term Exposure to Fine Particulate Matter : MESA Air (Multi-Ethnic Study of Atherosclerosis and Air Pollution)

OBJECTIVES This study evaluated the association of long- and short-term air pollutant exposures with flow-mediated dilation (FMD) and baseline arterial diameter (BAD) of the brachial artery using ultrasound in a large multicity cohort. BACKGROUND Exposures to ambient air pollution, especially long-term exposure to particulate matter <2.5 μm in aerodynamic diameter (PM(2.5)), are linked with cardiovascular mortality. Short-term exposure to PM(2.5) has been associated with decreased FMD and vasoconstriction, suggesting that adverse effects of PM(2.5) may involve endothelial dysfunction. However, long-term effects of PM(2.5) on endothelial dysfunction have not been investigated. METHODS FMD and BAD were measured by brachial artery ultrasound at the initial examination of the Multi-Ethnic Study of Atherosclerosis. Long-term PM(2.5) concentrations were estimated for the year 2000 at each participants residence (n = 3,040) using a spatio-temporal model informed by cohort-specific monitoring. Short-term PM(2.5) concentrations were based on daily central-site monitoring in each of the 6 cities. RESULTS An interquartile increase in long-term PM(2.5) concentration (3 μg/m(3)) was associated with a 0.3% decrease in FMD (95% confidence interval [CI] of difference: -0.6 to -0.03; p = 0.03), adjusting for demographic characteristics, traditional risk factors, sonographers, and 1/BAD. Women, nonsmokers, younger participants, and those with hypertension seemed to show a greater association of PM(2.5) with FMD. FMD was not significantly associated with short-term variation in PM(2.5) (-0.1% per 12 μg/m(3) daily increase [95% CI: -0.2 to 0.04] on the day before examination). CONCLUSIONS Long-term PM(2.5) exposure was significantly associated with decreased endothelial function according to brachial ultrasound results. These findings may elucidate an important pathway linking air pollution and cardiovascular mortality.

Air Pollution and Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

Research to date demonstrates a relationship between exposure to ambient air pollutants and cardiovascular disease (CVD). Many studies have shown associations between short-term exposures to elevated levels of air pollutants and CVD events, and several cohort studies suggest effects of long-term exposure on cardiovascular mortality, coronary heart disease events, and stroke. The biologic mechanisms underlying this long-term exposure relationship are not entirely clear but are hypothesized to include systemic inflammation, autonomic nervous system imbalance, changes in vascular compliance, altered cardiac structure, and development of atherosclerosis. The Multi-Ethnic Study of Atherosclerosis provides an especially well-characterized population in which to investigate the relationship between air pollution and CVD and to explore these biologic pathways. This article reviews findings reported to date within this cohort and summarizes the aims and anticipated contributions of a major ancillary study, the Multi-Ethnic Study of Atherosclerosis and Air Pollution.

Long-Term Air Pollution Exposure and Blood Pressure in the Sister Study.

Background Exposure to air pollution has been consistently associated with cardiovascular morbidity and mortality, but mechanisms remain uncertain. Associations with blood pressure (BP) may help to explain the cardiovascular effects of air pollution. Objective We examined the cross-sectional relationship between long-term (annual average) residential air pollution exposure and BP in the National Institute of Environmental Health Sciences’ Sister Study, a large U.S. cohort study investigating risk factors for breast cancer and other outcomes. Methods This analysis included 43,629 women 35–76 years of age, enrolled 2003–2009, who had a sister with breast cancer. Geographic information systems contributed to satellite-based nitrogen dioxide (NO2) and fine particulate matter (≤ 2.5 μm; PM2.5) predictions at participant residences at study entry. Generalized additive models were used to examine the relationship between pollutants and measured BP at study entry, adjusting for cardiovascular disease risk factors and including thin plate splines for potential spatial confounding. Results A 10-μg/m3 increase in PM2.5 was associated with 1.4-mmHg higher systolic BP (95% CI: 0.6, 2.3; p < 0.001), 1.0-mmHg higher pulse pressure (95% CI: 0.4, 1.7; p = 0.001), 0.8-mmHg higher mean arterial pressure (95% CI: 0.2, 1.4; p = 0.01), and no significant association with diastolic BP. A 10-ppb increase in NO2 was associated with a 0.4-mmHg (95% CI: 0.2, 0.6; p < 0.001) higher pulse pressure. Conclusions Long-term PM2.5 and NO2 exposures were associated with higher blood pressure. On a population scale, such air pollution–related increases in blood pressure could, in part, account for the increases in cardiovascular disease morbidity and mortality seen in prior studies. Citation Chan SH, Van Hee VC, Bergen S, Szpiro AA, DeRoo LA, London SJ, Marshall JD, Kaufman JD, Sandler DP. 2015. Long-term air pollution exposure and blood pressure in the Sister Study. Environ Health Perspect 123:951–958; http://dx.doi.org/10.1289/ehp.1408125

Common Genetic Variation, Residential Proximity to Traffic Exposure, and Left Ventricular Mass: The Multi-Ethnic Study of Atherosclerosis

Background Elevated left ventricular mass (LVM) is a strong predictor of negative cardiovascular outcomes, including heart failure, stroke, and sudden cardiac death. A relationship between close (< 50 m compared with > 150 m) residential proximity to major roadways and higher LVM has previously been described, but the mechanistic pathways that are involved in this relationship are not known. Understanding genetic factors that influence susceptibility to these effects may provide insight into relevant mechanistic pathways. Objective We set out to determine whether genetic polymorphisms in genes affecting vascular and autonomic function, blood pressure, or inflammation influence the relationship between traffic proximity and LVM. Methods This was a cross-sectional study of 1,376 genotyped participants in the Multi-Ethnic Study of Atherosclerosis, with cardiac magnetic resonance imaging performed between 2000 and 2002. The impact of tagged single-nucleotide polymorphisms (tagSNPs) and inferred haplotypes in 12 candidate genes (ACE, ADRB2, AGT, AGTR1, ALOX15, EDN1, GRK4, PTGS1, PTGS2, TLR4, VEGFA, and VEGFB) on the relationship between residential proximity to major roadways and LVM was analyzed using multiple linear regression, adjusting for multiple potential confounders. Results After accounting for multiple testing and comparing homozygotes, tagSNPs in the type 1 angiotensin II receptor (AGTR1, rs6801836) and arachidonate 15-lipoxygenase (ALOX15, rs2664593) genes were each significantly (q < 0.2) associated with a 9–10% difference in the association between residential proximity to major roadways and LVM. Participants with suboptimal blood pressure control demonstrated stronger interactions between AGTR1 and traffic proximity. Conclusions Common polymorphisms in genes responsible for vascular function, inflammation, and oxidative stress appear to modify associations between proximity to major roadways and LVM. Further understanding of how genes modify effects of air pollution on CVD may help guide research efforts into specific mechanistic pathways.

Traffic-related Air Pollution and the Right Ventricle. The Multi-ethnic Study of Atherosclerosis

RATIONALE Right heart failure is a cause of morbidity and mortality in common and rare heart and lung diseases. Exposure to traffic-related air pollution is linked to left ventricular hypertrophy, heart failure, and death. Relationships between traffic-related air pollution and right ventricular (RV) structure and function have not been studied. OBJECTIVES To characterize the relationship between traffic-related air pollutants and RV structure and function. METHODS We included men and women with magnetic resonance imaging assessment of RV structure and function and estimated residential outdoor nitrogen dioxide (NO2) concentrations from the Multi-ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease at baseline. Multivariable linear regression estimated associations between NO2 exposure (averaged over the year prior to magnetic resonance imaging) and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus, and hypertension. Adjustment for corresponding left ventricular parameters, traffic-related noise, markers of inflammation, and lung disease were considered in separate models. Secondary analyses considered oxides of nitrogen (NOx) as the exposure. MEASUREMENTS AND MAIN RESULTS The study sample included 3,896 participants. In fully adjusted models, higher NO2 was associated with greater RV mass and larger RV end-diastolic volume with or without further adjustment for corresponding left ventricular parameters, traffic-related noise, inflammatory markers, or lung disease (all P < 0.05). There was no association between NO2 and RV ejection fraction. Relationships between NOx and RV morphology were similar. CONCLUSIONS Higher levels of NO2 exposure were associated with greater RV mass and larger RV end-diastolic volume.

Association of Long-Term Air Pollution with Ventricular Conduction and Repolarization Abnormalities

Background: Short-term exposure to air pollution may affect ventricular repolarization, but there is limited information on how long-term exposures might affect the surface ventricular electrocardiographic (ECG) abnormalities associated with cardiovascular events. We carried out a study to determine whether long-term air pollution exposure is associated with abnormalities of ventricular repolarization and conduction in adults without known cardiovascular disease. Methods: A total of 4783 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis underwent 12-lead ECG examinations, cardiac-computed tomography, and calcium scoring, as well as estimation of air pollution exposure using a finely resolved spatiotemporal model to determine long-term average individual exposure to fine particulate matter (PM2.5) and proximity to major roadways. We assessed ventricular electrical abnormalities including presence of QT prolongation (Rautaharju QTrr criteria) and intraventricular conduction delay (QRS duration >120 milliseconds). We used logistic regression to determine the adjusted relationship between air pollution exposures and ECG abnormalities. Results: A 10-&mgr;g/m3 increase in estimated residential PM2.5 was associated with an increased odds of prevalent QT prolongation (adjusted odds ratio [OR] = 1.6 [95% confidence interval (CI) = 1.2–2.2]) and intraventricular conduction delay (1.7 [1.0–2.6]), independent of coronary-artery calcium score. Living near major roadways was not associated with ventricular electrical abnormalities. No evidence of effect modification by traditional risk factors or study site was observed. Conclusions: This study demonstrates an association between long-term exposure to air pollution and ventricular repolarization and conduction abnormalities in adults without clinical cardiovascular disease, independent of subclinical coronary arterial calcification.

Update in environmental and occupational medicine 2009.

Environmental and occupational health was a major focus of both the scientific and lay press in 2009. Population-based studies confirmed the importance of environmental pollutants in the development of cardiorespiratory morbidity and mortality. Concerns regarding climate change highlighted the important public health consequences of carbon dioxide and methane emissions. The promise of new manufactured nanomaterials has been tempered by emerging concerns regarding their environmental impact. In addition, a ruling by the U.S. Supreme Court in 2009 will force a revision of the U.S. Environmental Protection Agency (EPA) standards for the three major air pollutants, particulate matter, ozone, and nitrogen oxides (NOx), in 2010. In this review on environmental and occupational medicine, we provide an overview of studies in the American Journal of Respiratory and Critical Care Medicine and selected other studies from the literature focused on environmental and occupational health. Although by no means comprehensive, we attempt to highlight the progress that has been made in identifying major health consequences of environmental exposure and understanding the mechanisms by which these occur.

Particulate Matter Exposure and Cardiopulmonary Differences in the Multi-Ethnic Study of Atherosclerosis.

Background: Particulate matter (PM) exposure may directly affect the pulmonary vasculature. Although the pulmonary vasculature is not easily measurable, differential associations for right ventricular (RV) and left ventricular (LV) mass may provide an indirect assessment of pulmonary vascular damage. Objectives: We tested whether long-term exposure to PM < 2.5 μm (PM2.5) is associated with greater RV mass and RV mass/end-diastolic volume ratio relative to the LV. Methods: The Multi-Ethnic Study of Atherosclerosis performed cardiac magnetic resonance (CMR) imaging among participants 45–84 years old without clinical cardiovascular disease in 2000–2002 in six U.S. cities. A fine-scale spatiotemporal model estimated ambient PM2.5 exposure in the year before CMR; individually weighted estimates accounted for indoor exposure to ambient PM2.5. Linear regression models were adjusted for demographics, anthropometrics, smoking status, cardiac risk factors, and LV parameters, with additional adjustment for city. Results: The 4,041 included participants had a mean age of 61.5 years, and 47% were never smokers. The mean ambient PM2.5 was 16.4 μg/m3 and individually weighted PM2.5 was 11.0 μg/m3. PM2.5 exposure was associated with greater RV mass [ambient: 0.11 g per 5 μg/m3 (95% CI: –0.05, 0.27); individually weighted: 0.20 g per 5 μg/m3 (95% CI: 0.04, 0.36)] and a greater RV mass/end-diastolic volume ratio conditional on LV parameters. City-adjusted results for RV mass were of greater magnitude and were statistically significant for both measures of PM2.5, whereas those for RV mass/end-diastolic volume ratio were attenuated. Conclusions: Long-term PM2.5 exposures were associated with greater RV mass and RV mass/end-diastolic volume ratio conditional on the LV; however, additional adjustment for city attenuated the RV mass/end-diastolic volume findings. These findings suggest that PM2.5 exposure may be associated with subclinical cardiopulmonary differences in this general population sample. Citation: Aaron CP, Chervona Y, Kawut SM, Diez Roux AV, Shen M, Bluemke DA, Van Hee VC, Kaufman JD, Barr RG. 2016. Particulate matter exposure and cardiopulmonary differences in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 124:1166–1173; http://dx.doi.org/10.1289/ehp.1409451

From Olympians to mere mortals: the indiscriminate, global challenges of air pollution.

Beijing won its bid to host the 2008 Olympics while promising to substantially improve its air quality, spending in excess of 10 billion dollars to implement pollution control measures (1). Based on substantial and growing evidence that air pollution impacts cardiac and respiratory health (2), Olympic athletes and the public were concerned that notoriously poor air quality in Beijing might have detrimental impacts on athletes. Even after substantive (13–60%) reductions in individual air pollutant concentrations during the 2008 Games as reported in this issue of the Journal (pp. 1150–1159) by Huang and colleagues (3), daily average levels of pollutants such as fine particulate matter in Beijing remained four to nine times higher than in large metropolitan cities in the United States during the same time period (4). Athletes remained concerned about potential health impacts, some deferred competing in the Games (5), and Olympic teams set up training camps away from Beijing to avoid intense air pollution exposures (6). Over several years just prior to the 2008 Olympics, epidemiological studies reported that patterns of associations between fine particulate air pollution and cause-specific mortality were consistent with the hypothesis that air pollution exposure contributes to pulmonary and systemic oxidative stress, inflammation, and associated increased risk of atherosclerosis and ischemic cardiovascular and obstructive pulmonary diseases (2, 7). Recent reviews of the expanding literature (8) and emerging evidence from the Multi-Ethnic Study of Atherosclerosis (9) suggest that there are likely multiple, complex, interdependent mechanistic pathways linking air pollution to cardiopulmonary disease, but also provide growing evidence that pulmonary and systemic oxidative stress and inflammation play important roles. Against this backdrop, in this issue of the Journal, Huang and coworkers (pp. 1150–1159) report results of a Beijing Olympics–based study investigating the relationship between air pollution and exhaled breath and urinary biomarkers of pulmonary and systemic oxidative stress and inflammation (3). This quasiexperimental study evaluated 125 young and healthy medical students before, during, and after the 2008 Beijing Olympics. Huang and colleagues demonstrated substantial decreases in these biomarkers tracking with reductions in air pollution, followed by subsequent increases in these biomarkers after return toward typical levels of air pollution in Beijing. These results add to previously reported evidence, from the same research team, that these Olympics-related changes in air pollution in Beijing were also associated with changes in systemic inflammation, thrombosis, blood pressure, and heart rate (10). Also, a third study using the Beijing Olympics–related changes in air pollution (with a focus on black carbon) found that the reductions in air pollution were also associated with exhaled nitric oxide, a biomarker of acute respiratory inflammation (11). These studies have several important strengths. For example, Huang and colleagues (3) took advantage of the sharp reductions in pollutant levels achieved through intense restrictions on industrial operations and traffic in the Beijing area during the Olympics, followed by a rapid return to usual practices and more typical pre-Olympic pollutant concentrations after the Games. The use of quasiexperimental design in this panel study to estimate the effect of air pollution on the outcomes reduces the potential for confounding by long-term trends in health. Such confounding by trends in both the health outcomes of interest and air pollution levels over time has been a common challenge in air pollution health effects research. Furthermore, quasiexperimental studies of air pollution health effects are relatively unique, with a few notable exceptions. In the 1980s in Utah Valley, a labor dispute resulted in the intermittent operation of the local steel mill, the primary single source of air pollution in the valley, demonstrating significant associations between air pollution and hospital admissions for respiratory disease (12). A ban on coal sales in Dublin Ireland in 1990 resulted in an immediate and large reduction in particulate matter air pollution and corresponding significant reductions in respiratory and cardiovascular death rates (13). An initial analysis of the 1996 Atlanta Olympics took advantage of transiently reduced traffic levels and found some evidence of associations between changes in ozone and childhood asthma emergency room visits (14). However, compared with conditions in 2008 Beijing, the changes in air pollution were very small, and subsequent analyses were unable to disentangle the combined effects of meteorological conditions, reduced traffic, and intervention-related health effects (15). Related natural experiment studies also include studies of public smoking bans and evidence of related reductions in cardiovascular disease (16). Randomized experimental designs (including controlled exposure human studies) conceptually may be ideal for understanding the underlying mechanisms of air pollution–induced cardiac and pulmonary disease in humans, but obvious practical and ethical concerns significantly limit who can be exposed and the duration and intensity of exposure in such studies. Quasiexperimental designs with high pollution variability, such as the study in this issue of the Journal, allow important mechanistic inferences to be made about longer-term exposures under “real-world” conditions. Collectively, these recent Beijing Olympics studies lend support to the hypothesis that exposure to particulate matter induces inflammation and oxidative stress in the lungs and perhaps other tissues, which increases the tendency toward thrombosis and activates the sympathetic nervous system to increase the risk of cardiovascular death. These studies also suggest that even young and healthy individuals without pulmonary or cardiac disease may be susceptible to these effects of particulate matter, and provide additional promising novel biomarkers for investigating the mechanisms of air pollution–induced disease. Although this study measured multiple pollutants in an effort to understand how individual components of the complex air pollution mixture may impact disease, significant correlations between pollutants and the more general reduction of pollution that occurred during the Beijing Olympics limit the ability to make compelling inferences regarding the individual effects of specific pollutants on these markers. China and other rapidly industrializing nations face tremendous challenges over the next decades, with rapid development often competing with adverse environmental impacts, including increased levels of air pollution. Without serious efforts to control pollution, “business-as-usual” practices are likely lead to dramatic increases in concentrations not only in China, but worldwide. Although the emissions control policies that China has planned to implement may help to avert some of the public health impacts associated with air pollution exposures both locally and globally, many uncertainties remain (17). A recent global atmospheric chemistry model estimates that, without new legislation to prevent growth in air pollution, the average global citizen in 2050 will experience nearly the same air quality as the average East Asian citizen in 2005 (18). Although this model is hopefully a pessimistic scenario, it underscores the need for serious preventive action. This challenge of pollution control in the context of population and economic growth is not limited to developing nations like China. All nations bear the burden of controlling pollutants, which do not respect national borders. From countries with rapid expansion of industry to more established economies, and from Olympic athletes to “mere mortal” healthy young adults such as those evaluated in the study reported in this issue of the Journal, to individuals with preexisting health conditions—all face substantial challenges from air pollution now and in the future.