Research has shown that the expression of negative emotions in response to a real or perceived provocation seems to consistently correlate with acute cardiac events. A biomedical model incorporating simultaneous Heart-Brain endpoints with behavior which is manifested and shaped by latent cultural and social determinants is our challenge.
The published work of our group has shown that there are pathophysiologic distinctions in cerebral and cardiovascular determinants of Mental Stress Ischemia compared to ischemia which results from exercise and that these patients have a poor prognosis. Work of others have confirmed our initial reports regarding prognosis and independent reports that there is a survival advantage when rehabilitation strategies are tailored accordingly. Given that it has been shown that up to 75% of CAD subjects are vulnerable to myocardial ischemia in response to mental stressors this is a leading public health issue and merits the attention of serious scientific inquiry. Given the novelty and difficulty of these experimental designs which employ simultaneous biomedical measurements of heart and brain performance or electrophysiologic instability while inducing ischemia-- the risks for failure were high. However with each success we found that very few could replicate the comprehensive approach to this difficult problem. Thus, our institution has led the way in reporting fundamental observations related to the pathophysiologic antecedents and consequences of this clinical presentation.
Neurobehavioral faculty members have been involved following clinical trials:
- The NHLBI funded ENRICHD randomized clinical trial, which sought to determine the effect on medical prognosis of treating depression and low social support in immediate post-MI patients.
- The two NHLBI funded Projects (COPES and CODIACS) that successfully tested a patient preference, stepped-care approach to depression treatment for persistently depressed post-ACS patients.
- An ongoing randomized clinical trial of stress management treatment for new recipients of ICD and for ICD patients who have recently experienced a shock terminated ventricular arrhythmia that has, along with laboratory based indices, incidence of shock treated ventricular arrhythmias as its endpoint.
- An RCT investigation of ambulatory T-wave alternans in relation to daytime episodes of moderate emotional arousal, with a particular focus on anger.
- We have a published a study where we found that CRP levels are significantly correlated with a subject’s vulnerability to Mental Stress after controlling for degree of CAD, risk factors and medications. This establishes proof of principle that inflammatory processes may also be associated with other dimensions of CAD expression.
Development of Coronary Heart Disease
- This research is focused broadly on the role of stress and emotional factors in the development, progression and expression of CHD. Laboratory-based studies have served to identify the importance of anger and associated emotions for the provocation of myocardial ischemia in patients with CAD, and both atrial and potentially fatal ventricular arrhythmias in clinical populations. Ongoing studies focus on the pathophysiology of stress and emotion provoked cardiovascular phenomena that are prognostically relevant, and the underlying pathophysiology. This work has elaborated in particular, how the propensity to re-experience anger regarding past incidents is associated with a cascade that includes release of vasoactive proteins and alteration in autonomic tone consistent with dysregulation of inflammatory processes. This work has also shown that these processes are evident in patients with elevated symptoms of depression, which is a clinical presentation that increases recurrent ACS and mortality risk over 2-fold.
Heart Rate Variability
- Heart rate variability is a measurement of autonomic balance derived from ambulatory ECG monitoring. Heart rate variability can provide a measure of effects of acute or chronic stress. Completed investigations include a study of correlations of socioeconomic status and life stress with heart rate variability, as well as the impact of depression on HRV, and ongoing studies, done in collaboration with a large NIH-funded consortium in Psychiatry, are examining the effects of cumulative adverse life experience on autonomic function as measured by HRV.
- Our goal for the next academic year is to describe the pathophysiologic mechanisms of mental stress induced myocardial ischemia, which differs from those that are a result of exercise. We have the largest series of subjects to date (n=160) undergoing simultaneous imaging with PET during Mental Stress and then again with dobutamine as a surrogate for exercise in a population of CAD subjects. Our results thus far support our hypothesis of regional activation in the brain that promote parasympathetic withdrawal, increase in sympathetic tone and decrease LV flow/ function that is not observed in the dobutamine group (exercise surrogate) is thus far confirmed. A manuscript based on these results is in preparation. We have studies that show a gender interaction that has just been analyzed and these data will be prepared and submitted afterwards.
Peripheral Arterial Tonometry
- We have developed a noninvasive stress test, peripheral arterial tonometry (PAT), to index those most vulnerable to Mental Stress Ischemia.
- We have observed an inverse relationship of TNF-alpha and parasympathetic withdrawal in subjects who become ischemic and have specific regional brain activation. We plan to devote further investigation into this link in the future.
Vascular Biology Collaboration
- In the upcoming year we will work collaboratively with our Vascular Biology colleagues to develop other constructs which may contribute to Mental Stress Ischemia, such as our recent data suggesting an up regulation of ET-1.
- Psychological stress and sudden cardiac death have been strongly correlated in epidemiological studies, yet the underlying physiologic link remains poorly understood. The ICD population allows evaluation of effects of mental stress on arrhythmia. Dr. Lampert’s landmark study in this population described the effects of emotional stress with a standardized anger protocol upon ventricular tachycardia. This past year these observations were extended with publications concerning several clinical electrophysiologic correlates which may explain the increased risk in these patients. A recent report in JACC described an increase in T wave heterogeneity in those who are vulnerable to ventricular tachycardia as a result of psychological stress. Future directions include the mechanisms and prognostic implications of this effect, as well as effects of gender and psychological profile. Ongoing studies include emotional triggering of atrial fibrillation and the role of stress reactivity, as well as the impact of anger on T-wave heterogeneity in daily life, the theme of her current RO-1.