BEHAVIORALLY ELICITED HEART-RATE REACTIVITY AND ATHEROSCLEROSIS IN OVARIECTOMIZED CYNOMOLGUS MONKEYS (MACACA-FASCICULARIS)

It has been hypothesized that atherogenesis is accelerated among indiv iduals who exhibit heightened cardiovascular reactions to psychologic stress. We have reported previously that the coronary atherosclerosis of cholesterol-fed, male and reproductively intact (premenopausal) fem ale cynomolgus monkeys was exacerbated in animals that experienced the largest heart rate (HR) reactions to a fear-eliciting laboratory stre ssor. In this article, we report a similar relationship among 20 femal e monkeys that were rendered estrogen-deficient (by ovariectomy) and s ubsequently treated with replacement of both estrogen and progesterone . At the beginning of a 30-month study period, animals were fitted wit h ECG telemetry devices, and their HRs were recorded under baseline an d stressed conditions. Stress HR measurements were obtained during a s tandard challenge involving threatened capture and physical handling o f the animals. As part of a related experiment, monkeys were then ovar iectomized and, for the remainder of the study, administered 17 beta-e stradiol (continuously) and progesterone (cyclically) by subcutaneous Silastic implant (Dow Coming). Animals consumed a cholesterol-containi ng diet throughout, and HR measurements were repeated in the 24th mont h. At necropsy, the magnitude of animals' HR responses to stress corre lated significantly with intimal area measurements in the left anterio r descending and circumflex coronary arteries (r=.59 and r=.57, respec tively; P<.009). This association was due to a marked exacerbation of coronary atherosclerosis in animals comprising the upper third of the reactivity distribution. Although total and HDL cholesterol concentrat ions also covaried with HR reactivity, the greater atherosclerosis of ''high'' HR reactors persisted after statistical adjustment for concom itant variability in plasma lipids. HR reactivity was unrelated to blo od pressure, body weight, or social behavior.