Behaviorally Induced Heart Rate Reactivity and Atherosclerosis in Cynomolgus Monkeys

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.