Robert Soufer, M.D. Professor of Internal Medicine Chief, Cardiovascular Medicine VACT Healthcare Systems

B.A., New York University, 1974, M.D., New York Medical College, 1978; Medical Resident, Downstate Medical Center Kings County Hospital, 1979- 1981; Chief Medical Resident/Assistant Instructor in Medicine, Downstate Medical Center Kings County Hospital, 1981-1982; Postgraduate Fellow in Cardiology, Yale University School of Medicine, 1982-1984; Research fellow in Cardiology/Nuclear Medicine Resident, Yale University School of Medicine, 1984-1985; joined Yale Faculty, 1985.

April 8, 2004 Grand Rounds References

Neurobehavioral Correlates of Mental Stress in Cardiovascular Disease

I. Neuro-Cardiac Interaction

Data show that psychological factors play an important role in acute coronary syndromes. We and others, have found mentally demanding tasks such as mental arithmetic to provoke ischemia in approximately 50% of patients with ischemic heart disease. We have also found a specific psychological profile, characterized by emotional reactivity, and easily aroused anger and hostility, to be associated with this “mental stress ischemia”; conversely, we have not found an association between this profile and exercise ischemia. Follow up of these mental stress positive patients reveal a significantly poorer 1-2 year prognosis. Hence, mental stress ischemia may be a distinct phenomenon with unique risk factors and prognosis. The mechanisms of mental stress ischemia are, however, not well understood. Critical questions remain regarding the ways by which mental and psychological factors contribute to coronary syndromes. We believe that psychological, neurobiological and coronary vasomotor processes are key factors, expanding upon our pilot work, conducted in the context of our current funding. We are examining the functional CNS correlates of mental stress ischemia; these CNS correlates will be defined by positron emission tomography (PET) conducted while patients perform an arithmetic task that we have found to reliably provoke ischemia in half of those we have studied. This approach will illuminate CNS processes that may be serving to transduce mental stress susceptibility into risk for acute coronary events. Specific issues concerning gender interaction and relationship to psychological profiles/coping styles are currently being explored.

II. Mental Stress and Myocardial Blood Flow

In these studies we are examining changes in myocardial blood flow during the performance of a mentally demanding arithmetic task inpatients with CAD. In these experiments, we are examining coronary vascular pathophysiology in mental stress ischemia. We are quantitating myocardial blood flow with PET at baseline; during mental arithmetic stress testing, and during infusion of a vasodilatory agent. We are following this in the cardiac catheterization laboratory by examining the processes that determine dynamic myocardial blood flow. These studies will define the nature of alterations in coronary anatomy and vasomotor tone that characterize mental stress ischemia and then differentiate it from exercise induced ischemia. Based upon our pilot data, we speculate the following:

1. Mental stress ischemia is associated with absolute reductions in regional myocardial blood flow as measuredby PET,

2. These reductions in regional myocardial blood flow are precipitated by altered endothelial dependent vasomotor function, independent of epicardial disease severity, and

3. The psychological factors of emotion arousability, trait anger, and anger expression are related to this altered endothelial dependent vasomotor function.

In summary, taken together, Studies I and II (above) will contribute to a broader understanding of the psychological, neurobiological and myocardial mechanisms of mental stress ischemia. Further, they could contribute to the establishment of mental stress testing for diagnostic and prognostic purposes, and to the development of new behavioral therapies and pharmacotherapies (both cardiac and psychotropic) for the treatment of CAD.


Burg M, Benedetto C, Rosenberg R, Soufer R. Pre-surgical Depression Predicts Medical Morbidity 6-Months After Coronary Artery Bypass Artery Bypass Graft (CABG) Surgery. Psychosomatic Medicine 2003 ; 65 (1): 111-118.

Arrighi JA, Burg M, Cohen IS, Soufer R. “Simultaneous assessment of myocardial perfusion and function during mental stress in patients with chronic coronary disease.” J Nucl Cardiol 2003 10: 267-274.

Soufer R, Arrighi JA, Burg MM. “Brain, Behavior, Mental Stress and the Neuro Cardiac Interaction”. J Nucl Cardiol 2002; 9 (6): 650-662.

Soufer, R. and Checkerdjiev A, “Psychosocial stress and the brain: Implications for the neuro-cardiac interaction.” Cerebrum 2002; 4:67-78.

Arrighi JA, Burg MM, Cohen IS, Kao AH, Pfau S, Caulin-Glaser T, Zaret BL, Soufer R: Quantitative Myocardial Blood Flow Response to Mental Stress in Patients with Chronic Coronary artery Disease: Correlation with Angiography and Comparison With Flow Responses in Normals. Lancet 356:310-311, 2000.

Mcnulty PH, Jagasia D, Ng CK, Whiting JM, Garg P, Soufer R: Persistent changes in myocardial glucose metabolism during reperfusion of a limited duration coronary occlusion in rats. Circulation 101:917-922, 2000.

Jain D, Shaker SM, Burg M, Wackers FJT, Soufer R, ZaretBL: Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease. JACC 31 (6): 1314-22, 1998.

R Soufer, Bremner JD, Arrighi JA, Cohen IS, Zaret BL, Burg MM, Goldman-Rakic P: Cerebral cortical hyperactivation in response to mental stress inpatients with heart disease. Proc Natl Acad Sci USA 95:6454-6459, 1998.

Ng CK, Soufer R, and McNulty PH: Effect of hyperinsulinemia on myocardial F-18 labeled fluorodeoxyglucose uptake in humans. J Nucl Med 39:379-383, 1998.

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