2012 Progress Report: Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingham 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 Framingham 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, 2011 through July 31,2012
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-term 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:

Since funding began, we have worked closely with the Framingham data coordinators to geocode all participants from the Framingham Offspring Cohort Cycles 6-8 (complete) and Third Generation Cycles 1-2. We are working with the exposure assessment team to complete assignment of spatio-temporally resolved residential address-level modeled exposure to particulate matter and black carbon (expected completion September 2012).

In the past year, we have conducted preliminary analyses of the effects of air pollution exposures on vascular outcomes including flow-mediated dilation, flow velocity and blood pressure in the Offspring and Third Generation Cohorts. We also conducted preliminary analyses evaluating the impact of residential distance from an A1 or A2 road on cognitive function as assessed by the Mini-Mental State Exam (MMSE) in the Framingham Offspring Study (n=3,678). Preliminary evidence suggests a nonlinear association between distance to major road and lower cognitive function, but associations did not meet nominal statistical significance. Future analyses will incorporate tests of cognitive function from a more comprehensive neuropsychological battery, including measures such as the Trail Making Test, the Weschler Memory Scale (WMS), Weschler Adult Intelligence Scale (WAIS), and the Wide Range Achievement Test (WRAT).

We also have expanded the aims of the Framingham project and received approval to evaluate markers of inflammation, oxidative stress and hemostasis including: CD40 Ligand, CRP, fibrinogen, IL-6, IL-18, isoprostanes (8-epiPGF2a), LpPla2 (mass and activity), MCP-1, MPO, OPG, P-selectin, and TNF-receptor II. While working on exposure assignment for the Framingham cohorts, we have completed related work that builds on the aims of our project. We evaluated the association between short-term meteorological exposures on biomarkers of inflammation, endothelial function, and heart failure control in a cohort of 100 patients with Class II and III heart failure. In this study, we found that higher 2-day moving average of apparent temperature was associated with elevated levels of brain natriuretic peptide (BNP). Finally, C-reactive protein (CRP) followed similar pattern after 3-day moving average.

In another study, we followed a cohort of 3,886 individuals hospitalized for acute myocardial infarction (AMI) in 64 centers across the United States from 1989 to 1996. Institutionalized patients, those providing only post office boxes, and those whose addresses could not be geocoded were excluded, leaving 3,547 patients eligible for analysis. Addresses were geocoded, and distance to the nearest major roadway was assigned. Cox regression was used to calculate hazard ratios, with adjustment for personal characteristics (age, sex, race, education, marital status, distance to nearest acute care hospital), clinical characteristics (smoking, body mass index, comorbidities, medications), and neighborhood-level characteristics derived from U.S. Census block group data (household income, education, and urbanicity). There were 1,071 deaths after 10 years of followup. In the fully adjusted model, compared with living >1,000 m, hazard ratios (95% confidence interval) for living ≤100 m were 1.27 (1.01-1.60), for 100 to ≤200 m were 1.19 (0.93-1.60), and for 200 to ≤1,000 m were 1.13 (0.99-1.30) (P(trend)=0.016).

We completed analysis of our ongoing study of acute effects of PM2.5 and black carbon, measured at our Boston supersite, in addition to temporal-spatially resolved residential modeled exposure to black carbon on acute ischemic stroke onset. 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 (OR) of ischemic stroke onset was 1.34 (95% CI, 1.13-1.58) (P < 0.001) following a 24-hour period classified as moderate (PM2.5 15-40 μg/m3) by the U.S. Environmental Protection Agency's (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) (P = 0.006) 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.

We also evaluated the impact of long-term near-roadway exposure on renal dysfunction in a susceptible population. In this study, we found that living closer to a major roadway was associated with a significantly lower estimated glomerular filtration rate compared with living farther away. This work currently is under review.

Future Activities:

Future work will include completion of all modeled air pollution data in 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 vascular outcomes including flow mediated dilation, blood pressure, flow rates, peripheral arterial tonometry and biomarkers of inflammation, oxidative stress and hemostasis.

We will extend the aims of our project to evaluate chronic effects of long-term exposure on atherosclerosis in the aorta based on MRI data collected on the Framingham Offspring Cohort from 2002–2006. We also will examine sub-clinical and CT based pulmonary outcomes and a more extensive battery of neurocognitive assessments originally proposed.

 


Journal Articles on this Report : 3 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 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)
R834798 (2013)
R834798 (2014)
R834798 (Final)
R834798C003 (2012)
R834798C003 (2013)
R834798C003 (2014)
R834798C003 (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)
    R834798 (2013)
    R834798 (2014)
    R834798 (Final)
    R834798C003 (2012)
    R834798C003 (2013)
    R834798C003 (2014)
    R834798C003 (Final)
    R832416 (Final)
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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)
    R834798 (2013)
    R834798 (2014)
    R834798 (Final)
    R834798C003 (2012)
    R834798C003 (2013)
    R834798C003 (2014)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
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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

    Relevant Websites:

    http://www.hsph.harvard.edu/clarc/index.html Exit EPA Disclaimer

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2013 Progress Report
  • 2014 Progress Report
  • 2015
  • 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 Framingham 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