2011 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: January 1, 2011 through June 30,2011
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air


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 complete the geocoding of all participants from the Framingham Offspring Cohort Cycles 6-8 and Third Generation Cycles 1-2.  Geocoding of the Offspring Cohort is complete and we anticipate completing geocoding of the Third Generation Cohort by the end of July 2011.

Preliminary analyses have evaluated the impact of short-term exposure to air pollution on vascular function as assessed by flow mediated dilation (FMD) of the brachial artery and baseline brachial artery diameter in the Framingham Offspring Cohort (Cycle 7).  We also have examined the association between short-term exposures to air pollution and repeated measures of blood pressure in this population (Cycles 6-8). We observed inverse associations between pollutant exposures (PM2.5, black carbon [BC], and NO2) and flow mediated dilation (%), which achieved statistical significance for PM2.5  5- and 7-day moving averages, and 1-day averages of NO2.  Models restricted to individuals with diabetes suggested a larger magnitude of association, but wider confidence intervals. No statistically significant associations were observed for baseline diameter. These initial results were presented at the Annual Meeting of the American Heart Association Council on Cardiovascular Disease Epidemiology and Prevention in March 2011, in Atlanta, Georgia.  In our recent blood pressure analyses, no significant associations were observed between ambient pollution levels and systolic, diastolic, or mean arterial pressure.  These results will be presented at the International Society for Environmental Epidemiology meeting in Barcelona, Spain, in September 2011.  Further analyses of both blood pressure and fribromuscular dysplasia (FMD) will incorporate data from the Third Generation when it becomes available.

As an extension of the aims of this project, we evaluated the impact of long-term near-roadway exposure on renal dysfunction in a susceptible population. In this study, we evaluated the impact of living near a major roadway (A1/A2) on estimated glomerular filtration rate (eGFR) in 1,120 subjects hospitalized with acute ischemic stroke.  After adjusting for potential confounders, including clinical and socioeconomic indicators, we found that living closer to a major roadway was associated with a statistically significantly lower eGFR compared with living farther away (p-trend=0.03). When considering distance to roadway as a continuous variable, we found that living <100 m versus >500 m from a major roadway was significantly (p=0.007) associated with a 2.08 mL/min/1.73 m2 (95CI: 0.56- 3.60) lower eGFR.

Future Activities:

Future work will include integrating novel exposure assessment approaches and additional geocoding of Framingham participants into our modeling. We will complete the work we have begun on the vascular component of our project aims, and plan to begin work on examining associations between air pollution and cognitive function in the coming year. In addition, we have begun preliminary work extending 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.

Journal Articles:

No journal articles submitted with this report: View all 53 publications for this subproject

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
  • 2012 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