I 2( 'I ' 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



by the triad: hypercholesterolemia, cutaneous or 

 tendon xanthomata, and severe premature athero- 

 sclerosis (sometimes occurring even in childhood), 

 is the most severe stage of this inherited disorder. It 

 is probably homozygotic. A hypercholesterolemic 

 tendency without xanthomata also occurs; this 

 milder form is heterozygotic (3). Recently, Epstein 

 rt a/. (41 ), restudying the families originally published 

 l>\ Adlersberg, re-emphasized the interplay between 

 genetic tendency and the environment. C. B. Thomas, 

 in her study of the families of healthy medical stu- 

 dents, showed a definite trend for the offspring of 

 parents with hypertension and or coronary artery 

 disease to have more hypertension and coronary 

 disease than children of parents not so afflicted. If one 

 parent had either of these diseases the occurrence 

 among the offspring was intermediate. Also, she 

 reported a fourfold greater frequency of occurrence 

 of coronary artery disease among the siblings of the 

 afflicted parents than among siblings of parents not 

 so afflicted. She concluded that the gradation of the 

 disorder rates were consistent with the Mendelian 

 law of inheritance. However, she could not exclude a 

 multiplicity of genetic factors and associated modify- 

 ing environmental agents. 



Whether genetic and hereditary factors influence 

 atherosclerosis also by determining the anatomical 

 pattern of the circulatory tree, particularly that of 

 the coronary circulation, is difficult to evaluate — but 

 the possibility does exist (94). 



In addition, the studies of Gertler & White (54) 

 on young coronary patients have yielded information 

 regarding body build. Even though no particular 

 '"coronar\- habitus" could be established, young 

 patients with coronary disease as a group belonged 

 predominantly to the mesomorph body build. Re- 

 cently, attention has also been focused on personality 

 and character traits, as well as the responsiveness of 

 the autonomic nervous system, partially genetically 

 determined, and their possible relationship to 

 coronary disease proneness. But these interrelation- 

 ships need further clarification (136). 



No data are as yet available on the familial tend- 

 ency to accelerated blood clotting and thrombus 

 formation, other than the tendency of hyperlipemic 

 serum to shorten coagulation time. However, it is not 

 inconceivable that such genetic traits may be un- 

 c 1 1\ cred. 



From the evidence presented it can be concluded 

 that genetic and hereditary traits may be an important 

 predisposing factor in an individual's response to 

 dietary and environmental factors leading to athero- 



sclerosis, anatomically and clinically. But this is still, 

 for practical purposes, an uncultivated field of 

 systematic study of great importance. 



STRESS 



In recent years, interest has grown concerning the 

 possible influence of physical activity and psycho- 

 logical or emotional stress on the development of 

 atherosclerosis. It has also been suggested that both 

 of these types of "stress" may be involved in precipitat- 

 ing thrombosis or sudden occlusion of a blood vessel 

 in which pre-existing but clinically occult disease is 

 present. Further, such stress may act as the trigger 

 mechanism in aggravating the ischemia of an organ, 

 particularly of the heart and the brain, which already 

 has a deficient blood supply because of an athero- 

 sclerotic process. The presence of atherosclerotic 

 disease per se limits the ability of the circulation of an 

 organ to adjust to augmented demands placed upon it. 



As has been pointed out for other facets of the 

 problem in previous sections of this chapter, "stress," 

 too, exerts its role only in the presence of a life-span 

 pattern of diet high in cholesterol and fat, particularly 

 saturated fat. When this potentially atherogenic diet 

 is absent, differences attributable to stress and other 

 factors fail to appear. Therefore, differences in the 

 incidence of clinical coronary disease according to 

 occupation for instance, are found only in those 

 populations in which the over-all incidence of this 

 disease is high, presumably because of the dietary 

 factor. 



Physical Activity 



Results from the animal laboratory with regard to 

 the influence of enforced physical activity in the 

 presence of an atherogenic diet are contradictors. 

 Brown et a/. (24) found no differences in rabbits. 

 Kobernick & Niwayama (81 ), working with chol- 

 esterol-fed rabbits which were forced to exercise 

 adequately by combining a mechanical treadmill with 

 conditioning to electric shocks, found significantly less 

 atherosclerosis in the exercised rabbits as compared to 

 the sedentary controls — although the degree of 

 hypercholesterolemia was similar in both groups. 

 Brainard (23), working with rabbits exercised on a 

 treadmill, found no differences in the amount of 

 aortic cholesterol between the active and the seden- 

 tary group. Myasnikov (109) obtained positive 

 results in the rabbit in favor of a protection of the 



