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2. April
Morley Sutter
Dear Malcolm and All, Can anyone
describe the recent (50-year) epidemiology of atherosclerosis in Japan?
I am ignorant and confused. I would like to know: The prevalence and
incidence of myocardial > infarcrtion and resulting deaths over this period; the
prevalence and incidence of hemorrhagic stroke and resulting deaths over this period
and the same information for thrombotic stroke. > It is clear that Japan was in a
marked state of flux economically and socially during that period. An accurate
descrption of cardiovascular
> disease in that population would be instructive. Regards, Morley
William
Stehbens
Firstly, vital statistics are too unreliable
for scientific use. One of the recognized facts about Japanese statistics was that the
cause of many deaths was not certified by a qualified doctor and that CHD was an
undesirable cause of death.Stroke was a more desirable one, being indicative of
intelligence in the family. More recent autopsied series have revealed that stroke is not
as common as once believed and that CHD is much more common than original figures
suggested. This is a typical example of why vital statistics are unreliable. Moreover
since CHD is neither a specific disease not pathognomonic of ubiquitous
atherosclerosis,
the only endpoint to use for comparative purposes being the severity of
atherosclerosis.
This fact is sufficient to invalidate CHD epidemiology (covered in my book "The Lipid
Hypothesis of Atherogenesis", RG Landes Co, Austin, 1993). WE Stehbens
Morley Sutter
Dear Professor Stehbens, Thank you for your comments.Could you
tell me what is the most recent trend in severity of atherosclerotic lesions in the
population of Japan? I understand that you believe its "severity" in
individual cases is the appropriate measure of atherosclerosis. Regards, Morley Sutter
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8 April
Kilmer McCully
White bread contains only about 10% of the
folic acid, vitamin B6, and other vitamins, fiber, phytochemicals, antioxidants, and trace
minerals, compared with wheat kernels. Sugar contains none of these vitamins or
other mcronutrients whatsoever.
Primarily for these reasons, persons consuming te typical diet of
industrialized countries have a marginal intake of folic cid and B6, predisposing them to
elevation of homocysteine levels and vscular disease. Whole wheat bread contains
about 3 to 4 times as much B6 and folic acid as white bread, but less than contained in
whole wheat kernels. Margarine contains abundant transfats, enhancing the
atherogenic effect of homocysteine. Thus white bread, sugared foods, and margarine
account for two of the most atherogenic effects of the diet of developed countries,
hyperhomocysteinemia and dietary consumption of transfats. Kilmer
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9. April
Dag Viljen Poleszynski
‘Norwegian white flour is not quite as
bad as US flour. With an extraction rate of 78% it contains about 60% of the vitamins and
minerals of whole kernels. In general grains are not ideal foods, although
fermentation,
yeasts etc may make the nutrients more accessible and some of the antinutrients may be
changed. I still allow myself an occasional slice of white bread with sea food (a few
times per year), with lots of butter and mayonnaise, making the GI rather modest...Dag
Viljen
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William Stehbens
Dear Colleagues
CHD
is not a specific disease. It is a
non-specific complication of many diseases and is not pathognomonic of atherosclerosis
although about 90% of cases of CHD are secondary to atherosclerosis. The latter is a specific disease and therefore has
but one cause (causa vera sine qua non) - the essential prerequisite without which there
is no disease. If an epidemic of CHD ever
occurred, it would be necessary to determine which disease was responsible for the
specific epidemic. There is no evidence for
the occurrence of such an epidemic and, in view of the unscientific nature of vital
statistics in any country and the serious diagnostic error of CHD even in affluent
countries, to suggest there has been a rise or fall of CHD incidence is unsubstantiated
speculation.
Atherosclerosis
is a degenerative disease ubiquitous in every
animal according to the literature (and as my own research experience confirms). Therefore an increase in atherosclerotic CHD would
require an aggravating factor that increased the severity of atherosclerosis and thereby
induced a shift to the left in CHD age distribution. There is no evidence of this
either. To
argue about the incidence of CHD early last century because Osler and James Mackenzie
considered it rare, is futile. The increase
in average life span in affluent countries increased from about 50 years at the beginning
of the last century to about 75 years by the end of the century with CHD mostly occurring
in those above 60-65 years of age. Its
prevalence would have increased in any aging population.
Arteriosclerosis
is commonly used synonymously with atherosclerosis and at one time incorporated
"atherosclerosis", arteriolosclerosis and Mönckeberg's sclerosis. The "stiffening" of arteries with age
(arteriosclerosis) is but one feature of atherosclerosis and is due to loss of elasticity,
SMC depletion and increasing fibrosis of the wall. Significantly
haemodynamics can produce atherosclerosis and its complications whereas cholesterol
overfeeding does not produce either.
Pathologically
atherosclerosis consistently varies in severity and rate of progressionm from site to
site, vessel to vessel and vascular bed to vascular bed.
This fact alone negates the possibility of any specific causal effect
deriving from any environmental or circulating humoral factor! Ample experimental and iatrogenic evidence
substantiates this assertion. Prerequisite
for those interested in atherosclerosis and CHD and writing on the topic is to learn or
become conversant with the pathology.
References to epidemic rise etc.
Stehbens WE, Lancet i:606,1987 - Epidemic rise
of CHD.
Angiology 41:85,1990 - Diagnostic error of CHD
Med Hypoth 45:449,1995 CHD epidemic
Int J Epidemiol 20:818,1991 - limitation of
epidemiological methods
Perspect Biol Med 36:97,1992 Causality (CHD)
Exp Mol Pathol 70:103 and 120 2001 -
(CHD and
atherosclerrosis - data review)
The last reference (two papers) is an overall
brief review of the lipid hypothesis (referred to by Dr Ravnskov very early on) and the
cause of atherosclerosis.
Regards,
WE Stehbens
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Malcolm Kendrick
Dear Prof Stehbens, I would agree with many things that you
wrote in your e-mail, but I would have to disagree with a number of things as well. Life expectancy has
increased in the last one hundred years, true. However, this is primarily due to a
reduction in child mortality, and women dying in childbirth. The average is
a meaningless figure to use in this argument. What is more interesting is to look at
the mode. And this has moved to the right by 18 months in the UK since 1900. In short,
once you get past the age of 16 your life expectancy has remained pretty much
unchanged. When child mortality rates are > 300 per 1000 that has a somewhat drastic
impact on average life expectancy. So it is not true to say that there are many more
elderly people alive than there were before. Many more people now have the chance to be
elderly. Whilst
I would agree, again, that epidemiological evidence of CHD 'epidemics' is subject to
severe bias in reporting, I do not think there can be any doubt that, currently, the
MONICA study demonstrates very clearly that the rate of CHD in different countries varies
widely. To use two countries that I am very familiar with, the UK and France, the rate of
CHD in these countries varies - age matched - by at least 400%. And this ratio is constant
between 35 - 44 year old and 45 - 64 year olds. This data is very robust. So something
causes 400% more CHD in one country than in another. (If one were to look at rural Chinese
vs. Urban emigrant Asian Indians, the ratio is approx 30:1 or 1:30)
Equally
I do not think there can be any doubt that the rate of CHD in Eastern Europe over the last
10 years has exploded. In Russia, life expectancy reduced from 64 to 57 years in males
over a four year time period. 65% of this was due to an increase in the rate of death from
CHD. I would call that an epidemic. In short, currently, the rates of CHD do vary widely
between different populations, and that variability has to be caused by something.
With regard to
atherosclerosis. A meaningless word, I would agree. It means almost anything that people
want it to mean. But I have studied the word of Duguid, Virchow, Kritchevsky and spent too
many hours reading about the morphology of early and advanced atherosclerotic lesions. I
do not think that the development of an unstable plaque is a normal, or natural process.
It is a disease process. I do not think that plaques are caused by lipid abnormalities,
but they have to be caused by something. I speak as someone who watched a twenty one year
old male, in Scotland, die of an MI with one, single, ruptured atherosclerotic plaque in
the LAD artery. That's not normal, that's disease.
From what you have written, the logical
extrapolation is that the rate of CHD in all countries in the world is the same, it has
never gone up or down, and that dying of CHD is a normal, natural process. That, I cannot
believe. Regards Malcolm Kendrick
P.S. With regard to the distribution of
plaques, I would ask you to explain why, with chicken pox, for example, the spots appear
where they do i.e. in different places in every person. Hast thou never heard of chaos
theory?
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14. April
William Stehbens
Dear Colleagues, My apologies that comment on atherosclerosis
was inadvertently relayed to a larger list of e-mail addresses than I
intended.
In
reply to Dr Kendrick: The increase in life expectancy has been the result of many more
factors than reduction in child mortality and obstetric deaths. Improvements to the
standard of living, hygiene, housing and food availability have contributed as well as
antibiotics, immunization, diagnostics and the standard of medicine. The point I make is that in an aging population,
more people live beyond 60-65 years, the time of life when CHD deaths predominantly
occur. Early in the 20th century practitioners were not generally aware of coronary
occlusion and myocardial ischemia from whatever cause and neither was atherosclerosis
differentiated from syphlitic aortitis to any extent.
Vital statistics are crude indicators of CHD and as such are
scientifically worthless. Monocausal death
certificates do not indicate the true incidence of a particular disease state even when
certified by a qualified doctor (and doctors have not always involved been in their
submission). The level of error is
considerable at virtually every step in the preparation of vital statistics and in autopsy monitored CHD deaths the error is
conservatively "30% with some studies demonstrating an even wider degree of error
(see the first two references I sent you). In
any event CHD is not a specific disease but a complication of many different diseases and
it would be invalid to extrapolate from CHD mortality or morbidity data to the etiology of
atherosclerosis which is ubiquitous and CHD is not.
The late DR AR Feinstein (Clinical
Epidemiology, Saunders 1985) wrote "no knowledgeable clinician or pathologist in the
second half of the 20th century believes that single choices of death certificate
diagnoses can indicate specific causes of death and that those choices represent to actual
occurrences of the specific disease". In
total agreement with this summation, I do not wish to waste my time arguing about CHD
rates for Eastern Europe or the Monica Study.
My primary interest at present is the etiology
of atherosclerosis. I am surprised at Dr
Kendrick's gross misinterpretation of my recent email regarding this disease. There is much misrepresentation of atherosclerosis
whereby currently many clinicians and cardiologists fabricate their own pathogenesis of
atherosclerosis displaying little knowledge of its true pathological
development. Duguid's papers based on random photomicrographs
of advanced disease demonstrated shortcomings that should have denied them publication and
furthermore Virchow and Duguid were from a bygone era prior to the more recent information
derived from ultrastructural and experimental vascular surgery. I presume you refer to David Kritchevesky who was
mostly interested in lipids rather than recent pathology.
I have never stated that atherosclerotic lesions either the initial
elastic tissue changes of atrophic lesions or the fibromusculo-elastic intimal
proliferative lesions nor the more advanced lesions with primary pathological
complications (intimal tears, ulcerations, dissections, ectasia, aneurysms or
tortuosities) are normal even though they become ubiquitous. Does Dr Kendrick mistakenly equate ubiquitous with
normal for the latter term is often used ambiguously as either healthy or within the
statistical range. I have never indicated in
any way that the CHD rate is the same in all countries.
I have stated only that it is not possible to deduce from vital statistics
whether there has been an increase or decrease in CHD mortality rates.
Of course I have heard of the chaos
theory. The distribution of chicken pox lesions has never
interested me but for a long time I have been concerned about the lack of logic exhibited
by so many university graduates. Regards, WE
Stehbens
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Bogdan Sikorski
Dear Malcolm, Prof. Stehbens and others The following web site might be of
interest:
http://www.chd-taskforce.de/ Although I have no clinical training, and I have
not closely followed research on CHD, I feel my contribution to this discussion on CHD
might be of some value.Intuitively, I tend to agree with arguments put forward by Prof.
Stehbens, but I would like to question your assertion that all animals (in their wild
habitat!, not in the animal house) suffer from atherosclerosis. We know that wild
elephants do, but do wild or even domesticated cats?While it is a fact that average life
span has increased lately, it is also true that many people used to live to old age
(>80) in other centuries. There must be some research on causes of death in the oldies
in the 18th and 19th century.On that note, I always object to the assertion that current
average life span of say 80 (in Australia) is predominantly indicative of good health
policies and improved medical care. To some extent yes, but other factors must play a
role! As discussed previously by Barry, people dying today were borne in 20s and
30's and their health outcomes would have been predominantly affected at birth and in
their early adulthood. The fruits of today's policies and of current dietary
madness, as
well as of for instance recent introduction of prolonged statin treatment will only be
evident in 20 or so years. My prediction is that the life span will decline in another 10
years.But back to CHD.Malcolm quotes increase in the incidence of CHD in Eastern Europe
over the last 10 years as a good indicator.I suggest that these data are very unreliable
for a variety of reasons, some mentioned by Prof. Stehbens for Japan, and other local more
specific and far more important reasons.I would totally disregard data from
Russia. Here
we have a country in which health system has been almost totally ruined, where medics
commonly have not been paid for months if not years, where most hospitals are barely
working, et c. How can any one expect any meaningful data to emerge from such a national
disaster. Anyway, 10 years ago it was Soviet Union, and now it is a number of independent
states including Russia. How can anyone compare statistics collected for the latter with
those collected for the former. Russia's life expectancy has decreased because of extreme
poverty!!!!!!!!!!!!!!!!!!!!!!!!! No need to go into details.I suggest that what is
happening in Russia now should be compared to USA in 30's during the great
depression.Thousands of soldiers killed in Chechnia would also be a factor. And what about
a huge rise in a murder rate? And what about a huge increase in alcoholism combined with
malnutrition. (before everyone drank, including at work, but they had relatively good
meals in their factory staff canteens - no more - free market has taken care of that). I
do not belive in that 65% decline being due to CHD. Even if that has been collated by WHO
- they do not know how they got it. Unreliability of death certificate has been
discussed,
and in the present day Russia that factor has to be multiplied by 10. Who would have time
or even inclination to correctly determine the cause of death, during their daily struggle
for survival.Anyway, comparisons between countries are very unreliable and not very
productive, as documented by Uffe. There are better ways to epidemiologicaly determine
factors that might influence health outcomes. One such way is to compare similar
communities living in a relative proximity. Only then, one can control for or virtually
eliminate confounding factors and identify those that might contribute to differences in a
measured endpoint(s).Interestingly, such studies have been conducted in Poland by Prof.
Aleksandrowicz in the 60s and 70s (the one quoted in JK's book, Uffe). He investigated
health outcomes in peasant communities which lived nearby (and therefore were virtually
identical) with a particular focus on the quality of water they drunk (one was soft and
the other high mineral (particularly Mg) content). It goes without saying that marked
differences existed between those communities in terms of incidence of many
diseases,
including cardiovascular diseases. Now, his research has been published but only in
Polish, and therefore according to currently accepted "scientific standards" it
does not exist!Finally, I would like to disagree with Prof. Stehbens' assertion that
because severity and location of atherosclerosis is not uniform within a body (as indeed I
have previously stated in one of my e-mails to the group) that one can exclude causal
contribution from environmental (e.g. dietary) factors. Hemodynamic contributors
(including arterial wall mechanistic contributors) typically associated with
atherosclerotic lesions can be found in every human being, yet certain groups of people do
not (or did not) develop atherosclerosis at all, even in advanced age. Something must be
protecting them, or their environment must be lacking that decisive contributing
factor. Regards Bogdan
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20 April
Fred and Alice Ottoboni
Dear Uffe and
skeptics:
The following is an email received on April 8, 2002 from the National Heart,
Lung, and
Blood Institute (NHLBI) It is in response to our inquiry about the origin and development of the New Cholesterol
Guidelines. Questions we asked
were:
Are they official gov't policy? Why the absence of open meetings as normally
required for development of standards? Why were the New Guidelines not published in
the Federal Register? You will be interested
in the NHLBI response, particularly in light of the fact the since the issuance of the New
Guidelines, statin sales have increased tremendously. This suggests that the New
Guidelines are indeed having a powerful influence on medical decisions and drug
use.
Yet, the email below indicates that that the New Guidelines do not represent
Federal Policy. A copy of the email follows here:
Dear Sir: I apologize for the delay in
responding to your March 17 query. The professional staff with whom I needed to
speak concerning your query have been unavailable and I have only recently been able to
consult with them. I have been advised that
the guidelines for cholesterol management released on May 15, 2001, were developed by a
panel of experts - the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III [ATP III]) convened by the National Cholesterol Education Program, an
educational program coordinated by the National Heart, Lung, and Blood Institute
(NHLBI).
The ATP III panel is not an advisory committee to the NHLBI but rather a group of recognized experts
(bolds by
me – Uffe) providing their scientific judgment about cholesterol management to
clinicians. The panel's recommendations for clinicians are based on a thorough
review of the scientific evidence by the panel. The
guidelines developed by the ATP III are not regulations and health professionals are not
required to follow them. Like the guidelines developed by the other educational programs
of NHLBI directed to high blood pressure, obesity, and asthma, the ATP III guidelines
state explicitly that they are intended to inform the clinical judgment of the physician
and not supplant it, and the physician's clinical judgment remains the final arbiter of
what is best for an individual patient. Accordingly, the clinical guidelines
developed by expert panels convened by NHLBI's educational programs do not appear in the
Federal Register since they do not have
the status of regulations and do not represent formal Federal policy (bolds by
me). In fact, another group, the U.S. Preventive
Services Task Force, has issued guidelines
for cholesterol measurement that differ somewhat from the ATP III guidelines. The
full report of ATP III contains a review of the scientific evidence and presents the
panel's scientific rationale for its recommendations for clinicians, as well as an
extensive list of references. The full ATP
III report can be accessed on the NHLBI Web site by going to http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm
and clicking on ATP III Full Report.
Sincerely,
Sandra Lindsay, Public Liaison Coordinator, NHLBI
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23. April
William Stehbens
Dear
Dr AHOA
Clinical
experience will not resolve your dilemma. It
is knowledge of the pathology of atherosclerosis and of the limitations of epidemiology
that will be of service.
I have examined (by serial section)
several hundred cerebral arterial forks from humans, chimpanzee, gorilla, horse, dog, pig and extracerebral
arteries from rabbits and not in one animal was there an absence of intimal thickenings at
specific sites at the forks. The thickenings
occur at sites highly suggestive of haemodynamic localization and progress to more severe
atherosclerosis with age (time). They
commence in utero and I regard these thickenings as early proliferative lesions of
atherosclerosis, the severity varying with age, site and animal species. The "atrophic lesion" is a more rapidly
developing lesion and may also have a superimposed proliferative lesion, such
proliferative lesions also being observed in birds and reptiles. You do not specify which stage of human
atherosclerosis you are referring to although if you look at the literature on autopsy
studies of octogenarians and older subjects, you will find that all had atherosclerosis of
severe degree. I accept that some authors in
earlier years have alleged that some humans have none but such anecdotal evidence is
unacceptable and from today's level of knowledge, one can only deduce that either they
were not thorough, did not have good vision or had no access to microscopy. I have produced atherosclerosis in arteries and
veins where no intimal thickening existed, merely by haemodynamic means (Atherosclerosis
95: 127, 1992; Proc Roy Soc 185: 357, 1974).
The thickenings in rabbits at arterial forks rapidly progress to overt
atherosclerotic lesions when haemodynamic stress is increased in vessels even when
cholesterol levels are below 2.5mmol/L and with no dietary cholesterol. I am willing to assess any evidence you might
present to the contrary.
I have also seen photographs in
the literature of small intimal thickenings in rodents but by virtue of the size of these
animals and their short life span, one cannot expect to see more advanced lesions nor do
we see them in small spinal vessels. The
intimal thickenings are sites of predilection for spontaneous lipid deposition in humans,
sheep and birds and if you care to look closely, human coronary vessels are the same.
Causes of death two centuries ago would have
no bearing on causes of death in the last 50 years. Many
were said to die of symptoms, old age, diarrhoea etc.
Although the pathology of coronary occlusion and myocardial infarction
is well known in the latter part of the 19th century, clinicians in Europe and North
America were not aware of it until after Herrick's papers between 1911-1920 and CHD or its
equivalent was not included in the international
classification of causes of death until 1930. If
CHD deaths in hospital diagnoses in the early 1980s in Boston hospitals had an error of
over 30%, you can imagine the value of death certificates 200 or more years
ago.
I certainly have never alleged that health
policies and medical care are responsible for increased or decreased
longevity. Advances in medicine have undoubtably played an
important role as have successful industrialists and governments who provided jobs
enabling workers to improve the standard of living, diet and hygiene enjoyed by their
families. Diet and genetic factors may affect
blood vessels indirectly but do not cause atherosclerosis which I regard as inevitable
with time. However it is the rapidity of its
development which we must attempt to affect.
The concept of Barker that small babies are
prone to develop CHD prematurely is simply nonsense and similar views are to be found in
the literature. Unverifiable retrospective
studies contribute little.
I agree about vital statistics in
Russia. Russian medicine has been in a parlous state for
many years. Epidemiological studies on atherosclerosis are predominantly useless and
comparative studies of small neighbouring communities based on CHD are of the same
ilk. Until epidemiologists base their work on specific
pathological diagnostic endpoints, they will contribute little or nothing of
value. Petr Skrabanek expressed the view that there is an
epidemic of epidemiologists and a serious shortage of subjects suitable for them to
tackle.
Lastly you misrepresent what I said about
the localization of atherosclerosis. If the
disease consistently varies in severity from site to site, vessel to
vessel, and
vascular bed to vascular bed within each person, there is only one conclusion that can be
reached. The disease must have a local
cause which varies in degree at each particular site.
If the veins of venous by-pass grafts and therapeutic arteriovenous
shunts develop severe accelerated atherosclerosis when if left alone like veins
elsewhere,
they would exhibit only minimal changes during the remaining years of life, it is
impossible under these circumstances to explain causality of such phenomena by any
environmental, dietary or circulating humoral factor.
Again I would suggest that you read the
references I provided earlier. If you require
a wider coverage of degenerative vascular diseases see my chapter pp.175-269 in Stehbens
WE & Lie JT "Vascular Pathology" Chapman & Hall, London 1995. Other chapters of mine in the book are concerned
with complications. In any event this
publication will provide you with further references for more detail. The following provide some update and views the
publisher did not want me to include in the book.
Cardiovascular Pathology 6: 123-153, 1997 Pathobiology 65: 1-13, 1997 Acta Anat 157: 261-74, 1996
My
personal view is that most cardiologists and CHD epidemiologists do not want the truth to
surface. It has suited them to religiously
ignore the inconsistencies that I and others have drawn attention to. Furthermore I have developed several haemodynamic
models of atherosclerosis and its pathological complications in herbivores on a
herbivorous diet under conditions prevailing in Homo sapiens which together with its
iatrogenic production mentioned above, constitute the ultimate proof of
causality.
We all have a diet, yet do not eat the same
meals nor equal quantities. We all endure
haemodynamic stresses which differ from person to person, site to site and with time. We do not all have the same blood
pressure, pulse,
pulse pressure or flow velocity. The
diameter, configuration and arborization of our vessels vary as do our responses to
exercise, emotion etc. Therefore to assume
that haemodynamic stresses or their biochemical and biophysical effects are the same or of
the same order in everyone is worse than simplistic generalization. At present I know of no means of protecting
vessels from atherosclerosis and currently diet, statins or cardiologists or
epidemiologists (singly or in concert) do not cause regression of
atherosclerosis.
Incidentally, some time ago there was a
query about Ancel Keyes and protein. I cannot
recall that he had any special interest in protein.
However in his paper published in the J Mt Sinai Hosp (20: 118-139,
1953) which was probably the greatest stimulus to CHD epidemiology, he demonstrated in two
restricted age groups a relationship between the national death rate in 6 countries for
atherosclerotic and degenerative heart disease and the proportion of fat-calories
available in the respective diets. This is
yet another contrived relationship. Yerushalmy
and Hilleboe (NY State Med J 57: 2343, 1957) admonished Keyes for selecting only 6 of the
22 countries with available data. If all 22
countries had been used, the relationship was better for animal protein than for fat. They also selected 6 countries and demonstrated
that the available dietary fat (not necessarily consumed) had an inverse relationship with
cerebrovascular disease. Additional
weaknesses have been demonstrated in Keyes' paper.
Yours
sincerely, WE Stehbens.
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