Final Report: Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingharn Offspring and Third Generation Cohorts

EPA Grant Number: R834798C003
Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834798
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Air Pollution Mixtures: Health Effects across Life Stages
Center Director: Koutrakis, Petros
Title: Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingharn Offspring and Third Generation Cohorts
Investigators: Mittleman, Murray , Gold, Diane R. , Schwartz, Joel
Institution: Harvard University
EPA Project Officer: Ilacqua, Vito
Project Period: January 1, 2011 through December 31, 2015 (Extended to December 31, 2016)
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

Long- and short-term exposures to ambient air pollution are associated with adverse acute and chronic cardiovascular and perhaps cognitive function, but these effects are poorly understood. We are using data from the Framingham Offspring and Third Generation Cohorts, well-characterized populations that have not been previously investigated in association with ambient environmental exposures, to: 1) determine whether long-term exposures to ambient pollutants and mixtures are associated with cognitive impairment and cognitive interference; 2) test whether short- and long-term exposures to pollutants, mixtures and sources are associated with acute and chronic vascular and endothelial function; and 3) consider whether markers of biological susceptibility and vulnerability differentially influence these associations, allowing us to identify subpopulations at increased risk for harmful effects of air pollution.

Summary/Accomplishments (Outputs/Outcomes):

We have published a series of manuscripts examining the associations between short- and long-term exposure to ambient air pollution with measures of cognitive function, vascular function, lung function, adiposity, and biomarkers of oxidative stress, inflammation, and glucose homeostasis among participants from the Framingham Heart Study Offspring and Third Generation cohorts. We have also published two manuscripts on analytic methods related to air pollution research. Below we highlight our findings by topic.

Methodology

In Mostofsky et al. (2012), we illustrated several options for modeling the associations between air pollution constituents and health outcomes that could account for the impact of PM2.5 using data from 1,060 participants admitted to the Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA. We examined the associations between levels of constituents and ischemic stroke onset, and explained the differences in interpreting results from each model. We have also shown that the rankings of the association between constituents and ischemic stroke onset were rather consistent across models.

In Mittleman and Mostofsky (2014), we discussed exchangeability in the case-crossover design. Sources of non-exchangeability including confounding and bias arise in cohort and case-control studies when there are differences in the distribution of determinants of the outcome between exposure groups. In case-only studies, this issue is addressed by comparing each individual to his/herself. Although case-only designs use self-matching and only include individuals who develop the outcome of interest, issue of non-exchangeability are identical to those that arise in traditional case-control and cohort studies. In this paper, we described one type of case-only design, the case-crossover design, and we discussed how the concept of exchangeability can be used to understand issues of confounding, carryover effects, period effects and selection bias in case-crossover studies. We described approaches in the design and/or analysis stage that can be used to eliminate or minimize sources of bias.

Cognitive function

In Wilker et al. (2015), we examined the associations between long-term exposure to ambient air pollution and residential proximity to major roadways with measures of brain structure among 943 participants from the Framingham Offspring Cohort who were at least 60 years old. Annual average fine particulate matter (PM2.5) concentrations were estimated using a spatial-temporal satellite model which was capable of estimating PM2.5 concentrations at the participants’ residential addresses at a resolution of 10×10 km2. The continuous volume measures of brain structure include hippocampal volume, white matter hyperintensity, and total cerebral brain volume, and the binary outcomes include extensive white matter hyperintensity volume for age and covert brain infarcts. In this study, we found that an interquartile increase in PM2.5 (2 µg/m3) was associated with -0.32% (95% CI: -0.59, -0.05) smaller total cerebral brain volume and 1.46 (95% CI: 1.10, 1.94) higher odds of covert brain infarcts. Living further away from a major roadway was associated with 0.10 (95% CI: 0.01, 0.19) greater log-transformed white matter hyperintensity volume for an interquartile range difference in distance, but no clear pattern of association was observed for extensive white matter.

Vascular function

In Wilker et al. (2014a), we examined associations between long-term exposure to PM2.5 and residential proximity to major roadways with baseline brachial artery diameter, mean flow velocity, flow-mediated dilation %, and hyperemic flow velocity. In this study, we found that an interquartile range difference in annual average PM2.5 (1.99 µg/m3) was associated with 0.16% (95% CI: 0.05, 0.27) lower flow-mediated dilation% and 0.72 (95% CI: 0.06, 1.38) cm/s lower hyperemic flow velocity%. We also found that living closer to major roadways was associated with lower flow-mediated dilation (-0.32%, 95% CI: -0.58%, -0.06%). However, results for hyperemic flow velocity had wide CIs: -0.68 cm/s (95% CI: -2.29, 0.93).

In Ljungman et al. (2014), we examined associations of short-term exposure to ambient air pollutants measured at the Harvard Boston Supersite with measures of hyperemic response to ischemia and baseline pulse amplitude, a measure of arterial tone among 2,369 study participants. For the air pollutants we measured PM2.5, black carbon (BC), sulfate (SO42-), nitrogen oxides (NOx), and ozone (O3). We found that higher exposure to air pollutants was associated with higher baseline pulse amplitude. In particular, a higher 3-day average of PM2.5, black carbon and higher particle number were associated with higher baseline pulse amplitude by 6.4% per 5 μg/m3 PM2.5 (95% CI: 2.0, 10.9), 7.5% per 0.4 μg/m3 black carbon (95% CI: 1.9, 13.6) and 13.2% per 15,000 #/cm3 particle number (95% CI: 4.7, 22.5). However, there were no consistent associations between the air pollution exposures assessed and hyperemic response.

As an extension of our work on digital microvascular function, we used a k-means approach to construct five distinct pollution mixtures from elemental analyses of particle filters, air pollution monitoring data, and meteorology, and examined whether the clusters modify the associations between PM2.5 and baseline pulse amplitude (Ljungman et al., 2016). We found that PM2.5 on days with mixtures containing a relatively high number of particles compared to mass concentration and with local sources of combustion such as traffic, commercial heating oil and wood burning was more strongly associated with higher baseline pulse amplitude than PM2.5 other days. In particular, higher PM2.5 on days with low mass concentrations but high proportion of ultrafine particles from traffic was associated with 18% (95% CI: 4.6, 33) higher baseline pulse amplitude per 5 μg/m3 and days with high contributions of oil and wood combustion with 16% (95% CI: 0.2, 34) higher baseline pulse amplitude. We observed no variation in associations of PM2.5 with hyperemic response to ischemia observed across air pollution clusters.

Atherosclerosis

In Dorans et al. (2016), we examined residential proximity to major roadways and annual average PM2.5 with coronary artery calcium Agatston score (CAC), and CAC progression. In this study, we used an updated spatial-temporal model which could estimate average PM2.5 concentrations at participants’ residential addresses at the solution of 1×1 km2. We observed a weak association of residential proximity to a major roadway with average annual change in CAC: living further from a roadway was associated with a higher average annual change in CAC. Otherwise, we found no associations with odds of having detectable CAC, average natural log-transformed CAC, or detectable CAC progression. In a following study (Dorans et al., 2017), we also examined associations with aortic calcium Agatston score (TAC) and abdominal aortic calcium Agatston score (AAC). Among 3,506 participants, we did not find consistent associations of major roadway proximity or PM2.5 (1×1 km2) with the presence or extent of TAC or AAC. And there were no association with incident AAC or annual change in AAC.

Lung function

In Rice et al. (2013), we investigated associations of short-term exposure to PM2.5, NO2 and O3 measured at the Harvard Supersite with pulmonary function testing. Among 3,262 participants, we found negative associations with FEV1 and FVC for exposure to each of the 3 criteria pollutants within current EPA standards. Exposure to pollutant concentrations in the “moderate” range of the EPA Air Quality Index was associated with a 20.1 ml lower FEV1 for PM2.5 (95% CI: 233.4, 26.9), a 30.6 ml lower FEV1 for NO2 (95% CI: 260.9, 20.2), and a 55.7-ml lower FEV1 for O3 (95% CI: 2100.7, 210.8) compared with the “good” range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC.

In Rice et al. (2015), we examined long-term exposure to PM2.5 (10×10 km2) and residential proximity to major roadways with measures of lung function, including FEV1, FVC, and FEV1/FVC among 6,339 participants. In this study, we found that living less than 100 m from a major roadway was associated with a 23.2 ml (95% CI: 244.4, 21.9) lower FEV1 and a 5.0 ml/year (95% CI: 29.0, 20.9) faster decline in FEV1 compared with more than 400 m. Each 2 mg/m3 increase in average of PM2.5 was associated with a 13.5 ml (95% CI: 226.6, 20.3) lower FEV1 and a 2.1 ml/year (95% CI: 24.1, 20.2) faster decline in FEV1. The associations with FVC were similar. Associations with FEV1/FVC ratio were weak or absent.

We have also examined associations of long-term exposure to PM2.5 (1×1 km2) and residential proximity to major roadways with CT-measured lung volume, mass, density, visual emphysema, airway size, and airway wall area (Rice et al., 2017; under review). In this study, we found that living closer to a major road was associated with a 58.2 ml (95% CI: 10.7, 105.6) higher lung volume for the 25th vs 75th percentile of distance.

Oxidative stress and inflammatory biomarkers

In Li et al. (2016b) we examined associations of short-term exposure to ambient air pollution with biomarkers of oxidative stress (myeloperoxidase and urinary creatinine-indexed 8-epi-PGF2a) among 2,350 participants from the Framingham Offspring Cohort examination 7 and 8. We found positive associations of PM2.5 and black carbon with myeloperoxidase across multiple moving averages. Additionally, 2- to 7-day moving averages of PM2.5 and SO42- were consistently positively associated with 8-epi-PGF2a. In a following study, we have also examined the associations with systemic inflammation biomarkers (CRP, tumor necrosis factor receptor 2 (TNFR2), interleukin-6, fibrinogen, and TNFα) (Li et al., 2017; under review). We found that the 3- to 7-day moving averages of PM2.5 and SO42- were positively associated with CRP concentrations. For example, a 5 µg/m3 higher 5-day moving average PM2.5 was associated with 4.2% (95% CI: 0.8, 7.6) higher circulating CRP. Positive associations were also observed for NOx with interleukin-6, and for BC, SO42-, and ozone with TNFR2. However, BC, SO42-, and NOx were negatively associated with fibrinogen, and SO42-was negatively associated with TNFα.

Glucose homeostasis and obesity

In Li et al. (2017; under review), we investigated the associations of both short- and long-term exposure to ambient air pollution and measures of glucose homeostasis, including glucose, hemoglobin A1c, insulin, adiponectin, resistin, and leptin. We also calculated HOMA-IR. The annual average PM2.5 was estimated using the updated spatial temporal model (1×1 km2). We found that participants who lived 64 m (25th percentile) from a major roadway had 0.27 mg/dl (95% CI: 0.05, 0.49) higher fasting glucose than participants who lived 413 m (75th percentile) away. Longer day moving averages of black carbon and nitrogen oxides were positively associated with fasting glucose whereas the associations for ozone were negative. However, associations for annual average PM2.5 (1×1 km2) were generally null.

We have also investigated associations of annual average PM2.5 (1×1 km2) and residential proximity with body mass index and CT measures of abdominal adiposity and liver fat (Li et al., 2016a and 2017). We examined associations for subcutaneous and visceral adipose tissue volumes, and found that Participants who lived 60 m from a major roadway had 0.37 kg/m2 higher body mass index (95% CI: 0.10, 0.65), 78.4 cm3 higher subcutaneous adipose tissue (95% CI: 4.5, 152.3), and 41.8 cm3 higher visceral adipose tissue (95% CI: 24.7, 88.2) than those who lived 440 m away (Li et al., 2016a). We also examined associations for liver-to-phantom ratio (LPR), a measure of liver fat and lower values of LPR represent more liver fat (Li et al., 2017). We found that participants who lived 58 m (25th percentile) from major roadways had lower LPR (β=-0.003, 95%CI: -0.006, -0.001) and higher prevalence of hepatic steatosis (prevalence ratio=1.16, 95% CI: 1.05, 1.28) than those who lived 416 m (75th percentile) away. The annual average PM2.5 was not associated with liver fat measures.

Projects additional to the Framingham Heart Study

In addition to our work on the Framingham Heart Study, with the support of the grant, we developed collaborations with researchers in other institutions and completed projects that are related to our primary aims. These additional studies covered a wide range of the adverse health effects of ambient air pollution, including cerebrovascular function, cognitive function, and renal function.

In Rosenbloom et al. (2012), we followed a cohort of 3,886 individuals hospitalized for acute myocardial infarction in 64 Centers across the U.S. from 1989 to 1996. Addresses were geocoded, and distance to the nearest major roadway was assigned. Cox regression was used to calculate hazard ratios, with adjustment for personal, clinical and neighborhood-level characteristics. There were 1,071 deaths after 10 years of follow-up. In the fully adjusted model, compared with living > 1,000 m, hazard ratio for living ≤ 100 m was 1.27 (95% CI: 1.01-1.60), for 100 to ≤ 200 m was 1.19 (95% CI: 0.93-1.60), and for 200 to ≤ 1,000 m was 1.13 (95% CI: 0.99-1.30).

In Wilker et al. (2012), we inves­tigated the associations of ambient tem­perature with four biomarkers of heart failure including B-type natriuretic peptide (BNP), CRP, tumor necrosis factor (TNF), and Endothelin-1 in a in a cohort of 100 patients with Class II and III heart failure. In this study, we found that higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5 ºC change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% (95% CI: 1.1, 22.5) and 11.4% (95% CI: 1.2, 22.5) higher BNP. A 5 ºC change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2) higher CRP. No clear associations with TNF or endothelin-1 were observed.

In Wilker et al. (2013), we examined the associations between distance to the nearest high-traffic roadway and mortality among 1,683 patients ≥ 21 years old admitted to BIDMC with ischemic stroke between 1999 and 2008. We observed higher post-stroke mortality among people living closer to high-traffic roadways. Patients living 100 m or less from high-traffic roadways had a 20% (95% CI: 1, 43) higher rate of post-stroke mortality than patients living more than 400 m away.

In Lue et al. (2013), we also evaluated the impact of long-term near- roadway exposure on renal dysfunction in a population of 1,103 consecutive Boston-area patients hospitalized with confirmed ischemic stroke. In this study, we found that patients living closer to a major roadway had lower estimated glomerular filtration rate (eGFR) than patients living farther away. Comparing patients living 50 m versus 1,000 m from a major roadway was associated with a 3.9 ml/min/1.73 m2 lower eGFR (95% CI: 1.0-6.7): a difference comparable in magnitude to the reduction in eGFR observed for a 4-year increase in age in population-based studies.

In Wellenius et al. (2012b), we reviewed the medical records of 1,705 Boston area patients hospitalized with neurologist-confirmed ischemic stroke and abstracted data on the time of symptom onset and clinical characteristics. The estimated odds ratio of ischemic stroke onset was 1.34 (95% CI: 1.13-1.58) following a 24-hour period classified as moderate (PM2.5: 15-40 μg/m3) by the EPA Air Quality Index compared with a 24-hour period classified as good (≤ 15 μg/m3). Considering PM2.5 levels as a continuous variable, we found the estimated odds ratio of ischemic stroke onset to be 1.11 (95% CI: 1.03-1.20) per interquartile range increase in PM2.5 levels (6.4 μg/m3). The increase in risk was greatest within 12 to 14 hours of exposure to PM2.5 and was most strongly associated with markers of traffic-related pollution.

In Mostofsky et al. (2014), we conducted a time-stratified case-crossover study of 1,705 patients residing in the Boston metropolitan region that were hospitalized with neurologist-confirmed ischemic stroke to evaluate whether changes in temperature trigger an ischemic stroke in the following hours and days and whether humid days are particularly harmful. We found that the incidence rate ratio of ischemic stroke was 1.09 (95% CI: 1.01-1.18) times higher following a 5 ºC decrement in average apparent temperature over the 2 days preceding symptom onset. The higher risk associated with cooler temperatures peaked in the first 14-34 hours. There was no statistically significant difference in the association between temperature and ischemic stroke across seasons. The risk of ischemic stroke was not meaningfully different across subgroups of patients defined by health characteristics. The association between ischemic stroke and ambient temperature was stronger on days with higher levels of relative humidity.

In Wilker et al. (2014b), we explored associations of residential proximity to green space with all-cause mortality among patients ≥ 21years old who were admitted to BIDMC between 1999 and 2008 with acute ischemic stroke. There were 929 deaths among 1,645 patients with complete data. We found that the hazard ratio comparing patients living in locations in the highest quartile of green space to the lowest quartile was 0.78 (95% CI: 0.63–0.97). This association remained statistically significant after adjustment for residential proximity to a high-traffic road.

In Wilker et al. (2016), we examined associations between exposures to PM2.5 and residential proximity to major roads and markers of small vessel disease among 236 participants in the Massachusetts Alzheimer’s Disease Research Center Longitudinal Cohort participated in neuroimaging studies. We measured brain parenchymal fraction (BPF), white matter hyperintensities (WMH), and cerebral microbleeds. In this study, we found no associations between living closer to a major roadway or for a 2 µg/m3 increment in PM2.5 and smaller BPF, greater WMH volume, or higher odds of microbleeds. However, a 2 µg/m3 increment in PM2.5 was associated with -0.19 (95% CI: -0.37, -0.005) lower natural log-transformed WMH volume. Other associations had wide confidence intervals.

In collaboration with Dr. Greg Wellenius at Brown University, we examined associations of air pollution with cognitive function (Wellenius et al., 2012a), cerebral hemodynamics (Wellenius et al., 2013), leptin (Wang et al., 2014a), and depressive symptoms (Wang et al., 2014b) in the MOBILIZE (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly) cohort. In Wellenius et al. (2012a), we found that residential proximity to a major roadway was associated with poorer performance on cognitive tests of verbal learning and memory, psychomotor speed, language, and executive function, with those residing within 100 m of a major roadway having the worst performance in general. In Wellenius et al. (2013), we used transcranial Doppler ultrasound to measure beat-to-beat flow velocity in the middle cerebral artery at rest and in response to changes in end-tidal CO2 and arterial blood pressure. In this cohort, exposure to PM2.5 during the previous 28 days was associated with higher resting cerebrovascular resistance and lower cerebral blood flow velocity. In Wang et al. (2014a), we examined associations between long-term exposure to traffic pollution and serum leptin in the MOBILIZE Boston Study, a prospective cohort study in older adults. In this study, we found evidence that leptin was associated with annual mean residential black carbon levels but not with residential distance to nearest major roadway. In Wang et al. (2014b), we investigated the association between exposure to ambient air and traffic pollu­tion and the presence of depressive symptoms among 732 Boston-area adults ≥ 65 years of age. The depressive symptoms were assessed during home interviews using the Revised Center for Epidemiological Studies Depression Scale (CESD-R). In this study, we found no evidence of a positive association between depressive symptoms and long-term exposure to traffic pollution or short-term changes in pollutant levels. For example, we found an odds ratio of CESD-R score ≥ 16 of 0.67 (95% CI: 0.46, 0.98) per interquartile range (3.4 μg/m3) increase in PM2.5 over the 2 weeks preceding assessment.

Finally, in Gold and Mittleman (2013), we completed a literature review on the cardiovascular effects of air pollution and provided a selective update on new findings (2010-2012) in human epidemiological and controlled human exposure research. We also extended the American Heart Association 2010 review of potential approaches to protection against the cardiovascular effects of air pollution at the individual, community, and public policy levels. We also included an update on sources of vulnerability and susceptibility. In Ljungman and Mittleman (2014), we assessed the current evidence on the association of air pollution exposure with incidence of ischemic and hemorrhagic stroke considering long-term and short-term exposure to ambient pollutants. We concluded that studies of both long-term and short-term air pollution exposure suggest consistent evidence of increased risk of ischemic stroke and moderately consistent evidence supporting an association with hemorrhagic stroke, and a few studies exploring susceptible subgroups have indicated stronger associations in individuals with several cardiovascular risk factors, diabetes mellitus, previous stroke, and of older age.

Conclusions:

Throughout our work, we have shown that in the Northeastern region of the United States, where the levels of ambient air pollution were relatively low, exposure to higher levels of ambient air pollution were associated with adverse health measures of brain structure and function, vascular function, lung function, artery calcification, adiposity, and higher levels of biomarkers of oxidative stress, systemic inflammation, and glucose homeostasis. The observational nature of our studies warrants future longitudinal studies to confirm or refute our findings.


Journal Articles on this Report : 31 Displayed | Download in RIS Format

Other subproject views: All 53 publications 36 publications in selected types All 36 journal articles
Other center views: All 410 publications 347 publications in selected types All 347 journal articles
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Journal Article Gold DR, Mittleman MA. New insights into pollution and the cardiovascular system: 2010 to 2012. Circulation 2013;127(18):1903-1913. R834798 (2013)
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  • Journal Article Lue S-H, Wellenius GA, Wilker EH, Mostofsky E, Mittleman MA. Residential proximity to major roadways and renal function. Journal of Epidemiology & Community Health 2013;67(8):629-634. R834798 (2013)
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  • Journal Article Mittleman MA, Mostofsky E. Exchangeability in the case-crossover design. International Journal of Epidemiology 2014;43(5):1645-1655. R834798 (2014)
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  • Journal Article Mostofsky E, Wilker EH, Schwartz J, Zanobetti A, Gold DR, Wellenius GA, Mittleman MA. Short-term changes in ambient temperature and risk of ischemic stroke. Cerebrovascular Diseases Extra 2014;4(1):9-18. R834798 (2014)
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  • Journal Article Rice MB, Ljungman PL, Wilker EH, Gold DR, Schwartz JD, Koutrakis P, Washko GR, O'Connor GT, Mittleman MA. Short-term exposure to air pollution and lung function in the Framingham Heart Study. American Journal of Respiratory and Critical Care Medicine 2013;188(11):1351-1357. R834798 (Final)
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  • Journal Article Rosenbloom JI, Wilker EH, Mukamal KJ, Schwartz J, Mittleman MA. Residential proximity to major roadway and 10-year all-cause mortality after myocardial infarction. Circulation 2012;125(18):2197-2203. R834798 (2012)
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  • Journal Article Wang Y, Eliot MN, Kuchel GA, Schwartz J, Coull BA, Mittleman MA, Lipsitz LA, Wellenius GA. Long-term exposure to ambient air pollution and serum leptin in older adults: results from the MOBILIZE Boston Study. Journal of Occupational and Environmental Medicine 2014;56(9):e73-e77. R834798 (Final)
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  • Journal Article Wellenius GA, Burger MR, Coull BA, Schwartz J, Suh HH, Koutrakis P, Schlaug G, Gold DR, Mittleman MA. Ambient air pollution and the risk of acute ischemic stroke. Archives of Internal Medicine 2012;172(3):229-234. R834798 (2012)
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  • Journal Article Wellenius GA, Boyle LD, Wilker EH, Sorond FA, Coull BA, Koutrakis P, Mittleman MA, Lipsitz LA. Ambient fine particulate matter alters cerebral hemodynamics in the elderly. Stroke 2013;44(6):1532-1536. R834798 (2013)
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  • Journal Article Wilker EH, Mostofsky E, Lue S-H, Gold D, Schwartz J, Wellenius GA, Mittleman MA. Residential proximity to high-traffic roadways and poststroke mortality. Journal of Stroke & Cerebrovascular Diseases 2013;22(8):e366-e372. R834798 (2013)
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  • Journal Article Wilker EH, Wu C-D, McNeely E, Mostofsky E, Spengler J, Wellenius GA, Mittleman MA. Green space and mortality following ischemic stroke. Environmental Research 2014;133:42-48. R834798 (2014)
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  • Journal Article Wilker EH, Ljungman PL, Rice MB, Kloog I, Schwartz J, Gold DR, Koutrakis P, Vita JA, Mitchell GF, Vasan RS, Benjamin EJ, Hamburg NM, Mittleman MA. Relation of long-term exposure to air pollution to brachial artery flow-mediated dilation and reactive hyperemia. American Journal of Cardiology 2014;113(12):2057-2063. R834798 (2014)
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  • Journal Article Wilker EH, Preis SR, Beiser AS, Wolf PA, Au R, Kloog I, Li W, Schwartz J, Koutrakis P, DeCarli C, Seshadri S, Mittleman MA. Long-term exposure to fine particulate matter, residential proximity to major roads and measures of brain structure. Stroke 2015;46(5):1161-1166. R834798 (2015)
    R834798 (Final)
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  • Full-text from PubMed
  • Abstract from PubMed
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  • Full-text: Stroke-Full Text HTML
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  • Abstract: Stroke-Abstract
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  • Other: Stroke-Full Text PDF
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  • Journal Article Wilker EH, Martinez-Ramirez S, Kloog I, Schwartz J, Mostofsky E, Koutrakis P, Mittleman MA, Viswanathan A. Fine particulate matter, residential proximity to major roads, and markers of small vessel disease in a memory study population. Journal of Alzheimer's Disease 2016;53(4):1315-1323. R834798 (Final)
    R834798C003 (Final)
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  • Journal Article Ljungman PL, Wilker EH, Rice MB, et al. Short-term exposure to air pollution and digital vascular function. Am J Epidemiol. 2014a;180:482-489. R834798C003 (Final)
    R834798C004 (Final)
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  • Journal Article Wang, Y., Eliot, M.N., Koutrakis, P., Gryparis, A., Schwartz, J.D., Coull, B.A., Mittleman, M.A., Milberg, W.P., Lipsitz, L.A., and Wellenius, G.A. (2014). Ambient Air Pollution and Depressive Symptoms in Older Adults:Results from the MOBILIZE Boston Study. Environmental Health Perspectives 122, 553 – 558. R834798C003 (Final)
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    Journal Article Wang, Y., Eliot, M.N., Kuchel, G.A., Schwartz, J., Coull, B.A., Mittleman, M.A., Lipsitz, L.A., and Wellenius, G.A. (2014). Long-Term Exposure to Ambient Air Pollution and. R834798C003 (Final)
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    Journal Article Mostofsky, E., Schwartz, J., Coull, B., Koutrakis, P., Wellenius, G.A., Suh, H.H., Gold, D.R., and Mittleman, M.A. (2012). Modeling the Association between Particle Constituents of Air Pollution and Health Outcomes. American Journal of Epidemiology 176, 317 – 326. R834798C002 (Final)
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    Journal Article Wellenius, G.A., Boyle, L.D., Coull, B.A., Milberg, W.P., Gryparis, A., Schwartz, J., Mittleman, M.A., and Lipsitz, L.A. (2012a). Residential Proximity to Nearest Major Roadway and Cognitive Function in Community-Dwelling Seniors:Results from the MOBILIZE Boston Study. Journal of the American Geriatric Society 60, 2075–2080. R834798C003 (Final)
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    Journal Article Wellenius, G.A., Wilhelm-Benartzi, C.S., Wilker, E.H., Coull, B.A., Suh, H.H., Koutrakis, P., and Lipsitz, L.A. (2012c). Ambient Particulate Matter and the Response to Orthostatic Challenge in the Elderly:The Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly (MOBILIZE) of Boston Study. Hypertension 59, 558-563. R834798C003 (Final)
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    Journal Article Ljungman PL, Mittleman MA. Ambient air pollution and stroke. Stroke. 2014b;45:3734-3741. R834798C003 (Final)
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    Journal Article Cole, T.B., J.C. Fisher, T.M. Burbacher, L.G. Costa, and C.E. Furlong, Neurobehavioral assessment of mice following repeated postnatal exposure to chlorpyrifos-oxon. Neurotoxicol Teratol, 2012. 34(3):p. 311-322. R834798C003 (Final)
    R834514C004 (Final)
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    Journal Article Wilker, E.H., Yeh, G., Wellenius, G.A., Davis, R.B., Phillips, R.S., and Mittleman, M.A. (2012). Ambient Temperature and Biomarkers of Heart Failure:A Repeated Measures Analysis. Environmental Health Perspectives 120, 1083 – 1087. R834798C003 (Final)
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    Journal Article Serum Leptin in Older Adults:Results from the MOBILIZE Boston Study. Journal of Occupational and Environmental Medicine 56, e73-e77. R834798C003 (Final)
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    Journal Article Rice MB, Ljungman PL, Wilker EH, et al. Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham Heart Study. Am J Respir Crit Care Med. 2015;191:656-664. R834798C003 (Final)
    R834798C004 (Final)
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    Journal Article Dorans KS, Wilker EH, Li W, et al. Residential proximity to major roads, exposure to fine particulate matter and aortic calcium:The Framingham Heart Study, a cohort study. BMJ open. 2017;7:e013455. R834798C003 (Final)
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    Journal Article Dorans KS, Wilker EH, Li W, et al. Residential proximity to major roads, exposure to fine particulate matter, and coronary artery calcium:The Framingham Heart Study. Arterioscler Thromb Vasc Biol. 2016. R834798C003 (Final)
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    Journal Article Li W, Dorans KS, Wilker EH, et al. Residential proximity to major roadways, fine particulate matter, and adiposity:The Framingham Heart Study. Obesity. 2016a;24:2593-2599. R834798C003 (Final)
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    Journal Article Li W, Dorans KS, Wilker EH, et al. Residential proximity to major roadways, fine particulate matter, and hepatic steatosis:The Framingham Heart Study. Am J Epidemiol. 2017. R834798C003 (Final)
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    Journal Article Li W, Wilker EH, Dorans K, Rice MB, Schwartz J, Coull B, Koutrakis P, Gold DR, Keaney JFJ, Lin H, Vasan R, Benjamin EJ, Mittleman MA. Short-Term Exposure to Air Pollution and Biomarkers of Oxidative Stress:The Framingham Heart Study. JournAL Of the American Heart Association 2016; DOI:10.1161/JAHA.115.002742:1-8. R834798 (2016)
    R834798C003 (Final)
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    Journal Article Ljungman PL, Wilker EH, Rice MB, Austin E, Schwartz J, Gold DR, Koutrakis P, Benjamin EJ, Vita JA, Mitchell GF, Vasan RS, Hamburg NM, Mittleman MA. The Impact of Multipollutant Clusters on the Association Between Fine Particulate Air Pollution and Microvascular Function. Epidemiology 2016; 27:194-201. R834798 (2016)
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    Supplemental Keywords:

    Scientific Discipline, Air, air toxics, Health Risk Assessment, Air Pollution Effects, Biochemistry, Environmental Monitoring, Biology, ambient air quality, children's health, complex mixtures, health effects, particulates, sensitive populations, air pollutants, biological sensitivities, exposure and effects, lung epithelial cells, susceptible populations, chemical composition, neurotoxicity, human exposure, toxicity, coronary artery disease, cardiopulmonary, cardiotoxicity, environmental effects, human health, mortality

    Relevant Websites:

    The Harvard CLARC website, with links to investigators, projects, reports and publications can be found at:  Air Pollution Mixtures: Health Effects Across Life Stages Exit

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report

  • Main Center Abstract and Reports:

    R834798    Air Pollution Mixtures: Health Effects across Life Stages

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834798C001 Relative Toxicity of Air Pollution Mixtures
    R834798C002 Cognitive Decline, Cardiovascular Changes, and Biological Aging in Response to Air Pollution
    R834798C003 Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingharn Offspring and Third Generation Cohorts
    R834798C004 Longitudinal Effects of Multiple Pollutants on Child Growth, Blood Pressure and Cognition
    R834798C005 A National Study to Assess Susceptibility, Vulnerability, and Effect Modification of Air Pollution Health Risks