A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk

Abstract

Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk.

Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [¹⁸F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress.

Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004).

Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.

Keywords: PTSD; cardiovascular disease; depressive disorders; stress.

Figure 1.

Cardiac, Brain and Inflammation Imaging Study Protocol. Patients receive FDG intravenously at baseline followed by counting control and then cardiac, brain and inflammation PET-CT imaging after a 30 minute FDG uptake period. The protocol is repeated with mental stress tasks. FDG cardiac scans show uptake in yellow where myocardium is ischemic, greater with stress. FDG brain functional scans show red/yellow activity in cortex. Increased FDG uptake is seen in the thoracic arteries indicating inflammation and FDG activity tracks bone marrow activity as well. The CT is used for volumetric assessment of subcutaneous and visceral adiposity.

Figure 2.

Effect of mental stress on cardiac glucose uptake. There was an 18% greater increase in glucose uptake with stress versus rest in the MSI+ (N=4) compared to MSI− CHD (N=6) patients (*p=.19).

Figure 3.

Relationship between change in glucose in the medial prefrontal cortex with mental stress and change in spleen glucose uptake with mental stress in CHD patients (r=0.69, p0.038).

Figure 4.

Relationship between change in amygdala glucose uptake with mental stress and change in spleen glucose uptake with mental stress (r=.69, p=.04).

Figure 5.

Relationship between change in medial prefrontal cortex (superior orbital) glucose uptake and change in myocardial uptake with mental stress (r=.85, p=.004).