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 class 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 prone 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 prone 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 constitutional 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 (Allbutt) 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.
=Sex=
There is no doubt that men are far more prone 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 repetition of this will produce
permanent high tension. In hospitals, the stevedores as a class 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 institutions, 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 sexual 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 prone to
live at high speed and wear themselves out sooner than the normal
person. The sexual 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 prone 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
adventitia 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 passed 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
passed 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 adventitia 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 sexes.
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 Wassermann
reaction was positive. Acute aortitis 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.
Mesaortitis 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 Wassermann reaction found in a large percentage of one series.
In fifty cases, 90 per cent either gave a positive Wassermann 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"
manifestations of syphilis. That syphilis is responsible for the
arterial disease in the vessels of the brain, resulting in apoplexy or
sudden cardiac death in middle life, has long been known. In fact, it is
claimed (Osler) that all aneurysms occurring in persons under thirty
years of age are due to syphilitic aortitis. In the late stages of
syphilis the arterial lesions may be of a diffuse character.
=Chronic Drug Intoxications=
Lead, tobacco, and according to some, tea and coffee, are to be classed
as causal factors in the production of arteriosclerosis. Certain it is
that all these substances have a tendency to raise the arterial
pressure, but whether the drug itself causes first a degeneration, and
later a hypertension results, or vice versa, is not yet positively
known. We have just mentioned that lead particularly has a marked effect
in producing arterial lesions. Other drugs as adrenalin, barium
chloride, physostigmin, etc., while producing experimental
arteriosclerosis, hardly could produce the disease in man. =Alcohol= has
been blamed for much, and as an etiologic factor in the production of
arteriosclerosis formerly was accorded a first place. More recently much
doubt has been thrown on this supposition by the work of Cabot, who
showed that the mere drinking of even large quantities of spirits had no
effect in producing arterial disease.
This observation has been recently substantiated by Hultgen, who
carefully studied clinically 460 cases of chronic alcoholism. He says,
"There are no cardiovascular symptoms which might be termed
characteristic of chronic alcoholism, unless it be the peculiar fetal
qualities of the heart sounds which we know as embryocardia. I find this
very frequent among drinkers, but I can offer only a tentative
explanation for it, namely the following: Embryocardia can only occur
with low tension blood pressure, and in the absence of renal
insufficiency. Hence it might be considered as a useful condition of no
pathologic significance at all. That alcohol is a sclerogenic pharmakon
and productive of arteriosclerosis with its usual train of symptoms may
be a fact, but its demonstration would be difficult and is really not
shown by my tabulations. There were cardiovascular changes, such as
myocarditis, aortitis, valvular heart disease and arteriosclerosis in
chronic alcoholics in 54.3 per cent of 461 cases, but this by no means
constitutes a proof of the causal relationship between these lesions and
the abuse of liquors. I believe it, nevertheless, to be good reasoning
to ascribe the bulk of cardiovascular symptoms to the sclerogenic action
of alcohol, while abstaining from an interpretation of its
pathogenesis." Just what role =tobacco= plays is difficult to say. My
own opinion is, that of itself when used in moderation, it has no ill
effects. However, as tobacco is a drug that may raise the blood
pressure, excessive use must be held responsible for the production of
arteriosclerosis. It is difficult to separate its effects from those
produced by eating and drinking.
=Overeating=
There can be no doubt but that the constant overloading of the stomach
with rich or difficultly digestible food is responsible for a large
number of cases of arteriosclerosis. Every one must have noted the
increase in force and volume of the heart beat after the ingestion of a
large meal. The constant repetition of such processes conceivably can
lead to damage to the vessel walls through hypertension.
In the metabolism of food in the intestines there are substances
produced which are poisonous when absorbed directly into the
circulation. Ordinarily these substances are rendered harmless either
before absorption or are detoxicated in the liver to harmless
substances. It is conceivable that a constant overproduction of such
poisons would eventually damage the defensive mechanism of the body to
such an extent that some of the poisons would circulate in the blood. An
expression of a surplus of one, at least, of these decomposition
products is the appearance of indican in the urine. It is not believed
that indicanuria has the importance attached to it which some authors
would have us believe. It is found too often and in too many varying
conditions, nevertheless it undoubtedly does reveal the presence of
perverted metabolism.
In how far the toxins absorbed from the intestinal tract are responsible
for the production of arterial disease, it is not possible to say. Some
observers lay great stress on this factor as a cause of
arteriosclerosis. The author believes that the role played by the
absorption of products of perverted intestinal metabolism is an
important one. The primary change is an increased tension in the
arterioles which later leads to thickening of the coats of the vessels
and to the other consequences of arterial disease. A vicious circle is
thus established which has a tendency to become progressively worse.
=Mental Strain=
More and more does one become impressed with the fact that patients with
arteriosclerosis are very often those who take life too seriously and
either from ambition or from an exalted sense of duty lead especially
strenuous lives. Not always are these persons addicted to drug or liquor
habit. Many are rather abstemious in their habits. It is not so often
that we see as a victim of arteriosclerosis, the carefree person who
laughs his way through life without worrying about the morrow. He is not
so prone to arteriosclerosis. Worry is a far more potent cause of
breakdown than actual manual work. It is the rule to find thickened
arteries among neurasthenics. This may be only part of a generalized
degeneration of all tissue in the body. The blood pressure in such
persons is usually low. So many men of our better class live under a
continuous mental strain in the business world. The increase in
arteriosclerosis cases is real, not apparent. The intense mental strain
seems to cause a marked increase in blood pressure (for short periods of
mental effort this has been proved) over a period of time sufficient to
cause permanent changes in the vessel walls. The same sequence of events
repeats itself; high tension, arterial strain, compensatory thickening,
hypertrophied heart, etc.
Certainly the character of the arterial tissue has much to do with the
determination of degenerative changes which may result from the action
of one or more of the etiologic factors.
=Muscular Overwork=
Muscular overwork is to be reckoned with as an etiologic factor. One
sees it especially among the laboring class in both whites and negroes.
Possibly other factors, as alcohol and coarse heavy food, contribute to
the early arterial degeneration. Hypertrophy of the heart occurs in
athletes, and statistics gathered among the oarsmen especially, show a
relatively high mortality at the different decades traceable to the high
tension produced while in training. This question deserves more
consideration than has been accorded it.
=Renal Disease=
Chronic disease of the kidneys (contracted red kidney) is one of the
most certain producers of hypertension; in fact, some maintain that high
tension, even without demonstrable kidney lesions, as revealed by
careful urine examinations, is a valuable sign pointing to chronic
nephritis. This is doubted by others, myself among them. Just what
causes the increase in blood pressure sometimes to over 270 mm. of Hg,
is not definitely known. It seems most probable that it is some poison
elaborated by the diseased kidneys and absorbed into the general
circulation. There it acts primarily on the musculature of the
arterioles causing tonic contraction and an increase of work on the part
of the heart to force the blood through narrowed channels. One fact is
certain. We see patients in coma due to renal disease with blood
pressure much over 200 mm of Hg. As these cases clear up, the pressure
may fall, and should they seemingly recover, the recovery is accompanied
with a marked decrease in blood pressure, finally reaching the normal
for the individual. Moreover, in the course of a severe acute or
subacute nephritis, hypertension is associated with headache, partial or
total blindness, and drowsiness. When the pressure is reduced, all these
symptoms disappear.
There is also the chronically shrunken and scarred kidney known
pathologically as the arteriosclerotic kidney. It is probable that there
are two groups of cases which we may designate: (1) primary; (2)
secondary. In the primary group the kidney disease antedates the
sclerosis of the arteries, and the sclerosis is most probably dependent
on the constant high tension. We know that prolonged hypertension will
produce severe forms of arteriosclerosis. The arterial disease in this
group is caused by the renal disease.
In the second group the kidney changes are apparently due to the general
arteriosclerosis which, affecting the kidney vessels, causes changes
leading to atrophy and subsequent fibrous tissue ingrowth of scattered
areas. These cases are not necessarily associated with hypertension; on
the contrary there is more apt to be hypotension. Where the first group
occurs for the most part in young and active middle-aged people, the
second group is the result of involutionary processes which accompany
advanced age.
However careful a urinalysis may be, there is no assurance that one can
predict the pathologic state of the kidney. Often so-called normal urine
will be secreted by a badly diseased kidney, whereas a urine which
contains considerable albumin and many casts may be secreted by a kidney
which is only temporarily the seat of inflammation. What matters after
all is not the state of the kidney which the pathologist describes, but
the actual functional response of the kidney in the body to the various
tests now well known.
=Ductless Glands=
At the present time the tendency among some writers is to make the
ductless glands the responsible agents in almost all diseases.
Arteriosclerosis is no exception to this tendency. Sajous, for example,
divides the morbid process producing arteriosclerosis into three types;
(1) autolytic, (2) adrenal, (3) denutrition. In the first type he finds
the pancreas to be the most important gland. It supplies an internal
secretion which "takes a direct part in the protein metabolism of the
tissue cells, and also in the defensive reactions within these cells, as
well as in the phagocytes and in the blood stream." This being the case
exaggeration of this digestive process has tissue destruction as its
result, arteriosclerosis among them.
In the adrenal type Sajous argues that adrenalin produces lesions
experimentally, therefore the adrenal gland has a profound influence by
its internal secretion in connection with the sympathetic system in
producing degenerations leading to arteriosclerosis.
The denutrition type has as its particular gland the thyroid. The
sclerotic process in the arteries is due to the lack of thyroid as in
cases of myxedema. After a long resume of his ideas he concludes "that
arteriosclerosis is the result of excessive or deficient activity of
certain ductless glands, the thyroid and adrenal in particular."
No one can dogmatically deny the part which the ductless glands may play
in the production of arteriosclerosis, but it hardly seems that there is
enough actual experimental evidence to show that they take such an
important part as Sajous believes. Until further and more convincing
evidence is offered by competent investigators, I prefer to look with
some skepticism upon the ductless gland theory of the causation of
arteriosclerosis. The field lends itself too easily to speculation and
imagery. Some are already allowing themselves the mental debauch of this
nature.