This resubmission will investigate the associations between exposure to arsenic and other environmental exposures on vascular function and platelet activity among newly diagnosed untreated patients with type 2 diabetes (T2D). Candidate: The primary objective of this application is to support Dr. Jonathan Newman's career development into an independent translational cardiovascular physician-scientist in the field of environmental medicine, diabetes and cardiovascular disease (CVD). Dr. Newman's career goal is to integrate environmental medicine with cardiovascular care such that cardiovascular outcomes can be improved, particularly for patients with T2D and an elevated risk of CVD. His proposed training plan focuses on 4 areas: (1) research methods and analysis; (2) translational laboratory methods; (3) vascular structure and function; 4) environmental medicine and epidemiology. Environment: New York University (NYU) Medical Center is a national leader in research and is one of the top 20 medical schools in NIH funding. The Department of Environmental Medicine at NYU is one of the nation's oldest and foremost centers for research into the health effects of environmental pollution. The Division of Cardiology is a top-ranked division nationally, with the largest research budget in the Department of Medicine at NYU. Research: The population of patients with T2D continues to grow. CVD is the leading cause of morbidity and mortality in patients with T2D. There remains an unmet clinical need to identify modifiable risk factors for CVD in patients with T2D. Exposure to inorganic arsenic and other environmental toxicants may be novel targets for CVD risk reduction for these patients. However, there have been no clinical studies of environmental exposures on vascular function and thrombotic risk among untreated patients newly diagnosed with T2D. To investigate the role of inorganic arsenic and other environmental exposures on vascular function and platelet activity in an urban T2D population, we propose to study a prospective cohort of 100 newly diagnosed individuals with T2D, without the confounding effects of diabetes treatment.
Our specific aims are to: (1) evaluate the association between inorganic arsenic exposure and measures of vascular function; (2) evaluate the association between inorganic arsenic exposure and measures of thrombotic risk; and (3) explore the independent association between environmental exposures other than arsenic and measures of vascular function and thrombotic risk. Our proposed innovative study will prospectively assess the association between biomarkers of vascular and platelet function and environmental exposures, a potential novel risk factor for CVD in patients with T2D. The proposed study will support a robust training plan in translational research and environmental and cardiovascular disease epidemiology, and will support the development of the PI into an independent translational physician-scientist. There is an unmet need to address the excess risk of CVD among patients with T2D, and this study represents an innovative approach to a novel class of risk factors.

Public Health Relevance

Cardiovascular disease is the leading cause of morbidity and mortality for patients with type 2 diabetes. The number of patients with type 2 diabetes in the United States continues to grow. Exposure to inorganic arsenic and other environmental toxicants is common, and may be important for the pathogenesis of cardiovascular disease especially in patients with diabetes. To better understand the links between environmental exposures and cardiovascular disease, we propose to study vascular function and thrombotic risk in a cohort of untreated, newly diagnosed patients with type 2 diabetes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL125991-03
Application #
9398156
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Pandey, Mona
Project Start
2016-01-01
Project End
2020-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
New York University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10010
Newman, Jonathan D; Rockman, Caron B; Kosiborod, Mikhail et al. (2017) Diabetes mellitus is a coronary heart disease risk equivalent for peripheral vascular disease. Am Heart J 184:114-120
Shah, Binita; Ganguzza, Lisa; Slater, James et al. (2017) The Effect of a Vegan versus AHA DiEt in Coronary Artery Disease (EVADE CAD) trial: study design and rationale. Contemp Clin Trials Commun 8:90-98
Newman, Jonathan D; Schwartzbard, Arthur Z; Weintraub, Howard S et al. (2017) Primary Prevention of Cardiovascular Disease in Diabetes Mellitus. J Am Coll Cardiol 70:883-893
Nhek, Sokha; Clancy, Robert; Lee, Kristen A et al. (2017) Activated Platelets Induce Endothelial Cell Activation via an Interleukin-1? Pathway in Systemic Lupus Erythematosus. Arterioscler Thromb Vasc Biol 37:707-716
Newman, Jonathan D; Echagarruga, Christina T; Ogando, Yoscar M et al. (2017) Hyperglycemia enhances arsenic-induced platelet and megakaryocyte activation. J Transl Med 15:55
Newman, Jonathan D; Navas-Acien, Ana; Kuo, Chin-Chi et al. (2016) Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study. Am J Epidemiol 184:806-817
Akintoye, Emmanuel; Shi, Liuhua; Obaitan, Itegbemie et al. (2016) Association between fine particulate matter exposure and subclinical atherosclerosis: A meta-analysis. Eur J Prev Cardiol 23:602-12