LIPID METABOLISM 



1 1 81 



regarded by investigators as capable of exerting a 

 significant influence on serum lipids. 



It is much simpler to speak of ■"abnormalities" in 

 serum lipids than to define what is ''normal." The 

 difficulty has arisen because of a discrepancy between 

 what is statistically normal and what is probably 

 physiologically desirable. Many authorities now 

 believe that statistical means for serum total choles- 

 terol in a population (like that of the United States) 

 that is beset with cases of atherosclerosis, clinical and 

 subclinical, may be misleading if they are used as 

 criteria of biologic normality. For example, in popula- 

 tion groups in which clinically manifest athero- 

 sclerosis is very rare, the mean serum total cholesterol 

 is frequently at least 30 per cent lower than it is in 

 the United States (118). 



Stress 



Despite many attempts to characterize "stress," 

 this phenomenon remains to be defined in generally 

 acceptable terms and its physiologic effects codified. 

 The "epidemiology" of stress is exceedingly complex. 

 The response of the individual to his environment 

 seems to be much more critical than the events 

 overtly taking place in the environment. Hence, it is 

 difficult to assess the degree of stress inherent in a 

 given occupation unless one also knows how the 

 individual is reacting to the "life situation" with 

 which he is confronted. For these and other reasons 

 the effect of stress on serum lipids remains contro- 

 versial (11, 179). It has been reported that students 

 displav a transient elevation of the serum cholesterol 

 level immediately prior to important examinations 

 (197) and that accountants exhibit similar elevations 

 when deluged with income tax returns (73). Even if 

 it is granted that such changes occur, it is not yet 

 known whether the lipid elevations result principally 

 from direct neurohumoral stimulation or because of 

 some associated change in the habits of the person 

 concerned. For example, it is well known that under 

 stress, activity rates may change and certain persons 

 may eat more or otherwise change their pattern of 

 living. 



There is some evidence that a certain type of "per- 

 sonality profile" is associated with predisposition to 

 coronary heart disease and that patients with such a 

 profile secrete significantly more epinephrine and 

 norepinephrine than control subjects (74, 75, 147). 

 The coronary-prone individual is characterized as 

 exhibiting excessive, frankly competitive drive and an 

 enhanced sense of time urgency (42). In addition, 



this type of individual may display a rapid, frequent, 

 forced, audible inspiration, tense facial and body 

 musculature, frequent fist clenching and a propensity 

 for hastening the pace of conversation. Such individ- 

 uals have been found to have higher serum cholesterol 

 and increased urinary excretion of vanillyl mandelic 

 acid than those exhibiting the converse of this be- 

 havior pattern. Vanillyl mandelic acid (VMA) con- 

 stitutes about 75 per cent of the metabolic end 

 products of norepinephrine and epinephrine. It has 

 already been mentioned that these catecholamines 

 stimulate mobilization of free fatty acids from adipose 

 tissue. Chronic administration of epinephrine (187) 

 has been found capable of inducing a rise in serum 

 cholesterol and phospholipids. Presumably this effect 

 is secondary to fatty acid mobilization from adipose 

 tissue. It is too early to draw any conclusions from 

 attempts to relate coronary proneness to behavior 

 pattern and catecholamine excretion rate. 



Sex 



Surveys have shown that American females be- 

 tween 20 and 50 years of age have significantly lower 

 levels of serum total cholesterol and low-density lipo- 

 proteins than age-matched American males (i2g). 

 It is obvious that the mode of life of females usually 

 differs from that of males in a given culture, and the 

 effect of such a differing pattern of activity upon serum 

 lipids and susceptibility to coronary heart disease is 

 difficult to assess. Nevertheless, a number of studies 

 have suggested that the endocrine differences between 

 male and female can adequately account for the fact 

 that during their reproductive period, women have 

 lower levels of certain serum lipids. In general, ad- 

 ministration of androgenic hormones to patients is 

 associated with a rise in concentration of /3-lipopro- 

 teins, while estrogenic hormones induce a fall in this 

 same lipoprotein fraction (58, 59). 



Whether such differences in lipid levels can account 

 for the established disparity in susceptibility to coro- 

 nary-artery disease between men and women remains 

 to be proved. However, supporting evidence is to be 

 found in the fact that women who have undergone 

 oophorectomy have "male" serum lipids and an 

 increased incidence of coronary-artery disease (212), 

 and that men treated with estrogen for prostatic 

 carcinoma have "female" lipids and less than the 

 expected degree of atherosclerosis (173). A recent 

 report from Edinburgh (151) has revealed that, over 

 a five-year period, one hundred men who had recov- 

 ered from a myocardial infarction, and who were 



