The Biology of Myocardial Infaretion
By GUNNAR BIORCK, M.D., F.R.C.P.
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SUMMARY
Myocardial infarction is a dreaded companion of the civilization of our time. The
"heart attack," the coronary thrombosis, the myocardial infarction lurk behind the
corner, striking strangers, patients, friends, and ourselves. The toll taken by this
single "disease" in many hospitals equals or even exceeds that from almost all other
diseases together. Must it be so? This is the question many physicians, and the lay
public, are asking themselves today.
Identification of some areas where our knowledge is particularly deficient is stressed.
We must concentrate our efforts on reevaluating practices and procedures that have
brought both the greatest success and the worst failures, at the same time that we ask
ourselves what goals could be considered realistic.
If myocardial infarction is the evil of our time, what does this mean in a greater
biological context-in the evolution of human life and endeavor as viewed in perspective?
Are we dealing with a "disease" in the restricted sense of the word, or are we dealing
with a way of life and a consequent mode of death? If so, what can be done to achieve
the goals of health as defined by the World Health Organization? In what terrain are
the forces to be assembled and the battle to be fought-and by whom.
Additional Indexing Words:
Coronary heart disease
Hospital mortality from coronary heart disea
Intensive care units
gists of this country. Your nation is at the top
of the list both with regard to prevalence and
incidence of that disease and with regard to
research concerning its causes, effects, treatment, and prevention. And yet, the subject
proposed to me, "The Biology of Myocardial
Infarction," is close to my heart; something I
have been living with the last 25 years, and
with which I have been wrestling as biochemist, physician, sociologist, and hospital
administrator. I have been forced to analyze
the problems at different levels and with
various techniques. I shall try to convey
some of my experiences, thoughts, and unanswered questions.
T HE American Heart Association has
asked me to give the first Paul Dudley
White International Lecture. For this honor
I express my sincere thanks.
I pay tribute to this great nation as a
leader in science, in medicine, in cardiology,
and to Paul Dudley White, scientist, physician, teacher of cardiology, and ambassador
of good will. He is known to the whole world
as an inspiring example of the American
people at their best. I have had the good
fortune to know Paul White for more than
20 years as teacher, research companion, and
friend.
A visitor from abroad cannot be expected
to bring much new information on the subject of myocardial infarction to the cardiolo-
Coronary Heart Disease and
Myocardial Infarction
Myocardial infarction is an acute event in
the course of a chronic disease of multifactorial origin. The "biology" of this event relates
both to the predisposing causes and mechanisms, and to possible precipitating factors
From the Karolinska Institutet and Serafimerlasarettet, Stockholm, Sweden.
International Lecture read at the Fortieth Scientific
Sessions of the American Heart Association, San
Francisco, California, October 20-22, 1967.
Circulation, Volume XXXVII, June 1968
Angina pectoris
Statistical approach
(fig. 1).
1071
BIORCK
1072
Clinical manifestations:
Causes:
Arrhythmia
Sudden death
Lipid metabolism
Carbohydrate metabolism
Coronary heart disease
Occlusion: Angina
Infarct
Hypertension
Others
Progres sive
heart failure
Figure 1
Causes and clinical manifestations of coronary heart disease.
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Trends in mortality from coronary heart disease (B 26) in S\wden
Death rates per 100 000 nean population
6000
-
4000
Pr 00 000
80-84_
-4000
- 75-79I
2000
_
__
70 -'
65-69.
1000
aoo
600
4'
FEMALES
MALES
Pr 100 OOCD
= _
2000
-1000
60-64
__
_
400
600
-400
200
200
a
u
, 100
100
= 45-49
.280
_
_
60
s0
60
40
40
40-44
20
20
10
8
6
4
_~~~~~~
lk..
_J
I
__ _
-
35-39
10
8
6
2
1
1951-
1956-4960
1961-196
1964-1986
1951-19
1956-1960
19614963
1964-I6
Figure 2
Trends in mortality from coronary heart disease (B 26) in Sweden (Reprinted with permission
Bi6rck, G.: Liikartidningen 64: 5231, 1967.10)
from
Circulation, Volume XXXVII, June 1968
1073
BIOLOGY OF MYOCARDIAL INFARCTION
What we know about myocardial infarction
we know from clinical case material, from
autopsy studies,1 and, in addition, from
epidemiological field studies24 and international statistics based on death certificates.5 7
We have reason to believe that morbidity
and mortality patterns in coronary heart
disease are not everywhere congruent.
Many issues are still ambiguous. An infarct
has been considered to be caused by an
Pr
occlusion of a coronary artery, mainly by a
thrombus. However, in many instances, no
thrombus is found8 despite microscopic evidence of damage to the myocardium. Some
patients present the classic clinical picture of
myocardial infarction. Others succumb in a
few minutes to fatal arrhythmias. Some develop angina pectoris; others, progressive heart
failure indistinguishable from myocardial
weakness from other causes.9
I
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.
-
55
w
60
Figure 3
Mortality for men from all causes and from coronary heart disease (B 26) in the United States
and in Sweden for 1963-1964. Death rate levels per 100,000 mean population for men in the
U.S.A. at the age of 40, 45, 50 years and so on, and the corresponding ages of men in Sweden
with equal death rates (age in years in the circlets).
Circulation, Volume XXXVII, June 1968
1074
Clinical research is generally based on hospital patients. Infarct patients brought to the
hospital may live long enough for us to engage in a battle whose outcome is always uncertain. In sudden death the battle is over
before it has begun. In progressive cardiac
failure of the aged the acute dramatic element
is often missing. This is why, in part, we know
little about many coronary manifestations outside the hospital, and why classical infarcts
have stolen the show.
What Makes the Myocardial Infarct
Such a Big Problem?
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At my hospital in Stockholm, the Seraphimer, deaths from myocardial infarction now
make up 40% of all medical service deaths.10
The number of patients admitted with myocardial infarction has been increasing every
year during the last 30 years. This is evident
in data from both the General Hospital in
Malmd'1-12 and the Seraphimer Hospital,'3 15
the two medical services in Sweden where
this development has been most closely
studied.
In Malmd, we found that the 4-week hospital mortality from cardiac infarction fluctuated around 30% in each 5-year-period between 1934 and 1959.16
In Stockholm, there has been an alarming
rise in the mortality figures back to and even
exceeding levels I remember from the early
1940's in Nylin's department.'14 15
Impressions from hospitals may be misleading and have to be correlated with information about the population served by the
hospital. Such data are scarce. Malmo is a
useful example because there is only one
large hospital serving a community of 14 million inhabitants.17 Framingham is another
example.2
Figures from the Central Statistical Office
in Sweden (fig. 2) show a moderate increase
in mortality from coronary heart disease (B
26) in men over recent years, and a corresponding decrease in women-a trend observed almost everywhere.
Despite our high hospital mortality rate our
figures on death from coronary disease are,
BIORCK
internationafly, quite low (fig. 3). Sweden
and Denmark seem to follow the same pattern.18 Norway, while starting lower, is now
in the process of overtaking us. Finland is
far above us all, holding a position as an
equal to the Anglo-Saxons: United States,
United Kingdom, Canada, Australia, New
Zealand, and Ireland.7 Why that is so, we do
not know.
These figures relate to deaths from all coronary disease (B 26), and not particularly
from myocardial infarcts.
The fraction of all coronary death certificates in which infarction was stated as the
cause of death has been shown to vary considerably between age-groups, being high in
younger groups and low in older groups.16
For a long time I was inclined to interpret
these findings as indicating that a greater
proportion of older persons die from progressive cardiac failure, ascribable to atherosclerotic heart disease.
What has begun to worry me increasingly
is the knowledge about sudden death unravelled parallel with new techniques of
cardiac resuscitation and coronary care in
much the same way that the cardiac catheter
paved the way for fuller recognition of congenital heart disease. The best source of information still seems to be the Framingham
study in which one out of six men who
developed symptoms of new heart disease
during a 12-year observation period died unexpectedly within less than an hour. These
deaths appear to have made up 40% of all
male coronary deaths during the period of
observation.'l
Even more impressive figures have recently
been collected by Morris4 on a population
of 7,000 male British physicians, aged 40 to
64 years, in whom sudden death appears to
be more than twice as frequent as other
types of death ascribed to ischemic heart disease. If this is true, what is the place of the
myocardial infarct? We do not know how to
classify sudden death in relation to an infarct. In contemporary lingo it may represent
"electrical failure" rather than "power failure,"
and this may escape the notice of even the
Circulation, Volume XXXVII, June 1968
BIOLOGY OF MYOCARDIAL INFARCTION
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most careful pathologist. But there is a fair
suspicion, substantiated by findings in a recent
analysis from our department, that the better
we prepare for the instant care in our hospitals of patients with "heart attacks," whether
living, dying, or already dead, the greater
will be the transfer of the sudden death
cases now in the death-certificate group
outside the hospital to the the hospital sector.
There they may be given a diagnosis of
myocardial infarction (especially in case of
survival) .8, 15 Such a process will make considerable impact on statistics and planning,
particularly as the older citizens who represent the vast number of victims of coronary
heart disease avail themselves of Medicare or
other inventions of our great societies. We
should not forget that although much emphasis is commonly placed on infarcts among
middle-aged executives, the President's commission in this country stated that 72% of all
cardiovascular deaths in the U. S. occurred
in persons 65 years or over.20 The corresponding figure in Sweden today would be 84%.
In this connection attention should be
drawn to the fact that mortality from coronary
heart disease (B 26) shows a fair correlation
to mortality "from all causes."7 The high
coronary death rates in some Westem countries are found in countries with a high
"biological age" (for example, a high overall
mortality from all causes) and vice versa.
The percentage of coronary deaths in relation to total deaths in age groups over 60
years is rather similar in all Northwestern
European countries, irrespective of differences in the younger age groups, whereas
Italy, Portugal, and Japan have much lower
relative frequency of CHD-deaths at all ages.
The United States and Canada have a higher
proportion of CHD-deaths.7
This observation reflects another aspect
of coronary artery disease. It has frequently
been stated that more and more of its victims
belong to younger age groups. Even though
the upward trend in the youngest male age
groups is getting steeper in my country, the
numbers are still small and count little in the
total picture. Rather the average age of
Circulation, Volume XXXVII, June 1968
1075
Swedes who become hospitalized with a first
myocardial infarct has been rising over the
last 25 years, about 5 years for men and 10
years for women. This rise is of the same
order as the increase in life expectancy at
birth over a corresponding period and is far
in excess of the increase in life expectancy at
age 50.
At what time in your life do you get your
extra years added or subtracted? It may be
in early life, as suggested by Hardin Jones.2'
I think it is important to bring this question
into any consideration of the biology of myocardial infarction.
I have repeatedly stressed that most of
the information from vital statistics concerns
coronary heart disease overall and not myocardial infarction. We cannot easily project
hospital data onto the population at large.
But now that we are mobilizing forces to
combat more effectively the acute manifestations of coronary heart disease, we ought to
know more of the incidence of sudden death,
myocardial infarction, and other clinical
manifestations of coronary heart disease in
our communities. This will necessitate some
kind of coronary heart disease registry in
defined populations, a world-wide Framingham study, without upper limits as to age
and with emphasis on types of "new disease,"
on modes of death, and on disability and
rehabilitation. A recommendation to that end
was recently forwarded by a scientific group
within the WHO.
The Course and Prognosis of
Myocardial Infarction
While it is difficult to deal with the natural
history of myocardial infarction as an isolated
phenomenon, something may nevertheless be
said about its course and prognosis.
In the large groups of cases with primary
myocardial infarction in Malmo, to which I
have referred, the future course of the
"disease" could be empirically described in
figure 4.16
Other large hospital statistics give similar
results. Information on the subsequent course
of patients with angina pectoris, which is
BIORCK
1076
SOME
ASPECTS ON THE NATURAL H;STQRY OF
ANGINA
ANGINA
PECTORIS
2 MOS NON CHAR
OS CHEST
SINCE MOREt
ATTACK
36%
gENJERAL CHiARACTERISTICS
DISCOMFORT DISCOMFORT
PRIOR THAN 2 MOS.
TO THE
ACMiE
NO ANGINA,
NO CHEST
HS
N
MYOARDIAL :NFA!TION.
4
is%
1,821 CASES
. &h.LU
IOIAL
PRIMARY INFARCTION 1,530
.64.0 f
ONE PREVIOUS ATTACK 238
.13.1 f,
TWO Ot MORE 53 -2.9 f.
32%
PRIMARY INFA201JiON
ai IS AN IMPORTANT
FACTOR
WITH REGARD TO
SEX tATIO AND IMMDIATE
PROGNOSIS.
AGE SEX RATIO MORT.,
24
6.0:1
(40
12
411
40.49
23
3.2:1
50-59
4ACUTE PERIOD
(4 WEEKS)
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1.51:
0.9:1
60-69
70-79
33
47
64
1.1l
*o-.
MEAN AGE: MALES
60-.,
FEMALES 66.5 YEARS.
66 PER CENT OF THE MALES,
74 PER CENT Of THE FEMALES
WITHIN THE RANGE OF MEAN
AGE tIl YES.
5 YEARS
LONG -
TEM
FG&S
IN
PATIENTS SURVIVING THE ACUTE
PERIOD (4 WEEKS)
TIE AFTER 5 0 20 ns.
10 AS
SURVIVING, 56
PER CENT
34
12
PATIENTS
CAUSE
DLIEII
gv
SURlvlVlVG 04 WEEKS. PER CENT
Of ALL
67EARS
DEATHS.
CORONARY DIS.
CERESROVASC.
OTHER CARDIOVASC.
\NON CARDIOVASC.
74%
7%
9%
1%*
20 YEARS
WURVIVING.
PER
CENT
PE tR CENT
Figure 4
Some aspects of the natural history of myocardial infarction. (Reprinted with permission from
Biorck, G.: Course and prognosis in some cardiac diseases. 1962, Pergamon Press.16)
sparse since the early reports of White and
associates22 and of Block and co-workers23
indicates that the prognosis in angina pectoris
is equivalent to that for survivors of an acute
myocardial infarct.24 However, the average
course and prognosis give little information
on the many factors that influence the fate of
the individual patient. Rather they include
and obscure such factors. Some of these relate
to the patient, others to the treatment given.
We know that age is very important in
determining the mortality risk during the
first weeks of the acute infarct, mortality
here being almost linearly related to age.25
Ci7culation, Volume XXXVII, Jane 1968
BIOLOGY OF MYOCARDIAL INFARCTION
1077
Table 1
Excess Mortality in Patients Surviving the Acute Phase of Primary Myocardial
Infarction*t
Number of deaths! expected deaths after
15 yr
10 yr
5 yr
2 yr
Age
No. of
(yr)
patients
1 yr
Males
30-39
40-49
15
94
27.7
33.4
12.4
6.8
51.2
16.6
8.4
4.2
5.6
13.2
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50-59
60-69
70-79
80
Females
30-39
40-49
50-59
60-69
70-79
80
206
209
83
7
4
20
68
141
106
12
17.1
8.5
5.6
26.7
6.2
3.5
3.0
1.9
13.6
5.0
3.3
1.9
1.3
12.3
10.0
5.0
18.6
5.7
3.3
8.8
3.7
2.2
3.7
2.1
1.4
5.2
7.1
4.0
2.2
1.5
5.5
2.9
1.6
20 yr
2.5
1.4
1.2
4.1
2.0
*Number of expected deaths calculated from census data (age and sex specific death rates,
Swedish town population 1941-1950).
tReprinted with permission from Bidrck, G.: Course and prognosis in some cardiac diseases.
1962, Pergamon Press.16
The apparent higher mortality in women can
mainly be explained by their being older at
the time of attack. For this reason, mortality
figures on infarction materials always must
be related to the age of the group. International comparisons are confounded by the fact
that "biological age" in any two populations
may correspond to different chronological
ages.
When it comes to long-term prognosis, it
is clear that older age-groups have a shorter
absolute survival after infarction than the
But if comparisons of remaining life-expectancy are made between
survivors of a myocardial infarct and the
uninvolved population of the same age,
younger persons fare less well than older
ones,'6 that is, for them the mortality risk is
greater (table 1).
Other factors that seem to influence longterm survival in infarction are antecedent
diabetes-overt or latent-and hypertension.
This may be explained merely as the addition
of two risks to each other.'2 16
The size of the infarct, judged from determination of the enzymes GOT and LDH,
appears to influence the immediate prognosis
as well as the long-term prognosis.26 7
younger groups.
Circulatios, Volumee XXXVII, June 1968
These data may become obsolete in view
of present trends in treatment, which is the
other big factor influencing course and prognosis. We cardiologists have not been able
to show improvement, either in immediate or
in long-term prognosis over the past 25 years.
Immediate prognosis with the patients may
even have worsened in recent years, probably
as a result of patients with more severe
conditions being admitted to the hospital.
Both in Malmo and in Stockholm hospital communities, there is a continuous increase in
the mean age of patients at their first infarct
which per se would increase the immediate
mortality. Therefore, even a constant mortality rate might represent some improvement.
On the other hand, several recent reports from
special coronary care units indicate considerable reductions of immediate mortality.28-32
This is a new feature which must be taken into
account in future predictions of the course
and prognosis in patients with coronary heart
disease. It has been true also of our own
unit.
It is fair to say that we simply do not
know what effects our previous endeavors
have had on long-term prognosis in myocardial infarction and in coronary heart discoronary care
BIORCK
1078
ease at large. But at the present time, when
coronary care units are mushrooming in many
countries, and when the U. S. is contemplating
a 50 million dollar venture into preventive
dieting, it may be useful to consider what we
are aiming at in our fight against this disease.
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Which Are Our Aims?
The challenges are: (1) to postpone the
first manifestations of coronary artery disease
(especially myocardial infarction and lethal
arrhythmias), (2) to reduce the acute mortality (especially in myocardial infarctions and arrhythmias), (3) to postpone
repeated attacks (especially of myocardial
infarction and arrhythmias), and (4) to improve the condition of the survivor (rehabilitation).
With these in mind should we aim primarily at fighting coronary heart disease or
myocardial infarction? Shall we attempt the
long range elimination or reduction of the
causes of atherosclerotic processes in the coronary vascular wall, which is an enormous
undertaking, or should we aim at the instant
and energetic battle against the occluding
thrombus, the lingering arrhythmias, and the
myocardial weakness as they present themselves in the acute event? It seems to me
that there has recently been a shift of emphasis within the medical profession away from
preventive aspects of coronary heart disease
that have been so favored for a decade or so,
and toward the coronary care unit and the
philosophy of immediate action, a move from
strategy to tactics.
The strategical approach, if I may say so,
derives from a biological philosophy based
on animal experimentation and epidemiological surveys. It tries to modify and counteract
pathogenic mechanisms, particularly in persons earmarked as especially vulnerable candidates for fuiture disease. The tactical approach is an expression of a humanitarian
philosophy: to fight death and save life,
vigorously, unyieldingly, and at almost any
price.
Although these goals are, of course, not
mutually exclusive, we must be aware that
for years to come in many countries, including
the United States, medicine will have to decide on priorities, because medical manpower
will remain scarce, and the costs of acute
medicine will be rapidly mounting. Let us,
therefore, try to examine the prospects of both
avenuesl
The Strategical Approach
Studies since the time of Anitchkov relating
vascular pathology to lipid biochemistry in
rabbits or chickens have added much to the
brickwork of understanding coronary heart
disease. But humans are not rabbits and are
not in cages. Disease as a "patterned response"33 may also be studied elsewhere, in
human populations, where nature or history
create their own experimental conditions. The
identification of certain metabolic patterns in
man leading to coronary atherosclerosis, and
of other nervous reflex patterns involved in
the genesis of arrhythmias,34 has forced the
question of the phylogenetic meaning of such
patterns, which once may have been of great
survival value but in our present form of
life may be conducive to disease and
death.35 3 The "agent" of disease may be
neither outside nor exclusively within; disease may develop as a result of maladaptation
of an old-fashioned biological machinery exposed to the forces of quite another life
situation than it was evolved to master.
What have we learned about the occurrence
of myocardial infarction in our zoological
ancestors and relatives?37 While atherosclerosis of the aorta with advancing age seems to
be as frequent in many animal species as in
man, coronary atherosclerosis is a rare feature observed, for example, in some wild
birds such as pigeons, which may die from
myocardial infarction. There may even be
"epidemics" of myocardial infarction in some
birds during the breeding period. But it is
only in the large primates, such as gorillas
and chimpanzees, that the human pattern of
coronary arteries, diseased before puberty, is
observed. It has been stated that records and
observations on disease and death of mammals and birds in zoological gardens indicate
Circulation, Volume XXXVII, June 1968
BIOLOGY OF MYOCARDIAL INFARCTION
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that coronary artery disease, myocardial fibrosis, and infarction reflect effects of physiological and psychological responses to social
stimuli of various kinds rather than the influence of age per se. Studies of primates
seem to have revealed the impact on the
circulation of emotional factors, which resemble those operating within ourselves.
Among these are sexual frustration and restrained aggression. This may provide the
missing link in our search for causes and
mechanisms of human disease, for we may
share with these animals enough of an
emotional, or even conceptual, frame of reference to permit an experimental analysis of
the ways of life that lead to disease and death.
It will be of utmost interest to study their
physiological parameters, such as lipids, blood
sugar control, and hemostasis, under different
psychological conditions, acutely, and over
the course of time. For human physiology
and pathophysiology must be conceived in
terms of our genetic-environmental past and
the meaning of diabetes in relation to starvation, of hypertension and of thrombosis in
relation to fight, flight, and blood loss,
and so forth. The secrets of the relative immunity of the female may be illuminated in
this perspective.
The importance of the genetic element in
coronary heart disease has always been
emphasized by Paul White.38 Studies of
family trees39 and on twins40 support this
conviction. But there is always an interplay
between genetic endowment and environmental demands. The strategy of prevention
before overt disease or after an infarction is
based on the concept of diverting an inherently unfavorable course into a more
favorable one.
Much wishful thinking (in both directions!)
has accompanied studies of the preventive
effects of reduction of blood lipids, either by
dieting or by the use of drugs and the preventive effects of the long-term use of anticoagulants and female sex hormones, and of
giving up smoking. These endeavors, as well
as those directed toward diabetic tendencies
in coronary patients all belong to the strategic
Circulation, Volume XXXVII, June 1968
1079
forces. It is my feeling that the evidence in
favor of a definite effect of lowering blood
lipids is getting stronger, not least through
Leren's41 careful 5-year study of 400 male
survivors of myocardial infarction in Oslo,
Norway. He found a significant reduction
of the incidence of new angina pectoris and
of recurrent infarction in patients under the
age of 60, while sudden deaths, more frequent
in patients with angina pectoris or an abnormal ECG, or both, were not affected. Giving
up smoking has been shown to improve
prognosis,42 and preliminary data concerning
anti-diabetic measures in infarct patients with
abnormal intravenous glucose tolerance appear promising.43 The effects of such interference with pathogenic mechanisms may, in
principle, be of several kinds (fig. 5).
However, it remains to be seen whether
the results will be substantial or only of
marginal value, as appears increasingly to
be true of long-term use of anticoagulants.
Gofman and co-workers recently struck a
sad note in this respect.44 Their feeling is that
blood lipid levels are of little prognostic value
in already manifest coronary heart disease
in persons over 50 years of age, and that
moderate reductions of blood lipids will have
no influence on life expectancy beyond 55
years of age.45 Diet changes in order to
have effect would have to begin early and
be drastic. The lower the dividends become
with age, the more imperative will it be to
establish the predictive value of biological
indices in young individuals and to act
selectively on young candidates.46 4 This
action may take the forms outlined in table
2. Although most preventive measures might
be accomplished by natural remedies, it is
probably more in line with our present
technology to expect that artificial means will
take the place of natural ones, and the use of
drugs will be considered more acceptable
than the cultivation of healthy habits.
The Tactical Approach
The remarkable and rapid developments
of intensive cardiac care, culminating in the
modern coronary care unit, have created in
1080
BIORCK
Table 2
Preventive Measures
Remedies
Artificial
Natural
1. Restore man's primitive functions:
2. Reduce demands on metabolism:
Physical exercise
Diet
S
Drugs:g (Atromid
Tolbutamide
3. Reduce demands on nervous
system:
4. Counteract inappropriate natural
Equanimity and sleep
Drugs: Alcohol
Sedatives
I
Drugs: Anticoagulants
responses:
Quit cigarette smoking
5. Refrain from dangerous habits:
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a short time an almost revolutionary situation
with regard to medical tactics. Nevertheless,
Oliver and co-workers in Edinburgh28 have
recently warned against making too optimistic
predictions of the results of such treatment
in the front line of the infarct battle. High
fatality rates still prevail in such places. Their
own short-term gains, so far, in 400 patients
were judged to be 5% of all patients, or 21%
of the potential deaths.
A recent report from the London hospital29
stated that of 150 patients treated in a coronary care unit, 21 died and 129 survived, 10
of whom had been resuscitated from otherwise fatal arrhythmias. These figures are said
to represent a reduction in mortality by 50%.
However, other estimates, for example those
from Grendahl's study from OSlo48 are much
lower.
We do not know as yet whether the imA.
B.
C.
Ml
t
MI
MsI
mediate gain will be maintained, or lost,
during the following years (fig. 6).
This should probably become evident rather
soon in view of the fact that myocardial
infarcts recur most frequently within the first
year or two after the preceding infarct'8
(fig. 7). Such follow-up studies will determine the medical economy of coronary care
units. Once established, however, they have
probably come to stay, regardless of economy.
Health Unmasked-or What?
We have now completed two thirds of the
twentieth century. During the last decade
man has broken the genetic code, computerized a considerable part of management,
industry, and science, conquered outer space,
and landed digging television cameras on the
moon. What has been accomplished with regard to coronary heart disease and myocardial infarction?
Although we have known for 10 years what
should be done and what could be done, both
t
PER CENT 1 00
SURVI| VAL
t
80
D.
ml
-
A
B
CONVENTIONAL TREATMENT
'CORONARY
TREATMEN T
A/B
HYPOTHESES
CARE"
ALTERNATIVE
tI
_ 7lv1
60
Figure 5
Alternative effects of preventive modifying pathogenetic mechanisms in prevention of myocardial infarction (MI). (A) No effect. (B) Delayed infarction,
little or no effect on longevity if patient survives. (C)
Delayed infarction and correspondingly delayed death.
(D) Delayed infarction and also more than correspondingly delayed death.
40
20
Figure 6
Estimates of survival after myocardial infarction.
Circulation, Volume XXXVII, June 1968
BIOLOGY OF MYOCARDIAL INFARCTION
1081
15
RECURRENCE, BY AGE
IA.
AND
SEX.
i
i
I.
t
,,,,,,,,,,,,,,
.I
LU
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u
I
I
z
Xi
TOTAL MATERIAL
MALES <60
MALES > 60
-.,\
IFEMALES
<60
FEMALES
>60
5
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
.~.W
..,
..
15
10
YEARS AFTER PRIMARY INFARCTION
5
Figure 7
Rate of recurrence of myocardial infarction by age and sex. (Reprinted with permission from
Biirck, G.: Course and prognosis in some cardiac diseases. 1962, Pergamon Press.16)
with regard to strategy and to tactics-as is
obvious to anyone ransacking "progressive"
medical articles from 10 years ago-our moves
have been cautious, hesitant, and slow. It is
to your credit that they have been less slow
here in the United States than elsewhere.
More patients than ever are dying from
myocardial infarction in most countries. Are
we, then, attempting an impossible job, fighting the inescapable?
Some years ago, Maurice Campbell took
the trouble to examine the apparent increase
in death rates from heart disease in England
between 1876 and 1959.49 50 He arrived at
the conclusion that the very palpable increase
-including deaths from coronary heart disease-could be accounted for by assuming
that one quarter of younger persons whose
lives had been saved from death by tuberculosis and other infectious diseases had ultimately died instead from heart disease at about
the time other people die from such diseases.
He also predicted that the increase in cardiac
Circulation, Volume XXXVII, June 1968
deaths would continue rapidly until 1967,
slowly to 1977, and finally would settle
around a steady figure about 1990. This opinion has not remained unchallenged,51 but the
test of the hypothesis will come with time.
It cannot easily explain the different trends for
men and women unless additional hypotheses
are included. However, I think it is essential
that Campbell's concept be carefully considered by statistical experts. It has been
pointed out that the trends in young people
as against those in old people are important
for the validity of Campbells claims. For if
Campbell is right in principle, then the increase of coronary heart disease may be due
to an unmasking of a fundamental biological
tendency in man which presents itself in the
very moment humanity (or part of it) is
liberated from infectious diseases and other
primitive challenges (such as diseases of
infancy, nutritional disease, and starvation),
and not necessarily because of exposure to
the dangers of affluence. Is coronary disease
more
BIORCK
1082
or myocardial infarction an expression of the
true biology of privileged man, or is it a new
pathological entity in man exposed to increasingly unbiological social challenges?
What Are "Realistic Goals?"
There is no doubt that a great many infarcts,
and more or less sudden deaths are "premature." But at what age does death cease to be
premature?
A long revered expression, often emphasized by Paul White, is that our task is not
only to add years to life, but life to years.
This is true, too.
Addressing your Commission on Heart
Disease, Cancer and Stroke, 3 years ago,
President Johnson envisaged the need to adjust yourselves and your economy "to a life
span and a work span for the average man or
woman of 100 years." Survival to a hundred
years of age-how come?
The curves in figure 8 depict 200 years of
gains in saving lives in my country: great
advances in younger years, less in old age.
It will take great strides to move the curve
to the hypothetical position (of LBJ) on the
right. But even greater may be the impact on
society of caring for the tremendous, aged
population that would result from it-a society
with four, or even five generations living side
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200- 1
100
50-
20 -'
4/'
10
5-
*1
2
1
'
*--_. 1761-70
*-..-- 1821- 30
* 1881 - 90
* _- 1961
L B J.
0.5
0,3
0
10 20 30 40 50 60 70 80 90 100
YEARS
MORTALITY I N SWEDEN 1761 - 1961
Figure 8
Two hundred years of gains in saving lives in Sweden compared with L.B.J.'s tentative aim for
life.
Ciiculationz,
Volume XXXVII, June 1968
BIOLOGY OF MYOCARDIAL INFARCTION
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by side-at a time when automation reduces
the need for human labor in our societies
and "the population explosion" in other parts
of the world is considered to be humanity's
greatest peril. As pointed out by two of the
leading medical statesmen of our time, Irvine
Page52 and George Pickering,53 we must accept death as a biological law: "It is the
diseases which kill (that) make way for the
new life. Without them none of us would be
living as we are to-day." This is a somewhat
more diplomatic way of stating what one of
Pickering's predecessors as Regius professor at
Oxford, William Osler, once expressed in a
remarkable valedictorian address about the
uselessness of men above 60 and comfortable
ways to get rid of them.54
Are there any means by which the numbers
of premature myocardial infarcts and deaths
could be reduced, without unduly delaying
by those very means the long day's journey
into night? Nature rarely gives something for
nothing: What other conditions will we, then,
encounter on our passage from here to Eternity?
These are questions for which I have no
answers. Perhaps such questions should not
be asked.
And yet while we are striving with our
low-fat diets and our automated defibrillators,
in years to come the artificial heart and the
transplanted heart may present us with
problems not yet surmounted in the history
of medicine and ethics. For whom and from
whom? For one who has been involved in the
problems of kidney transplantation, which is
in principle a simpler matter than transplantation of a heart, the words of Jean Hamburger55 sound in the ear: 'As a result of
medical progress, our technical decisions may
become easier, but moral problems, on the
contrary, will be increasingly significant."
Medical science fiction has repeatedly shown
itself to come true far earlier than expected.
Sooner or later, transplantation of hearts may
be here, and like all transplantation surgery,
it will be expensive in its demands, of all
kinds. The triumph of the surviving individual
may have to be paid for by a new biological
Circulation, Volume XXXVII, June 1968
1083
solidarity among men, a sacrifice, akin to that
of the Aztecs, who performed the world's
most heroic cardiac surgery, but more meaningful-at least so we may hope.
In our civilization and our time coronary
heart disease is probably the most important
single determinant of the limits of human
life, mediated through sudden death or
through myocardial infarction. The biology of
myocardial infarction is, therefore, part of the
biology of human life, of body and mind.
Medical science is constantly pressing
forward to conquer new grounds, to test new
possibilities. But medical technology is not an
aim in itself. It has to be handled to serve
a true biological purpose, which also means
a humanitarian one. For this we are
responsible to society.
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The Grand Design
Science is the century-old endeavor to bring together by means of systematic thought
the perceptible phenomena of this world into as thorough-going an association as possible. To put it boldly, it is the attempt at the posterior reconstruction of existence by
the process of conceptualization.-ALBERT EINSTEIN.
Circulation, Volume XXXVII, June 1968
The Biology of Myocardial Infarction
GUNNAR BIÖRCK
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Circulation. 1968;37:1071-1085
doi: 10.1161/01.CIR.37.6.1071
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