ARRA IMPACT REPORT:
Environmental Determinants of Cardiovascular Disease


Public Health Burden
Cardiovascular diseases (CVD) remain the number one cause of death and disability in the United States. While there are several well-established lifestyle risk factors for CVD, such as smoking, diet and physical activity, numerous environmental contaminants have also been shown or are suspected to contribute to CVD-related mortality and disability. Such exposures include air pollution, heavy metals, and organophosphate pesticides.

Basic Research
ARRA-funded basic research projects in environmental cardiovascular diseases are focused on gaining fundamental knowledge on the molecular pathophysiology and vascular changes caused by chronic exposure to heavy metals such as arsenic and pesticides. Research on the contributions of pesticides is focused on understanding the relationship between exposures to pesticides in the rural Deep South and the contributions to the higher mortality of CVD among African Americans.

  • Studies using liver cell culture and transgenic mouse models (apolipoprotein E-knockout) found arsenic exposure to accelerate and exacerbate progression of atherosclerosis. This exacerbation appears to be mediated by activation of pathways involved in immune responses resulting in a hyper-inflammatory state.1
  • Understanding molecular alterations in liver vascular cells are providing possible mechanistic insight into arsenic-induced vascular disease processes.2
  • A field study on proatherogenic oxidized lipidmetabolism, asmeasured by paraxonase-1 (PON1) enzyme in blood samples (of 80 African Americans and 120 Caucasians) using selective pesticides as substrates, suggests that increased PON1 activity is associated with decreased odds of atherosclerosis in a group of African American and Caucasian Southerners.3

Environmental Epidemiology
The development of atherosclerosis, the primary underlying pathogenic process of CVD, begins in early life and continues to progress over an individual’s lifetime, ultimately resulting in CVD in some individuals. Scientists hypothesize chronic exposure to some environmental contaminants during childhood and adolescence may contribute to this process and lead to development of CVD later in life. Studies using early markers of abnormal cardiovascular function will help clarify how early life environmental exposures may lead to future CVD risk. Several ARRA-funded grants are exploring early markers of environmental exposure response in relation to CVD and/or assessing the utility of these markers in studies of young adults and children.

  • Researchers at the University of Southern California conducted ancillary studies within two ongoing studies of the association between lifetime exposure to air pollution and carotid intima media thickness (CMIT) in both college students and elementary-school children (10-12 year olds). With ARRA funds, the researchers were able to objectively measure the extent of carotid atherosclerotic vascular disease in a subset of subjects. Preliminary findings suggest that CIMT measurement is a reliable measure of early atherosclerosis in research involving otherwise healthy young adults and children.4
  • Researchers at Syracuse University have assessed the association between increased lead exposure and vascular function in response to acute stress in children. With ARRA funds scientists were able to conduct proteomic analysis on and to complete the analysis of lipid profiles of stored biological samples. This study reported that children who consumed fish had a significantly better lipid profile that indicated being more heart healthy, but also had higher levels of blood mercury compared to children who did not consume fish. These observations are being readied for publication.5

Contributing NIH Institutes & Centers

  • National Institute of Environmental Health Sciences (NIEHS)

  1. 3R01ES013781-02S1 - BARCHOWSKY, AARON - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
  2. 3R01ES013781-02S1, http://www.ncbi.nlm.nih.gov/pubmed/19349368, http://www.ncbi.nlm.nih.gov/pubmed/21684831 - BARCHOWSKY, AARON - UNIVERSITY OF PITTSBURGH AT PITTSBURGH - PITTSBURGH - PA
  3. 3R21ES015107-03S1, http://www.ncbi.nlm.nih.gov/pubmed/21960140 - CHAMBERS, JANICE ELAINE - MISSISSIPPI STATE UNIVERSITY - MISSISSIPPI STATE - MS
  4. 3R01ES014708-04S1 - AVOL, EDWARD - UNIVERSITY OF SOUTHERN CALIFORNIA - LOS ANGELES - CA
    3R01ES014447-04S1 - AVOL, EDWARD - UNIVERSITY OF SOUTHERN CALIFORNIA - LOS ANGELES - CA
  5. 3R01ES014708-04S1 - AVOL, EDWARD - UNIVERSITY OF SOUTHERN CALIFORNIA - LOS ANGELES - CA