To elucidate the role of biobehavioral factors in the etiology, pathogenesis and course of coronary heart disease (CHD) and to use this knowledge to devise more effective prevention, treatment and rehabilitation approaches.

BACKGROUND:

The integrating theme of the study is that hostility affects both behaviors and biologic functions in ways that increase the risks of developing coronary atherosclerosis or suffering an acute CHD event. Disciplines involved include psychology, internal medicine, cardiology, psychiatry, pharmacology, biostatistics, epidemiology, and molecular biology.

DESIGN NARRATIVE:

There were five subprojects in the original program project grant. Subproject 1 examined the social, behavioral and biologic concommitants of both natural and experimental interpersonal conflicts as a function of multimodal hostility assessments. Subproject 2 examined the role of hostility and social support in survival among CHD patients and attempted to identify the behavioral mediators of survival effects. Subproject 4 evaluated the effects of hostility, both alone and jointly with risk factors and social factors, on CHD incidence in over 5,000 participants in the University of North Carolina Alumni Heart Study. Subproject 5 evaluated the effects of age, smoking, lipids, and adrenergic receptors on physiologic reactivity of hostile and nonhostile men to anger induced by interpersonal challenges in the lab as well as the events of daily life. Subproject 7 extended the evaluation of anger-associated biologic reactivity in hostile and nonhostile persons by studying biobehavioral responses of 200 women employed in a real world high stress work situation; it also evaluated the impact of a stress management intervention designed to reduce anger on biobehavioral reactivity in these same employees.

The study was renewed in fiscal year (FY) 1997 to expand the primary focus on hostility to include a set of psychosocial, behavioral, and biological characteristics that increased coronary heart disease risk and appeared to cluster in certain individuals and groups, especially those low in socioeconomic status (SES). Subproject 1 examined in approximately 360 subjects the synergistic effects of SES and psychosocial risk factors such as depression, hostility, and social isolation on biological and behavioral factors suspected or known to contribute to atherogenesis. Subproject 2 evaluated the role of the central nervous system serotonin function as a potential mediator of the clustering of health-damaging psychosocial and biobehavioral characteristics in the same individuals and low SES groups. Subproject 3, the Psychosocial Risk for Cardiovascular Disease in Youth Project (PRCVDYP), used three ongoing general population studies of youth as a basis for examining the development of psychosocial risk for cardiovascular disease. The investigators hypothesized that low SES youth would exhibit, in addition to increased levels of the psychosocial and behavioral risk factors under study, increased sympathetic nervous system tone and reactivity to mental challenge, as well as decreased peripheral nervous system tone. They also hypothesized that depression, social isolation, and harsh parenting will interact with low SES to increase cardiovascular disease risk. Subproject 4 used a rat model to investigate early experience, serotonin and adult function.

The study was renewed in FY 2004 and includes three subprojects. Subproject 1 will determine the role of gene-environment interactions in the expression of psychosocial and biobehavioral risk factors for cardiovascular disease. Variants will be identified in candidate genes and chromosomal loci that are associated with the endophenotypes of hostility, personality, other psychosocial risk factors, health behaviors, and the following responses to rest and stress -- cardiovascular and neuroendocrine function, platelet activation and serotonin transporter function, circulatory inflammatory markers and the tendency of all of these characteristics to cluster in the same individuals and low socioeconomic groups. A total of 400 probands (half African American, half Caucasian, half women) and at least one sibling for each proband will be recruited for a total of 800 to 1200 subjects. Subproject 2 will explore in 400 subjects the genetics of glucose metabolism, hostility, and cardiovascular disease risk factors. Subproject 3 will examine the genetics, hostility and biology of stress in daily life in 400 probands and one sibling for every proband.

We will recruit 500 probands (half African American and half Caucasian, half men and half women, and half scoring in the top and half in the bottom 20% on an established hostility scale), at least one sibling from each proband and as many parents as possible.

Healthy normal volunteers