statins do not save lives
outrider
25 issue of the Canadian Medical Association
Journal. www.cmaj.ca
Women please note:
"...no statin trials with even the slightest hint
of a mortality benefit in women (JAMA, JACC, BMJ)
and women should be told so in the guidelines."
E. Vos
Dear Editor:
I very much enjoyed reading the thoughtful
article by Manuel et al (1) in the April 12th
issue of CMAJ. They are correct in surmising and
demonstrating the wrong-headedness of the present
aggressiLve guidelines for the prevention of
cardiovascular complications in clinical
practice, though not for all the right reasons.
What the authors of this article discussed in a
sensible, balanced way was the outcomes of
reduced CAD events including death. What they did
not discuss, and should have, was the adverse
outcomes of the medications (primarily statins)
used to prevent the CAD events. It was clearly
shown that for low risk individuals the benefits
of treatment were small (1 death prevented for
1550 patients treated for 5 years). This means
that even rare adverse events caused by the
treatment will, in comparison, be significant.
Even 1 severe rhabdomyolysis event or 1 severe
hepatitis event per thousand per year caused by a
statin will be significant in these low-risk
individuals (more than half a million of whom
were recommended for treatment).
It is true that cardiovascular mortality has been
decreased in primary prevention trials with
statins in high risk populations but total
mortality has not been significantly decreased,
which suggests that the adverse events caused by
the treatment have balanced out the positive
outcomes attributed to the treatment in the
primary prevention group as Vos has documented
well in the previous eletter response. It is also
true, as Genest et al (2) have pointed out, that
the Therapeutics Letter (TL) in Issue 49,
(July/Aug/Sept 2003,
http://www.ti.ubc.ca/pages/letter49.htm) did show
a summary of trials that appeared to show a
benefit in terms of overall mortality for statins
when used for secondary prevention (i.e., in
persons who already have vascular disease) of CAD
events. This was not new information to the
Therapeutics Letter staff or readership, nor was
it a response to pressure from the medical
community as suggested by the Genest article. The
same information had, in fact, been published in
Issue 42, Aug/Sept/Oct 2001 of the TL
(http://www.ti.ubc.ca/pages/letter42.htm), prior
to their issue demonstrating the lack of overall
benefit of statins in primary prevention (Issue
48, Apr/May/June 2003,
http://www.ti.ubc.ca/pages/letter48.htm). Genest
et al also refer to the Heart Protection Study
(3), which showed a reduction in overall
mortality for secondary prevention but it also
had a 4-6 week pre-randomization period of
treatment after which 11,609 (36%) of the study
recruits were dropped due to problems related to
treatment. We therefore did not get an accurate
assessment of the safety and tolerance of this
statin dose in the general population.
Also, the authors of this study did not report
all serious adverse events. This latter fact
supports the argument by Vince Bain (4) in his
letter to the editor regarding Clinical Trials
Registry in this issue of CMAJ in which he
correctly states that all data collected in
intervention trials should be held by a third
party and made accessible to all researchers.
This might have prevented needless harm to
children treated with ineffective, but harmful
SSRI's to which pharmaceutical manufacturers
contributed by withholding research data from
publication (5).
In summary, there is no evidence to show reduced
overall mortality with the use of statins for
primary prevention of CAD events. There is
evidence to show benefit (reduced overall
mortality) from the use of statins for secondary
prevention of CAD events. From Manuel's data,
this secondary prevention group would number
approximately 500,000 (Manuel's Tables 3 and 4)
out of the total treatable population of
16,000,000 and would number approximately 400,000
out of the 2,530,000 (Manuel's Table 4) for whom
statins would be recommended using the 2003
guidelines (or out of the 2,000,000 for whom
statins would have been recommended by the 2000
guidelines). It therefore seems to me that, under
the 2000 guidelines 1.5 million people would have
been recommended statins without evidence of
overall benefit, and under the 2003 guidelines,
the 'number needed not to treat' would be over 2
million. In order to show benefit, most of the
trials ran for 5 years. The approximate cost of 5
years of treatment for the 2 million persons not
benefiting from it would be (at $1.65 per dose
based on 2003 wholesale cost plus 7%)
approximately $6 billion or $1.2 billion per year
(a number not dissimilar to those found in
Manuel's Figure 1). I'm sure that money could
provide more QALY's (Quality Adjusted Life Years)
in some other area of healthcare in Canada.
References
1. Manuel et al. The 2003 Canadian
recommendations for dyslipidemia management:
Revisions are needed. CMAJ 2005;172(8):1027-31.
2. Genest et al. The analysis by Manuel and
colleagues creates controversy with headlines,
not data. CMAJ 2005;172(8):1033-34.
3. Heart Protection Study Collaborative Group.
MRC/BHF Heart Protection Study of cholesterol
lowering with simvastatin 20536 high-risk
individuals: a randomized placebo-controlled
trial. Lancet 2002;360:7-22.
4. Bain V. Clinical Trials Registry-Letter to the
Editor. CMAJ 2005;172(8):979-80
5. Garland EJ. Facing the evidence:
antidepressant treatment in children and
adolescents. CMAJ. 2004 Feb 17;170(4):489-91
AND:
The look by Manuel et al of the dyslipidemia
guidelines is welcome but also overlooks the
all-cause mortality issue where statins have
essentially failed to deliver. There are no
statin trials with even the slightest hint of a
mortality benefit in women (JAMA, JACC, BMJ) and
women should be told so in the guidelines.
Likewise, evidence in over 70 year olds shows no
mortality benefit, i.e. the PROSPER trial finds
28 fewer cardiac deaths offset by 24 more cancer
deaths.
The all-cause mortality failure of statins is
possibly best illustrated by atorvastatin
(Lipitor): while both trials found cardio 'event'
benefit, first ASCOT (placebo vs. 10 mg/d) had
the mortality curves effectively touch at mean
study end (3.3 years) and now TNT (10 mg/d vs. 80
mg/d) found, on top-dose, 26 fewer CHD [coronary
heart disease] deaths offset by 31 more
nonvascular deaths at median study end (4.9
years). Incidentally, ASCOT even failed to find
cardiac benefit in women and diabetics.
It can be said no better than does the
ALLHAT study website (accessed 2005-4-11): "...but
trials [primarily in middle-aged men]
demonstrating a reduction in CHD from cholesterol
lowering have not demonstrated a net reduction in
all-cause mortality."
What is the point lowering 'events' in prevention
without lowering mortality from all causes, and
increasing harm from 'competing risk factors'
related to statin side effects if not to lowered
cholesterol itself.
The all-cause mortality failing with statins
clearly supports the call for more effective
approaches, and guidelines should reflect this
finding, certain in women, probable in most men
with astronomical numbers to treat.
Eddie Vos, Sutton (Qc);
Colin Rose, cardiologist, McGill University,
Montreal (Qc)
![Sbharris[atsign]ix.netcom.com's profile photo](http://lh3.googleusercontent.com/a-/ALV-UjURN6b50hrZp1VmOKY6vUoD4xke_qxfdpwlGhkd6mvzimVI=s40-c)
Sbharris[atsign]ix.netcom.com
"...no statin trials with even the slightest hint
of a mortality benefit in women (JAMA, JACC, BMJ)
and women should be told so in the guidelines."
E. Vos<<
COMMENT:
Somehow the essential caveat got missed that although there are no
purely PRIMARY prevention statin trials with mortality benefits in
women, you can't say that about secondary prevention in women. Women
did experience a significant *total* decrease in mortality in the 4S
trial, as did every other group in that trial. The total mortality
(women plus men) was 12% in the placebo vs. 8% in the simvastatin group
over 5.4 years median followup, for a decrease of 30% in chance of
dying. For women it was less, but still significantly lower. Of
course, many of the 4444 participants in the 4S trial had heart disease
and knew it.
But there are some women with heart disease who will read the "no
statin benefits for women" line in the article above, and think it
applies to them. It doesn't. Simvastatin significantly decreases risk
of dying for all causes, in this group (women with heart disease and
high cholesterol). It's outragious to shade the facts so as to (by
implication) suggest otherwise.
I'm also annoyed at the cancer increase in the PROSPER trial being
mentioned again and again. From what I can tell, it's an abberation. No
other statin trial has seen anything like it. Even the 4S trial when
run out open label beyond 10 years (with most of the former placebo
group naturally deciding to switch to simvastatin) had a lower cancer
mortality after 10 years in the simvastatin group. And total mortality
was STILL 414 deaths in the initial statin group vs 468 in the initial
placebo group (many of which had been on statins by this time for half
the time).
SBH
Sharon Hope
statin side effects.
"Sbharris[atsign]ix.netcom.com" <sbha...@ix.netcom.com> wrote in message
news:1116217930.2...@g44g2000cwa.googlegroups.com...
Sbharris[atsign]ix.netcom.com
SBH
zee
Did the TNT trial not show an increase in cancer?
Zee
Jim Chinnis
>Did the TNT trial not show an increase in cancer?
Unfortunately, it was not of sufficient statistical power to
determine whether cancer increased. All TRT participants were on
Lipitor, anyway--the difference was in the dose.
There was an observed increase in cancer in the 80 mg group, but
there were too few cases to conclude whether it was a chance
result.
The data obviously conflict somewhat. Mortality outcomes generally
require very long trials to sort out. In *primary* treatment, I
imagine trials would need to be much longer than they have been to
date to get real measures of cardiovascular mortality, cancer
mortality, and overall mortality. Both heart disease and most
cancers are slow to develop in healthy people.
--
Jim Chinnis Warrenton, Virginia, USA
Jim Chinnis
>There is no evidence of women's benefit from statins outweighing the risk of
>statin side effects.
There no evidence of left-handed men benefiting from statins,
either. Or right-handed men.
Juhana Harju
:: "Sharon Hope" <sh...@anet.net> wrote in part:
::
::: There is no evidence of women's benefit from statins outweighing
::: the risk of statin side effects.
::
:: There no evidence of left-handed men benefiting from statins,
:: either. Or right-handed men.
That is an impertinent comment as women are a larger population group than
men.
--
Juhana
Jim Chinnis
What was impertinent about it? Studies have been powered to detect
changes in outcomes across the entire treatment group, but not for
subgroups.
The constantly repeated mantra that statins have not been shown to
help women is misleading. Women have been represented in secondary
treatment studies, and these have shown positive effects.
Women and men do differ (!), and large studies for each sex would
be ideal, of course.
Jim Chinnis
Statins have not been shown to save lives during short-term
studies of people without cardiovascular disease.
(What a surprise!)
listener
news:0ukh815tj92mjppdf...@4ax.com:
And with those sage words.....End of thread!
L.
outrider
The FDA and the pharmaceutical companies haven't figured that out yet
Juhana. Women are being harmed by drugs tested and found to have some
(limited) efficacy on a minority population of middle-aged overweight
men.
Care for a couple dark-chocolate coated almonds...?
Zee
outrider
Yes of course the data conflict. Thank you for saying so. And yes,
mortality outcomes require very long trials to sort out. Many people
now approach 10 years of cholesterol lowering treatment. We are the
test.
zee
Jim Chinnis
>Yes of course the data conflict. Thank you for saying so. And yes,
>mortality outcomes require very long trials to sort out. Many people
>now approach 10 years of cholesterol lowering treatment. We are the
>test.
Ah, but it will be a retrospective, observational test, impossible
to ever sort out.
Jim Chinnis
>
Oh, if that's what Juhana meant, I agree. I was just referring to
the fact that subgroup analyses aren't generally feasible.
outrider
The following response to Dr. Harris came to me from Eddie Vos.
Dr. Harris makes two points: 4S and PROSPER.
1. 4S: Dr. Harris misrepresents 4S where in fact there was a 16%
INCREASE in female deaths (p=0.58) with 3 fewer CHD offset by 6 more
non-CHD deaths on simvastatin: Table 3 in
http://circ.ahajournals.org/cgi/content/full/96/12/4211 or /T3 . If
NOT
lowering deaths is success from putting half of 827 women with heart
disease on statin for 5 years, I would question Dr. Harris' criteria
for
success. Clearly, this is a failure of therapy especially since there
there are zero trials or meta analysis showing that statins could
possibly extend the lives of women qualifying for trials. From JAMA
2004
Medline 15138247: "For women with known cardiovascular disease,
treatment of hyperlipidemia ... does not affect total mortality." Can
data from 20,000 women in trials over 1 year in duration be all wrong?
A more serious shadow over 4S is the likelihood of sponsor run data
management misclassification of patients, as they admitted in the text
of Table 3 above to misclassifying a female as a male statin death.
NOTHING happens in the mortality curves for ~1.5 years; then placebo
starts dying at an increased and statin at a decreased rate, a never
explained phenomenon that inexplicably reverses during the study-end
follow up period, with original statin patients starting to die at a
relative increased rate!
2. Dr. Harris may be annoyed hearing about PROSPER's significant
increase in 'new' cancers in the statin group with fewer smokers, but
data are data. There is a glimpse as to cause in the response letters
published in Lancet and there are indeed many pathways by which statins
may promote cancer: reduced CoQ10, squalene, cholesterol,
farnesyl(ation) et al, angiogenesis in 'dormant' cancer nodes, and
whoknows, and as per most animal studies.
The PROSPER authors meta-analysed away their cancer mortality increase
(not smoking and group size adjusted not quite 'significant') by
comparing with trials in younger patients. Similarly, smoking for 5
years in younger groups may not reveal a carcinogenic effect from
tobacco. PROSPER is important because its rationale was to establish
all-cause effects in older people and there was zero mortality benefit
in this high risk group.
Dr. Harris cavalierly dismisses increased cancer deaths in PROSPER as
an
'aberration' but what about the 'first do no harm' concept? One letter
writer about PROSPER in Lancet said: it changed the way people died,
from heart disease to cancer. Given the choice at age 80, about the
mean
age of death in PROSPER, to die in the same week of cancer or heart
attack, please give me the latter. Few cardiologists putting people on
statin would disagree with this for themselves I'd imagine, and older
patients and women of any age should be informed of these study
results.
For those interested in mortality and statins, may I refer to
http://www.health-heart.org/cholesterol.htm with the J-LIT trial being
ominous, showing significant 2-4 times greater mortality in
'hyper-responders' to simvastatin in this massive 6 year observational
study in hypercholesterolemic Japanese, 2/3rds women and most deaths
from cancer.
Eddie Vos v...@health-heart.org
outrider
Mr. Chinnis
Your remark that statin benefit in right or left handed men has not
been shown either shows that you either have no comprehension of the
statin trials or that you do not care about mortality and where lack of
benefit in women in trials is now mathematical certainty.
Please show me just one trial with a female mortality benefit.
How would you feel about any drug in often fatal heart disease for
which the first mega-trial started with two pages of doctors thanked
for their
participation and over 8000 participants enrolled. However, the moment
a serious drug related mortality problem became evident within one
year, the
drug company controlling the trial, Merck, dumped all but 43 of the
people on the placebo who simply refused to die as quickly (36% as
fast) as those on statin.
Dumping the placebo group they could then pollute the back pages of my
NEJM for years, promoting their drug simply because it is well
'tolerated' and lowers cholesterol so marvelously effectively.
That early mega trial, EXCEL, should have killed statins BEFORE even
the
4S trial results were published in the early 1990's.
Can you find the mortality data in that early trial, well hidden in
over 10 publications fostered by the drug company?
Statins simply don't work if mortality is an issue and where trials
regarding omega-3 oils, for example, show numerically about 50 times
better/faster results after heart attacks than statins, even if one
takes the
statin studies at face value.
4S misreported at least in women; the larger HPS study simply refuses
to publish mortality curves in women or men, with or without diabetes:
a true scandal.
Lipitor saved nobody over placebo in ASCOT, and TNT just reported two
more dead on top dose Lipitor over the low ASCOT dose.
Nothing to be flippant about and if you are, at least know your trials.
Eddie Vos
vos {AT} health-heart.org
David Rind
When this issue came up a few months, I pointed out that the study that
could definitively answer the question was the enormous Heart Protection
Study (HPS). At the time, HPS had not published the relevant subgroup
analyses to really know what was going on with various causes of
mortality in various subgroups. However, as I mentioned a month or two
ago, HPS soon after that did publish these results:
The effects of cholesterol lowering with simvastatin on cause-specific
mortality and on cancer incidence in 20,536 high-risk people: a
randomised placebo-controlled trial [ISRCTN48489393]
Heart Protection Study Collaborative Group
Heart Protection Study, Clinical Trial Service Unit & Epidemiological
Studies Unit, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, UK
BMC Medicine 2005, 3:6 doi:10.1186/1741-7015-3-6
You can go to www.biomedcentral.com, sign up, and read the article for
free. It shows that women benefit in cardiac mortality with no hint of
an increase in noncardiac mortality. Also, the elderly benefit. Also,
there was no evidence of an increase in cancer deaths. Statins are
clearly beneficial in secondary prevention in women and the benefits
look just like those in men (same relative reduction in mortality).
There is no reason to expect that this same relationship would not hold
up in primary prevention, however the absolute risk in most women is so
small that treatment for primary prevention will not be of much absolute
benefit in many women.
--
David Rind
dr...@caregroup.harvard.edu
listener
@reader1.panix.com:
I doubt that any subgroup analyses will make one bit of difference to
those on the "anti-statin" side of the fence. Their minds are made up -
statins are poison and no one should be taking them.
L.
outrider
I find the discussion stimulating and educational, and hope the
"gentlemen" involved will continue. My purpose in asking Mr. Vos to
respond: was to supply a contra point of view from which we could all
learn.
No one person is entirely right. It is the sum of the parts which is.
Please step aside and let those who are able inform us.
Zee
Jim Chinnis
>
>
I for one greatly appreciated both Zee's efforts in getting Mr.
Vos to respond and Dr. Rind's incisive comments. Thanks to both.
Sharon Hope
sequitur.
The rate of serious statin side effects is far higher than the risk of CAD
in low-risk and moderate risk women.
Also, the total range of choices for increasing heart health is not
exhausted by "statins or death."
"Sbharris[atsign]ix.netcom.com" <sbha...@ix.netcom.com> wrote in message
news:1116219022.7...@o13g2000cwo.googlegroups.com...
Sbharris[atsign]ix.netcom.com
of CAD
choices for increasing heart health is not
exhausted by "statins or death." <<
COMMENT:
Well, you'd think it was, giving how you insist on focusing on
mortality.
But we're not talking about low and moderate risk women. This thread
didn't start out qualifying any group of women. The toral risk of major
coronary events in the 4S trial in women was 160 in 827 high risk women
over 5 years, which is 19%. That's high, and statins prevented about a
third of them. That's in line with other trial results. So what major
side effect can you expect from simvastatin which is as serious as a
heart attack, and that you can expect at least 7% chance of getting, in
5 years? Since for these women something like 7 in 100 would have a
heart attack in the next 5 years, preventable by a statin. That's your
benefit. Now, what's the risk which outweighs that? And who says so,
and cite the study.
SBH
Sbharris[atsign]ix.netcom.com
Dr. Harris makes two points: 4S and PROSPER.
>> 1. 4S: Dr. Harris misrepresents 4S where in fact there was a
16%
INCREASE in female deaths (p=0.58) with 3 fewer CHD offset by 6 more
non-CHD deaths on simvastatin: Table 3 in
http://circ.ahajournals.org/cgi/content/full/96/12/4211 or /T3 . If
NOT lowering deaths is success from putting half of 827 women with
heart
disease on statin for 5 years, I would question Dr. Harris' criteria
for success.<<
COMMENT:
You've got me, as I misread the MI data for mortality data. The 4S is
underpowered for women's deaths, since it has 4.3 times the number of
men, and these men had 7.4 times the number of deaths. There were only
52 deaths in the women, and they broke out as 27 statin/25 placebo (not
significant). However, the MI's in women were significantly less (by
about a third) very similar to the results in men. There's every reason
to think that a study adequately powered to look at female mortality in
statins will show the same result as for men, and as Dr. Rind points
out, the HPS is showing just that.
My criteria for success? Those 7 women in every 100 who don't have the
MI in 5 years, if they take a statin. Having a heart attack is a slight
inconvenience. May I see your statistics that suggest that 7% of women
who take statins will suffer some side effect which is worse than a
heart attack? Even if we didn't have the HPS data on mortality?
>>A more serious shadow over 4S is the likelihood of sponsor run data
management misclassification of patients, as they admitted in the text
of Table 3 above to misclassifying a female as a male statin death. <<
Did it chance the significance of the result?
>>NOTHING happens in the mortality curves for ~1.5 years; then placebo
starts dying at an increased and statin at a decreased rate, a never
explained phenomenon that inexplicably reverses during the study-end
follow up period, with original statin patients starting to die at a
relative increased rate! <<
Well, with small numbers of events you're going to have to expect such
fluxuations. Roll of the dice. Take two groups of dice rollers and they
will always have "inexplicable" departures from and returns to each
other, with one side winning and now the other. All this means is that
a bigger study is needed.
SBH
Juhana Harju
:::: The rate of serious statin side effects is far higher than the risk
:::: of CAD
:::: in low-risk and moderate risk women. .... Also, the total range of
:::: choices for increasing heart health is not
:::: exhausted by "statins or death."
:: Well, you'd think it was, giving how you insist on focusing on
:: mortality.
::
:: But we're not talking about low and moderate risk women. This thread
:: didn't start out qualifying any group of women. The toral risk of
:: major coronary events in the 4S trial in women was 160 in 827 high
:: risk women over 5 years, which is 19%. That's high, and statins
:: prevented about a third of them. That's in line with other trial
:: results. So what major side effect can you expect from simvastatin
:: which is as serious as a heart attack, and that you can expect at
:: least 7% chance of getting, in 5 years? Since for these women
:: something like 7 in 100 would have a heart attack in the next 5
:: years, preventable by a statin.
Even more lives would have been saved by fish oils and with almost no risk
of side effects.
--
Juhana
Sbharris[atsign]ix.netcom.com
increase in 'new' cancers in the statin group with fewer smokers, but
data are data. <<
Yes, they are, but with much larger studies than PROSPER showing no
such effects, and meta-analyses also, the PROSPER results are hard to
explain. Perhaps statins should not be given to people over 70, until
other studies have had a chance to break out groups similar to those in
PROSPER, to see if the subgroup effect is robust.
>>Dr. Harris cavalierly dismisses increased cancer deaths in PROSPER as
an 'aberration' but what about the 'first do no harm' concept? <<
If taken literally, it would prevent recommendations for many types of
exercise. Exercise is not benign. Some types of exercise increase
quality of life, but haven't been shown to decrease mortality. Perhaps
you don't die of a heart attack, but you do break a hip or get hit by a
car. Life is tradeoffs. There's nothing wrong with tradeoffs so long as
they are informed ones.
>>One letter writer about PROSPER in Lancet said: it changed the way
people died, from heart disease to cancer. Given the choice at age 80,
about the mean age of death in PROSPER, to die in the same week of
cancer or heart
attack, please give me the latter. <<
You're assuming sudden death and not the long drawn-out death of the
cardiac cripple with congestive failure. In any case, the comparison is
pointless until we find out if the cancer increase in this study is
real. No other human study suggests that it is. I think odds are good
that it's not. Statin cancer in lab animals is rodent liver cancer,
mostly. Not really relevent to humans.
>>For those interested in mortality and statins, may I refer to
http://www.health-heart.org/cholesterol.htm with the J-LIT trial
being
ominous, showing significant 2-4 times greater mortality in
'hyper-responders' to simvastatin in this massive 6 year observational
study in hypercholesterolemic Japanese, 2/3rds women and most deaths
from cancer. <<
COMMENT:
Cancer itself greatly lowers cholesterol, so I'm not surprised that
women with occult cancers had greater cholesterol drops with a statin.
This is not a controlled study. It's interesting, but says nothing
about cause and effect. At best, it suggests that you should take a
harder look at your great "statin successes" and perhaps screen them
for occult GI cancers that you'd missed.
SBH
Jim Chinnis
>Sbharris[atsign]ix.netcom.com wrote:
And even more with both statins and fish oil.
Jim Chinnis
>x-no-archive: yes
>And probably even more with low GL diet, pantethine and fish oil. With
>absolutely no adverse reactions, only benefits.
>
>Susan
Possibly, but the data are a lot skimpier. Pantethine hasn't been
shown to reduce mortality or MIs, has it?
I do a low-GL diet, but I don't know that the studies really have
shown that it will reduce cardiovascular disease or total
mortality. (I suspect it does, though.)
outrider
is the probable endothelial effect (but that is also achieved to some
degree with aspirin, no?).
A low GL diet may be great as long as people don't interpret that to
mean low carbohydrate, low fibre, and high saturated fat.
Zee
outrider
effects". That is simply NOT true for statins.
Zee
Juhana Harju
:: No Jim. You cannot say that. Juhana is saying "almost no risk of side
:: effects". That is simply NOT true for statins.
::
:: Zee
I agree. If some lipid lowering agents are needed I would combine
Polycosanol, Pantethine or Krill oil with fish oils. Those combinations
would probably be much safer than statin combined with fish oils and at
least as effective in reducing cardiovascular and total mortality. (It is
true that there are no studies that would have combined the supplements that
I am proposing.)
Even better option would be the Portfolio diet combined with fish oils.
--
Juhana
outrider
way for cholesterol lowering, or statin injury recovery, is confusion
of low GL with low carb and low fibre.
I make no such error.
Zee
outrider
post-menopausal women might want to avoid phyto-estrogens which are
abundant in soy products. Also, some cancers would contraindicate use
of soy.
This latter is especially ironic in women who took statins for years
and now have a diagnosis of ovarian, uterine or breast cancer, but
still need to lower cholesterol. Because of the cancer, they want to
avoid statins, but must avoid the most successful cholesterol lowering
non-drug method to date.
Zee
Jim Chinnis
>No Jim. You cannot say that. Juhana is saying "almost no risk of side
>effects". That is simply NOT true for statins.
>
>Zee
I *do* say that. But I didn't address at all tradeoffs re
side-effects.
Jim Chinnis
>I agree. If some lipid lowering agents are needed I would combine
>Polycosanol, Pantethine or Krill oil with fish oils. Those combinations
>would probably be much safer than statin combined with fish oils and at
>least as effective in reducing cardiovascular and total mortality. (It is
>true that there are no studies that would have combined the supplements that
>I am proposing.)
There are also no studies showing any outcomes improved with most
of the *individual treatments*, such as policosanol and pantethine
and krill oil.
>Even better option would be the Portfolio diet combined with fish oils.
Maybe.
Jim Chinnis
>It is well demonstrated to bring lipids into desirable ranges and
>ratios, with absolutely no adverse reactions. Workd for me, while I ate
>an extremely high fat diet.
>
>Sadly, there's no profit to be made by anyone in studies that might
>demonstrate its effect on mortality.
So governments have no research funds?
outrider
Jim Chinnis wrote:
> A better title for this thread would have been:
>
> Statins have not been shown to save lives during short-term
> studies of people without cardiovascular disease.
>
> (What a surprise!)
> --
> Jim Chinnis Warrenton, Virginia, USA
>From former BMJ editor Richard Smith's article on medical journals
being an arm of pharma marketing departments.
http://dx.doi.org/10.1371/journal.pmed.0020138
Examples of Methods for Pharmaceutical Companies to Get the Results
They Want from Clinical Trials:
" Conduct subgroup analyses and select for publication those that are
favourable."
outrider
There were 3 MORE female deaths in 4S on statin, not less, despite 19%
heart 'events' happening in that category of women. Either the 33%
'events' prevented were not fatal, or statin killed from other causes
to wind up with 3 more dead women in the statin group; or call it a
study fluke in over 2 x 400 women ... either way, no female lives were
extended despite about 2m$ worth of
statin-years of side-effects.
e.v.
outrider
Dr. Harris says that bigger studies are needed. Let's step back: in
600
people with heart attacks randomized to a canola high omega-3 margarine
showing both mortality and heart disease benefit in 2.25 years while
20,000 women randomized for let's say average also 2.25 years in statin
trials proving zero mortality benefit, one has to decide enough is
enough. That is 33 times more people and no mortality benefit while
the
canola study with conclusive benefit and had to be stopped early for
that reason (it was published in Lancet, AJCN and Circ.: links in par.
2
of http://www.health-heart.org/comments.htm ).
Another cholesterol study: take blood out of 1/2 million U.S. men of
about 49 years of age. Pick the top 0.8% for cholesterol (average 292
mg/dl) and lower their LDL by 1/8th for 7.4 years and find a difference
in mortality of three (3) between 2 groups of 1900 subjects on
cholesterol absorbing drug vs. placebo. That was the 100 or 200m$ LRC
trial. Bile acid sequestrant anyone? And this is a class of drugs
that
does not get into your bloodstream to affect the entire system as do
statins. Sequestrant is simply awful to swallow!
The cholesterol horse has been dead since 1977 when George V. Mann
buried it in his "End of an Era" editorial in NEJM. Flogging the horse
some more is a distraction but will not revive it. Time to place your
bets elsewhere I'm afraid.
e.v.
outrider
concede your suggested dietary approach seems to work for those with
diabetes.
Zee
outrider
I agree with Dr. Harris that cancer (malnutrition) lowers cholesterol,
often in the near fatal phase, but low cholesterol per se is also
linked
to more cancer while high cholesterol is linked to less cancer. What
the 6 year J-LIT study showed us are clinical results in a massive
baseline high cholesterol population and where those winding up with
the
lowest levels of cholesterol on simvastatin wound up, statistically
significant, most dead.
The J-LIT study authors called these people 'hyper-responders' (to
statin) and suggested caution in that regards. They did NOT say how a
clinician is to exercise such caution since fatal cancers are mostly
internal and only detectable by extensive and expensive screening
methods (colonoscopy before statin anyone?).
I note that J-LIT spent about 1/4 billion dollars on statin and then to
find greater mortality in those lowering cholesterol 'most
successfully'
is scary, especially in the light of PROSPER. Cardiologists or doctors
don't examine people for cancer (risk) before prescribing statin which
is a problem since we don't know in which patients statins may trigger
and/or promote cancer.
E.V.
outrider
Susan wrote:
> x-no-archive: yes
> "normal" spectrum of glucose tolerance.
>
> We already know that low fat diets don't work for CVD prevention,
that's
> why the statin pushers are so firmly behind advocating them.
>
> Some cites:
>
> J Nutr. 2002 Jul; 132(7): 1879-85. Related Articles, Links
>
>
> A ketogenic diet favorably affects serum biomarkers for
cardiovascular
> disease in normal-weight men.
>
> Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP,
Volek JS.
>
> Human Performance Laboratory, Department of Kinesiology, University
of
> Connecticut, Storrs 06269-1110, USA.
>
> Very low-carbohydrate (ketogenic) diets are popular yet little is
known
> regarding the effects on serum biomarkers for cardiovascular disease
> (CVD). This study examined the effects of a 6-wk ketogenic diet on
> fasting and postprandial serum biomarkers in 20 normal-weight,
> normolipidemic men. Twelve men switched from their habitual diet (17%
> protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30%
protein,
> 8% carbohydrate and 61% fat) and eight control subjects consumed
their
> habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle
> size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin
> responses to a fat-rich meal were determined before and after
treatment.
> There were significant decreases in fasting serum TAG (-33%),
> postprandial lipemia after a fat-rich meal (-29%), and fasting serum
> insulin concentrations (-34%) after men consumed the ketogenic diet.
> Fasting serum total and LDL cholesterol and oxidized LDL were
unaffected
> and HDL cholesterol tended to increase with the ketogenic diet
(+11.5%;
> P = 0.066). In subjects with a predominance of small LDL particles
> pattern B, there were significant increases in mean and peak LDL
> particle diameter and the percentage of LDL-1 after the ketogenic
diet.
> There were no significant changes in blood lipids in the control
group.
> To our knowledge this is the first study to document the effects of a
> ketogenic diet on fasting and postprandial CVD biomarkers independent
of
> weight loss. The results suggest that a short-term ketogenic diet
does
> not have a deleterious effect on CVD risk profile and may improve the
> lipid disorders characteristic of atherogenic dyslipidemia.
>
> PMID: 12097663 [PubMed - indexed for MEDLINE]
I repeat: "low-carb" would be wrong and possibly deadly in context of
FH.
There is abundant evidence that a high fat (omega 3s; Mediterranean
type diet et al) and high complex carb works for FH. But some with very
pronounced FH may be counselled to follow low-fat. Those people will
also likely be counselled to consider statin therapy.
Zee
Jim Chinnis
>x-no-archive: yes
>Yeah, they do. They use them to seed the development of new drugs, then
>hand over the research to big pharma.
>
>Government *could* do this, but they don't. We know how completely in
>the pockets of industry the NIH researchers are. Now they're saying
>they refuse to work unless the ethics rules are rolled back and all the
>conflicts in interest remain firmly in place.
>
>Susan
You're describing a failure of the governments of the world, or of
the citizenry that doesn't care if good research is ever done on
diet and supplements.
Much of the lack of usable nutrition research predates big pharma.
Good work could have been done long ago and wasn't.
Juhana Harju
:: x-no-archive: yes
::
:: Blood Glucose Concentration Linked to>Cardiovascular Risk in
:: Nondiabetic Men>
:: [...]
I agree that blood glucose and insuline levels are important risk factors.
But your claim that low carb diet would be the best to lower lipids is
simply not true.
Limiting carbs within the context of traditional Cretan Mediterranean diet
would probably be the best policy for anyone with high cholesterol and high
blood glucose (metabolic syndrome).
--
Juhana
Jim Chinnis
>Now produce the studies that found a role for
>fat in CVD in the absence of high GL.
Not fair! You don't think that nutritionists have ever
independently varied fats and GL to see what's what do you?!
Juhana Harju
:: I repeat: "low-carb" would be wrong and possibly deadly in context of
:: FH.
::
:: There is abundant evidence that a high fat (omega 3s; Mediterranean
:: type diet et al) and high complex carb works for FH. But some with
:: very pronounced FH may be counselled to follow low-fat. Those people
:: will also likely be counselled to consider statin therapy.
::
:: Zee
IMHO, Susan is partly right here. Your suggestion to follow Mediterranean
diet and complex carbs is OK, but in addition to that, someone with insulin
resistance should reduce the intake whole grains as well (and cut all
refined grains, of course).
--
Juhana
Jim Chinnis
>x-no-archive: yes
>We have no objective outcomes reported on statins, IMO, with researchers
>all having financial stakes in the drugs when they study them.
Well, you're right that if we throw out all the statin trials
because of conflicts of interest, then there are no data to show
that they have an effect on outcomes, either. The current system
for reporting research is a poor one, but I don't think everything
has to be thrown out, just taken with a grain of salt.
Hopefully, some of the nonsense is coming to an end. Some of the
statin trials had their designa and hypotheses published in
advance of the studies. That';s a great start on a good system,
IMO.
>If the lipid targets are an issue, then we know pantethine is effective,
>that fish oil, too, will lower TGLs, dramatically with high doses.
If the lipid targets are the real targets. Lipid targets are
themselves rather complex when all aspects are considered. If
agent X changes lipids in a way the reduces LDL and mortality,
that doesn't mean that reducing LDL with agent Y will reduce
mortality.
>I don't know of anyone who's gotten any of the alleged benefits of
>policosanol or guggulipid, but I got exactly what the research results
>were using pantethine, added to my low carb diet, which had already
>improved my lipid profile a great deal.
>
>Susan
We all have to work with what we can and balance the risks.
outrider
outrider
Susan wrote:
> x-no-archive: yes
>
>
> >
> > I repeat: "low-carb" would be wrong and possibly deadly in context
of
> > FH.
> >
> > There is abundant evidence that a high fat (omega 3s; Mediterranean
> > type diet et al) and high complex carb works for FH. But some with
very
> > pronounced FH may be counselled to follow low-fat. Those people
will
> > also likely be counselled to consider statin therapy.
> >
> > Zee
> >
>
for
> fat in CVD in the absence of high GL.
>
> quality are what's important, and that BG is a major component.
>
> CVD risk rises all along the continuum of normal fbg.
>
> No more opinions, I want you to cite good science with good data, not
> unfounded conclusions.
>
> *************A recent study involving over 40,000 middle-aged and
older
> American
> men over a period of six years found that there was no link between
> saturated fat intake and heart disease in men. It also supported the
> contention that linolenic acid (a form of fat) is preventive against
> heart disease. (Ascherio A et. al. Dietary fat and risk of coronary
> heart disease in men: cohort follow up study in the United States.
> British Medical Journal, 1996 Jul 13, 313:7049, 84-90.)"
>
> "Several studies have shown that high-carbohydrate low-fat diets lead
> to high triglycerides, elevated serum insulin levels, lower HDL
> cholesterol levels, and other factors known to raise the risk of
> coronary artery disease. (See Liu GC; Coulston AM; Reaven GM. Effect
> of high-carbohydrate low-fat diets on plasma glucose, insulin and
> lipid responses in hypertriglyceridemic humans. Metabolism, 1983 Aug,
> 32:8, 750-3. See also Coulston AM; Liu GC; Reaven GM. Plasma glucose,
> insulin and lipid responses to high-carbohydrate low-fat diets in
> normal humans. Metabolism, 1983 Jan, 32:1, 52-6. See also Olefsky JM;
> Crapo P; Reaven GM. Postprandial plasma triglyceride and cholesterol
> responses to a low-fat meal. American Journal of Clinical Nutrition,
> 1976 May, 29:5, 535-9. See also Ginsberg H et. al. Induction of
> hypertriglyceridemia by a low-fat diet. Journal of Clin Endocrinol
> Metab, 1976 Apr, 42:4, 729-35) "
>
> "The idea that saturated fats cause heart disease is completely
wrong,
> but the statement has been 'published' so many times over the last
> three or more decades that it is very difficult to convince people
> otherwise unless they are willing to take the time to read and learn
> what...produced the anti-saturated fat agenda." (Dr. Mary Enig,
> Consulting Editor to the Journal of the American College of
Nutrition,
> President of the Maryland Nutritionists Association, and noted lipids
> researcher.)
>
> "The diet-heart hypothesis [which suggests that high intake of
> saturated fat and cholesterol causes heart disease] has been
> repeatedly shown to be wrong, and yet, for complicated reasons of
> pride, profit and prejudice, the hypothesis continues to be exploited
> by scientists, fund-raising enterprises, food companies and even
> governmental agencies. The public is being deceived by the greatest
> health scam of the century." (Dr. George V. Mann, participating
> researcher in the Framingham study and author of CORONARY HEART
> DISEASE: THE DIETARY SENSE AND NONSENSE, Janus Publishing 1993.)
>
> High intake of fats from the Omega-3 group increase HDL cholesterol,
> which is considered protective against heart disease. Obviously it
> would be difficult to eat an Omega-3 rich diet while following a
> traditional fat reduced diet, especially if one were following one of
> the popular American diets that has one eating only 20-30 grams of
fat
> per day. (Franceschini G. et. al. Omega-3 fatty acids selectively
> raise high-density lipoprotein 2 levels in healthy volunteers.
> Metabolism, 1991 Dec, 40:12, 1283-6. See also Journal of the American
> College of Nutrition 1991:10(6);593-601)
>
> A recent American study showed that low-fat, high-carbohydrate diets
> (15% protein, 60% carbohydrate, 25% fat) increase risk of heart
> disease in post-menopausal women over a higher fat, lower
carbohydrate
> diet (15% protein, 40% carbohydrate, 45% fat). (Jeppeson, J., et. al.
> Effects of low-fat, high-carbohydrate diets on risk factors for
> ischemic heart disease in postmenopausal women. American Journal of
> Clinical Nutrition, 1997;65:1027-33)
>
> *************The largest and most comprehensive study on diet and
breast
> cancer to
> date, studying over 5,000 women between 1991 and 1994, showed that
> women with the lowest intake of dietary fat had a significantly
higher
> incidence of breast cancer than the women with the highest intake of
> dietary fat. It also found that women with the highest intake of
> starch had a significantly higher incidence of breast cancer than the
> women with the lowest intake of starch. The study found no evidence
> that saturated fat had any effect one way or the other on breast
> cancer, and that unsaturated fat had a significantly protective
effect
> against breast cancer. (Franceschi S et. al. Intake of macronutrients
> and risk of breast cancer. Lancet; 347(9012):1351-6 1996)
****************
>
> "The commonly-held belief that the best diet for prevention of
> coronary heart disease is a low saturated fat, low cholesterol diet
is
> not supported by the available evidence from clinical trials. In
> primary preventions, such diets do not reduce the risk of myocardial
> infarction or coronary or all-cause mortality. Cost-benefit analyses
> of extensive primary prevention programmes, which are at present
> vigorously supported by governments, health departments, and health
> educationalists, are urgently required....Similarly, diets focused
> exclusively on reduction of saturated fats and cholesterol are
> relatively ineffective for secondary prevention and should be
> abandoned. There may be other effective diets for secondary
prevention
> of coronary heart disease but these are not yet sufficiently well
> defined or adequately tested." (European Heart Journal, Volume 18,
> January 1997.)
>
> "We found no evidence of a positive association between total dietary
> fat intake and the risk of breast cancer. There was no reduction in
> risk even among women whose energy intake from fat was less than 20
> percent of total energy intake. In the context of the Western
> lifestyle, lowering the total intake of fat in midlife is unlikely to
> reduce the risk of breast cancer substantially." (Hunter, DJ et. al.
> Cohort studies of fat intake and the risk of breast cancer - A pooled
> analysis. New England Journal of Medicine, 334: (6) FEB 8 1996)
>
>
> 2) Title: DG-DISPATCH - ENDO 99: Diabetics Improve Health With Very
> High-Fat,
> Low
> Carb Diet
> Doctor's Guide
> June 15, 1999
>
> By Cameron Johnston
> Special to DG News
>
> SAN DIEGO, CA -- June 15, 1999 -- A very high-fat, low-carbohydrate
diet
> has
> been shown to have astounding effects in helping type 2 diabetics
lose
> weight
> and improve their blood lipid profiles.
>
> The results of three studies involving such a diet, which is similar
to,
> but
> has a few key differences from the famous "Dr. Atkins Diet", were
> presented
> today
> at the annual meeting of the Endocrine Society.
>
> Dr. James Hays, an endocrinologist and director of the Limestone
Medical
> Center in Wilmington, DE, admitted that the concept of a high-fat
diet in
> people
> who are already at higher risk of cardiovascular disease might seem
> incongruous.
> Nonetheless, this study of 157 men and women with type 2 diabetes
showed
> an
> impressive benefit in body mass index (BMI) triglycerides, HDL, LDL
and
> HbA1c.
>
>
> Most people are encouraged to reduce the amount of fat in their
diets,
> particularly saturated fats, and diabetics in particular are advised
to
> reduce
> their
> overall caloric intake, Dr. Hays explained in an interview in San
Diego
> during
> the
> conference.
>
> Whereas a normal diet would be in the order of 1800 to 2100 calories,
> with 60
> percent of calories coming from carbohydrates and 30 percent from
fat,
> patients
>
> in this diet were restricted to 1800 calories per day and were
> encouraged to
> get
> 50 percent of their caloric intake from fat, and just 20 percent from
> carbohydrates.
> The balance of 30 percent would come from proteins.
>
> A whopping 90 percent of the fat content in their diets was saturated
> fat,
> compared
> with just 10 percent that was monounsaturated fat.
>
> "I think this is at least worth considering for any diabetic," Dr.
Hays
> said in
> an interview.
> "The thing many diabetics coming into the office don't realize is
that
> other
> forms of
> carbohydrates will increase their sugars, too. Dietitians will point
them
> toward complex carbohydrates ... oatmeal and whole wheat bread, but
we
> have to
> deliver the message that these are carbohydrates that increase blood
> sugars,
> too."
>
> Higher-fat diets, on the other hand, seem to make the person feel
full
> faster
> so they eat less; higher-fat diets also tend to reduce postprandial
> hypoglycemia so the patients feel better after eating.
>
> "Every diabetic comes home from the doctor with instructions as to
what
> their
> diet should consist of, but they're not getting the information from
> dietitians about what complex carbohydrates they should eat,"
>
> Dr. Hays said:
> "The important thing here is no ketosis. We absolutely don't want
people
> to
> become
> ketotic, and so we said they had to have so many exchanges of fresh
> fruits and
> vegetables and we specified the ones they could eat."
>
> They were able to eat all the meat and cheese they wanted, but as for
> carbohydrates, they are restricted to eating unprocessed foods,
mainly
> fresh
> fruit and vegetables, he added.
>
> Subjects recruited into the study (84 men, 73 women) were all type 2
> diabetics
> and
> were required to undergo a standard American Diabetes Association
> modified diet
> for
> one full year before entry into the trial. Over the course of one
year,
> the
> subjects achieved a mean decline in total cholesterol of between 231
and
> 190
> mg/dl. Triglycerides declined from 229 to 182 mg/dl.
>
> Low-density lipoproteins (LDL cholesterol) fell from 133 to 105
mg/dl,
> while
> HDL
> increased from 44 to 47 mg/dl.
>
> HbA1c, which at the start of the study averaged 3.34 percent above
> normal,
> declined to the point that at one year, the mean was just 0.96
percent
> above
> normal.
>
> The average weight loss among subjects in the study was in the order
of
> 40
> pounds, Dr. Hays said.
>
> By the end of the one-year study, he added, 90 percent of the
patients
> had
> achieved ADA (American Diabetes Association) targets for HbA1c, HDL,
> LDL and triglycerides.
>
> Even among juvenile diabetics, he said, they might not be overweight
and
> they
> might have more or less normal lipid levels, but when they are on
this
> kind of
> diet
> it is possible to treat them with lower doses of insulin and make
their
> lives a
> little
> safer, he said.
>
> As for the response from cardiologists who see a high-fat diet as
> anathema to
> what they have been instructing their patients for years now, Dr.
Hays
> said he
> has
> three cardiologist patients who are now on the diet.
>
> "If you have a diet that results in weight loss, lower cholesterol,
and a
> better lipid profile, eventually, everybody will be eating that way.
> It's going
> to come
> whether we like it or not."
>
> The New England Journal of Medicine -- November 20, 1997 -- Vol. 337,
> No. 21
>
>
> Dietary Fat Intake and the Risk of Coronary Heart Disease in Women
> Frank B. Hu, Meir J. Stampfer, JoAnn E. Manson, Eric Rimm, Graham A.
> Colditz, Bernard A. Rosner, Charles H. Hennekens, Walter C. Willett
>
-------------------------------------------------------------------------
> -------
>
> Abstract
> Background. The relation between dietary intake of specific types of
> fat, particularly trans unsaturated fat, and the risk of coronary
> disease remains unclear. We
> therefore studied this relation in women enrolled in the Nurses'
Health
> Study.
>
> Methods. We prospectively studied 80,082 women who were 34 to 59
years
> of age and had no known coronary disease, stroke, cancer,
> hypercholesterolemia, or
> diabetes in 1980. Information on diet was obtained at base line and
> updated during follow-up by means of validated questionnaires. During
14
> years of follow-up, we
> documented 939 cases of nonfatal myocardial infarction or death from
> coronary heart disease. Multivariate analyses included age, smoking
> status, total energy intake,
> dietary cholesterol intake, percentages of energy obtained from
protein
> and specific types of fat, and other risk factors.
>
> Results. Each increase of 5 percent of energy intake from saturated
fat,
> as compared with equivalent energy intake from carbohydrates, was
> associated with a 17
> percent increase in the risk of coronary disease (relative risk,
1.17;
> 95 percent confidence interval, 0.97 to 1.41; P = 0.10). As compared
> with equivalent energy from
> carbohydrates, the relative risk for a 2 percent increment in energy
> intake from trans unsaturated fat was 1.93 (95 percent confidence
> interval, 1.43 to 2.61;
> P<0.001); that for a 5 percent increment in energy from
monounsaturated
> fat was 0.81 (95 percent confidence interval, 0.65 to 1.00; P =
0.05);
> and that for a 5
> percent increment in energy from polyunsaturated fat was 0.62 (95
> percent confidence interval, 0.46 to 0.85; P = 0.003). Total fat
intake
> was not significantly
> related to the risk of coronary disease (for a 5 percent increase in
> energy from fat, the relative risk was 1.02; 95 percent confidence
> interval, 0.97 to 1.07; P = 0.55).
> We estimated that the replacement of 5 percent of energy from
saturated
> fat with energy from unsaturated fats would reduce risk by 42 percent
> (95 percent confidence
> interval, 23 to 56; P<0.001) and that the replacement of 2 percent of
> energy from trans fat with energy from unhydrogenated, unsaturated
fats
> would reduce risk by
> 53 percent (95 percent confidence interval, 34 to 67; P<0.001).
>
> Conclusions. Our findings suggest that replacing saturated and trans
> unsaturated fats with unhydrogenated monounsaturated and
polyunsaturated
> fats is more effective
> in preventing coronary heart disease in women than reducing overall
fat
> intake. (N Engl J Med 1997;337:1491-9.)
>
>
> Source Information
> >From the Departments of Nutrition (F.B.H., M.J.S., E.R., W.C.W.),
> Epidemiology (M.J.S., J.E.M., E.R., B.A.R., W.C.W.), and
Biostatistics
> (B.A.R.),
> Harvard School of Public Health; and the Channing Laboratory (M.J.S.,
> J.E.M., E.R., G.A.C., B.A.R., C.H.H., W.C.W.) and the Division of
> Preventive
> Medicine (J.E.M., C.H.H.), Department of Medicine, Brigham and
Women's
> Hospital and Harvard Medical School -- all in Boston. Address reprint
> requests to Dr.
> Hu at the Department of Nutrition, Harvard School of Public Health,
665
> Huntington Ave., Boston, MA 02115.
>
> Ann Intern Med 1998 Apr 1;128(7):524-33
>
>
>
> Metabolic risk factors worsen continuously across the spectrum of
> nondiabetic glucose tolerance. The Framingham Offspring Study.
>
> Meigs JB, Nathan DM, Wilson PW, Cupples LA, Singer DE
> Massachusetts General Hospital, Harvard Medical School, Boston
> University School of Public Health, 02114, USA.
> jme...@sol.mgh.harvard.edu
>
> BACKGROUND: Categorical definitions for glucose intolerance imply
that
> risk thresholds exist, but metabolic risk for type 2 diabetes
mellitus
> or cardiovascular
> disease may increase continuously as glucose intolerance increases.
> OBJECTIVE: To examine the distributions of the following metabolic
risk
> factors across the
> spectrum of glucose tolerance: overall and central obesity,
> hypertension, low levels of high-density lipoprotein cholesterol, and
> increased triglyceride and insulin
> levels. DESIGN: Cross-sectional analysis. SETTING: The
community-based
> Framingham Offspring Study. PARTICIPANTS: 2583 adults without
previously
> diagnosed diabetes. MEASUREMENTS: Clinical data; fasting glucose,
> insulin, and lipid levels; and glucose and insulin levels taken 2
hours
> after oral challenge
> were collected from 1991 to 1993. Glucose tolerance was determined by
> 1980 World Health Organization criteria. Patients with normal glucose
> tolerance were
> categorized into quintiles of fasting glucose. The distributions of
each
> metabolic risk factor and the metabolic sum of the six risk factors
were
> assessed across seven
> categories from the lowest quintile of normal fasting glucose level
> through impaired glucose tolerance and previously undiagnosed
diabetes.
> RESULTS: The mean
> age of patients was 54 years (range, 26 to 82 years); 52.7% of
patients
> were women. Glucose tolerance testing found that 12.7% of patients
had
> impaired glucose
> tolerance and 4.8% had previously undiagnosed diabetes.
> Multivariable-adjusted mean measures of risk factors and odds ratios
for
> obesity, elevated waist-to-hip ratio,
> hypertension, low levels of high-density lipoprotein cholesterol,
> elevated triglyceride levels, and hyperinsulinemia showed continuous
> increases across the spectrum
> of nondiabetic glucose tolerance. Although a threshold effect near
the
> upper range of nondiabetic glucose tolerance could not be ruled out
for
> triglyceride levels in
> men and for insulin levels 2 hours after oral challenge in men and
> women, no other metabolic risk factors showed clear evidence of
> thresholds for increased risk.
> CONCLUSIONS: Metabolic risk factors for type 2 diabetes mellitus and
for
> cardiovascular disease worsen continuously across the spectrum of
> glucose tolerance
> categories, beginning in the lowest quintiles of normal fasting
glucose
> level.
>
> PMID: 9518396, UI: 98175274
>
>
>
>
>
> Susan
I think you have not read carefully what I have said. And in the
conclusion above, what I have said is corroborated by this which you
posted "...metabolic risk fators for type 2 diabetes..."
zee
Juhana Harju
:: x-no-archive: yes
::
:: Juhana Harju wrote:
::: Susan wrote:
::::: x-no-archive: yes
:::::
::::: Blood Glucose Concentration Linked to>Cardiovascular Risk in
::::: Nondiabetic Men>
::::: [...]
:::
::: I agree that blood glucose and insuline levels are important risk
::: factors. But your claim that low carb diet would be the best to
::: lower lipids is simply not true.
:: Well, yeah, it is true, quite a bit of research demonstrates it,
:: particularly with HbA1c, which I believe will become an important
:: benchmark for CVD risk widely used in the non-diabetic population.
:: Only low carb lowers it a LOT and keeps it low.
No research demonstrates that low carb is effective in reducing cholesterol.
Just compare it to the Portfolio diet. Low carbers often eat a lot of red
meat. Red meat, high heme iron and high ferritin has been shown to increase
the risk of diabetes and CVD.
::: Limiting carbs within the context of traditional Cretan
::: Mediterranean diet would probably be the best policy for anyone
::: with high cholesterol and high blood glucose (metabolic syndrome).
:::
:: You know, there is no such thing as a one size fits all diet. I
:: have to eat lower carb than some other folks do. I do better if I
:: limit sat fat, some folks do fine eating nothing but. The notion
:: that you can ignore every other aspect of environment and lifestyle
:: and just adopt a particular diet as ideal for everyone is ridiculous.
'Ridiculous' is a strong word here. Actually the Mediterranean diet has been
transferred to different populations and it has been shown to work
everywhere. There are studies about Mediterranean diet trials in India,
Austalia etc. Still I do agree that people with high blood glucose should
limit even whole grains. The advantage doing it within the context of
Mediterranean diet is that then you get proteins in a healthy package (from
beans and fish) in addition to safe and heart healthy fats (from olive oil,
nuts and fish).
--
Juhana
Juhana Harju
:: x-no-archive: yes
:: Juhana Harju wrote:
::: IMHO, Susan is partly right here. Your suggestion to follow
::: Mediterranean diet and complex carbs is OK, but in addition to
::: that, someone with insulin resistance should reduce the intake
::: whole grains as well (and cut all refined grains, of course).
:::
:: Except for whoe rye kernels, whole grains aren't good for those who
:: are IR, either. Glucose meters tell the tale.
I thought that whole barley and whole grain pasta have a low glychemic index
also, but I am not a diabetic, so I might be wrong. :-)
--
Juhana
Juhana Harju
:: x-no-archive: yes
::
:: High-Grain Diet May Increase Risk of Cardiovascular Disease
::
:: American Journal Clinical Nutrition January 2003 77: 43-50
::
:: [...]
Well, to have a more balanced view, lets have a look at this review (the
full study is also available):
American Journal of Clinical Nutrition, Vol. 70, No. 3, 451S-458S, September
1999
© 1999 American Society for Clinical Nutrition
Supplements
Cereals, legumes, and chronic disease risk reduction: evidence from
epidemiologic studies1,2,3
Lawrence H Kushi, Katie A Meyer and David R Jacobs, Jr
1 From the Division of Epidemiology, University of Minnesota School of
Public Health, Minneapolis.
There is growing evidence that cereals and legumes play important roles in
the prevention of chronic diseases. Early epidemiologic studies of these
associations focused on intake of dietary fiber rather than intake of grains
or legumes. Generally, these studies indicated an inverse association
between dietary fiber intake and risk of coronary artery disease; this
observation has been replicated in recent cohort studies. Studies that
focused on grain or cereal intake are fewer in number; these tend to support
an inverse association between intake of whole grains and coronary artery
disease. Studies on the association of dietary fiber with colon and other
cancers have generally shown inverse relations, but whether these relations
are attributable to cereals, other fiber sources, or other factors is less
clear. Although legumes have been shown to lower blood cholesterol
concentrations, epidemiologic studies are few and inconclusive regarding the
association of legumes with risk of coronary artery disease. It has been
hypothesized that legumes, in particular soybeans, reduce the risk of some
cancers, but epidemiologic studies are equivocal in this regard. Overall,
there is substantial epidemiologic evidence that dietary fiber and whole
grains are associated with decreased risk of coronary artery disease and
some cancers, whereas the role of legumes in these diseases appears
promising but as yet inconclusive.
http://www.ajcn.org/cgi/content/abstract/70/3/451S
--
Juhana
Zee
Montreal cardiologist and McGill University professor Colin Rose: CAD
caused by atherogenic diet, not a deficiency of statins. As
usual...Rose nails it.
~~~~~~~~~~~~~~~~~~~~~~~~~
"If there are any lipid experts left with no connection to the drug
industry let them appoint themselves to a 'working group' and write a
consensus opinion. If they don't want to appoint themselves I can try
to arrange for them to be appointed. Until then I will use statins only
for patients with severe, symptomatic, congenital lipid problems. Dr.
Dobson wonders what I would 'explain to grieving family members that he
failed to prescribe a statin for someone who was unable to control
their LDL with diet and who went on to suffer a fatal heart attack'?
Well, I am glad he asked. I would tell them that a heart attack is
caused by rupture of an atherosclerotic plaque that has been present
for many years, that atherosclerotic plaque begins in childhood in
Westernized societies due to the early introduction of atherogenic
diets, that the disease is not due to a deficiency of statins, that
heart attacks cannot be predicted in individuals by measuring LDL, that
there is no 'safe' LDL, and that statins do not prolong life in primary
prevention in blinded, controlled trials and probably accelerate the
disease in unblinded, 'statin-protected' populations due to their moral
hazard effect. I would also say that the death was not in vain if it
convinced all of the family members of the necessity of adopting
non-atherogenic diets and habits and of encouraging all around them to
do likewise."
Zee
Juhana Harju wrote:
> Susan wrote:
> :: x-no-archive: yes
> :: Juhana Harju wrote:
>
> ::: IMHO, Susan is partly right here. Your suggestion to follow
> ::: Mediterranean diet and complex carbs is OK, but in addition to
> ::: that, someone with insulin resistance should reduce the intake
> ::: whole grains as well (and cut all refined grains, of course).
One study posted did corroborate what I said in its conclusion
statement; consider "metabolic syndrome" ie) insulin resistance. Not
all complex carbs (with good protein and high fibre preferably) will be
grains. Consider channa dal. A little study on nutrition would go a
long way here....
Zee
Jim Chinnis
>
>Jim Chinnis wrote:
>> A better title for this thread would have been:
>>
>> Statins have not been shown to save lives during short-term
>> studies of people without cardiovascular disease.
>>
>> (What a surprise!)
>> --
>> Jim Chinnis Warrenton, Virginia, USA
>
>
>
>>From former BMJ editor Richard Smith's article on medical journals
>being an arm of pharma marketing departments.
>http://dx.doi.org/10.1371/journal.pmed.0020138
>
>Examples of Methods for Pharmaceutical Companies to Get the Results
>They Want from Clinical Trials:
>
>" Conduct subgroup analyses and select for publication those that are
>favourable."
This why good studies publish their designs before they start. A
number of the statin trials did exactly that and found reduced
mortality in secondary prevention.
Juhana Harju
:: Most low carbers learn more about healthy EFAs, GL, the role of fiber
:: and antioxidant rich foods than low fat dieters. Starches are
:: frankly impoverished of nutrients when compared to colorful, leafy
:: plant foods.
Personally I am no dieter. I have always been lean and I don't have any need
to follow any weight control, cholesterol lowering or glycemic control diet.
Still I have a healthy diet. My TC is 4 and the ratio of LDL to HDL is good.
No problem with triglyserides either.
I have always wondered why low carbers pay attention only to the quality of
carbs, but not to the package in which protein comes nor to the quality of
fats. For me it is obvious that one should aim to eat the healthiest foods
from each of the macronutrient groups.
--
Juhana
Zee
What number...compared to study-by-marketing-department.
Reduced mortality...for who?
Good studies don't have to wait to publish marginal positive results
until several years after the bounty has rolled in which was based on
pushing selective results (HPS).
Zee
Juhana Harju
:: x-no-archive: yes
::: I have always wondered why low carbers pay attention only to the
::: quality of carbs, but not to the package in which protein comes nor
::: to the quality of fats. For me it is obvious that one should aim to
::: eat the healthiest foods from each of the macronutrient groups.
:::
:: That's just a faulty and unsubstantiated assumption on your part. I
:: learned about the importance of the CLA, omega 6/3 content and
:: arachidonic acid content in feedlot beef as a health risk from low
:: carb resources. When red meat is studied using feedlot beef rather
:: than grass fed free range beef, the results indict agribusiness
:: practices, not beef. Low carb reading is where I also learned only
:: to buy wild, not farm raised fish, and why.
Not so unssubstantiated. I have been following the comments and discussions
of low carbers here in Finland where I live and the ignorance is enormous. I
do agree that there are also some low carbers who are quite knowledgeable.
When it comes to CLA, please notice that not all evidence is positive. Also
the high heme iron is likely to be a problem even if red meat is from
pasteurizing cattle. Fatty fish has healthier lipids than red meat, even if
the cattle has been fed with grass.
--
Juhana
Juhana Harju
:: And some very low GI foods have a high insulin release.
Like which and why?
--
Juhana
elgoog
Susan wrote:
> x-no-archive: yes
>
>
> Juhana Harju wrote:
>
(the
> > full study is also available):
> >
> > American Journal of Clinical Nutrition, Vol. 70, No. 3, 451S-458S,
September
> > 1999
> > © 1999 American Society for Clinical Nutrition
> >
> > Supplements
> >
> > Cereals, legumes, and chronic disease risk reduction: evidence from
> > epidemiologic studies1,2,3
> > Lawrence H Kushi, Katie A Meyer and David R Jacobs, Jr
> > 1 From the Division of Epidemiology, University of Minnesota School
of
> > Public Health, Minneapolis.
> >
> > There is growing evidence that cereals and legumes play important
roles in
> > the prevention of chronic diseases.
>
> industry. How many papers have we seen opening with the lie, "it has
> long been known that HRT protects menopausal women from CVD?" It was
> never true, but it was generally accepted.
>
> Just like the equally disingenuous low fat/high carb dogma.
> This seems to be pushing cereals, and basing it on fiber content. I
eat
> waaaay more fiber since giving up grains. Low GL foods are low
because
> of the high fiber content, which isn't metabolized. If one wants
> benefits from fiber, one should limit starches and add more veggies.
>
> Further, the alleged colon protection by grains turned out to be
false,
> but high consumption of cured meats and high GL are associated with
it.
>
> Susan
Yabbut, if you are going to eat cereal, then whole grain is better than
not. If you're going to eat that stuff they pass off as "bread" in the
supermarket, then whole grain is better than not. More important is to
control the portions, and if you want more fiber, eat more fruit and
veggies.
Juhana Harju
:: x-no-archive: yes
::: 'Ridiculous' is a strong word here. Actually the Mediterranean diet
::: has been transferred to different populations and it has been shown
::: to work everywhere.t
::
:: That doesn't mean something else, such as low carb doesn't work.
:: Further, if you look at just lowering cholesterol, you're missing the
:: big picture. [...]
There is mounting evidence for the Mediterranean type of diet. Just have a
look at the Lyon Heart Study. I am not looking just lowering cholesterol. I
am also looking at reducing cardiac arrythmias, reducing the risk of
thrombosis, increasing insulin sensitivity, increasing antioxidants,
increasing nutrient density, reducing inflammation and CRP, reducing
homocysteine...
--
Juhana
Zee
What number?
{Compared to study-by-marketing department hype).
Reduced mortality...for who?
Good studies don't wait to publish marginal positive results until
several years after spending millions pushing selective results (HPS).
Zee
Juhana Harju
:: x-no-archive: yes
:: Surely you're aware of studies demonstrating that GI is not a good
:: predictor of individual results, or of insulin index?
Do you mean that glycemic load is more important or what?
--
Juhana
Juhana Harju
:: x-no-archive: yes
::
::
:: Zee wrote:
::: Juhana Harju wrote:
:::
:::: Susan wrote:
:::::: x-no-archive: yes
::::::
:::::: High-Grain Diet May Increase Risk of Cardiovascular Disease
::::::
:::::: American Journal Clinical Nutrition January 2003 77: 43-50
::::::
:::::: [...]
::::
:::: American Journal of Clinical Nutrition, Vol. 70, No. 3, 451S-458S,
:::: September 1999
:::: Cereals, legumes, and chronic disease risk reduction: evidence from
:::: epidemiologic studies.
:::: Lawrence H Kushi et al.
::::
:::: There is growing evidence that cereals and legumes play important
:::: roles in
:::: the prevention of chronic diseases. [...]
:::: Overall,
:::: there is substantial epidemiologic evidence that dietary fiber and
:::: whole
:::: grains are associated with decreased risk of coronary artery
:::: disease
::
:: Here's how glucose level makes a diet atherogenic:
::
:: Glucose can glycate endothelial>cell proteins & LDL amino acid
:: residues making them
:: more prone to>oxidation (unoxidised LDL isn't atherogenic).
::
:: Glycation of collagen>in the artery wall also activates the
:: macrophages which become
:: foam>cells, the critical event in the formation of a fatty>streak.
::
http://www.ncbi.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11730813&dopt=Abstract
::
:: Glycation>of LDL promotes migration of smooth muscle cells into the
:: artery>wall,
:: whichs leads to the growth in size from a fatty streak to a
:: plaque>proper.
::
http://www.ncbi.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11480453&dopt=Abstract
I do understand that glycation plays a part in it, but lets strive to have a
balanced view here. Take the Asian diets for example. Their diets are high
in carbs and high glycemic index rice and still the heart disease incidence
is low. Mediterranean diets are also high carb and still the cardiovascular
disease incidence has been low.
--
Juhana
Juhana Harju
:: x-no-archive: yes
::
:: Juhana Harju wrote:
:: Yabbut, your eyes are closed to any evidence of that which you do not
:: already believe.
I don't think so. I am always ready to learn more.
--
Juhana
Stacey Bender
> I eat black
> soybeans, which are almost completely made up of protein and fiber.
Any pointers on how to fix them? I'd like to give them a try.
Juhana Harju
:: x-no-archive: yes
::
:: Juhana Harju wrote:
::
::: discussions of low carbers here in Finland where I live and the
::: ignorance is enormous. I do agree that there are also some low
::: carbers who are quite knowledgeable.
:: All the low carb plans emphasize food quality and fat quality.
:: Every one.
Well, people have different understanding what food and fat quality actually
means. Many people think that it is healthy to eat anything that is organic.
Personally I think that it is healthier to eat some healthy non-organic
foods than to eat unhealthy organic foods. There is also a wide range of low
carbers. Many of them start a diet high in red meat not knowing that it is
important to eat a lot of veggies, too. I have red many messages of low
carbers who have not red a single book presenting a diet plan.
There are also wide range of low carb plans. Some earlier plans of Atkins
are very different from the latest. And so on.
::: When it comes to CLA, please notice that not all evidence is
::: positive. Also the high heme iron is likely to be a problem even if
::: red meat is from pasteurizing cattle. Fatty fish has healthier
::: lipids than red meat, even if the cattle has been fed with grass.
::
:: Not so, there's absolutely no good evidence finding any unhealthy
:: role for naturally grass fed red meat in the human nutrition.
:: There's no evidence at all, actually, because variables have not
:: been controlled for.
Some variables are known. EPA, DHA and phospholipids are healthy variables,
heme iron and saturated fat are unhealthy variables, at least in excess.
--
Juhana
David Rind
> >>2. Dr. Harris may be annoyed hearing about PROSPER's significant
> increase in 'new' cancers in the statin group with fewer smokers, but
> data are data. <<
>
>
> Yes, they are, but with much larger studies than PROSPER showing no
> such effects, and meta-analyses also, the PROSPER results are hard to
> explain. Perhaps statins should not be given to people over 70, until
> other studies have had a chance to break out groups similar to those in
> PROSPER, to see if the subgroup effect is robust.
Lots of other studies have done so at this point. A meta-analysis of
statins in the elderly (published as part of PROSPER, if I recall
correctly) showed no evidence of increased cancer with statins in the
elderly. HPS, published later, had plenty of elderly patients and also
showed no such increase. The PROSPER results look like they were a
fluke. That said, TNT had a nonsignificant 13% increase in cancer
mortality in the high dose arm -- though this may be explained by the
"people have to die of something" argument. (Note, the 25% increase in
noncardiac mortality in TNT leading to no reduction in all-cause
mortality cannot be explained away by the same argument. It may also
have been a statistical fluke or it may be evidence of a problem.)
--
David Rind
dr...@caregroup.harvard.edu
Sharon Hope
You are switching your argument.
The thread is statins do not save lives. The rate of non-fatal cardiac
events is a different thread.
"Sbharris[atsign]ix.netcom.com" <sbha...@ix.netcom.com> wrote in message
news:1116310483....@o13g2000cwo.googlegroups.com...
>>>The rate of serious statin side effects is far higher than the risk
> of CAD
> in low-risk and moderate risk women. .... Also, the total range of
> choices for increasing heart health is not
> exhausted by "statins or death." <<
>
> COMMENT:
>
> Well, you'd think it was, giving how you insist on focusing on
> mortality.
>
> But we're not talking about low and moderate risk women. This thread
> didn't start out qualifying any group of women. The toral risk of major
> coronary events in the 4S trial in women was 160 in 827 high risk women
> over 5 years, which is 19%. That's high, and statins prevented about a
> third of them. That's in line with other trial results. So what major
> side effect can you expect from simvastatin which is as serious as a
> heart attack, and that you can expect at least 7% chance of getting, in
> 5 years? Since for these women something like 7 in 100 would have a
> heart attack in the next 5 years, preventable by a statin. That's your
> benefit. Now, what's the risk which outweighs that? And who says so,
> and cite the study.
>
> SBH
>
Sharon Hope
covered, and hasn't been for decades.
"Jim Chinnis" <jchi...@SPAMalum.mit.edu> wrote in message
news:itbk81lihanfuk375...@4ax.com...
> Susan <mcf...@NOgmailNO.com> wrote in part:
>
>>x-no-archive: yes
>>
>>
>>Jim Chinnis wrote:
>>> Susan <mcf...@NOgmailNO.com> wrote in part:
>>>
>>>
>>>>It is well demonstrated to bring lipids into desirable ranges and
>>>>ratios, with absolutely no adverse reactions. Workd for me, while I ate
>>>>an extremely high fat diet.
>>>>
>>>>Sadly, there's no profit to be made by anyone in studies that might
>>>>demonstrate its effect on mortality.
>>>
>>>
>>> So governments have no research funds?
>>> --
>>> Jim Chinnis Warrenton, Virginia, USA
>>
>>Yeah, they do. They use them to seed the development of new drugs, then
>>hand over the research to big pharma.
>>
>>Government *could* do this, but they don't. We know how completely in
>>the pockets of industry the NIH researchers are. Now they're saying
>>they refuse to work unless the ethics rules are rolled back and all the
>>conflicts in interest remain firmly in place.
>>
>>Susan
>
> You're describing a failure of the governments of the world, or of
> the citizenry that doesn't care if good research is ever done on
> diet and supplements.
>
> Much of the lack of usable nutrition research predates big pharma.
> Good work could have been done long ago and wasn't.