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Dr. WRIGHT. I should like to call Dr. E. Cowles Andrus, of Johns Hopkins, to open the talk on arteriosclerosis and atherosclerosis, hardening of the arteries.

The CHAIRMAN. Very well, Dr. Andrus.



Dr. ANDRUS. I shall speak briefly on this matter of hardening of the arteries and arteriosclerotic heart disease, beginning with a few fundamentals.

The fact is that if every organ in the body needed to be supplied with blood at its maximum needs all the time, there would not be enough blood to go around. Now, the fact that blood can be shunted to where it is most needed in adequate amounts rests upon the property with which the system of blood vessels is endowed to change their caliber. There is an example of that which you can all feel by feeling the pulse. Every time the heart beats a pulse wave goes throughout the vascular system and the volume of the arteries is actually increased by the amount which the heart puts out with each pulse.

Arteriosclerosis is a process which causes this capacity of the arterial system to vary its caliber to be lost to a greater or lesser extent. For a long time it was supposed that that was an inevitable consequence of aging. As a matter of fact, changes in the arteries, in the sense that they become less elastic, less distensible, do occur as we get older, so that the capacity suddenly or to an important degree to change the caliber is lost to some extent. However, if that was all that happened to us, disease of the arteries would be a much less severe affair than it is.

There is another process which is not a disease of aging which may be present even in childhood in rare examples, and which is coming to be somewhat better understood, though still in a crude fashion. This we distinguish, as contrasted with the simple stiffening of the arteries with age, by another name; we call this atherosclerosis.

Stated in a somewhat oversimplified fashion, this is a fatty degeneration of the arteries. It involves the deposit of fatty substances, undoubtedly absorbed from the blood in the inner coats of the arterial wall, leading to irregular thickenings in the arterial wall. And as the process advances it promotes the formulation of clots in the blood vessels so involved.

Now, that is vastly more common than one might suppose. In the big blood vessel, the big arterial trunk, called the aorta, it occurs in almost everybody. There it does not make very much difference, except for an occasional accident.

But the hazard of this process lies in the fact that it involves other arteries, some smaller, which are also vital, and the most common and most disastrous examples of such involvment are those of the arteries which supply the heart muscle itself, the so-called coronary arteries, and the arteries to the brain.

The statistics with regard to the occurance of these accidents are rather staggering. It is estimated, I think on reliable grounds, that there are about 300,000 deaths from heart attacks—that is the common term applied to coronary thrombosis, the clot forming in the coronary arteries in the United States each year. Happily, one of the things that has been learned about this is that it is not so uniformly fatal as was originally supposed. Less than one-fifth of the individuals die in in their first attack. But it is an extremely important abnormality.

Thus far I must confess our knowledge about it is pretty crude. But one particular direction of advance has been fruitful to knowledge if not to application to man. It is alwas true for the experimental scientist in medicine that there is a great advantage to be able to produce or to find the disease in animals upon which experiments may be conducted. Beginning with the observations of a Russian, Anitschkow before the First World War, in 1912, it was observed first that rabbits, if fed a high fat diet, and later that fowls, if fed a diet high in fat, would develop this disease. There are some species differences, but the process is very similar to that in man.

Within the last few years the disease has been produced in dogs, whose circulatory system is more similar to man than that of the fowl. That has given opportunity to apply various methods of relief or prevention to this experimental disease.

I would like to make it clear that in speaking of relief and prevention I am presently confining my remarks to the experimental disease produced in animals. It is not too much to hope that some phase of this may be in the end applicable to the disease in man, but I think it would raise false hopes to indicate that that was true with certainty at present.

I will speak of two directions in which knowledge has advanced in this disease which may be hopeful. The diet of an animal is relatively simple and can be controlled and to some extent the progress of this disease can be controlled by controlling the diet. Attempts to do similar things in man lead to impalatable and intolerable dietary restrictions.

Another line of possibly fruitful investigation stems from a fact which has long been known, that this disease in the human species is vastly more common and more severe in men under the age of 50 than in women. That leads to the inference that it is somehow a characteristic of the sex.

And it has been shown that when the disease is produced in cockerels, if those birds are "feminized” by giving female sex hormones the disease in the arteries can be caused to retrogress. I think that attempts will undoubtedly be made to do this in man. Thus far the observations have been limited to the fact that certain fatty substances in the blood which tend to be high in individuals who have manifestations of atherosclerosis can be reduced in concentration by the administration to the male of the female sex hormone.

Another line of investigation which is being developed is directed at the reduction of the absorption of these fatty substances from the diet with the intent of preventing their accumulation.

Thus far the links in this chain are not very closely tied together, but I think that one has genuine reason to hope that if the present momentum of study and knowledge in this field can be maintained or accelerated that some degree of control of this disease can be accomplished.

I think that is all.

Dr. WRIGHT. Gentlemen, are there any questions you would like to ask Dr. Andrus?

The CHAIRMAN. Mr. Dolliver?

Mr. DOLLIVER. As to the incidence of this disease and the accumulation of the fatty substances on the inside of the vessels, is there a uniform distribution throughout the body, or does it tend to accumulate in certain areas?

Dr. ANDRUS. It tends to accumulate in certain areas, but not the same from individual to individual. In large series—I mean thousands of autopsies—it has been shown, to take the coronary arteries, the arteries that supply the heart muscle, that 70 percent of the men in the sixth decade of life have relatively advanced grades of atherosclerosis in the coronary arteries. Obviously, 70 percent of the people at that age do not die of that, but for various reasons—imposed stress or other imponderable reasons—the plaque, the accumulation, happens to develop at a vital point in some and not in others.

Mr. DOLLIVER. Is there any medical explanation for the variation of this deposit in the different areas?

Dr. ANDRUS. There are medical conjectures. High blood pressure trends to foster the deposit of these substances. They tend to occur where stress is greatest and in a branching system like the arterial tree it will tend to occur near where branches leave.

There are three major branches which supply the heart muscle. One of the arteries is involved vastly more commonly than the others. But, as I say, one can only conjecture why, in some phases of this.

Mr. DOLLIVER. Would you care to express your own conjecture on that?

Dr. ANDRUS. Well, I think it is a matter of stress; it is a matter of pressure exerted in the artery. There is not any doubt that the tendency to the serious development of this disease has a hereditary element. It also is fostered and its consequences are evidently more serious with overnutrition. It is notably low in its incidence among the peoples who are undernourished.

Studies have been made in such places as Asia, in which undernourished populations have been examined, and the incidence found to be

Mr. DOLLIVER. Is it your conjecture that it may be the result of a high-protein diet or a high-fat diet?

Dr. ANDRUS. Well, I would not like to be as definite as that. Of course, there is a widespread opinion held in the medical profession that a high-fat diet conduces to this. It also conduces to overnutrition. We do not know that for certain, I think, sir.

Mr. DOLLIVER. The lethal blow in this kind of a disease is generally some occlusion or something of that kind ?

Dr. ANDRUS. It is.

Mr. DOLLIVER. What generally brings that about? Is there any general cause of that occlusion?

Dr. ANDRUS. Well, again, one can speak from averages rather than from the individual. It is often very difficult in the individual to learn precisely what event or what stress has led to this.

As I say, it occurs more frequently in those who are overweight. It is much more frequent in men than in women. It is more frequent in those with high blood pressure than it is in those with normal

very low.

blood pressure. And it tends to occur in the background of stress and fatigue. Overwork is, I think, undoubtedly a contributing cause.

I cannot trace cause and effect exactly, but it seems to be true in many instances.

Mr. DOLLIVER. Thank you, Doctor.
The CHAIRMAN. Any further questions? Mr. Carlyle ?

Mr. CARLYLE. Doctor, is it usually thought by those who have made a careful study of this subject that most coronary occlusions are brought about by a flake which gets into the blood stream?

Dr. ANDRUS. By a what, sir?

Mr. CARLYLE. By what I call a flake. You used the word “pipe,” or it was used this morning. I was just wondering if it were true that the larger arteries might corrode or some substance might gather and a flake would get into the blood stream.

Dr. ANDRUS. That is possibly true in a small number of instances, but much more frequently the thrombosis, the clotting, seems to take place at a site because this particular process, the plaque in the wall, has caused a roughening of the very smooth lining of the arteries and has led to a formation of a clot there. Occasionally the plaque will break from stress and will tend partially to occlude the artery, and then a clot will form in that case.

Mr. CARLYLE. If that clot should hit the brain then you would have a hemorrhage?

Dr. ANDRUS. Well, the particular clot that forms in the coronary artery cannot get to the brain because it is strained out by the finer branches of the coronary artery.

Mr. CARLYLE. The same substance would not cause the brain hemorrhage and a coronary occulsion; would it?

Dr. ANDRUS. Not the very same thing. There is a connection there which I think you may be thinking about, which Dr. Wright is particularly qualified to talk further about. When the clot forms in the coronary artery the heart muscle in the domain of that artery is injured. When the heart muscle is injured a clot may form on the inside of the heart. It is that clot that may break off and go to the brain, so that paralysis, or fatal cerebral embolism, which is the name we give to it, may be one of the complications and consequences of a coronary occlusion.

Mr. CARLYLE. Doctor, is it known to the medical profession what does cause a coronary occlusion?

Dr. ANDRUS. Well, sir, my remarks ought to have demonstrated, I think, that we do not know.

Mr. CARLYLE. I came in just a little late, but from what I heard you say I thought that.

Dr. ANDRUS. There are conjectures and there are things which we believe contribute enough to advise the patient to avoid. Overnutrition, fatigue and unusual exertion seem to precipitate these attacks.

Mr. CARLYLE. Let me ask you this additional question, Doctor: When a person has had a coronary thrombosis and has taken the prescribed treatment and has apparently recovered, is it ordinarily expected that an additional trouble will develop?

Dr. ANDRUS. I think the occurrence of a second coronary occlusion is more common. Another coronary occlusion is more common than the first one was, if I may put it that way. Given a coronary occlusion the patient is likely to have another one, but not inevitably so. There are plenty of instances in which an individual has returned to his previous occupation and carried it out for 25 years and died in the normal span. It is not inevitable.

Mr. CARLYLE. But, of course, the fact that one occlusion has been experienced makes it more likely that the patient would have another one?

Dr. ANDRUS. I think that is true, sir. Mr. CARLYLE. That is all. Mr. DOLLIVER. May I ask one other question ? The CHAIRMAN. Mr. Dolliver. Mr. DOLLIVER. I overlooked a matter I had in my mind, Doctor. That is with respect to the diagnosis of this condition. Can diagnosis be determined by blood chemistry; or what is the method?

Dr. ANDRUS. To which condition are you referring?

Mr. DOLLIVER. The gathering of this material, or the lessening of the diameter of the blood vessel.

Dr. ANDRUS. The diagnosis of arteriosclerosis or coronary sclerosis is still in a pretty indefinite stage. We diagnose the consequences of it but we cannot diagnose with accuracy the presence of atherosclerosis.

Mr. DOLLIVER. Thank you.
The CHAIRMAN. Any other questions, gentlemen ?

Doctor, I have before me a recent article in Look magazine, the issue of September 8, 1953, which is headed, Science Is Conquering Polio, Heart Disease, and Cancer, by William L. Laurence. By way of information it is stated that William L. Laurence, one time a philosophy teacher, has been a medical and science reporter for the New York Times since 1930. He has won two Pulitzer prizes in journalism and as early as 1940 foresaw the approach of the atomic age.

In this article, which I have not had the opportunity to read through, the opening paragraph states:

The conquest of polio, heart disease, and cancer, three of mankind's most terrifying scourges, is in sight. Within the next 10 years science will bring them under control and in the process will solve some of nature's greatest riddles. The victory, which will be counted among man's highest achievements in his never-ending exploration of the universe, will make you 10 years younger in 1963.

I assume that there can be some truth in a statement of that kind, but I would imagine there would be some difficulty in definitely fixing this fine result to take place within 10 years. Is it your opinion that with what is now taking place optimism in this respect would be justified ?

Dr. ANDRUS. Well, I must say I think that Mr. Laurence's expression is a pious hope. I doubt it myself, although I would give a lot to see that come true.

I think one can be encouraged by the progress in the field of research in vascular disease, in hypertension and in atherosclerosis. I am prepared to believe that we may never, or at least for a long, long time, get to the fundamental mechanism. I do not think that it is too much to hope that in a decade we may be able to influence the progress of the disease favorably, to slow it down.

Dr. WRIGHT. Dr. Andrus, would it not be wise to again emphasize the fact that we are dealing with a number of diseases, and that whereas it is quite conceivable that rheumatic fever might yield

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