Serum Lipids and Atherosclerosis

That hyperlipemia may be responsible for atherosclerosis has long been hypothecated on the grounds of what might be termed circumstantial evidence. The first experimental proof of this concept was provided by Anitschkow's demonstration in 1913 that atheroma can be produced in rabbits by feeding cholesterol. In recent years similar lesions have been induced by similar methods in five other species: the dog (when fed thiouacil in addition to cholesterol), the chicken, the rat, the hamster, and the guinea pig. The use of these observations, however, to defend the argument that atherosclerosis in man originates from excessive levels of circulating lipids is open to several objections. First, it has not been conclusively shown that the experimental lesions are identical with those seen in human arteries, although they are similar. Second, the levels of serum cholesterol which are necessary to produce the disease in animals are far higher than those encountered in most patients. An exception is the finding of Katz, in chickens, that feeding small amounts of cholesterol, with resultant blood levels which are only slightly above normal, still leads to moderately severe atheromatosis of the aorta. Third, the causal relationship between hypercholesterolemia and atherosclerosis which has been so clearly established in other species has not been, and probably cannot be, equally well shown in human beings. For the present, at least, clinical investigators, hampered by the limitations of man as an experimental animal, must be content to determine whether, and how frequently, an association between serum lipids and arterial disease exists, and in so doing must recognize that, while such an association, if sufficiently close, may suggest cause and effect, it does not constitute proof. Attempts to demonstrate this sort of relationship have taken four lines of approach. It is our purpose critically to review a few of the most significant and representative of recent investigations which have been reported in each of these areas.