atherogenic diet

We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the "treated" segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the "untreated" group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p < .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The antiatherogenic effect of propranolol on dominant animals was independent of the influences of serum lipid concentrations, blood pressure, and resting heart rate. We conclude that treatment with ,B-adrenergic-blocking agents may confer a degree of protection against CAA among individuals behaviorally predisposed to coronary heart disease. Circulation 76, No. 6, 1364-1372,1987. THERE IS increasing evidence that the behavioral attributes of individuals contribute to risk for atherosclerosis and coronary heart disease (CHD). Among human beings, the so-called type A behavior pattern (and, more specifically, the propensity to experience excessive anger or hostility) has been found to be predictive of CHD events in prospective studies of initially healthy individuals.1-7 Similarly, we have observed that when male cynomolgus monkeys fed atherogenic diets are housed in an unstable or stressful social setting, the highly aggressive and competitive dominant animals develop greater coronary artery atherosclerosis than their more submissive, subordinate counterparts.8' 9 Because these associations also appear to be independent of concomitant variability in From the Department of Comparative Medicine, Bowman Gray School ofMedicine ofWake Forest University, Winston-Salem, NC, and the Departments ofPsychology and Psychiatry, University of Pittsburgh. Supported in part by grants from NHLBI (HL 14164 and ROI HL 26561). Address for correspondence: Jay R. Kaplan, Ph.D., Bowman Gray School of Medicine, 300 S. Hawthorne Rd., Winston-Salem, NC 27103. Received April 16, 1987; revision accepted August 27, 1987. Presented as the Irvine H. Page Arteriosclerosis Research Award Lecture at the Annual Meeting of the American Heart Association, Dallas, November 1986. 1364 "established" risk factors for CHD and atherosclerosis, such as hyperlipoproteinemia, elevated blood pressure, and (among human beings) cigarette smoking and age, the mechanism(s) mediating behavioral influences on coronary disease remain unclear. In this regard, several investigators have proposed that recurrent activation of the sympathetic nervous system (such as occurs with intense behavioral arousal) may initiate or exacerbate atherogenesis, possibly via hemodynamic disturbances associated with abrupt rises in heart rate and blood pressure. 1013 Specifically, it has been hypothesized that cardiovascular responses to behavioral stimuli, if appreciable in magnitude and frequent in occurrence, may cause injury to the arterial endothelium. 14, 15 Such injury may then be followed by accumulation of plasma lipoproteins in the intima, the release of mitogenic substances by the damaged endothelium or by activated platelets, and intimal smooth muscle cell proliferation.6, 17 If behavioral stimuli can potentiate atherogenesis through accompanying activation of the sympathetic nervous system, it is also reasonable to hypothesize that individuals exhibiting the most pronounced cardiovascular reactions under "stress" will similarly be at CIRCULATION by gest on N ovem er 2, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-ATHEROSCLEROSIS heightened risk for exacerbated atherosclerosis. Such speculation is consistent, for example, with the observation that type A ("coronary prone") individuals experience larger cardiovascular responses than do their type B (noncoronary-prone) counterparts when exposed to frustrating mental tasks or other psychological