The overall long range goal of this program project is to generate novel data on the causal mechanisms of mental stress ischemia (MSI), to identify new endophenotypes susceptible to MSI, to determine the clinical importance of MSI in a diverse and contemporary patient population with stable coronary artery disease (CAD), and to identify genotype variants that may put individuals at increased risk for MSI. This program project will consist of three projects and three cores. We will study 650 participants with broadly defined CAD. We propose to examine rain, genetic, vascular, hormonal, and behavioral correlates of MSI and their potential role in future cardiac events. This project will lead to new knowledge related to the mechanisms of MSI which could have tremendous influence on the ability to successfully treat this phenomenon. Project 1: Mental Stress Ischemia: Prognosis and Genetic Influences. Dr. Sheps, PI, will study the relationship between MSI and cardiovascular outcomes and the role of genetic factors on MSI susceptibility. He will perform exercise and mental stress testing, genetic studies and follow up studies on all 650 patients. Project 2: Vascular Responses During Mental Stress. Dr. Arshed Quyyumi, PI, will study vascular mechanisms, i.e., abnormal vascular reactivity and pro-inflammatory responses as they relate to mental stress and MSI. He will examine peripheral vascular function in the same cohort of patients during mental stress, and coronary vascular responses in a sub group of 80 patients. Studies will be repeated at year two of follow-up to assess potential influences on disease progression. Project 3: Depression and Mental Stress Ischemia: Brain Mechanisms. Dr. Viola Vaccarino, PI, will study brain mechanisms, with a focus on neurobiological pathways related to depression. She will examine the link between depression and MSI in the whole PPG population and will perform brain imaging and neuroendocrine assessments in a subgroup of 160 patients. These studies will be supported by an Administrative and Laboratory Core, an Imaging Core, and a Biostatistics and Data Management Core. The knowledge gained from this program project should lead to

Public Health Relevance

This research has potential to identify genetic variants, vascular abnormalities and neuropsychological features that place individuals at high risk for development of mental stress ischemia and therefore adverse outcomes. If successful, this research will contribute in significant ways to the development of the new field of personalized medicine in which individuals at high risk can be identified early in the disease process and targeted for preventative interventions.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL101398-03
Application #
8318063
Study Section
Special Emphasis Panel (ZHL1-PPG-Z (F3))
Program Officer
Kaufmann, Peter G
Project Start
2010-09-01
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$2,213,556
Indirect Cost
$785,455
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Rooks, Cherie R; Ibeanu, Ijeoma; Shah, Amit et al. (2016) Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing. Brain Behav Immun 51:92-8
Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina et al. (2016) Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes. Circ Res :
Patel, Riyaz S; Ghasemzadeh, Nima; Eapen, Danny J et al. (2016) Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease. Circulation 133:361-9
Vaccarino, Viola; Bremner, J Douglas (2016) Behavioral, emotional and neurobiological determinants of coronary heart disease risk in women. Neurosci Biobehav Rev :
Corban, Michel T; Hung, Olivia Y; Mekonnen, Girum et al. (2016) Elevated Levels of Serum Fibrin and Fibrinogen Degradation Products Are Independent Predictors of Larger Coronary Plaques and Greater Plaque Necrotic Core. Circ J 80:931-7
Hayek, Salim S; MacNamara, James; Tahhan, Ayman S et al. (2016) Circulating Progenitor Cells Identify Peripheral Arterial Disease in Patients With Coronary Artery Disease. Circ Res 119:564-71
Shah, Amit; Vaccarino, Viola (2015) Heart Rate Variability in the Prediction of Risk for Posttraumatic Stress Disorder. JAMA Psychiatry 72:964-5
Pimple, Pratik; Shah, Amit J; Rooks, Cherie et al. (2015) Angina and mental stress-induced myocardial ischemia. J Psychosom Res 78:433-7
Pimple, Pratik; Shah, Amit; Rooks, Cherie et al. (2015) Association between anger and mental stress-induced myocardial ischemia. Am Heart J 169:115-21.e2
Corban, Michel T; Hung, Olivia Y; Eshtehardi, Parham et al. (2014) Myocardial bridging: contemporary understanding of pathophysiology with implications for diagnostic and therapeutic strategies. J Am Coll Cardiol 63:2346-55

Showing the most recent 10 out of 20 publications