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Epidemiologic and experimental data are reviewed to determine whether treatment with beta-adrenergic blocking agents ('beta blockers') is likely to be antiatherogenic. Both indirect and direct evidence are considered. Indirect evidence is derived from studies of the effects of beta blockers on the risk factors for atherosclerosis, or on the disease sequelae of atherosclerosis. Direct evidence refers to studies in which atherosclerosis is an endpoint. Regarding indirect evidence, the data generally are consistent with a retarding or neutral effect of beta blockers on atherosclerosis. For example stroke incidence is reduced when hypertension is treated with beta blockers. About half of these same studies also show a reduction in the incidence of myocardial infarction, a complication that may be more closely related to atherosclerosis extent and severity than is stroke, which can have a nonatherosclerosis origin. The most important potential negative effect of beta blockers occurs with respect to serum lipid concentrations. However, there is no evidence that atherosclerosis is worsened as a result of pharmacologically induced alterations of serum lipids. The direct evidence more clearly indicates a retarding effect of beta blockers on atherosclerosis, with 11 of 13 studies having outcomes in this direction. However, interpretation of these studies is complicated by the fact that all of the data are derived from animal models, some of which are not similar to human beings in the development of atherosclerosis. Also, the studies are diverse, not only in the research designs and species utilized, but also in the type of beta blocker employed, the degree of beta blockade achieved, and the anatomic location of lesions. In summary, the data suggest that treatment with beta blockers may retard atherosclerosis. A more definitive answer requires efforts in two directions: (a) studies on atherosclerosis in selected populations of human beings, using cineangiography or autopsy material; and (b) additional, well-controlled studies in appropriate animal models.

Epidemiologic evidence increasingly implicates psychosocial variables in the development of coronary heart disease in human beings, an association that appears to be independent of the effects of other coronary disease risk factors. It has been hypothesized that behavioral influences on coronary heart disease are mediated by activation of the sympathetic nervous system, perhaps through exacerbation of coronary artery atherosclerosis. This article summarizes several studies of the effects of stress and sympathetic arousal on atherosclerosis in a nonhuman primate model of atherogenesis. The application of a behavioral stressor involving periodic reorganization of social group memberships resulted in worsened coronary atherosclerosis among male cynomolgus monkeys (Macaca fascicularis) fed a cholesterol-containing diet, relative to control animals housed in groups of fixed (stable) membership, but only among those monkeys that retained dominant social status during the course of the study. This effect could not be attributed to concomitant variability in blood pressure or serum lipid concentrations. When the same experimental procedures were applied to males fed a diet low in saturated fat and cholesterol, the manipulation of group memberships similarly led to development of greater atherosclerosis in the coronary arteries. In related observations, monkeys that exhibited the largest heart rate responses to a standardized behavioral challenge had more extensive coronary atherosclerosis than animals showing a less pronounced cardiac responsivity to stress. In a final investigation, we observed that the exacerbated atherosclerosis of dominant monkeys consuming an atherogenic diet and housed in unstable social groups could be prevented by long-term administration of a beta-adrenoreceptor-blocking agent, propranolol hydrochloride.

We report here the effect of diet and social environment on the carotid bifurcation atherosclerosis of 60 adult male cynomolgus monkeys (Macaca fascicularis) fed either an atherogenic diet (AD) or a more "prudent" diet (PD). Animals within each dietary condition lived either in unstable social groupings (which had their memberships reorganized on a regular basis) or in stable groupings. The experiment lasted 22 months, after which animals were necropsied and the extent of atherosclerosis was measured both at the carotid bifurcation and at other arterial sites. Carotid bifurcation atherosclerosis (CBA) was significantly more extensive and severe among animals fed the AD diet. Among these animals, all of which were normotensive, lesion extent was positively associated with both plasma cholesterol concentrations and heart rate response to behavioral stress, and negatively associated with the ability to clear glucose. No experimental variables correlated with the CBA of the PD animals; these lesions, some of which were extensive, were probably pre-existing. The social conditions and individual behavior patterns of the animals had no effect on CBA in either group, despite a pronounced effect on the coronary arteries (CA) of the same animals. While the overall correlation between CBA and CA atherosclerosis was not high, animals with extensive CBA almost always had extensive CA atherosclerosis. The factors influencing CBA in the cynomolgus monkey may be similar to those affecting humans.

Over 50 epidemiologic, clinical, and experimental studies of behavioral influences on atherosclerosis and CHD have been reviewed; of these investigations, no more than five were published prior to 1975. Despite some inconsistencies and occasional conceptual and methodologic problems in the studies comprising this relatively young literature, the preponderance of available evidence indicates that psychosocial variables play a significant role in coronary disease. To summarize briefly, the Type A behavior pattern has been found predictive of new CHD in nearly all prospective studies of initially healthy individuals, and therapeutic modification of Type A has been shown to reduce risk of recurrent nonfatal MI. Among most prospective studies of post-MI patients and of persons at heightened risk for CHD due to elevations in traditional risk factors, however, Type A has not been found to predict, respectively, recurrence of MI or initial clinical events. Additionally, Type A individuals have shown more extensive coronary artery atherosclerosis on angiographic examination than Type Bs in a minority of studies, and, generally, only where Type A behavior has been measured by the SI. It is noted that many of these clinical studies may be faulted, though, for their use of small and heterogeneous patient samples and for possible biases in the selection and recruitment of subjects. In contrast to the globally defined Type A pattern, a high potential for hostility and an inability or unwillingness to express anger (anger-in) have emerged as significant predictors or correlates of coronary disease in all epidemiologic and clinical studies in which these variables have been examined. These consistent results suggest that a predisposition to hostility and anger, and the inhibited expression of such feelings, represent a "toxic" component of the Type A pattern. Several recent prospective investigations indicate also that high levels of life stress and possession of poor or inadequate social resources are predictive of CHD. The concepts of life stress, social network, and social support, as well as relationships among these variables, are not well-understood, however, and much additional work is needed to identify specific pathogenic and protective attributes of the social environment. In addition to studies of the psychosocial antecedents of CHD in human beings, there now are several published studies of behavioral influences on the development of coronary lesions in animal models.(ABSTRACT TRUNCATED AT 400 WORDS)

The purpose of this investigation was to examine the psychophysiologic responses of Type A and Type B individuals, among persons with and without coronary heart disease (CHD). Subjects were 58 adult male volunteers; 24 had a history of myocardial infarction or clinically diagnosed angina pectoris (CHD) and 34 had been designated free of coronary disease following recent cardiologic examination (non-CHD). All subjects had normotensive resting blood pressures; among CHD patients, no subject was currently on beta-adrenergic blocking medication. Measures of heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) were obtained during a baseline period and while subjects performed a series of difficult and frustrating cognitive tasks. Each subject was also administered the Structured Interview for Type A--Type B assessment (SI) and the Jenkins Activity Survey (JAS). Results indicated that, independent of the A/B typology, CHD patients experienced significantly greater DBP elevations during the experimental tasks than did non-CHD controls. Type A subjects (as determined by the SI) exhibited greater task-related increases in SBP and DBP than did Type Bs, but changes in HR did not differ between these two groups. Type A--Type B assessments based on the JAS were unrelated to subjects SBP, DBP, or HR responses, and neither SI- nor JAS-defined Type As differed reliably from Type Bs on measures of task performance. Overall, these results are consistent with the hypothesis that heightened cardiovascular reactivity under stress may mediate relationships between behavioral factors and CHD.

The swivel-tether system has been used extensively in biomedical research involving nonhuman primates, yet there has been little or no investigation into potential adverse influences of this form of restraint on research results. In the study described here, a portable electrocardiographic telemetry system was used for continuous monitoring of the heart rate of 26 cynomolgus monkeys while: (a) pair-caged, 8 weeks prior to tethering; (b) singly-caged, tethered; (c) singly-caged, tethered, administered propranolol (30 mg/kg/day) in the diet; (d) group-housed (five monkeys per group), 1 week after group formation; and (e) group-housed (five monkeys per group), 4 weeks after group formation. Tethering resulted in persistent elevations in heart rate relative to the other conditions. Administration of propranolol, a beta-adrenergic antagonist, resulted in an abrupt, sustained decrease in heart rate indicating that the increase in heart rate associated with tethering was due to persistent stimulation of the sympathetic nervous system. Since multiple aspects of cardiovascular function are influenced by the sympathetic nervous system, and other organs and systems (e.g., pituitary-gonadal) also may be affected, investigators using the swivel-tether system should be cognizant of these potential effects when designing experiments and interpreting the results.

The purpose of this investigation was to test the hypothesis that subjects (Ss) can exert voluntary, bidirectional heart rate (HR) control in the absence of concomitant changes in respiration rate (RR) and muscle activity (chin EMG). Feedback-assisted HR control was studied under four experimental conditions involving increasing levels of somatic restraint: (a) No somatic controls, (b) RR pacing, (c) EMG feedback, to maintain constant muscle activity, and (d) RR pacing plus EMG feedback. Fifteen Ss, eight females and seven males, were assigned to each of these four conditions (N = 60). The HR control task involved ten increase and ten decrease trials in random order, each lasting 60 sec and preceded by a 60-sec resting baseline period. The results indicated that Ss produced significant HR increases (Xdelta = +3.4 bpm), but were unable to effect decreases (Xdelta = -.3 bpm). Furthermore, the magnitude of the obtained HR changes did not differ by experimental condition, i.e., by level of somatic restraint. While concomitant bidirectional RR changes were found, the pacing procedure effectively reduced, and on HR increase trials, nearly eliminated, RR involvement. No increases in EMG activity were found on HR increase trials for any of the four experimental conditions, whereas all groups showed some EMG decreases on HR deceleration trials. With respect to the question of somatic mediation of autonomic control, it is concluded that HR increases produced under paced respiration "favor" an interpretation of unmediated HR acceleration.

In order to investigate the effects on behaviour of hypertension, age, and the types of antihypertensive agents, we have conducted a retrospective analysis in 100 hypertensive patients receiving chronic treatment in our Hypertension Clinic. A group of 80 normotensive subjects, matched for age, were included in the study. Half of the hypertensive patients were under the age of 50 (young group) and half were over the age of 50 yrs (old group). The antihypertensive agents had not been administered according to any specific protocol, but represented the choice of the individual clinicians treating the patients in the clinic. All patients had received treatment for at least one year, and usually for two years. The behavioural tests performed were designed to measure sensory-perceptive ability, cognitive ability and psychomotor function and were those employed and described in our previous studies. The results achieved were varied, but indicated that older age was associated with an impairment in performance as was blood pressure. Test performances in the young hypertensives were similar to those achieved by older normotensives. These results were more prominent in cognitive and psychomotor functions than in the sensory-perceptive tests. The antihypertensive drugs used also affected these results; the worst behavioural performances tended to be in patients receiving the central nervous system agonists (methyl-dopa and clonidine) and better performances in patients receiving beta-blockers alone when compared with the other groups. Surprisingly, patients receiving diuretics showed poorer performance levels, but these were better in patients who received a beta-blocker in combination with their diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma cortisol (F) response to intravenous adrenocorticotropin (ACTH) infusion (following dexamethasone suppression) was examined in adult female Macaca fascicularis that had been living for 22 months in social groups consisting of four to six females and one male. A portion of these females were ovariectomized (n = 21), while the rest were reproductively intact (n = 23). The social behavior of all animals was monitored with a focal sampling procedure, and dominance ranks were determined on the basis of fight outcomes. Further, intact females were swabbed vaginally to determine onset of menstruation and were sampled for plasma progesterone (P) every three days during the luteal phase of their cycles. Among the results was that the plasma F response to ACTH infusion was greater in subordinate animals than in dominants (P < .02). Subordinates and dominants did not, however, differ in plasma F measured at baseline. It was found further that plasma F concentrations were greater in ovariectomized than in intact females at baseline and following ACTH injection (P < .01). Finally, there was an appreciable elevation in plasma F across all animals during the 15- and 30-minute post-ACTH injection measurements (P < .01). Subsequent analyses of data from intact females showed interrelationships among dominance rank, reproductive function (indicated by luteal phase plasma P concentrations), adrenal size, and adrenal response to ACTH infusion. These data indicated that subordinate females were at a reproductive disadvantage compared to dominants, a result that may have been mediated, in part, by the increased adrenal size and enhanced adrenal responsiveness of subordinate females., (Copyright © 1986 Wiley‐Liss, Inc., A Wiley Company.)

The effects of parental history of hypertension and menstrual phase on systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR) responses to two frustrating cognitive tasks were examined in 47 normotensive, young adult women. Subjects with and without a parental history of hypertension were scheduled to be tested during either the follicular (days 7-11 of a 28-day cycle) or luteal (days 17-22) phase of the menstrual cycle. During the laboratory session, HR, SBP, DBP, and self-report of affective states were measured while subjects performed two cognitive tasks (mental arithmetic and concept formation). Results indicated that the magnitude of SBP responses to the two tasks was significantly greater in subjects tested during the follicular phase than in subjects tested in the luteal phase of the menstrual cycle. No effect of parental hypertension was observed on cardiovascular response measures, though offspring of hypertensive parents reported experiencing significantly less anger during the tasks than subjects with normotensive parents.

Socially stressed adult male cynomolgus monkeys (Macaca fascicularis) fed a low fat, low cholesterol diet developed more extensive coronary artery atherosclerosis than unstressed controls. Groups did not differ in serum lipids, blood pressure, serum glucose, or ponderosity. These results suggest that psychosocial factors may influence atherogenesis in the absence of elevated serum lipids. Psychosocial factors thus may help explain the presence of coronary artery disease (occasionally severe) in people with low or normal serum lipids and normal values for the other "traditional" risk factors.

The relative effectiveness of biofeedback techniques on the voluntary control of heart rate was examined by randomly assigning 32 Ss to one of four feedback conditions in a bi-directional heart-rate control task: (1) no feedback, (2) binary feedback--S was signaled when an interbeat interval had changed in the correct direction, (3) "real-time," proportional feedback--S was provided information about the relative duration of successive interbeat intervals, and (4) numerical, proportional feedback--each interbeat interval was represented as a numeral indicating its relationship to pre-trial mean by direction and magnitude. Significant over-all heart-rate changes were evidenced for both increase and decrease directions, but no differences were found between the feedback conditions. While these data suggest that feedback may be a relatively insignificant factor in voluntary heart-rate control, it was recommended that further investigation examine the role of feedback within the context of other training, mediating and motivational variables.

Examining the stability of individual differences in behaviorally induced heart-rate reactivity in children, 34 boys having a mean age of 101.9 months were presented a cognitive task to perform "as rapidly and accurately as possible" at each of 2 experimental sessions scheduled 1 week apart, and recordings of heart rate were obtained during periods of rest and task performance on each occasion of testing. Task-related heart-rate reactivity across the 2 experimental sessions revealed substantial and highly reproducible individual differences, as evidenced (1) by subsets of subjects representing clearly differentiated groups of heart-rate reactors and non-reactors, and (2) by correlation of subjects' mean heart-rate responses between the first and second sessions. Individual differences in heart-rate reactivity were independent of subjects' task performance.

This investigation examined the role of anabolic steroids on baseline heart rate (HR) and HR responses to the threat of capture in Macaca fascicularis. Ten cynomolgus monkeys were randomly assigned either to a steroid or to a sham control group. Steroid-treated animals were given testosterone injections biweekly for 10 weeks, whereas sham controls received injections of sesame oil on an identical schedule. Pretreatment and posttreatment HRs were evaluated to establish both baseline and acute-stress responses. Results revealed that animals given testosterone experienced a statistically significant increase in baseline HR when contrasted with the sham controls. No difference between the groups was detected in response to the threat of capture.

The cynomolgus macaque provides a suitable primate model for studying how psychosocial factors contribute to coronary artery atherogenesis. Important interactions with diet, sex, and behaviorally elicited cardiovascular reactivity are described.

We report here on the social behavior of 30 adult male cynomolgus macaques (Macaca fascicularis), half of which were chronically administered propranolol HCl. All monkeys were maintained in groups of five, fed an atherogenic diet, and subjected to a social manipulation involving repeated disruption of social groups through redistribution of group memberships. One year of intensive behavioral observations were made, involving quantification of 27 kinds of social interaction typically exhibited by this species in captivity. Propranolol treatment resulted in a significant reduction in heart rate and blood pressure. Comparisons between propranolol-treated and untreated monkeys revealed no effects of beta-blockade on social dominance, aggressiveness, or active aspects of affiliation (e.g., grooming). The fact that few behavioral differences were found between conditions in this investigation indicates to us that such effects as were observed may owe as much to chance as to the action of the drug. Overall, these findings suggest that chronic beta-adrenergic blockade has minimal effects on the most prominent features of macaque monkey social behavior, especially those behavioral factors (aggressiveness and competitiveness) associated with risk for coronary disease in this species and in human beings.

It has been suggested that individual differences in behaviorally induced cardiovascular reactivity may mediate associations between behavioral factors and atherosclerotic disease. The present study provides data relevant to this hypothesis within an animal model. Experimental animals were 26 adult, male cynomolgus monkeys that had been fed a moderately atherogenic diet for 22 months. In the weeks preceding termination of these animals, monkeys were fitted with electrocardiogram (EKG) telemetry devices and their heart rates (HRs) recorded under baseline and stressed conditions. Stress-period HR measures were obtained during a standard challenge involving threatened capture and physical handling of the animals. At necropsy, the coronary arteries were subjected to pressure fixation and sections taken from the left main, left anterior descending, left circumflex, and right coronary arteries. Mean intimal area measurements, calculated for each artery, were then compared between animals identified as High (n = 8) and Low (n = 8) HR reactors during stress. Results indicated that High HR reactors had significantly greater coronary artery atherosclerosis than did Low HR reactive animals, both in individual arteries and on an overall coronary index. Atherosclerosis in the thoracic aorta was found to differ similarly between High and Low HR reactors. Additional analyses revealed that High HR reactors were significantly more aggressive, more ponderous, and had greater heart weights than did Low HR reactors. Although groups did not differ in resting HRs, body weights, or lipid values, high-density lipoprotein (HDL) cholesterol comprised a slightly smaller fraction of the total serum cholesterol of High, relative to Low, HR reactive monkeys. It is concluded that these findings provide initial support for the hypothesis that cardiovascular hyperresponsiveness under stress is related to the development of atherosclerosis.

Elevated "casual" heart rate (HR) has been found to be an independent predictor of coronary heart disease (CHD) in human beings. The current study provides data on the association between coronary artery atherosclerosis (CAA) and naturally occurring individual differences in the casual HRs of cynomolgus macaques (Macaca fascicularis). The data demonstrate that naturally occurring differences in casual HR are related to CAA (plaque area in mm) with high HR monkeys having lesions more than twice as extensive as those of low HR monkeys (high HR; n = 7, 159 beats/min: 0.76 mm2 +/- 0.21 SD; low HR; n = 8, 133 beats/min: 0.31 mm2 +/- 0.30; t = 3.01, p less than 0.01). The data show further that the distribution of individual differences in casual HR is consistent and stable over periods of at least 12 months. Importantly, the relationship between elevated casual HR and CAA was independent of the association between an index of HR "responsivity" to stress and CAA, found in the same monkeys. Similar to a recent finding in human beings, high casual HR also was associated with significantly lowered serum concentrations of high-density lipoprotein cholesterol; differences in CAA were, however, independent of the lipid difference. The CAA differences may depend instead on HR-induced differences in coronary blood flow between high and low HR monkeys. Subsequent work with beta-adrenergic blockade suggested that elevated casual HRs in monkeys are associated with sympathetic arousal.

This investigation examined the cardiovascular and affective reactions of offspring of hypertensive and normotensive parents on exposure of subjects to a frustrating cognitive task. Subjects were 44 normotensive, male undergraduate volunteers, 22 with and 22 without a parental history of hypertension. Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) measurements were recorded under resting (baseline) conditions and during subjects' performance of a 3-min mental arithmetic task. Subjects were also administered state forms of the State-Trait Anxiety and Anger Inventories following baseline measurements and immediately after the experimental task. Results indicated that relative to sons of normotensive parents, offspring of hypertensives showed significantly greater HR and DBP elevations during mental arithmetic. However, neither task performance nor task-related changes on the state measures of anxiety and anger varied reliably with differences in parental status. When subjects were divided into groups of high- and low-affect (i.e., anxiety, anger) responders, the HR reactions of persons having hypertensive and normotensive parents were found to differ significantly only among subjects who reported experiencing the most appreciable anxiety--and to a lesser extent, anger--when performing the mental arithmetic task. This finding suggests that persons at familial risk for hypertension possess a heightened cardiovascular response "potential" which is expressed, in part, in relation to concomitant affective experiences of the individual.

We previously reported that the coronary atherosclerosis of cholesterol-fed, male cynomolgus monkeys (Macaca fascicularis) was exacerbated among animals that exhibited the largest heart rate (HR) reactions to a standard laboratory stressor. Here we report a similar relationship between behaviorally induced HR reactivity and atherosclerosis in females of the same species. Twenty-one female monkeys were fed a moderately atherogenic diet for 30 months. Near the end of this period, animals were fitted with electrocardiogram telemetry devices and their HRs were recorded under baseline and stressed conditions. Stress period HR measurements were obtained during a standard challenge involving threatened capture and physical handling of the animals. At necropsy, sections taken from the left anterior descending, left circumflex, and right coronary arteries were examined histologically. Mean intimal area measurements were then compared between animals identified as High (n = 7) and Low (n = 7) HR reactors. High HR reactive animals were found to have significantly greater coronary artery atherosclerosis than Low reactors; atherosclerosis at the right carotid bifurcation also differed significantly between High and Low reactive monkeys. Groups did not differ in baseline HR, blood pressure, and total or HDL cholesterol concentrations. Relative to Low HR reactors, however, High reactive animals weighed less and were less ponderous, had greater heart weights (adjusted for differences in body weight), were behaviorally less aggressive, and had lower luteal phase progesterone concentrations. These relationships were corroborated in correlation analyses employing data of all 21 study animals.

The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis in adult male cynomolgus monkeys (Macaca fascicularis). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment in the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean intimal area measurement, based on all arterial sections, served as a coronary index for each animal. Results indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed in stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (i.e., unstable) subordinates. A similar pattern was observed in the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen in the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences in total serum cholesterol or high density lipoprotein cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an individual behavioral characteristic) is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (i.e., under behavioral challenge).

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.

Parent-offspring and sibling resemblances in blood pressure and heart rate responses to behavioral stress were evaluated in a sample of 142 families residing in an upper-middle-class community in the Pittsburgh metropolitan area between 1983 and 1985. The sample consisted of 121 daughters and 96 sons ranging in age from 7 to 18 years, and 141 mothers and 119 fathers ranging in age from 31 to 62 years. Three stressors were presented to all participants: serial subtraction, mirror image tracing, and isometric handgrip exercise. Multivariate analyses of the stress responses were based on maximum likelihood estimations of the magnitude of association, which provided collective significance tests, and were adjusted for familial resemblance of resting pressure and heart rate as well as body mass index. These analyses showed significant parent-offspring and sibling associations in resting blood pressure and body mass index, which replicate those found in previous epidemiological investigations. The novel findings in this study were the sibling similarities in heart rate responses to mirror image tracing and in systolic blood pressure responses to isometric handgrip exercise. An analysis of a subset of the sample--only those nonmedicated parents compliant with instructions not to smoke or drink caffeinated or alcoholic beverages for 3 hr prior to testing and their children--showed a parent-offspring resemblance in systolic blood pressure responses to isometric exercise. This analysis, along with the significant sibling association from the full sample, suggests that systolic blood pressure responses to static exercise might aggregate in the family. The results are discussed in light of previous twin data. The relative paucity of significant parent-offspring associations of physiological parameters during serial subtraction and mirror image tracing tasks implies that non-familial influences are most important in determining cardiovascular responses to psychological stress.