During the past decade, major progress has been made in the evolution of technology directed toward the accurate measurement of regional myocardial perfusion in patients. The deficiencies of some of the older methods (thermodilution and gas clearance) are better appreciated and improved approaches (Doppler catheters, positron-emission tomography, and digital subtraction angiography) have been developed. The new approaches should play a major role in research and for most applications the older methods will gradually be replaced. Efforts to bring these new methods to community hospitals and practicing cardiologists should be stimulated. Doppler catheters, positron-emission tomography, and digital-subtraction angiography are commercially available and Doppler catheters and digital-subtraction angiography could be easily incorporated into routine cardiac catheterization procedures. The Doppler catheter is the most inexpensive and probably the simplest to apply. In our opinion, routine measurements of coronary flow reserve will significantly improve the care of patients with coronary obstructive disease and other diseases that impair myocardial perfusion. If coronary reserve measurements are used frequently, patient selection for coronary angioplasty and bypass surgery will no longer depend entirely on visual assessment of percent diameter stenosis, a very poor criterion in many situations. Also, patients with chest pain syndromes, normal coronary vessels, and impaired coronary reserve will be identified and perhaps some effective treatment for this condition will be devised.(ABSTRACT TRUNCATED AT 250 WORDS)

The distinction between normotension and hypertension, which is traditionally based on measurements of blood pressure made in the clinic, is arbitrary. The situation is further clouded by the fact that blood pressure varies greatly from moment to moment in any one individual, as shown by ambulatory recordings. The fundamental pattern of diurnal blood pressure variations is governed by the sleep-wakefulness cycle, on which the effects of different activities are superimposed. Although hyperreactivity of blood pressure to behavioral stimuli could in theory contribute to the elevation of blood pressure in hypertensive subjects, this would not by itself explain the sustained elevation of blood pressure that is usually seen throughout the day and night in such patients. It is not known how blood pressure variability contributes to the vascular changes associated with hypertension; three possibly relevant factors are the average level of pressure over time, the peaks of pressure, and the shape of the pressure waveform (dP/dt). Hyperreactivity of blood pressure occurring in the doctor's office may be of considerable practical importance in the evaluation of patients with mild hypertension and may confound the relationship between clinical and overall blood pressure and also the evaluation of the response to antihypertensive treatment. Recordings of blood pressure made outside the clinic may help to overcome these problems.

This article reviews key experimental studies concerning the possible contribution of behavioral stress to the development of primary hypertension. In animal preparations, chronic exposure to stressors in conjunction with predisposing genetic factors of high sodium/low potassium intake can lead to hypertension and cardiac pathology. Studies with human subjects are less definitive, but several lines of evidence suggest that high heart rate and blood pressure reactivity to behavioral stressors may indicate an increased susceptibility to hypertension, including an association between high reactivity and both borderline hypertension and a positive family history of hypertension, observations that stressors involving active coping evoke enhanced beta-adrenergic myocardial activity, resulting in cardiac output that is excessive relative to overall tissue oxygen consumption, and observations of decreased short-term sodium and fluid excretion during stressors in some individuals and an association between high salt intake and increased peak blood pressure levels evoked by exposure to stress. Indicated directions for future animal research include studies of the interactive effects of chronic stress with other environmental factors, such as high and low calcium intake, while in humans, future studies should incorporate monitoring of cardiovascular responses to real-life events, and should also include long-term follow-up investigations to evaluate more directly the predictive significance of high cardiovascular reactivity to stress.

This article provides a selective overview of epidemiologic studies on the relationship between psychosocial factors and blood pressure elevation. The review focuses on English-language reports published since 1975 and emphasizes two broad areas of research: changes in mean blood pressures of third world populations undergoing modernization, and psychosocial correlates of elevated blood pressure in low socioeconomic status (SES) and black populations within the continental United States. The recent modernization studies provide additional evidence that rapid sociocultural change is associated with increased prevalence of hypertension. To account for these effects, several studies have advanced the general thesis that modernization impacts traditional value systems of third world populations in ways that frequently engender discrepancies between their newly acquired aspirations for a Western lifestyle and their socioeconomic resources to successfully pursue that lifestyle. There is overlap between this formulation and recent investigations of hypertension in low SES and black populations in the United States. The report concludes with a discussion of epidemiologic studies of anger and hypertension, emphasizing some of the complexities that characterize this area of research.

Significant progress has been made in the past few years in defining the role of behavioral stress in the precipitation of cardiac arrhythmias. This is largely attributable to the development of relevant biobehavioral models and the advent of quantitative methods for assessing myocardial electrical stability in conscious animals. Classic and instrumental aversive conditioning has been shown to decrease electrical stability even in the normal heart. During evolving myocardial ischemia or infarction, the stress states can precipitate major arrhythmias, including ventricular fibrillation. Natural emotions have also been shown to be capable of altering the propensity to fibrillation. Notably, provocation of an angerlike state has been shown to decrease the vulnerable period threshold by 40% to 50%. The poststress phase can be particularly hazardous, as suggested by the profound myocardial perfusion abnormalities that have been observed within 1 to 3 min after cessation of anger. Cryogenic blockade of the thalamic gating system or its output from the frontal cortex to the brainstem blunts significantly the profibrillatory influence of stress. This indicates that discrete pathways within the central nervous system mediate the deleterious influence of aversive states on heart rhythm. Adrenergic factors appear to constitute the major effector component. This is supported by the observation that pharmacologic or surgical sympathectomy is capable of annulling the arrhythmogenic influence of diverse types of stress. The generally deleterious influence of the adrenergic system appears to be counteracted by vagal activity. The underlying mechanism is a muscarinically mediated inhibition of norepinephrine release from sympathetic nerve endings and a blunting of the actions of the adrenergic transmitters at the receptor level.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies conducted on animals indicate that biobehavioral variables and diet can interact to facilitate atherogenesis. An unstable or threatening environment and stable behavioral predispositions of the individual appear to be interactive variables that may be useful for understanding behavioral contributions to atherogenesis. The interaction of threat with stable behavioral predispositions is echoed in psychophysiologic experiments relating human behavior to physiochemical reactivity. These stable behavioral predispositions in humans include hostility and aspects of the type A behavior pattern. Possible interactions among genetic predisposition, reactivity, and atherogenesis are also discussed.

Epidemiologic and clinical evidence derived from studies of human beings suggests that psychosocial phenomena may account for much of the variability in atherosclerosis extent and severity that is unexplained by the "traditional" risk factors (serum lipids, hypertension, and smoking). Animal preparations provide an opportunity to test hypotheses concerning the role of psychosocial phenomena in atherogenesis and to explore the mechanisms by which the effects of such phenomena are mediated. Here we review a relatively large series of studies of cynomolgus monkeys (Macaca fascicularis), a 5 kg animal having a complex social organization. The data indicate that, among male animals, individual behavior characteristics (social status and aggressiveness), physiologic responsiveness to psychological challenge, and stability of the social environment all interact to affect atherogenesis. Among female animals, individual patterns of aggressiveness appear to influence ovarian function, which in turn affects atherosclerosis. Future advances in the behavioral medicine aspects of atherogenesis are likely to arise through elucidation of the pathophysiologic pathways by which these behavioral responses and characteristics contribute to the events (endothelial injury, smooth muscle cell proliferation, lipid accumulation, calcification, and necrosis) associated with plaque pathogenesis. Such research can be pursued in studies utilizing nonhuman primates as well as in complementary studies involving human subjects.

Recently the nature of the cellular and molecular events in atherogenesis have been elucidated better. Some of these findings may be important in explaining individual differences in susceptibility to atherosclerosis that are independent of known risk factors. Nonhuman primates are valuable models for the study of mechanisms of diet-induced atherosclerosis. Cynomolgus macaques are useful for studies of male-female differences in atherosclerosis, since they share with premenopausal white women a relative protection against coronary atherosclerosis compared with males. These animals are also useful for psychosocial atherosclerosis research since social status affects the extent of atherosclerosis, and experimentally induced social stress increases extent of coronary artery atherosclerosis. Nonhuman primates have also been useful for studies of individual differences in susceptibility to diet-induced atherosclerosis and its risk factors. These studies have indicated that about 75% of the variability in the plasma cholesterol response to dietary cholesterol is attributable to genetically determined differences in cholesterol absorption and lipoprotein catabolism. There is preliminary evidence suggesting the existence of "mesenchymal susceptibility" in nonhuman primates; i.e., differences in risk of atherosclerosis that are independent of exposure to known risk factors. Efforts are being made to establish colonies of rhesus monkeys that possess contrasting degrees of mesenchymal susceptibility.

Systems in the brain control blood pressure by maintaining life-sustaining, resting (tonic) levels and adjusting blood pressure in association with changes in regional blood flow appropriately coupled to behavior or environmental stimulation. Tonic levels of blood pressure are mediated by neurons in the medulla oblongata. The critical neurons appear to correspond to the epinephrine-containing cells of the so-called C1 group located in the rostral ventral lateral medulla. These also mediate baroreceptor reflex responses. Behaviorally coupled changes in blood pressure are often highly stereotyped and vary depending on the behavior being performed in both animals and humans. These reactive circulatory adjustments are largely mediated by forebrain regions working in concert with the medullary centers. Some of the largest increases in blood pressure occur in response to aversive emotional arousal. In hypertensive animals and humans, such changes, which are normally buffered by reflex mechanisms in the brainstem, are exaggerated. In the rat, the neural pathway mediating the coupling, through aversive emotional conditioning, of blood pressure responses to acoustic stimuli involves the transmission of sensory signals through the primary auditory projection system to the medial geniculate body, where the input is then relayed subcortically to the amygdala. The amygdala, presumably by way of connections with the hypothalamus, and from there to the brainstem or spinal cord, controls the learned emotional response. These findings, which implicate a largely unrecognized sensory relay to the amygdala in emotional learning, represent the first demonstration of a direct link between primary sensory system and autonomic control regions in the mammalian brain.

The risk factors for sudden coronary heart disease (CHD) death have been well described. Sudden CHD deaths should be classified as those occurring in individuals with and those in individuals without a prior history of clinical heart disease. The extent of coronary artery disease, left ventricular dysfunction, and cardiac arrhythmias are the primary pathophysiologic determinants of ventricular fibrillation and sudden death. Psychosocial factors influence the threshold of response to the numerous physical and social environmental stimuli that can precipitate sudden death. The degree of pathology is probably inversely related to the intensity of the stimuli necessary to precipitate sudden CHD death. In the presence of extensive disease the precipitants of sudden deaths are probably ubiquitous in the environment and unlikely to be prevented. Thus, prevention of the basic cardiac disease is of higher priority.

Over the past 10 years behavioral approaches to the treatment of coronary heart disease (CHD) have become widely recognized as being a significant complement to traditional medical and surgical therapies. The success of approaches to secondary prevention now relate to quality, as well as quantity, of life. A multifaceted program, including dietary management, smoking cessation, physical exercise, modification of type A behavior, and psychological counseling are components of many cardiac rehabilitation programs. Behavioral interventions are effective in reducing traditional risk factors for CHD events, and for improving the quality of life among victims of a disease with significant psychological, as well as physical, consequences. However, the effectiveness of behavioral interventions for prolonging life is less certain and requires more careful evaluation. The mechanisms by which behavioral treatments may influence clinical CHD end points is also in need of further investigation.