From The Cholesterol Myths
by Uffe Ravnvskov, MD, PhD
NewTrends Publishing, pp 64-65.
People with high cholesterol live
the longest. This statement seems so incredible that it takes a
long time to clear one's brainwashed mind to fully understand
its importance. Yet the fact that people with high cholesterol
live the longest emerges clearly from many scientific papers.
Consider the finding of Dr. Harlan Krumholz of the Department of
Cardiovascular Medicine at Yale University, who reported in 1994
that old people with low cholesterol died twice as often from a
heart attack as did old people with a high cholesterol.1
Supporters of the cholesterol campaign consistently ignore his
observation, or consider it as a rare exception, produced by
chance among a huge number of studies finding the opposite.
But it is not an exception; there are now a
large number of findings that contradict the lipid hypothesis.
To be more specific, most studies of old people have shown that
high cholesterol is not a risk factor for coronary heart
disease. This was the result of my search in the Medline
database for studies addressing that question.2Eleven
studies of old people came up with that result, and a further
seven studies found that high cholesterol did not predict
all-cause mortality either.
Now consider that more than 90 % of all
cardiovascular disease is seen in people above age 60 also and
that almost all studies have found that high cholesterol is not
a risk factor for women.2 This means that high
cholesterol is only a risk factor for less than 5 % of those who
die from a heart attack.
But there is more comfort for those who have
high cholesterol; six of the studies found that total mortality
was inversely associated with either total or LDL-cholesterol,
or both. This means that it is actually much better to have high
than to have low cholesterol if you want to live to be very old.
High Cholesterol Protects Against Infection
Many studies have found that low cholesterol
is in certain respects worse than high cholesterol. For
instance, in 19 large studies of more than 68,000 deaths,
reviewed by Professor David R. Jacobs and his co-workers from
the Division of Epidemiology at the University of Minnesota, low
cholesterol predicted an increased risk of dying from
gastrointestinal and respiratory diseases.3
Most gastrointestinal and respiratory diseases
have an infectious origin. Therefore, a relevant question is
whether it is the infection that lowers cholesterol or the low
cholesterol that predisposes to infection? To answer this
question Professor Jacobs and his group, together with Dr.
Carlos Iribarren, followed more than 100,000 healthy individuals
in the San Francisco area for fifteen years. At the end of the
study those who had low cholesterol at the start of the study
had more often been admitted to the hospital because of an
infectious disease.4,5 This finding cannot be
explained away with the argument that the infection had caused
cholesterol to go down, because how could low cholesterol,
recorded when these people were without any evidence of
infection, be caused by a disease they had not yet encountered?
Isn't it more likely that low cholesterol in some way made them
more vulnerable to infection, or that high cholesterol protected
those who did not become infected? Much evidence exists to
support that interpretation.
Low Cholesterol and HIV/AIDS
Young, unmarried men with a previous sexually
transmitted disease or liver disease run a much greater risk of
becoming infected with HIV virus than other people. The
Minnesota researchers, now led by Dr. Ami Claxton, followed such
individuals for 7-8 years. After having excluded those who
became HIV-positive during the first four years, they ended up
with a group of 2446 men. At the end of the study, 140 of these
people tested positive for HIV; those who had low cholesterol at
the beginning of the study were twice as likely to test positive
for HIV compared with those with the highest cholesterol.6
Similar results come from a study of the MRFIT
screenees, including more than 300,000 young and middle-aged
men, which found that 16 years after the first cholesterol
analysis the number of men whose cholesterol was lower than 160
and who had died from AIDS was four times higher than the number
of men who had died from AIDS with a cholesterol above 240.7
Cholesterol and Chronic Heart Failure
Heart disease may lead to a weakening of the
heart muscle. A weak heart means that less blood and therefore
less oxygen is delivered to the arteries. To compensate for the
decreased power, the heart beat goes up, but in severe heart
failure this is not sufficient. Patients with severe heart
failure become short of breath because too little oxygen is
delivered to the tissues, the pressure in their veins increases
because the heart cannot deliver the blood away from the heart
with sufficient power, and they become edematous, meaning that
fluid accumulates in the legs and in serious cases also in the
lungs and other parts of the body. This condition is called
congestive or chronic heart failure.
There are many indications that bacteria or
other microorganisms play an important role in chronic heart
failure. For instance, patients with severe chronic heart
failure have high levels of endotoxin and various types of
cytokines in their blood. Endotoxin, also named
lipopolysaccharide, is the most toxic substance produced by
Gram-negative bacteria such as Escherichia coli, Klebsiella,
Salmonella, Serratia and Pseudomonas. Cytokines
are hormones secreted by white blood cells in their battle with
microorganisms; high levels of cytokines in the blood indicate
that inflammatory processes are going on somewhere in the body.
The role of infections in chronic heart
failure has been studied by Dr. Mathias Rauchhaus and his team
at the Medical Department, Martin-Luther-University in Halle,
Germany (Universitätsklinik und Poliklinik für Innere Medizin
III, Martin-Luther-Universität, Halle). They found that the
strongest predictor of death for patients with chronic heart
failure was the concentration of cytokines in the blood, in
particular in patients with heart failure due to coronary heart
disease.8 To explain their finding they suggested
that bacteria from the gut may more easily penetrate into the
tissues when the pressure in the abdominal veins is increased
because of heart failure. In accordance with this theory, they
found more endotoxin in the blood of patients with congestive
heart failure and edema than in patients with non-congestive
heart failure without edema, and endotoxin concentrations
decreased significantly when the heart’s function was improved
by medical treatment.9
A simple way to test the functional state of
the immune system is to inject antigens from microorganisms that
most people have been exposed to, under the skin. If the immune
system is normal, an induration (hard spot) will appear about 48
hours later at the place of the injection. If the induration is
very small, with a diameter of less than a few millimeters, this
indicates the presence of “anergy,” a reduction in or failure of
response to recognize antigens. In accordance, anergy has been
found associated with an increased risk of infection and
mortality in healthy elderly individuals, in surgical patients
and in heart transplant patients.10
Dr. Donna Vredevoe and her group from the
School of Nursery and the School of Medicine, University of
California at Los Angeles tested more than 200 patients with
severe heart failure with five different antigens and followed
them for twelve months. The cause of heart failure was coronary
heart disease in half of them and other types of heart disease
(such as congenital or infectious valvular heart disease,
various cardiomyopathies and endocarditis) in the rest. Almost
half of all the patients were anergic, and those who were
anergic and had coronary heart disease had a much higher
mortality than the rest.10
Now to the salient point: to their surprise
the researchers found that mortality was higher, not only in the
patients with anergy, but also in the patients with the lowest
lipid values, including total cholesterol, LDL-cholesterol and
HDL-cholesterol as well as triglycerides.
The latter finding was confirmed by Dr.
Rauchhaus, this time in co-operation with researchers at several
German and British university hospitals. They found that the
risk of dying for patients with chronic heart failure was
strongly and inversely associated with total cholesterol, LDL-cholesterol
and also triglycerides; those with high lipid values lived much
longer than those with low values.11,12
Other researchers have made similar
observations. The largest study has been performed by Professor
Gregg C. Fonorow and his team at the UCLA Department of Medicine
and Cardiomyopathy Center in Los Angeles.13 The
study, led by Dr. Tamara Horwich, included more than a thousand
patients with severe heart failure. After five years 62 percent
of the patients with cholesterol below 129 mg/l had died, but
only half as many of the patients with cholesterol above 223
mg/l.
When proponents of the cholesterol hypothesis
are confronted with findings showing a bad outcome associated
with low cholesterol—and there are many such observations—they
usually argue that severely ill patients are often malnourished,
and malnourishment is therefore said to cause low cholesterol.
However, the mortality of the patients in this study was
independent of their degree of nourishment; low cholesterol
predicted early mortality whether the patients were malnourished
or not.
Smith-Lemli-Opitz Syndrome
As discussed in The Cholesterol Myths
(see sidebar), much evidence supports the theory that people
born with very high cholesterol, so-called familial
hypercholesterolemia, are protected against infection. But if
inborn high cholesterol protects against infections, inborn low
cholesterol should have the opposite effect. Indeed, this seems
to be true.
Children with the Smith-Lemli-Opitz syndrome
have very low cholesterol because the enzyme that is necessary
for the last step in the body’s synthesis of cholesterol does
not function properly. Most children with this syndrome are
either stillborn or they die early because of serious
malformations of the central nervous system. Those who survive
are imbecile, they have extremely low cholesterol and suffer
from frequent and severe infections. However, if their diet is
supplemented with pure cholesterol or extra eggs, their
cholesterol goes up and their bouts of infection become less
serious and less frequent.14
Laboratory Evidence
Laboratory studies are crucial for learning
more about the mechanisms by which the lipids exert their
protective function. One of the first to study this phenomenon
was Dr Sucharit Bhakdi from the Institute of Medical
Microbiology, University of Giessen (Institut für Medizinsche
Mikrobiologie, Justus-Liebig-Universität Gießen), Germany along
with his team of researchers from various institutions in
Germany and Denmark.15
Staphylococcus aureus α-toxin
is the most toxic substance produced by strains of the
disease-promoting bacteria called staphylococci. It is able to
destroy a wide variety of human cells, including red blood
cells. For instance, if minute amounts of the toxin are added to
a test tube with red blood cells dissolved in 0.9 percent
saline, the blood is hemolyzed, that is the membranes of the red
blood cells burst and hemoglobin from the interior of the red
blood cells leaks out into the solvent. Dr. Bhakdi and his team
mixed purified α-toxin with human serum (the fluid in which the
blood cells reside) and saw that 90 percent of its hemolyzing
effect disappeared. By various complicated methods they
identified the protective substance as LDL, the carrier of the
so-called bad cholesterol. In accordance, no hemolysis occurred
when they mixed α-toxin with purified human LDL, whereas HDL or
other plasma constituents were ineffective in this respect.
Dr. Willy Flegel and his co-workers at the
Department of Transfusion Medicine, University of Ulm, and the
Institute of Immunology and Genetics at the German Cancer
Research Center in Heidelberg, Germany (DRK-Blutspendezentrale
und Abteilung für Transfusionsmedizin, Universität Ulm, und
Deutsches Krebsforschungszentrum, Heidelberg) studied endotoxin
in another way.16 As mentioned, one of the effects of
endotoxin is that white blood cells are stimulated to produce
cytokines. The German researchers found that the
cytokine-stimulating effect of endotoxin on the white blood
cells disappeared almost completely if the endotoxin was mixed
with human serum for 24 hours before they added the white blood
cells to the test tubes. In a subsequent study17 they
found that purified LDL from patients with familial
hypercholesterolemia had the same inhibitory effect as the
serum.
LDL may not only bind and inactivate dangerous
bacterial toxins; it seems to have a direct beneficial influence
on the immune system also, possibly explaining the observed
relationship between low cholesterol and various chronic
diseases. This was the starting point for a study by Professor
Matthew Muldoon and his team at the University of Pittsburgh,
Pennsylvania. They studied healthy young and middle-aged men and
found that the total number of white blood cells and the number
of various types of white blood cells were significantly lower
in the men with LDL-cholesterol below 160 mg/dl (mean 88.3
mg/l), than in men with LDL-cholesterol above 160 mg/l (mean
185.5 mg/l).18 The researchers cautiously concluded
that there were immune system differences between men with low
and high cholesterol, but that it was too early to state whether
these differences had any importance for human health. Now,
seven years later with many of the results discussed here, we
are allowed to state that the immune-supporting properties of
LDL-cholesterol do indeed play an important role in human
health.
Animal Experiments
The immune systems in various mammals
including human beings have many similarities. Therefore, it is
interesting to see what experiments with rats and mice can tell
us. Professor Kenneth Feingold at the Department of Medicine,
University of California, San Francisco, and his group have
published several interesting results from such research. In one
of them they lowered LDL-cholesterol in rats by giving them
either a drug that prevents the liver from secreting
lipoproteins, or a drug that increases their disappearance. In
both models, injection of endotoxin was followed by a much
higher mortality in the low-cholesterol rats compared with
normal rats. The high mortality was not due to the drugs
because, if the drug-treated animals were injected with
lipoproteins just before the injection of endotoxin, their
mortality was reduced to normal.19
Dr. Mihai Netea and his team from the
Departments of Internal and Nuclear Medicine at the University
Hospital in Nijmegen, The Netherlands, injected purified
endotoxin into normal mice, and into mice with familial
hypercholesterolemia that had LDL-cholesterol four times higher
than normal. Whereas all normal mice died, they had to inject
eight times as much endotoxin to kill the mice with familial
hypercholesterolemia. In another experiment they injected live
bacteria and found that twice as many mice with familial
hypercholesterolemia survived compared with normal mice.20
Other Protecting Lipids
As seen from the above, many of the roles
played by LDL-cholesterol are shared by HDL. This should not be
too surprising considering that high HDL-cholesterol is
associated with cardiovascular health and longevity. But there
is more.
Triglycerides, molecules consisting of three
fatty acids linked to glycerol, are insoluble in water and are
therefore carried through the blood inside lipoproteins, just as
cholesterol. All lipoproteins carry triglycerides, but most of
them are carried by a lipoprotein named VLDL (very low-density
lipoprotein) and by chylomicrons, a mixture of emulsified
triglycerides appearing in large amounts after a fat-rich meal,
particularly in the blood that flows from the gut to the liver.
For many years it has been known that sepsis,
a life-threatening condition caused by bacterial growth in the
blood, is associated with a high level of triglycerides. The
serious symptoms of sepsis are due to endotoxin, most often
produced by gut bacteria. In a number of studies, Professor
Hobart W. Harris at the Surgical Research Laboratory at San
Francisco General Hospital and his team found that solutions
rich in triglycerides but with practically no cholesterol were
able to protect experimental animals from the toxic effects of
endotoxin and they concluded that the high level of
triglycerides seen in sepsis is a normal immune response to
infection.21 Usually the bacteria responsible for
sepsis come from the gut. It is therefore fortunate that the
blood draining the gut is especially rich in triglycerides.
Exceptions
So far, animal experiments have confirmed the
hypothesis that high cholesterol protects against infection, at
least against infections caused by bacteria. In a similar
experiment using injections of Candida albicans,
a common fungus, Dr. Netea and his team found that mice with
familial hypercholesterolemia died more easily than normal mice.22
Serious infections caused by Candida albicans
are rare in normal human beings; however, they are mainly seen
in patients treated with immunosuppressive drugs, but the
finding shows that we need more knowledge in this area. However,
the many findings mentioned above indicate that the protective
effects of the blood lipids against infections in human beings
seem to be greater than any possible adverse effects.
Cholesterol as a Risk Factor
Most studies of young and middle-aged men have
found high cholesterol to be a risk factor for coronary heart
disease, seemingly a contradiction to the idea that high
cholesterol is protective. Why is high cholesterol a risk factor
in young and middle-aged men? A likely explanation is that men
of that age are often in the midst of their professional career.
High cholesterol may therefore reflect mental stress, a
well-known cause of high cholesterol and also a risk factor for
heart disease. Again, high cholesterol is not necessarily the
direct cause but may only be a marker. High cholesterol in young
and middle-aged men could, for instance, reflect the body’s need
for more cholesterol because cholesterol is the building
material of many stress hormones. Any possible protective effect
of high cholesterol may therefore be counteracted by the
negative influence of a stressful life on the vascular system.
Response to Injury
In 1976 one of the most promising theories
about the cause of atherosclerosis was the Response-to-Injury
Hypothesis, presented by Russell Ross, a professor of pathology,
and John Glomset, a professor of biochemistry and medicine at
the Medical School, University of Washington in Seattle.23,24
They suggested that atherosclerosis is the consequence of an
inflammatory process, where the first step is a localized injury
to the thin layer of cells lining the inside of the arteries,
the intima. The injury causes inflammation and the raised
plaques that form are simply healing lesions.
Their idea is not new. In 1911, two American
pathologists from the Pathological Laboratories, University of
Pittsburgh, Pennsylvania, Oskar Klotz and M.F. Manning,
published a summary of their studies of the human arteries and
concluded that “there is every indication that the production of
tissue in the intima is the result of a direct irritation of
that tissue by the presence of infection or toxins or the
stimulation by the products of a primary degeneration in that
layer.”25 Other researchers have presented similar
theories.26
Researchers have proposed many potential
causes of vascular injury, including mechanical stress, exposure
to tobacco fumes, high LDL-cholesterol, oxidized cholesterol,
homocysteine, the metabolic consequences of diabetes, iron
overload, copper deficiency, deficiencies of vitamins A and D,
consumption of trans fatty acids, microorganisms and
many more. With one exception, there is evidence to support
roles for all of these factors, but the degree to which each of
them participates remains uncertain. The exception is of course
LDL-cholesterol. Much research allows us to exclude high LDL-cholesterol
from the list. Whether we look directly with the naked eye at
the inside of the arteries at autopsy, or we do it indirectly in
living people using x-rays, ultrasound or electron beams, no
association worth mentioning has ever been found between the
amount of lipid in the blood and the degree of atherosclerosis
in the arteries. Also, whether cholesterol goes up or down, by
itself or due to medical intervention, the changes of
cholesterol have never been followed by parallel changes in the
atherosclerotic plaques; there is no dose-response. Proponents
of the cholesterol campaign often claim that the trials indeed
have found dose-response, but here they refer to calculations
between the mean changes of the different trials with the
outcome of the whole treatment group. However, true
dose-response demands that the individual changes of the
putative causal factor are followed by parallel, individual
changes of the disease outcome, and this has never occurred in
the trials where researchers have calculated true dose-response.
A detailed discussion of the many factors
accused of harming the arterial endothelium is beyond the scope
of this article. However, the protective role of the blood
lipids against infections obviously demands a closer look at the
alleged role of one of the alleged causes, the microorganisms.
Is Atherosclerosis an Infectious Disease?
For many years scientists have suspected that
viruses and bacteria, in particular cytomegalovirus and
Chlamydia pneumonia (also named TWAR bacteria) participate
in the development of atherosclerosis. Research within this area
has exploded during the last decade and by January 2004, at
least 200 reviews of the issue have been published in medical
journals. Due to the widespread preoccupation with cholesterol
and other lipids, there has been little general interest in the
subject, however, and few doctors know much about it. Here I
shall mention some of the most interesting findings.26
Electron microscopy, immunofluorescence
microscopy and other advanced techniques have allowed us to
detect microorganisms and their DNA in the atherosclerotic
lesions in a large proportion of patients. Bacterial toxins and
cytokines, hormones secreted by the white blood cells during
infections, are seen more often in the blood from patients with
recent heart disease and stroke, in particular during and after
an acute cardiovascular event, and some of them are strong
predictors of cardiovascular disease. The same is valid for
bacterial and viral antibodies, and a protein secreted by the
liver during infections, named C-reactive protein (CRP), is a
much stronger risk factor for coronary heart disease than
cholesterol.
Clinical evidence also supports this theory.
During the weeks preceding an acute cardiovascular attack many
patients have had a bacterial or viral infection. For instance,
Dr. Armin J. Grau from the Department of Neurology at the
University of Heidelberg and his team asked 166 patients with
acute stroke, 166 patients hospitalized for other neurological
diseases and 166 healthy individuals matched individually for
age and sex about recent infectious disease. Within the first
week before the stroke, 37 of the stroke patients, but only 14
of the control individuals had had an infectious disease. In
half of the patients the infection was of bacterial origin, in
the other half of viral origin.27
Similar observations have been made by many
others, for patients with acute myocardial infarction (heart
attack). For instance, Dr. Kimmo J. Mattila at the Department of
Medicine, Helsinki University Hospital, Finland, found that 11
of 40 male patients with an acute heart attack before age 50 had
an influenza-like infection with fever within 36 hours prior to
admittance to hospital, but only 4 out of 41 patients with
chronic coronary disease (such as recurrent angina or pervious
myocardial infarction) and 4 out of 40 control individuals
without chronic disease randomly selected from the general
population.28
Attempts have been made to prevent
cardiovascular disease by treatment with antibiotics. In five
trials treatment of patients with coronary heart disease using
azithromyzin or roxithromyzin, antibiotics that are effective
against Chlamydia pneumonia,yielded successful
results; a total of 104 cardiovascular events occurred among the
412 non-treated patients, but only 61 events among the 410
patients in the treatment groups.28a-e In one further
trial a significant decreased progression of atherosclerosis in
the carotid arteries occurred with antibiotic treatment.28f
However, in four other trials,30a-d one of
which included more than 7000 patients,28d antibiotic
treatment had no significant effect.
The reason for these inconsistent results may
be that the treatment was too short (in one of the trials
treatment lasted only five days). Also, Chlamydia pneumonia,
the TWAR bacteria, can only propagate inside human cells and
when located in white blood cells they are resistant to
antibiotics.31 Treatment may also have been
ineffective because the antibiotics used have no effect on
viruses. In this connection it is interesting to mention a
controlled trial performed by Dr. Enrique Gurfinkel and his team
from Fundación Favaloro in Buenos Aires, Argentina.32
They vaccinated half of 301 patients with coronary heart disease
against influenza, a viral disease. After six months 8 percent
of the control patients had died, but only 2 percent of the
vaccinated patients. It is worth mentioning that this effect was
much better than that achieved by any statin trial, and in a
much shorter time.
Does High Cholesterol Protect Against
Cardiovascular Disease?
Apparently, microorganisms play a role in
cardiovascular disease. They may be one of the factors that
start the process by injuring the arterial endothelium. A
secondary role may be inferred from the association between
acute cardiovascular disease and infection. The infectious agent
may preferably become located in parts of the arterial walls
that have been previously damaged by other agents, initiating
local coagulation and the creation of a thrombus (clot) and in
this way cause obstruction of the blood flow. But if so, high
cholesterol may protect against cardiovascular disease instead
of being the cause!
In any case, the diet-heart idea, with its
demonizing of high cholesterol, is obviously in conflict with
the idea that high cholesterol protects against infections. Both
ideas cannot be true. Let me summarize the many facts that
conflict with the idea that high cholesterol is bad.
If high cholesterol were the most important
cause of atherosclerosis, people with high cholesterol should be
more atherosclerotic than people with low cholesterol. But as
you know by now this is very far from the truth.
If high cholesterol were the most important
cause of atherosclerosis, lowering of cholesterol should
influence the atherosclerotic process in proportion to the
degree of its lowering.
But as you know by now, this does not happen.
If high cholesterol were the most important
cause of cardiovascular disease, it should be a risk factor in
all populations, in both sexes, at all ages, in all disease
categories, and for both heart disease and stroke. But as you
know by now, this is not the case
I have only two arguments for the idea that
high cholesterol is good for the blood vessels, but in contrast
to the arguments claiming the opposite they are very strong. The
first one stems from the statin trials. If high cholesterol were
the most important cause of cardiovascular disease, the greatest
effect of statin treatment should have been seen in patients
with the highest cholesterol, and in patients whose cholesterol
was lowered the most. Lack of dose-response cannot be attributed
to the knowledge that the statins have other effects on plaque
stabilization, as this would not have masked the effect of
cholesterol-lowering considering the pronounced lowering that
was achieved. On the contrary, if a drug that effectively lowers
the concentration of a molecule assumed to be harmful to the
cardiovascular system and at the same time exerts several
beneficial effects on the same system, a pronounced
dose-response should be seen.
On the other hand, if high cholesterol has a
protective function, as suggested, its lowering would
counterbalance the beneficial effects of the statins and thus
work against a dose-response, which would be more in accord with
the results from the various trials.
I have already mentioned my second argument,
but it can’t be said too often: High cholesterol is associated
with longevity in old people. It is difficult to explain away
the fact that during the period of life in which most
cardiovascular disease occurs and from which most people die
(and most of us die from cardiovascular disease), high
cholesterol occurs most often in people with the lowest
mortality. How is it possible that high cholesterol is harmful
to the artery walls and causes fatal coronary heart disease, the
commonest cause of death, if those whose cholesterol is the
highest, live longer than those whose cholesterol is low?
To the public and the scientific community I
say, “Wake up!”
REFERENCES
1. Krumholz HM and others. Lack of association
between cholesterol and coronary heart disease mortality and
morbidity and all-cause mortality in persons older than 70
years. Journal of the American Medical Association 272,
1335-1340, 1990.
2. Ravnskov U. High cholesterol may protect
against infections and atherosclerosis. Quarterly Journal of
Medicine 96, 927-934, 2003.
3. Jacobs D and others. Report of the
conference on low blood cholesterol: Mortality associations.
Circulation 86, 1046–1060, 1992.
4. Iribarren C and others. Serum total
cholesterol and risk of hospitalization, and death from
respiratory disease. International Journal of Epidemiology
26, 1191–1202, 1997.
5. Iribarren C and others. Cohort study of
serum total cholesterol and in-hospital incidence of infectious
diseases. Epidemiology and Infection 121, 335–347,
1998.
6. Claxton AJ and others. Association between
serum total cholesterol and HIV infection in a high-risk cohort
of young men. Journal of acquired immune deficiency
syndromes and human retrovirology 17, 51–57, 1998.
7. Neaton JD, Wentworth DN. Low serum
cholesterol and risk of death from AIDS. AIDS 11,
929–930, 1997.
8. Rauchhaus M and others. Plasma cytokine
parameters and mortality in patients with chronic heart failure.
Circulation 102, 3060-3067, 2000.
9. Niebauer J and others. Endotoxin and immune
activation in chronic heart failure. Lancet 353,
1838-1842, 1999.
10. Vredevoe DL and others. Skin test anergy
in advanced heart failure secondary to either ischemic or
idiopathic dilated cardiomyopathy. American Journal of
Cardiology 82, 323-328, 1998.
11. Rauchhaus M, Coats AJ, Anker SD. The
endotoxin-lipoprotein hypothesis. Lancet 356, 930–933,
2000.
12. Rauchhaus M and others. The relationship
between cholesterol and survival in patients with chronic heart
failure. Journal of the American College of Cardiology
42, 1933-1940, 2003.
13. Horwich TB and others. Low serum total
cholesterol is associated with marked increase in mortality in
advanced heart failure. Journal of Cardiac Failure 8,
216-224, 2002.
14. Elias ER and others. Clinical effects of
cholesterol supplementation in six patients with the Smith-Lemli-Opitz
syndrome (SLOS). American Journal of Medical Genetics
68, 305–310, 1997.
15. Bhakdi S and others. Binding and partial
inactivation of Staphylococcus aureus a-toxin by human plasma
low density lipoprotein. Journal of Biological Chemistry
258, 5899-5904, 1983.
16. Flegel WA and others. Inhibition of
endotoxin-induced activation of human monocytes by human
lipoproteins. Infection and Immunity 57, 2237-2245,
1989.
17. Weinstock CW and others. Low density
lipoproteins inhibit endotoxin activation of monocytes.
Arteriosclerosis and Thrombosis 12, 341-347, 1992.
18. Muldoon MF and others. Immune system
differences in men with hypo- or hypercholesterolemia.
Clinical Immunology and Immunopathology 84, 145-149, 1997.
19. Feingold KR and others. Role for
circulating lipoproteins in protection from endotoxin toxicity.
Infection and Immunity 63, 2041-2046, 1995.
20. Netea MG and others. Low-density
lipoprotein receptor-deficient mice are protected against lethal
endotoxemia and severe gram-negative infections. Journal of
Clinical Investigation 97, 1366-1372, 1996.
21. Harris HW, Gosnell JE, Kumwenda ZL. The
lipemia of sepsis: triglyceride-rich lipoproteins as agents of
innate immunity. Journal of Endotoxin Research 6,
421-430, 2001.
22. Netea MG and others. Hyperlipoproteinemia
enhances susceptibility to acute disseminated Candida albicans
infection in low-density-lipoprotein-receptor-deficient mice.
Infection and Immunity 65, 2663-2667, 1997.
23. Ross R, Glomset JA. The pathogenesis of
atherosclerosis. New England Journal of Medicine 295,
369-377, 1976.
24. Ross R. The pathogenesis of
atherosclerosis and update. New England Journal of Medicine
314, 488-500, 1986.
25. Klotz O, Manning MF. Fatty streaks in the
intima of arteries. Journal of Pathology and Bacteriology.
16, 211-220, 1911.
26. At least 200 reviews about the role of
infections in atherosclerosis and cardiovascular disease have
been published; here are a few of them: a) Grayston JT, Kuo CC,
Campbell LA, Benditt EP. Chlamydia pneumoniae strain TWAR and
atherosclerosis. European Heart Journal Suppl K, 66-71,
1993. b) Melnick JL, Adam E, Debakey ME. Cytomegalovirus and
atherosclerosis. European Heart Journal Suppl K, 30-38,
1993. c) Nicholson AC, Hajjar DP. Herpesviruses in
atherosclerosis and thrombosis. Etiologic agents or ubiquitous
bystanders? Arteriosclerosis Thrombosis and Vascular Biology
18, 339-348, 1998. d) Ismail A, Khosravi H, Olson H. The role of
infection in atherosclerosis and coronary artery disease. A new
therapeutic target. Heart Disease 1, 233-240, 1999. e)
Kuvin JT, Kimmelstiel MD. Infectious causes of atherosclerosis.
f.) Kalayoglu MV, Libby P, Byrne GI. Chlamydia pneumonia
as an emerging risk factor in cardiovascular disease.
Journal of the American Medical Association 288, 2724-2731,
2002.
27. Grau AJ and others. Recent bacterial and
viral infection is a risk factor for cerebrovascular ischemia.
Neurology 50, 196-203, 1998.
28. Mattila KJ. Viral and bacterial infections
in patients with acute myocardial infarction. Journal of
Internal Medicine 225, 293-296, 1989.
29. The successful trials: a) Gurfinkel E.
Lancet 350, 404-407, 1997. b) Gupta S and others. Circulation
96, 404-407, 1997. c) Muhlestein JB and others. Circulation 102,
1755-1760, 2000. d) Stone AFM and others. Circulation
106, 1219-1223, 2002. e) Wiesli P and others. Circulation
105, 2646-2652, 2002. f) Sander D and others. Circulation
106, 2428-2433, 2002.
30. The unsuccessful trials: a) Anderson JL
and others. Circulation 99, 1540-1547, 1999. b)
Leowattana W and others. Journal of the Medical Association
of Thailand 84 (Suppl 3), S669-S675, 2001. c) Cercek B and
others. Lancet 361, 809-813, 2003. d) O’Connor CM and
others. Journal of the American Medical Association.
290, 1459-1466, 2003.
31. Gieffers J and others. Chlamydia
pneumoniae infection in circulating human monocytes is
refractory to antibiotic treatment. Circulation 104,
351-356, 2001
32. Gurfinkel EP and others. Circulation
105, 2143-2147, 2002.
About the author
Dr. Ravnskov is the author of The Cholesterol
Myths and chairman of The International Network of Cholesterol
Skeptics (thincs.org).
Risk Factor
There is one risk factor that is known to be
certain to cause death. It is such a strong risk factor that it
has a 100 percent mortality rate. Thus I can guarantee that if
we stop this risk factor, which would take no great research and
cost nothing in monetary terms, within a century human deaths
would be completely eliminated. This risk factor is called
“Life.”
Barry Groves,
www.second-opinions.co.uk.
Familial Hypercholesterolemia - Not as Risky
as You May Think
Many doctors believe that most patients with
familial hypercholesterolemia (FH) die from CHD at a young age.
Obviously, they do not know the surprising finding of the
Scientific Steering Committee at the Department of Public Health
and Primary Care at Radcliffe Infirmary in Oxford, England. For
several years, these researchers followed more than 500 FH
patients between the ages of 20 and 74 and compared patient
mortality during this period with that of the general
population.
During a three- to four-year period, six of
214 FH patients below age 40 died from CHD. This may not seem
particularly frightening but as it is rare to die from CHD
before the age of 40, the risk for these FH patients was almost
100 times that of the general population.
During a four- to five-year period, eight of
237 FH patients between ages 40 and 59 died, which was five
times more than the general population. But during a similar
period of time, only one of 75 FH patients between the ages of
60 and 74 died from CHD, when the expected number was two.
If these results are typical for FH, you could
say that between ages 20 and 59, about 3 percent of the patients
die from CHD, and between ages 60 and 74, less than 2 percent
die, in both cases during a period of 3-4 years. The authors
stressed that the patients had been referred because of a
personal or family history of premature vascular disease and
therefore were at a particularly high risk for CHD. Most
patients with FH in the general population are unrecognized and
untreated. Had the patients studied been representative for all
FH patients, their prognosis would probably have been even
better.
This view was recently confirmed by Dr. Eric
Sijbrands and his coworkers from various medical departments in
Amsterdam and Leiden, Netherlands. Out of a large group they
found three individuals with very high cholesterol. A genetic
analysis confirmed the diagnosis of FH and by tracing their
family members backward in time, they came up with a total of
412 individuals. The coronary and total mortality of these
members were compared with the mortality of the general Dutch
population.
The striking finding was that those who lived
during the 19th and early 20th century had normal mortality and
lived a normal life span. In fact, those living in the 19th
century had a lower mortality than the general population. After
1915 the mortality rose to a maximum between 1935 and 1964, but
even at the peak, mortality was less than twice as high as in
the general population.
Again, very high cholesterol levels alone do
not lead to a heart attack. In fact, high cholesterol may even
be protective against other diseases. This was the conclusion of
Dr. Sijbrands and his colleagues. As support they cited the fact
that genetically modified mice with high cholesterol are
protected against severe bacterial infections.
“Doctor, don’t be afraid because of my high
cholesterol.” These were the words of a 36-year-old lawyer who
visited me for the first time for a health examination. And
indeed, his cholesterol was high, over 400 mg/dl.
“My father’s cholesterol was even higher,” he
added. “But he lived happily until he died at age 79 from
cancer. And his brother, who also had FH, died at age 83. None
of them ever complained of any heart problems.” My “patient” is
now 53, his brother is 56 and his cousin 61. All of them have
extremely high cholesterol values, but none of them has any
heart troubles, and none of them has ever taken
cholesterol-lowering drugs.
So, if you happen to have FH, don’t be too
anxious. Your chances of surviving are pretty good, even
surviving to old age.
References:
Scientific Steering Committee on behalf of the
Simon Broome Register Group.
Risk of fatal coronary heart
disease in familial hypercholesterolaemia. British Medical
Journal 303, 893-896, 1991;
Sijbrands EJG and others. Mortality
over two centuries in large pedigree with familial
hypercholesterolaemia: family tree mortality study. British
Medical Journal 322, 1019-1023, 2001.
You might find the following articles informative
too:
Lipitor - The Human Cost
Lipitor: Side Effects And Natural Remedy
|