CHAPTER VI

ETIOLOGY

The causes of arteriosclerosis are many and varied. No two persons have the same resisting power toward poisons that circulate in the blood.

Some go through life exposed to all the infectious diseases without ever becoming infected, while others fall easy victims to every disease that comes, no matter how careful they may be, and it is quite the same in regard to the resistance of the arterial tissues. If the tubing is of first cla.s.s quality and the individual does not place too much strain on it, he may live to the biblical three-score years and ten, and possess arteries which have undergone such slight changes that they are not palpable. Such a person is, however, the exception. On the other hand, if the tissue is of poor quality, even the ordinary wear and tear of life causes early changes in the vessels, and a person of forty may have hard arteries.

We have described in a previous chapter the changes which normally occur in the arteries as age advances. An artery that is normal for a man of fifty years would be distinctly abnormal for a boy of fifteen.

Two broad divisions of arteriosclerosis may be made: (1) congenital, or the result of inherited tendency; (2) acquired.

=Congenital Form=

When Dr. O. W. Holmes was asked how to live to the age of seventy, he replied that a man should begin to pick his ancestors one hundred years before he was born. Our parents determine the character of the tissues with which we start in life, and this determines our general resistance.

We might properly speak of congenital arteriosclerosis where the affected individual had poor arterial tissue with which to begin life, for that, in a sense, is a congenital defect, and arterial tissue that is poor in quality is p.r.o.ne to disease.

The author is more and more impressed with the part that heredity plays in the determination of arterial degeneration. Especially does syphilis in the parents or grandparents leave its stigma in the succeeding generations in the shape of poor arterial tissue which is p.r.o.ne to early degeneration. Recently W. W. Graves has called attention to a malformation of the vertebral border of the scapula which consists in a concavity instead of the normal convexity of the bone. To this malformation he has given the name, scaphoid scapula. He considers this to be but one manifestation of a general lack of development in the individual. He speaks of this maldevelopment as a blight and considers that syphilis in the ancestors is responsible for the condition in the offspring. He finds that even in children, the subjects of the scaphoid scapula, the arteries are very definitely thickened. While confirmation of his observations is lacking, there is no doubt that we must lay the blame for much of the arteriosclerosis in our patients to the poor quality of arterial tissue transmitted by ancestors who have acquired some const.i.tutional disease. It may have been syphilis, it may have been the degeneration produced by alcohol or other drug. We can not ignore the part which heredity plays. The various factors to be considered in the production of the acquired form of arteriosclerosis appear to me to be but contributory factors to a very great extent, the essential and fundamental factor being the quality of arterial tissue with which the individual is endowed.

Arteriosclerosis may occur in infants. Cases have been reported of calcification of the arteries in infants and children. The arteriosclerosis may occur without nephritis or rise of blood pressure.

Cerebral hemorrhage in a child of two years has been seen. Heredity in these cases plays a most important role. In many of the reported cases there was no question of congenital syphilis. Aneurysms, single or multiple, have been found in the arteries of children, and even the pulmonary artery may show sclerotic changes.

=Acquired Form=

As a rule the cases usually seen belong in this group because it seems as if a connection could be established almost always between one or more of the etiologic factors to be described and the disease. While this apparently is the case, we must never lose sight of the part which the quality of the tissue plays. When we leave this out of our calculations we undoubtedly make many false deductions. When two men of the same age who have been exposed to the same conditions as far as we can learn, are found to have quite different arteries, the one normal, the other thickened, we must postulate congenitally poor tissue on the part of the latter. Such tissue readily becomes diseased following conditions which would very likely have produced no noticeable effect on perfectly normal, healthy tissue.

=Hypertension=

Hypertension must still be reckoned with in the etiology of arteriosclerosis although the role that it was thought to play does not seem so important. Changes of blood pressure alone are not considered by many to be sufficient for the production of arteriosclerosis. This may play some part, but there are many other factors mostly unknown which determine in any case the production of arterial lesions.

With every systole of the heart, blood is forced out into the arterial system against a certain amount of resistance represented by the tonicity of the capillary area, and the amount of cohesion between the viscous blood and the walls of arterioles. When a dilatation of the capillaries over any large area takes place, the blood pressure falls, provided there is no compensatory contraction in other areas to make up for the decreased resistance in the dilated vessels. The viscosity of the blood, as such, probably has very little effect on the resistance to the flow. With the systole of the heart there is a sudden dilatation of the arch of the aorta, and a wave of expansion follows, which is transmitted to the periphery and is lost only in the capillaries.

The blood pressure is constantly changing. Physiologically there are relatively wide variations in the pressure in a perfectly normal individual. There are some persons who have hypotension, a blood pressure much below the normal. Such persons have usually small hearts, small aortas, and they seem to have but little resistance to disease.

Many diseases, especially the prolonged fevers, diminish markedly the blood pressure. Whether the hypertension is the cause of the structural changes that are found in the walls of the vessels, or is the result of the diminished area of the arterial tree through which the same amount of blood has to be driven as before the vessel walls became narrowed, is still disputed. As has been stated, experimental evidence would tend to place the initial blame upon the poisons circulating in the blood, which first damage the vessel walls. The subsequent changes then produce thickening and inelasticity. Some think (Allb.u.t.t) that the hypertension is primary. There are cases seen clinically that lend support to this view and there is experimental evidence also (v. Chap. II). Not infrequently individuals in middle life begin to show increase of arterial blood pressure without discoverable cause. In such case it may be that there is slowly progressing chronic nephritis. The urine if examined only superficially in single specimens may not reveal any abnormalities. Careful functional examination by means of the newer tests may reveal functional deficiency. It must not be supposed that all cases of increasing hypertension are cases of chronic nephritis. The opinion has already been expressed (Chap. III) concerning this point.

Experience has convinced me that the opinion expressed in former editions is not altogether correct.

=Age=

No age is exempt from the lesions of arteriosclerosis if we consider the two groups. However, the disease is seen for the most part in persons past middle life. The relative frequency with which it is found in the different decades depends on so many factors that it is of no value to tabulate them. As has been stated, arteriosclerosis of all types is an involution process that advances with age. Longevity is a question of the integrity of the arterial tissue, and no one can tell what sort of "vital rubber" (Osler) any one of us has. However, many with poor tubing may make such use of it that it will outlast good tubing that is badly treated. Unfortunately we have no way of telling early enough with just what sort of arterial tissue we are starting life.

=s.e.x=

There is no doubt that men are far more p.r.o.ne to arterial disease than women are; all statistics are in accord on this point. This is explained by the greater exposure of men to those conditions of life which tend to produce circulatory strain, and so to produce arteriosclerosis, or vice versa. Arteriosclerosis in women is not often seen until after the fiftieth year. Cases of the most extreme grade of pipe stem arteries are, however, seen in old women, and calcified arteries are not hard to find among the inmates of an old woman's home.

=Race=

Some of the most beautiful examples of arteriosclerosis in this country are seen in the negro. Not only is this disease more frequent in the black race, but the age of onset is much earlier than in the Caucasian.

The accidents of arteriosclerosis, viz., aneurysm, cerebral hemorrhage, etc., are more common among the negro males. The etiologic factors that are most often found in the history are the prevalence of syphilis and hard physical labor.

=Occupation=

Certain occupations have a distinct causal relationship to arteriosclerosis; among such are particularly those entailing prolonged muscular exercise, especially if much lifting is necessary. Every one is familiar with the phenomena accompanying the exertion of lifting. The breath is drawn in, the glottis is closed, and the muscles of the chest wall are held rigidly while the exertion lasts. This causes a great increase in blood pressure, and constant repet.i.tion of this will produce permanent high tension. In hospitals, the stevedores as a cla.s.s have marked arteriosclerosis, and, almost without exception, they are comparatively young men. Occupations that are accompanied with prolonged mental strain, such as now occur to the heads of large manufacturing and financial inst.i.tutions, also predispose to early arterial changes.

Psychic activity, especially when it is accompanied by worry, is a potent factor in the production of the increased blood pressure which is the chief factor in producing arterial disease. It has been suggested that s.e.xual continence in high-strung men produces changes in the nervous system which can conceivably lead to the production of high tension and further to arteriosclerosis. This, however, I can not think has any foundation in fact except in so far as such men are p.r.o.ne to live at high speed and wear themselves out sooner than the normal person. The s.e.xual continence _per se_ is not harmful. There are, however, men who seem not to be harmed by the constant wear and tear of our modern life. These are the exceptions.

Workers in factories where paint is made and the ingredients hand-mixed, are p.r.o.ne to develop arteriosclerosis early in life. It has been found that the laborers most apt to be victims of lead intoxication are those who are careless in their habits of cleanliness, particularly in regard to the fingernails. The continuous absorption of lead into the system, brings about a condition of hypertension that has its inevitable results.

The fact is that any occupation which entails either the absorption of toxic substances, or prolonged muscular labor, will hasten markedly the onset of arterial disease.

=Food Poisons=

The opinion that arteriosclerosis is due in large part to poisoning by end products or by-products of protein digestion is now receiving much support. Experiments on dogs and rabbits have lent some confirmation to chemical observations. It has been shown that dogs fed for a long time on putrefied meat developed inflammation and degeneration of the advent.i.tia and media, with hyperplasia and calcification of the intima of many arteries. In the pulmonary and carotid arteries, in the vena cavas and myocardium, there were extensive necroses and hyaline degeneration. Moreover, injections of sodium urate and ergot caused necroses in the muscularis and elastica of the aorta, pulmonary artery, vena cavas inferior and heart muscle, but there was no calcification.

Guinea pigs which were fed indol in small doses by the mouth over a long period showed atheromatous degeneration of the aorta.

=Infectious Diseases=

As more study has been given to the arteries in persons who have died of the acute infectious diseases, more has come to light concerning the effects of the toxins of these diseases on the vessel walls. In the arteries of children who have died of measles, scarlet fever, diphtheria, cerebrospinal meningitis, etc., degenerative changes in the arteries occur, modified only by the length of time that the toxins have acted.

Thayer has shown that the arteries of those who have pa.s.sed through an attack of moderately severe or severe typhoid fever are as a rule more readily palpable than are the vessels of persons of corresponding years who have never had the disease. Clinically the typhoid toxin appears to cause the early production of arteriosclerosis. The changes in the arteries occur for the most part, and always earlier, in the peripheral arteries, and the media is chiefly affected. Minute yellowish patches are found on the aorta, carotids, and coronaries. In persons who have pa.s.sed through an attack of one of the fevers, and have later died from some other cause, regenerative changes are sometimes found to have taken place in the arteries, consisting of an ingrowth of elastic fibers from the intact advent.i.tia to the diseased media.

That there are some other factors than the infectious disease which are concerned in the production of arterial changes seems evident from a study[14] made recently among a group of almshouse inmates ranging in age from 38 to 90 years. The study included 500 persons of both s.e.xes.

Careful histories were taken to determine the presence of antecedent infectious disease. The radial artery was palpated to determine the presence of sclerosis. Among the cases giving a history of one infectious disease the following table gives the results:

------------------------------------------------------------- DISEASE NO. + ++ +++ POSITIVE NEGATIVE ------------------------------------------------------------- Measles 47 10 6 12 28 19 Infectious arthritis 38 9 6 4 19 19 Pneumonia 30 5 8 5 18 12 Typhoid 27 6 8 3 17 10 Scarlet fever 10 0 0 4 4 6 Smallpox 14 1 4 0 5 9 Miscellaneous 12 2 5 2 9 3 ------------------------------------------------------------- 178 33 37 30 100 78 -------------------------------------------------------------

[14] Warfield, L. M.: Jour. Lab. and Clin. Med., November, 1917.

A summary of the cases showed: 252 cases without sclerosis; 248 with sclerosis; 147 cases with infections but no sclerosis; 180 cases with infections and sclerosis.

This study failed to throw any positive light on the question.

Infectious diseases undoubtedly play a certain role, particularly those continuing a long time and certain particular infectious diseases, as measles.

=Syphilis=

Syphilis is one of the most important of the etiologic factors in the production of arteriosclerosis. It has been shown that in 85 per cent of cases of aortic insufficiency in persons, usually males, over forty-five years, who did not have chronic infective endocarditis, the Wa.s.sermann reaction was positive. Acute aort.i.tis affecting the ascending and transverse portions of the arch of the aorta is very commonly seen, and the irregular, scattered, slightly raised, yellowish-white patches of sclerosis in the arch which are found years after the syphilitic lesion, are considered by some to be very characteristic of syphilis.

Mesaort.i.tis is the primary lesion and acts as a _locus minoris resistentiae_ where an aneurysm forms.

Hypertensive cardiovascular cases have been serologically studied, and a positive Wa.s.sermann reaction found in a large percentage of one series.

In fifty cases, 90 per cent either gave a positive Wa.s.sermann reaction or luetin test, were known to have syphilis, or had children with hereditary syphilis. This suggests what might be called "familial cardiovascular syphilis."

Hypertensive disease is possibly one of the common so-called "late"