The redoutable Guardian!!
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Let them eat cake, butter, cream ... For decades the advice
has been to cut cholesterol and protect your heart. Now some
doctors think it makes no difference
Jerome Burne Tuesday April 6, 2004 The Guardian
There is almost no connection between the amount of
cholesterol in your blood and your risk of a heart attack.
Not only that, if you don't already have heart disease, you
probably won't live any longer if you bring your cholesterol
level down. Finally, statins, the cholesterol-reducing drugs
we are all being urged to take, are of little use to women.
These are just a few of the highly controversial claims
being made by a loose network of researchers, known
collectively as the Cholesterol Skeptics, who are mounting a
direct challenge to one of the cornerstones of public health
policy - the notion that reducing cholesterol saves lives at
risk from heart disease. Any doctor will tell you that if
your cholesterol level is higher than five (millimoles per
litre) that you should bring it down, probably through
taking one of the statins family.
According to the Cholesterol Skeptics, however, this will
not only involve the NHS in a massively increased drug bill
when many cheaper options are available, but will only
benefit men who already have a heart condition. Can such
views, which fly so directly in the face of the entire
medical establishment, have any basis in fact?
The proponents certainly make some challenging points. For
instance, they say that there is precious little evidence
that a longer life results for those millions of people who
for years have dutifully taken their drugs and endured cholesterol-
reducing diets. In fact, a number of trials have found
that, even though the number of deaths from heart disease
does fall when cholesterol is reduced by a range of means
among patients in primary care - that is, at GP level -
there is often an increase in the overall death rate from
other causes.
Writing in the British Medical Journal (BMJ) at the end of
last year, for instance, Rebecca Warburton, a professor at
the University of Victoria in Canada, reviewed studies of
statins and concluded: "Statins in primary prevention have
not consistently reduced the incidence of myocardial
infarction [heart attack] or stroke. Other studies have even
found that over the age of 50, reducing cholesterol
increases the death rate.
The notion that cholesterol is linked to heart disease goes
back to the middle of last century, along with the idea of
bringing cholesterol levels down with a low-fat diet to
protect the heart. But both of these ideas have been
strongly challenged. For example, plenty of studies show
that only 50% of people who develop heart problems have high
cholesterol, while a study in the BMJ in 2001 found no link
between changing fat in the diet and heart disease.
"At a global level the link with cholesterol and heart
disease is far more tenuous than is generally supposed,"
says Malcolm Kendrick, a GP from Cheshire who is the most
active Skeptic in Britain. "For instance, in Russia at the
moment, heart attack rates are rising dramatically but their
cholesterol levels are the reverse of what we see in the US
and the UK. They often have high levels of the so-called
"good" HDL cholesterol and low levels of the "bad" LDL, but
they still keel over from heart disease."
Even in the west the link is pretty thin according to Joel
Kauffman, a professor at University of the Sciences in
Philadelphia. A review he did of statin use last year
pointed out that what does correlate with high cholesterol
is age, a majorfactor in heart disease. "When you correct
for age," he concluded "there is almost no correlation
between high cholesterol and heart disease."
This challenge comes at a time when the government, the
medical profession and the pharmaceutical industry are
united in their approval of cholesterol-reducing drugs.
Government figures out last week, for instance, show that
heart attack deaths are declining and part of the credit for
this is given to statins.
This month the New England Journal of Medicine is due to
publish the results of a large trial reporting that the
heart patients who reduced their cholesterol down as far as
two, had a 16% drop in their risk of experiencing such
"vascular events" as heart attacks and strokes. One of the
cholesterol-reducing drugs, Lipitor, is among the best-
selling prescription drugs in the world with sales worth
$16bn (£8.75bn). The message from this trial is likely to be
that when it comes to cholesterol "you can't go too low".
So what are the Skeptics basing their apparently highly
idiosyncratic challenge on? At this point it is worth making
clear the difference between primary care - your GP
prescribing statins because he considers you have a raised
risk of heart disease - and secondary care, which you get
after a heart attack in hopes of preventing another one.
Even the Skeptics generally agree that the studies show that
taking statins after you have obviously got heart disease
can reduce your chances of a further attack.
"But the fact that bringing down cholesterol can help some
male heart patients," says Kendrick "doesn't mean it's going
to protect otherwise healthy people whose cholesterol is
over five. Since the average level in the UK is 5.7, that is
an awful lot of people."
But what about trials showing that statins reduce the risk
of heart attacks and strokes by a quarter among healthy
volunteers? That sounds impressive. But how impressive, say
the Skeptics, depends on how you work out the percentages.
Heart attacks among healthy people are quite rare, so the
actual percentage of people having a heart attack while on
statins is just 3% compared to 4% on a placebo. That is
indeed a drop of 25% but it is also a mere 1% fewer heart
attacks over five years, which is not quite so wonderful. In
Sweden official advice is to reserve statins largely for
secondary care.
If pushed, experts in favour of aggressive cholesterol
reduction may well admit that the value to women is less
clear. That is because, although women tend to have higher
levels through life, they develop heart disease 15 to 20
years later. An increasing number of doctors are putting post-
menopausal women on statins to protect their hearts now that
HRT has been discredited. Is this wise?
A resounding "no" was the answer from an analysis of five
statin trials conducted by a team of researchers at the
University of British Columbia (UBC) in Canada and published
last year. Stressing that only 28% of the participants were
women, the team concluded: "The results do not support the
use of statins by women without heart disease."
The UBC group also raised new queries about side effects.
Statins are generally described as safe and well tolerated.
But the same report concluded that although patients on
statins had a 1.4% lower rate of heart attacks, this was
cancelled out by a 1.8% rate of "serious adverse events
associated with the drug", including cancer. That, they say,
is almost certainly an underestimate since only two of the
trials provided details of any serious side effects. The
researchers said they had asked the drug producers for the
missing data but received no reply.
To an outsider what is curious about this debate is that
both sides are using the same data; much of the disagreement
is based on how you interpret it. But that is not all that
is going on. Two recent developments have given a big
impetus to the Skeptics. The first is the huge surge in the
popularity of the Atkins diet. So far the results seem to
show that eating a diet high in fat doesn't automatically
result in a rise in cholesterol. This strikes at the roots
of the cholesterol hypothesis," says Kendrick - though the
jury is still out on the long-term effects of an Atkins-
style diet and bigger trials are ongoing. Another aspect of
the Atkins argument is that a diet high in carbohydrates,
especially refined carbohydrates such as sugar, damages
arteries in the long run.
Akey factor in developing heart disease, say the Skeptics,
is inflammation. This is the defensive reaction produced by
the body when it feels under attack, the redness that flares
up round a cut or bruise. An inflamed point on an artery
makes it more likely that plaque will form.
In the past two years, two major studies have found that the
amount of inflammation in your body is a better indicator of
your heart-attack risk than your cholesterol level.
Inflammation is measured by something called C-reactive
protein (CRP). Some claim such findings make the cholesterol
hypothesis redundant. This could supply an answer to the
question raised by the Skeptics' challenge: If cholesterol
reduction isn't that beneficial, why do the drugs reduce the
number of heart attacks? Probably, say the Skeptics, by
reducing inflammation.
The body produces inflammation via a number of complicated
pathways many of which involve a molecular switch known as
NF kappaB and recent studies show that statins are pretty
effective at dimming NF kappaB. However this is what a
number of other effective heart treatments also seem to do,
such as aspirin and omega three fatty acids found in fish
oils, not to mention garlic and vitamin E.
If this turns out to be what is going on, and trials are
under way to test the idea, this seems likely to shunt
cholesterol reduction into a small corner of the overall
picture of heart disease and allow statins to be marketed as
"inflammation fighters". Other ways of reducing your C-
reactive protein level include stopping smoking, losing
weight and exercising.
The cholesterol hypothesis is unlikely to be abandoned in a
hurry, given the weight of financial and political muscle
behind it. But the Skeptics have raised questions that
could ultimately have an impact on the way we think about
heart disease.
Guardian Unlimited © Guardian Newspapers Limited 2004