The Benefits of High Cholesterol
By Uffe Ravnskov, MD, PhD
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.2 Eleven 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 postitive 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.
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.
From The Cholesterol Myths by Uffe Ravnvskov,
MD, PhD, NewTrends Publishing, pp 64-65.
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