Myocardial ischemia, an important measure of the clinical activity of ischemic heart disease (IHD), occurs when the myocardium does not receive enough blood supply resulting from either coronary constriction or high demand or both. Mental stress has been shown to be a trigger inducing myocardial ischemia. Mental stress-induced myocardial ischemia (MSIMI) is suggested due to reduction of coronary blood supply rather than increased myocardium demand. MSIMI is clinically important as to its high predictability for increased adverse cardiac events. Despite this, no pharmacological modalities have been proven to improve MSIMI. Previous studies suggest stress management and exercise may be beneficial. Depression, a particularly prevalent problem in patients with cardiovascular diseases, is proven to be a risk factor for increased adverse cardiac outcomes in patients with IHD, independent of conventional cardiac risks. Our recent study demonstrated that depression symptoms were associated with increased likelihood of MSIMI, which is possibly an underlying mechanism of depression adversely affect the prognosis of IHD. It has been suggested that selective serotonin reuptake inhibitors (SSRIs) may improve cardiac outcome which may not be related to improvement of depression. One mechanism of SSRIs that may be cardiac protective is related to their ability of reducing platelet activity. The proposed project plans to investigate the response of MSIMI to sertraline compared to placebo. Further, it plans to determine whether the modification of MSIMI is related to improvement of depression symptoms, cardiovascular reactivity to stress, and/or of platelet aggregation. To achieve these goals, we propose a randomized, placebo-controlled single center study using sertraline versus placebo for clinically stable IHD patients with MSIMI. A total of 120 IHD patients with MSIMI will be equally randomized into sertraline or placebo for 6 weeks. Ischemic activity during mental stress and exercise testing, cardiovascular reactivity, platelet activity, depression, anxiety, hostility, and level of perceived stress will be assessed at baseline and at the end of the 6-week intervention. This study will improve the outcome of IHD patients by helping us to better understand how successful the treatment of sertraline affects the cardiovascular system. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL085704-03
Application #
7491122
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Jobe, Jared B
Project Start
2006-09-01
Project End
2012-06-30
Budget Start
2008-08-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$574,208
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Feigal, Jacob P; Boyle, Stephen H; Samad, Zainab et al. (2017) Associations between positive emotional well-being and stress-induced myocardial ischemia: Well-being scores predict exercise-induced ischemia. J Psychosom Res 93:14-18
Jiang, Wei; Boyle, Stephen H; Ortel, Thomas L et al. (2015) Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study. Am Heart J 169:496-507.e1
Boyle, Stephen H; Matson, Wayne R; Velazquez, Eric J et al. (2015) Metabolomics analysis reveals insights into biochemical mechanisms of mental stress-induced left ventricular dysfunction. Metabolomics 11:571-582
Ersbøll, Mads; Al Enezi, Fawaz; Samad, Zainab et al. (2014) Impaired resting myocardial annular velocities are independently associated with mental stress-induced ischemia in coronary heart disease. JACC Cardiovasc Imaging 7:351-61
Samad, Zainab; Boyle, Stephen; Ersboll, Mads et al. (2014) Sex differences in platelet reactivity and cardiovascular and psychological response to mental stress in patients with stable ischemic heart disease: insights from the REMIT study. J Am Coll Cardiol 64:1669-78
Jiang, Wei; Samad, Zainab; Boyle, Stephen et al. (2013) Prevalence and clinical characteristics of mental stress-induced myocardial ischemia in patients with coronary heart disease. J Am Coll Cardiol 61:714-22
Boyle, Stephen H; Samad, Zainab; Becker, Richard C et al. (2013) Depressive symptoms and mental stress-induced myocardial ischemia in patients with coronary heart disease. Psychosom Med 75:822-31
Jiang, Wei; Velazquez, Eric J; Kuchibhatla, Maragatha et al. (2013) Effect of escitalopram on mental stress-induced myocardial ischemia: results of the REMIT trial. JAMA 309:2139-49
Jiang, Wei; Velazquez, Eric J; Samad, Zainab et al. (2012) Responses of mental stress-induced myocardial ischemia to escitalopram treatment: background, design, and method for the Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment trial. Am Heart J 163:20-6
Jiang, Wei; Oken, Harry; Fiuzat, Mona et al. (2012) Plasma omega-3 polyunsaturated fatty acids and survival in patients with chronic heart failure and major depressive disorder. J Cardiovasc Transl Res 5:92-9