2013 Progress 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)
Project Period Covered by this Report: August 1, 2012 through July 31,2013
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. 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, we will: (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.

Progress Summary:

Over the past year, we have continued to make progress on our specific aims. As projected on last year’s progress report, we have integrated all relevant exposure data, including spatially resolved model-based PM2.5 data into the Framingham master dataset for Offspring Cycles 6, 7, 8 and Generation 3 Cycles 1 and 2. We continued to work on analyses of both short- and long-term exposures to air pollutants, sources and mixtures on vascular and neurocognitive function including flow-mediated vasodilatation (FMD), flow velocity and peripheral arterial tonometry (PAT). We conducted preliminary analyses of the association between long-term exposures to air pollution sources and mixtures and cognitive outcomes beyond the Mini-Mental Status Examination. We extended our aims to include a detailed evaluation of lung structure and function including pulmonary function tests (FEV1, FVC), diffusing capacity (DLCO), and full chest computed tomography (CT) data to investigate subclinical chronic obstructive lung disease and airway thickening.

We evaluated the impact of residential proximity to a major roadway (primary or secondary highway) and spatially resolved average PM2.5 on brachial artery flow mediated dilation and reactive hyperemia in the Framingham Offspring and Third Generation cohorts (n = 5,146). We found that compared to living 400 m away from a major road, living 50 m from a major roadway was associated with 0.14% lower FMD (95%CI: -0.26%, -0.02%) and an interquartile range (IQR) increase in PM2.5 (1.99 µg/m3) was associated with -0.16% (-0.27,-0.06%) lower FMD%. Living near a major road was not significantly associated with hyperemic flow velocity, but an IQR increase in PM2.5 was associated with -0.70 cm/s lower hyperemic flow (95%CI: -1.36, -0.05 cm/s). Neither residential proximity to a major roadway nor exposure to PM2.5 was associated with baseline brachial diameter nor baseline mean flow velocity. This work will be presented at the International Society of Environmental Epidemiology (ISEE) meeting in Basel, Switzerland, August 2013.

We have conducted analyses investigating associations between short-term exposures to ambient air pollution and micro-vascular function measured with peripheral arterial tonometry in 1940 participants of the Offspring and Third Generation cohorts of the Framingham Heart Study. When analyzing one pollutant at a time without taking into account the context of its mixture and we found depressed micro-vascular function associated only with higher particle number levels for baseline pulse amplitude, but no associations for PM2.5. Using cluster analyses to separate days into 5 distinct clusters or mixtures of air pollution we found strong associations between higher 1-day moving average of PM2.5 and baseline pulse amplitude on days with mixtures characterized by pollution from combustion sources of traffic, heating oil and wood containing higher number of particles (25.0% per 5 µg/m3 of PM2.5 CI 95% 4.6; 49.2). These results will be presented at the 2013 ISEE meeting in Basel, Switzerland in August.

We evaluated associations between short-term exposure to air pollutants and lung function in the Framingham Offspring and Third Generation Cohorts. We found negative associations between 1- and 2-day moving averages of NO2 and O3 and both FEV1 and FVC. A 10 ppb increase in NO2 concentration 1 day prior to testing was associated with a -11.1 mL lower FEV1 (95% CI: -20.2, -2.0) and a 10 ppb increase in O3 1 day prior to testing was associated with a -14.7 mL lower FEV1 (95% CI: -27.2, -2.1). This work will be presented at the ISEE meeting in August 2013. Dr. Mary Rice submitted an NRSA proposal on her work evaluating subclinical COPD and air pollution exposure in Framingham, which was scored in the 8th percentile. 

In addition to our work on the Framingham Study, we have completed related work which builds on the aims of our project. In collaboration with Greg Wellenius at Brown University, we have two papers examining cognitive function and cerebral hemodynamics in the MOBILIZE (Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly) cohort. In the first, published in the Journal of the American Geriatric Society (2012), 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 the second published in Stroke (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. These results were published in Stroke.

We examined the association between residential proximity to high traffic roads and post-stroke mortality among 1,683 patients ≥21 years of age admitted to the Beth Israel Deaconess Medical Center (BIDMC) from January 1999 to October 2008 with neurologist-confirmed ischemic stroke residing in the Boston metropolitan region. Deaths were identified through June 2012. We found that patients living ≤100 m from high traffic roadways at the time of stroke onset had a 20% (95% CI: 1%, 43%) higher rate of post-stroke mortality than patients living > 400m away (p-trend = 0.02). These results were presented at the International Stroke Conference (ISC) in Honolulu, Hawaii in February, 2013, and are now published in the Journal of Stroke and Cerebrovascular Diseases.

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 to 6.7; p = 0.007): a difference comparable in magnitude to the reduction in eGFR observed for a 4-year increase in age in population-based studies. This work has been published in the Journal of Epidemiology and Community Health (2013).

We used the time-stratified case-crossover design to examine the association between apparent temperature and humidity and the risk of ischemic stroke among 1,705 Boston area patients hospitalized with neurologist-confirmed ischemic stroke. The incidence rate ratio of ischemic stroke was 1.09 (95% confidence interval 1.01-1.18) following a 5ºC decrement in average apparent temperature over the 2 days preceding symptom onset. The higher risk associated with cooler temperatures peaked in the first 14 to 34 hours. The association between ischemic stroke and temperature was stronger on days with higher levels of relative humidity. The preliminary results were presented at the ISC meeting in February 2013 and a manuscript describing this work is currently under review.

Future Activities:

Future work will include continuing to integrate additional exposure-measures including particle constituents and additional model-based data into the Framingham master dataset for Offspring Cycles 6, 7, 8 and Generation 3 Cycles 1 and 2. We will complete analyses and publish manuscripts on acute and chronic effects of air pollution measures, including mixtures and sources on vascular outcomes including FMD, flow rates, blood pressure, peripheral arterial tonometry, pulse wave morphology and velocity and biomarkers of inflammation, oxidative stress and hemostasis. In addition, we will complete manuscripts on short- and long-term exposures on pulmonary function and extend this work to include chest CT data to evaluate subclinical pulmonary disease. We will also continue to develop analyses of neurocognitive outcomes.


Journal Articles on this Report : 8 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
Type Citation Sub Project Document Sources
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)
R834798 (2014)
R834798 (Final)
R834798C003 (2013)
R834798C003 (2014)
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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 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 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, Coull BA, Milberg WP, Gryparis A, Schwartz J, Mittleman MA, Lipsitz LA. 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 2012;60(11):2075-2080. R834798 (2012)
    R834798 (2013)
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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)
    R834798 (2014)
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    R834798C002 (Final)
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    R834797 (2016)
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  • Journal Article Wilker EH, Yeh G, Wellenius GA, Davis RB, Phillips RS, Mittleman MA. Ambient temperature and biomarkers of heart failure: a repeated measures analysis. Environmental Health Perspectives 2012;120(8):1083-1087. R834798 (2012)
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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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  • Supplemental Keywords:

    Air pollution, ambient particles, multi-pollutant mixtures, cognitive function, vascular function, inflammation, susceptibility, vulnerability, 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

    Progress and Final Reports:

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