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 #
1R01HL085704-01
Application #
7137746
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Jobe, Jared B
Project Start
2006-09-01
Project End
2011-07-31
Budget Start
2006-09-01
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$585,641
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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