This is a resubmission of a proposal for continuing support to utilize the model provided by the denervated heart of human cardiac transplant recipients to test an elaboration of the psychophysiological reactivity hypothesis of coronary artery disease (CAD). The hypothesis that the intact cardiac autonomic control system is required to buffer increases in blood pressure variability in response to psychological challenge will be tested. Recent evidence suggests that blood pressure variability is a risk factor to cardiac disease independent of mean arterial pressure. It is hypothesized that diminished cardiac autonomic control permits elevated challenge-induced blood pressure variability responses which in turn are associated with increased risk of CAD. Beat-to-beat heart period and blood pressure and arterialized plasma norepinephrine will be measured in 28 cardiac transplant recipients and equal-sized samples of age- and gender-matched normal control and renal transplant subjects during a quiet resting baseline and in response to mental arithmetic and Stroop color-word tasks. Cardiac autonomic control, operationalized as heart period variability, and blood pressure variability will be computed by established time series methods. The absence of cardiac autonomic control, as indicated by virtual absence of heart period variability, is well-established in cardiac transplant recipients. It is predicted that due to this greatly reduced cardiac autonomic control, psychological challenge will lead to significantly greater increases in low frequency blood pressure variability in cardiac transplant recipients compared to the other two groups and that this difference will be stable over the first year following transplantation. Cardiac transplant recipients represent the most dramatic case of diminished cardiac autonomic control and, therefore, the clearest test of this hypothesis. However, the hypothesis is relevant not only to cardiac transplant patients, in whom the development of CAD is greatly accelerated compared to the population as a whole, but also in individuals with intact cardiac nerves but reduced cardiac autonomic control. These include patients with depression, anxiety disorders, and diabetic neuropathy, as well as healthy individuals high in hostility, all of whom have increased risk of CAD. Thus, although in this application, only cardiac transplant recipients and appropriate control groups are studied, support for this hypothesis is relevant to many populations, healthy and otherwise, with reduced autonomic control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH043977-05
Application #
2415915
Study Section
Health Behavior and Prevention Review Committee (HBPR)
Project Start
1990-09-01
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Norton, Michele R; Sloan, Richard P; Bagiella, Emilia (2005) New approach to the statistical analysis of cardiovascular data. J Appl Physiol 98:2298-303
McKinley, Paula S; Shapiro, Peter A; Bagiella, Emilia et al. (2003) Deriving heart period variability from blood pressure waveforms. J Appl Physiol 95:1431-8
Bagiella, E; Sloan, R P; Heitjan, D F (2000) Mixed-effects models in psychophysiology. Psychophysiology 37:13-20
Sloan, R P; Shapiro, P A; Bagiella, E et al. (1999) Cardiac autonomic control buffers blood pressure variability responses to challenge: a psychophysiologic model of coronary artery disease. Psychosom Med 61:58-68
Shapiro, P A; Sloan, R P; Bagiella, E et al. (1996) Heart rate reactivity and heart period variability throughout the first year after heart transplantation. Psychophysiology 33:54-62
Sloan, R P; Shapiro, P A; Bagiella, E et al. (1996) Relationships between circulating catecholamines and low frequency heart period variability as indices of cardiac sympathetic activity during mental stress. Psychosom Med 58:25-31
Sloan, R P; Shapiro, P A; Bagiella, E et al. (1995) Temporal stability of heart period variability during a resting baseline and in response to psychological challenge. Psychophysiology 32:191-6
Shapiro, P A; Sloan, R P; Bigger Jr, J T et al. (1994) Cardiac denervation and cardiovascular reactivity to psychological stress. Am J Psychiatry 151:1140-7
Sloan, R P; Shapiro, P A; Bagiella, E et al. (1994) Brief interval heart period variability by different methods of analysis correlates highly with 24 h analyses in normals. Biol Psychol 38:133-42
Sloan, R P; Shapiro, P A; Bagiella, E et al. (1994) Effect of mental stress throughout the day on cardiac autonomic control. Biol Psychol 37:89-99

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