Woman and statins - A good debate
keith
by Gary Schwitzer, University of Minnesota School of Journalism & Mass
Communication
May 17, 2007
http://blog.lib.umn.edu/schwitz/healthnews/080114.html
Should women be downing statins? Online debate.
Last week's BMJ, the May 12 edition, carried a debate about whether
women should be offered statin drugs to prevent cardiovascular
disease.
Dr. Scott Grundy of the University of Texas Southwestern Medical
School supports the idea.
He lists the fact that he has been a consultant to the following
companies that market statins: Merck, Pfizer, Bristol Myers Squibb,
and Astra Zeneca. http://www.bmj.com/cgi/content/full/334/7601/982
Malcolm Kendrick of the UK hates the idea. He writes:
"To date, none of the large trials of secondary prevention with
statins has shown a reduction in overall mortality in women.Perhaps
more critically, the primary prevention trials have shown neither an
overall mortality benefit, nor even a reduction in cardiovascular end
points in women. This raises the important question whether women
should be prescribed statins at all.
I believe that the answer is clearly no. Not only do statins fail to
provide any overall health benefit in women, they represent a massive
financial drain on health services. This money could be diverted to
treatments of proved value.
In addition to the lack of benefit and expense, statins carry a
substantial burden of side effects. Lifetime drug treatment can also
create other problems. Firstly, women may falsely believe that they
are being protected and may therefore be less likely to make
beneficial lifestyle changes. Secondly, mass medicalisation is a
dangerous road with many psychological and societal consequences."
http://www.bmj.com/cgi/content/full/334/7601/983
Good debate, with some passionate responses from readers available
online.
Posted by schwitz at May 17, 2007 07:41 AM | TrackBack
MarilynMann
debate here, including Dr. Kendrick. Go to www.thincs.org. Some of
them seem to believe that there is no link between LDL levels and
heart disease.
Marilyn
William Wagner
MarilynMann <ma...@comcast.net> wrote:
Goggle "thincs william wagner"
My 15 miniutes ;))
Bill
--
S Jersey USA Zone 5 Shade
http://www.ocutech.com/ High tech Vison aid
This article is posted under fair use rules in accordance with
Title 17 U.S.C. Section 107, and is strictly for the educational
and informative purposes. This material is distributed without profit.
MarilynMann
My point being
1. I think they are wrong about that (you and I agreed to disagree on
that point, however).
2. They don't always come out and say that they don't think LDL
levels are linked to heart disease because they know they would lose
credibility. Instead they attack use of statins in certain situations
as not being evidence based. People can reasonably differ on the
situations in which statins should be used for primary prevention, or
in women, or whatever. But in looking for advice on that subject,
someone like Uffe Ravnskov would not be the first person I'd go to.
Marilyn
MarilynMann
doesn't seem like a big problem to me.
Have a great weekend.
Marilyn
MarilynMann
>
> The fact that you consistently fail to provide a rationale or basis amid
> all your reams of cutting and pasting is a tad annoying, though.
>
Just because I post something doesn't necessarily mean I think it is
the last word on the subject. In most cases, I'm just doing it for
purposes of information and discussion. Seeing as I'm not a doctor or
a scientist, I'm not really in a position to provide a lot of
rationale or basis in most cases. However, that goes for most of the
people who post stuff in this forum. I'm sorry you find me annoying,
but I'm not sure I'm in a position to do anything about it.
I don't find you annoying. Whatever you want to say or post is fine
with me.
Marilyn
MarilynMann
Your standards seem to be very high and I don't think I will be able
to measure up.
Marilyn
William Wagner
MarilynMann <ma...@comcast.net> wrote:
Smoke from nearby fire not present
Still I know that can change
Luck if you will or chance
Any way grateful
MarilynMann
> x-no-archive: yes
>
> People at work tell you they don't want logical discussion with
> thoughtful analysis?
>
No, people respect my opinions.
Susan, if you have done all this reading and have come to the
conclusion that LDL levels have no relationship to heart disease, I
just don't think reasoned analysis is going to help you. I just am
not interested in arguing with you on that topic. Open any cardiology
journal and you will see the evidence you want.
>
> Folks who just want to chat about health care typically stick to alt
> groups, or might just read a sci.med group for info but not post.
>
It's hard for me to take what you are saying seriously when half the
posts here don't even have anything to do with heart disease. The
fact is, you just disagree with what I am saying and want to draw me
into an argument about it. I don't want to argue with you over LDL
levels as a risk factor. The evidence is just overwhelming on that
score . . .
>
>
Perhaps, if you have just begun reading about heart disease, it would
be helpful to read a bit more before offering opinions about it to
those who've been studying the
> science for years, unless you can make a case for those opinions.
>
That's just ridiculous. I have as much a right as anyone else to
participate here, and you are the only one who seems to be bothered by
my posts. No one else has complained to me. If you don't want to
read them, then don't.
Marilyn
Andrew B. Chung, MD/PhD
> Susan,
>
> This whole discussion is a new experience for me. People I work with
> usually tell me the opposite of what you are saying. Part of my job
> is dealing with partners in major law firms who are bent on pulling
> the wool over my eyes. I think I am pretty good at not letting them
> do that . . .
>
> Where are these "sci med standards" written?
>
> I just don't know why you are so upset with me. I only just recently
> started reading up on heart disease. I just am not an expert on
> this. Please just give me a break, will you?
>
> Thanks, Marilyn
Dear Marilyn,
Think of sci.med.cardiology as being like a bulletin board in the
middle of central park. Those who would attempt to regulate the
content are self-appointed.
May GOD bless you in HIS mighty way.
Prayerfully in Jesus' awesome love,
Andrew <><
--
Andrew B. Chung, MD/PhD
http://EmoryCardiology.com
"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets."
http://HeartMDPhD.com/Love/TheTruth
Po...@nospam.invalid
>Think of sci.med.cardiology as being like a bulletin board in the
>middle of central park.
Interesting.
I think of it as an attempt at serious roundtable discussion by a
handful of very knowledgeable people in the midst of a very crowded,
loud, and raucous barroom ;-)
Port
Andrew B. Chung, MD/PhD
... until you witness the following kind of behavior:
http://groups.google.com/group/sci.med.cardiology/msg/9a556d9aed5da940?
May GOD bless you.
Po...@nospam.invalid
>> >Think of sci.med.cardiology as being like a bulletin board in the
>> >middle of central park.
Port wrote:
>> I think of it as an attempt at serious roundtable discussion by a
>> handful of very knowledgeable people in the midst of a very crowded,
>> loud, and raucous barroom ;-)
"Andrew B. Chung, MD/PhD" wrote:
>... until you witness the following kind of behavior:
>http://groups.google.com/group/sci.med.cardiology/msg/9a556d9aed5da940?
... but that's my point. You'll find every type behavior imaginable in
a bar room. There may be outpourings of faith and goodwill and
sincerity on one end with fists and bar stools and beer bottles flying
on the other. Not to mention people in the middle that take no notice
of either end. Ya just never know ;-)
Port
MarilynMann
fine for him, but I don't feel compelled to listen to him. Also, he
calls himself an "independent researcher," although he doesn't do any
actual research, as far as I can see. Even he has a hard time
explaining why people with very high LDL levels often (not always)
suffer from early heart disease. Homozygous familial
hypercholesterolemia would be the most extreme example, but the
heterozygous form often leads to early heart disease as well. My
husband's family appears to be an example of this, although no genetic
analysis to look for a mutation has yet been done.
My reluctance to argue with you Susan stems from my impression that
your mind is already made up on the issue of LDL levels and whether
they are a risk factor or not. No one is saying LDL is the only risk
factor for heart disease -- it is one of many. But to say LDL is not
a risk factor at all seems to me to go against the weight of the
evidence. Explain to me why kids with heFH have endothelial
dysfunction and higher carotid intima-medial thickness? Does that
strike you as a good thing? Not in my view.
As I said before, I am not in any way shape or form telling you to
worry about your LDL level. That doesn't concern me at all. I just
don't see my position as being particularly controversial or out of
the mainstream or in need of constant argument or citation to back it
up.
Can't we all just get along?
Marilyn
MarilynMann
> > My feeling is that Uffe Ravnskov enjoys being an iconoclast.
> That's
> > fine for him, but I don't feel compelled to listen to him. Also, he
> > calls himself an "independent researcher," although he doesn't do any actual research, as far as I can see. Even he has a hard time
> > explaining why people with very high LDL levels often (not always)
> > suffer from early heart disease.
> He doesn't have to.
Why doesn't he? Doesn't that go to the heart of the whole issue he
has staked out a position on?
Why do half of all CVD deaths occur in those with
> normal cholesterol?
Probably because LDL is not the only risk factor for heart disease.
LDL may be a marker for the metabolic abnormalities
> that lead to CVD without being causal in any way. This is what the data
> and research are moving toward. The Pan Asian study was kind of the
> final nail in the coffin for many of us who've followed the lipids
> research for years.
>
> Homozygous familial
> > hypercholesterolemia would be the most extreme example, but the heterozygous form often leads to early heart disease as well. My
husband's family appears to be an example of this, although no
genetic analysis to look for a mutation has yet been done.
> My family would appear to be an example, too, yet a sharp reversal of
> diet radically altered my lipids risk profile without meds or even
> exercise at times.
>
Susan, here you seem to be avoiding the issue that we were
discussing. The issue is LDL levels. I take it that in your family
there are some other issues. If you cannot explain early heart
disease from familial hypercholesterolemia, in which the phenotype is
very high LDL levels, you are failing to explain something that is
very significant. Also, diet and exercise are not the issue here.
High LDL levels from FH cannot be controlled with diet and exercise to
any significant extent. Even if they could be, that would not mean
that high LDL was not a risk factor. It would just mean that one
could use diet and exercise instead of medication.
> First of all, I have no interest in argument, that's your thing.
Huh?
No one is saying LDL is the only risk
> > factor for heart disease -- it is one of many.
> Some are saying it's the least important, but you choose to ignore that.
I don't recall expressing an opinion on that. In fact, I don't have
one. Also, please clarify your position. Do you think LDL is a risk
factor, but not as important as some other risk factors, or do you
think it is not a risk factor at all?
> Explain to me why kids with heFH have endothelial
dysfunction and higher carotid intima-medial thickness? Does that
> > strike you as a good thing? Not in my view.
> What's that got to do with LDL as causative?
Um, because their LDL is very high and is often their only risk
factor, other than in some cases family history. I invite you to read
the literature on the subject of familial hypercholesterolemia.
> The mainstream gets it wrong routinely: SIDS, HRT are but two examples
> in which the mainstream opinions and recommendations turned out to be
> deadly. ADA and AHA dietary recommendations also fly in the face of
> good science, but cater to their financial sponsors, not public health.
>
Yes, it's true that mainstream opinion is often proven wrong. My
point is that there are many studies over a period of decades showing
that high LDL is a risk factor for heart disease. Presumably you are
aware of these and are not convinced. Why is it my job to try to
convince you?
>
> > Can't we all just get along?
>
> I *am* getting along. You're the one who seems to feel that only pats on the back and agreement with your opinions are acceptable communication.
Not really. I just don't fancy getting in endless arguments about the
same issue. It just seems like a waste of time.
Marilyn
Andrew B. Chung, MD/PhD
You would not expect anyone to behave as if they are entitled to have
authority in the middle of a melee.
At a public bulletin board however...
... there will be folks authoritatively trying to take down things
that offend them.
May GOD bless you.
Prayerfully in Jesus' awesome love,
Andrew <><
--
Andrew B. Chung, MD/PhD
http://EmoryCardiology.com
"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets"
bigvince
> x-no-archive: yes
>
> MarilynMann wrote:
>
> > Why doesn't he? Doesn't that go to the heart of the whole issue he
> > has staked out a position on?
>
> or strong predictive role for LDL in CVD, it's up to those statin
> pushers to prove why lower targets are being advocated for it.
>
>
>
> > Why do half of all CVD deaths occur in those with
>
> >>normal cholesterol?
>
> > Probably because LDL is not the only risk factor for heart disease.
>
>
> > Susan, here you seem to be avoiding the issue that we were
> > discussing. The issue is LDL levels.
>
> as to why.
>
> I take it that in your family
>
> > there are some other issues.
>
> as shit isn't LDL.
>
> If you cannot explain early heart
>
> > disease from familial hypercholesterolemia, in which the phenotype is
> > very high LDL levels, you are failing to explain something that is
> > very significant.
>
> , for example. But that doesn't make it a cause or risk factor for CVD.
>
> Also, diet and exercise are not the issue here.
>
> > High LDL levels from FH cannot be controlled with diet and exercise to
> > any significant extent.
>
>
> Even if they could be, that would not mean
>
> > that high LDL was not a risk factor. It would just mean that one
> > could use diet and exercise instead of medication.
>
> FH or not.
>
> > Huh?
>
> Where I see discussion, you see personal affront.
>
> > I don't recall expressing an opinion on that.
>
> reason for dismissing all of the writers among the cholesterol skeptics,
> then?
>
> In fact, I don't have
>
> > one. Also, please clarify your position. Do you think LDL is a risk
> > factor, but not as important as some other risk factors, or do you
> > think it is not a risk factor at all?
>
> underlying process, an artifact, not a cause.
>
> > Um, because their LDL is very high and is often their only risk
>
> > factor, other than in some cases family history. I invite you to read
> > the literature on the subject of familial hypercholesterolemia.
>
> underlying dynamic, which could be severe insulin resistance, high
> insulinogenic nutrition, adrenal/pituitary disorder, possibly
> subclinical. This is important to note, becasue statins worsen adrenal
> function.
>
> > Yes, it's true that mainstream opinion is often proven wrong. My
> > point is that there are many studies over a period of decades showing
> > that high LDL is a risk factor for heart disease. Presumably you are
> > aware of these and are not convinced. Why is it my job to try to
> > convince you?
>
> conclusions bought by statin makers that are not supported by the
> unbiased research. The Pan Asian study put that to rest for me.
>
> > Not really. I just don't fancy getting in endless arguments about the
> > same issue. It just seems like a waste of time.
>
> unfruitful.
>
> Susan
I've enjoyed this discussion as much as the one in the BMJ. The
question is really more if high LDL is truly a risk factor for CVD
then why if you lower it do you not see a great reduction in CVD. In
women that effect {reduction in mortality] has not yet been
demonstarted .Again we are talking about primary prevention and that
is were the vast majority of statins are used. Thanks Vince
Andrew B. Chung, MD/PhD
Because it is a risk factor and not the proximate cause of CVD.
The latter is visceral adipose tissue (VAT).
Lose the VAT and rates of CVD fall to practically zero.
Simply look at the rates of CVD in countries where folks do not have
VAT.
Truth is simple.
Prayerfully in Jesus' awesome love,
Andrew <><
--
Andrew B. Chung, MD/PhD
http://EmoryCardiology.com
"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets."
http://HeartMDPhD.com/Love/TheTruth
Tony Wesley
[I've been lurking in this discussion]
> Let's go back to the origin of this discussion, which is not about
> whether you or I will agree or disagree about LDL.
Okay, let's go back...
> You began by offering disbelief in LDL as the cause of CVD as the only
> basis for your attempt to dismiss all the information, analysis and
> discussion by a group of scientists, the cholesterol skeptics group.
That's not correct. Here's what Marilyn wrote:
"I suggest that people check out some of the people involved in the
debate here, including Dr. Kendrick. Go to www.thincs.org. Some of
them seem to believe that there is no link between LDL levels and
heart disease."
There is *no* dismissal here. If you believe that there is no link
between LDL and heart disease, those exact words could be used to
establish the bona fides of the people involved.
Since then, you've been playing bully.
bigvince
> On May 19, 9:05 am, Susan <neverm...@nomail.com> wrote:
>
> [I've been lurking in this discussion]
>
> > Let's go back to the origin of this discussion, which is not about
> > whether you or I will agree or disagree about LDL.
>
> Okay, let's go back...
>
> > You began by offering disbelief in LDL as the cause of CVD as the only
> > basis for your attempt to dismiss all the information, analysis and
> > discussion by a group of scientists, the cholesterol skeptics group.
>
> That's not correct. Here's what Marilyn wrote:
>
> "I suggest that people check out some of the people involved in the
> them seem to believe that there is no link between LDL levels and
> heart disease."
>
> There is *no* dismissal here. If you believe that there is no link
> between LDL and heart disease, those exact words could be used to
> establish the bona fides of the people involved.
>
> Since then, you've been playing bully.
"I suggest that people check out some of the people involved in the
debate here, including Dr. Kendrick. Go to www.thincs.org. Some of
them seem to believe that there is no link between LDL levels and
heart disease. "
I believe in context those words where meant to dismiss the
comments of Dr. Kendrick because he did not believe in the basic
premise that LDL levels at least in the 220 or lower range had much
effect on CVD. I believe that DR.Kendrick does not believe in that
connection. And if indeed lowering LDL in women or in primary care has
not been shown to lower CVD or more importantly mortality.The fact if
true that lowering LDL in women does not lower the rate of CVD comes
close to disproveing the LDL causes CVD theory. What doctors believe
is not nearly as important as what the evidence shows.If statin
therapy reduces CVD in women it should be given if not then it should
not. Dr. Kendricks opposition should be judged on the science not on
wheater he belives the LDL theory. As the other experts finiancial
connection to statin makers should not disallow his remarks. Thanks
Vince
MarilynMann
daughter's situation the primary prevention trials of statins in women
don't tell me much. There have been no such trials of women with
heFH, and there will never be any. In addition, there have been no
trials with clinical endpoints that take kids with heFH and start them
on statins at different ages and then FU to see what happens. No such
trials are planned either.
For a woman who is at high risk, I don't think taking a statin is an
unreasonable choice, even for primary prevention. Ideally, such a
choice would be preceded by a full discussion with her doctor of the
possible risks and benefits. I also think such a woman should be free
to choose not to take a statin.
To people who want to engage me in endless discussions of whether a
high LDL level is a risk factor for heart disease, I offer the
following:
The point is foreshadowed in William Shakespeare, King Henry the
Fourth (Part I), Act 3, Scene 1, when Owen Glendower brags "I can call
spirits from the vasty deep," and Hotspur replies, "Why, so can I, or
so can any man; But will they come when you do call for them?"
Marilyn
MarilynMann
Dr. Kendricks opposition should be judged on the science not on
> wheater he belives the LDL theory.
In theory I agree with you. However, I also think when seeking expert
advice it pays to consider the source. I'm a lawyer, and I would
definitely not advise you to pick an attorney from the yellow pages or
because he was your brother-in-law's college roommate. I would
strongly advise you, if possible, to go to the smartest lawyer you
know and ask for a recommendation for somebody with expertise and a
good reputation in the relevant area of law (if you can afford such a
person, but that's a different subject). When I am looking for a
doctor, I ask for a referral from a doctor I trust.
My point was that in deciding whether to use a statin in a particular
situation, I don't think Drs. Kendrick or Ravnskov are going to be the
best source of advice, because to the best of my knowledge they don't
believe in using statins at all. Do I disagree with every single
thing they say? No. But they have an agenda that they don't always
come right out and state.
Marilyn
bigvince
I however am more concerned that the evidence has show very little
benefit for statin therapy in primary prevention most studies show no
benefit in terms of mortality. Very small benefits even for people
with CVD absolute reductions 1 or 2 %. Also as you have concerns
about Dr. Kendrick and many others . I see that most who recommend
statin use tend to have financial connections to statin makers. Even
the FDA has recently tried to eliminate this practice on it's advisory
boards. I think it should be elimanated from treatment advisory boards
who set the guidelines . I feel it may have skewed the guidelines to a
to aggressive use of these drugs.And they do have real sometimes
serious side effects. I take it the finacial conflict does not trouble
you. Thanks Vince
MarilynMann
>
> I however am more concerned that the evidence has show very little
> benefit for statin therapy in primary prevention most studies show no
> benefit in terms of mortality. Very small benefits even for people
> with CVD absolute reductions 1 or 2 %.
I think your concerns are appropriate.
Also as you have concerns
> about Dr. Kendrick and many others .
I don't understand what you are saying here.
I see that most who recommend
> statin use tend to have financial connections to statin makers.
I'm not sure I would agree. Many doctors who prescribe statins have
no connection to the drug companies.
Even
> the FDA has recently tried to eliminate this practice on it's advisory
> boards. I think it should be elimanated from treatment advisory boards
> who set the guidelines . I feel it may have skewed the guidelines to a
> to aggressive use of these drugs.
I think your concerns regarding conflicts of interest are
appropriate. Even people who think they are impartial can be
influenced without realizing it.
And they do have real sometimes
> serious side effects.
Yes, you are right.
I take it the finacial conflict does not trouble
> you.
There you are wrong. Financial conflicts are a concern for me.
Marilyn
Po...@nospam.invalid
>why did you crosspost?
Didn't really see a reason why I shouldn't. I generally crosspost
responses to where ever they originate (just in case somebody in the
other group is following along) unless it's spam or a flame war (to
which I seldom respond at all) or to obviously unrelated groups (more
than 2-3 groups for example) or it makes no sense whatsoever (s.m.c. &
a.u.kooks for example). I generally don't initiate crossposts though,
without good reason. You'll have to ask the good doctor why he chose
that route. My guess is that he thought it might be of interest to
someone in the diabetes group as well -shrug- I dunno.
Why do you ask?
As long as we're on the subject, I would recommend Agent (the
Newsreader) to anyone having problems with unwanted crossposts. It has
the best set of filters I've found for dealing with them.
Port
Andrew B. Chung, MD/PhD
> convicted neighbor Mâck©® wrote:
> >why did you crosspost?
>
> Didn't really see a reason why I shouldn't. I generally crosspost
> responses to where ever they originate (just in case somebody in the
> other group is following along) unless it's spam or a flame war (to
> which I seldom respond at all) or to obviously unrelated groups (more
> than 2-3 groups for example) or it makes no sense whatsoever (s.m.c. &
> a.u.kooks for example). I generally don't initiate crossposts though,
> without good reason. You'll have to ask the good doctor why he chose
> that route. My guess is that he thought it might be of interest to
> someone in the diabetes group as well -shrug- I dunno.
A diabetic has the same risk of a having a heart attack as someone who
has already had a heart attack. This is what it means when folks
write that diabetes is a "risk equivalent" for coronary heart disease.
Truth is simple.
Prayerfully in Jesus' awesome love,
Andrew <><
--
Andrew B. Chung, MD/PhD
http://EmoryCardiology.com
"Unlike the 2PD-OMER Approach, weight loss diets can't be combined
with well-balanced diets"
Jim Chinnis
> I've enjoyed this discussion as much as the one in the BMJ. The
>question is really more if high LDL is truly a risk factor for CVD
>then why if you lower it do you not see a great reduction in CVD.
If you lower it 50% you get maybe a 30% reduction in CHD events. That's
actually very significant, given that the damage from atherosclerosis
develops over a lifetime.
Unfortunately, the only way to lower LDL that way in most people is with a
statin. So then you are left not knowing if the LDL is causative or just a
marker.
It's also quite possible that there is an underlying condition (or
conditions), partly genetic and partly not, that involve inflammatory
abnormalities (there is evidence for cytokines being involved) that drive
the development of both markers for CVD and the disease progression itself.
And it's possible that statins address some of those inflammatory
abnormalities.
--
Jim Chinnis Warrenton, Virginia, USA
William Wagner
Jim Chinnis <jchi...@SPAMalum.mit.edu> wrote:
........................................
: Mediators Inflamm. 2007;2007(1):78454. Epub 2006 Dec 27.
> And it's possible that statins address some of those inflammatory
> abnormalities.
A small study.
Bill perhaps outside (skin) reflects inside.
..............
Accumulation of oxidized low-density lipoprotein in psoriatic skin and
changes of plasma lipid levels in psoriatic patients.
? Tekin NS, Tekin IO, Barut F, Sipahi EY.
Department of Dermatology, Faculty of Medicine, Zonguldak Karaelmas
University, Kozlu, 67600 Zonguldak, Turkey.
Background. Psoriasis is a chronic inflammatory skin disease
characterized by an accelerated turnover of epidermal cells and an
incomplete differentiation in epidermis with lesion. However, the exact
etiology of psoriasis is unknown. Abnormalities in essential fatty acid
metabolism, free radical generation, lipid peroxidation, and release of
lymphokines have been proposed. Objective. Our purpose was to evaluate
the plasma lipids and oxidized low-density lipoprotein accumulation in
psoriatic skin lesion in order to ascertain the possible participation
of oxidative stress and oxidative modification of lipids in pathogenesis
of psoriasis. Methods. The study group included 84 patients with
psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid
profile was determined. Psoriatic and nonlesional skin samples of
psoriatic patients were evaluated for the presence of oxidized
low-density lipoprotein by using an immune-fluorescent staining method.
Results. The mean levels of lipids (total cholesterol, triglyceride, and
LDL cholesterol) in patients with psoriasis were found to be
significantly higher than those of healthy subjects. Psoriatic skins
were shown positive oxidized low-density lipoprotein staining. There was
no staining in nonlesional skin samples of the same individuals.
Conclusion. Lipid peroxidation mediated by free radicals is believed to
be one of the important causes of cell membrane destruction and cell
damage. This study shows for the first time the accumulation of oxidized
low-density lipoprotein in psoriatic skin lesion. We believe that
accumulation of ox-LDL in psoriatic skin may have an important role in
the immune-inflammatory events that result in progressive skin damage.
PMID: 17497039 [PubMed - in process]
--
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bigvince
> bigvince <Vince.Mirag...@gmail.com> wrote in part:
Lets just go over this. If you lower ldl in primary prevention it is
very difficult to show any reduction in events at least in terms of
primary prevention. The 30% you refer to is the reduction of relative
risk .The actual reduction of events is more like 1% or less again we
are talking primary prevention. In many groups such as women and the
elderly even that is hard to prove. For that people risk many and
sometimes serious side effects. I personally feel that until more
proff of reduction of mortality is proven that the push to use them is
inappropriate. And I agree that much of what ever benefit is attibuted
to statins is in fact that they have a antiinflamatory effect
independant of there lipid lowering abilitys. There are many other
agents that can reduce inflamation omega 3 s for example and they have
none of the negative side effect of statins. Here is a very good
article on statins. This is one of the best reviews on statins in
primary prevention I've
seen. From sacromento bee An article entitled ...."Inside Medicine:
Chances are, cholesterol pill is of little help"
By Dr. Michael Wilkes -
Published 12:00 am PDT Saturday, March 31, 2007 " Heart disease is a
major killer in the United States. Let's say I could give you a pill
to prevent a heart attack. You would need to take the pill every day
for five years at a cost of $3,000. Would you take it? Most
would."..... the article outlines the state of proven benefit from
this therapy ....".But now, let's say that the pill actually prevented
a heart attack in one of every 67 people who took the pill for five
years. That is, 66 people would take the pill and get no benefit --
only one would benefit," ... the article descibes the case of Jenny 50
year old who has a Doctor recommend statins with no discussion
....and the article says. " There was no discussion of the expected
benefit from the drug (which is probably much less than 1 in 67 over
five years)." the article describes the benefit of statins after heart
attacks but concludes ...."However, it is not good science to assume
that if something helps people after heart attacks, it might also help
people who have not had a heart attack" The article descibes the lack
of any data or that data shows only a small benefit for many who are
on these drugs and concludes ...."My point is twofold. First, given
the lack of scientific data proving a sizable benefit in otherwise
healthy, low-risk people, we might be pushing cholesterol reduction a
bit too hard. And second, people should be told, in simple language,
the expected benefits of taking a drug so they can decide for
themselves whether to take a pill for the rest of their lives.". the
author " Michael Wilkes, M.D., is a professor of medicine at the
University of California, Davis. " link
http://www.sacbee.com/296/story/146331.html
An interesting piece I agree with DR. Wilkes
bigvince
> An interesting piece I agree with DR. Wilkes- Hide quoted text -
>
> - Show quoted text -
Why question what the experts tell you a story just broke its not
about statins but By Lisa Richwine
Mon May 21, 6:50 PM ET
WASHINGTON (Reuters) - U.S. regulators are reviewing the safety of
GlaxoSmithKline's Plc's (GSK.L) (NYSE:GSK - news) diabetes drug
Avandia but have not yet determined the significance of risks reported
in a study released on Monday, a U.S. Food and Drug
Administration official said.
A study published in the New England Journal of Medicine said
Avandia increased the risk of cardiac-related deaths by 64 percent and
heart attacks by 43 percent. Dr. Robert Meyer, head of the FDA office
that reviews diabetes drugs, said other data contradicted those
findings. source http://news.yahoo.com/s/nm/20070521/bs_nm/glaxosmithkline_avandia_fda_dc_3
I guess my point is the regulatory process for these drugs is broken.
Thanks Vince
Jim Chinnis
>Lets just go over this. If you lower ldl in primary prevention it is
>very difficult to show any reduction in events at least in terms of
>primary prevention. The 30% you refer to is the reduction of relative
>risk .
Compare apples to apples. Both the LDL reduction and the CHD event rate
reduction are relative numbers. Conversion from relative to absolute rates
is covered in 6th grade or so. Let's move on.
And studies HAVE shown event reductions in primary prevention. Let's stop
beating this dead horse.
There are some interesting issues here, but I don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits in
primary prevention are two of them.
Jim Chinnis
>A study published in the New England Journal of Medicine said
>Avandia increased the risk of cardiac-related deaths by 64 percent and
>heart attacks by 43 percent. Dr. Robert Meyer, head of the FDA office
>that reviews diabetes drugs, said other data contradicted those
>findings. source http://news.yahoo.com/s/nm/20070521/bs_nm/glaxosmithkline_avandia_fda_dc_3
>I guess my point is the regulatory process for these drugs is broken.
>Thanks Vince
How would you know? I thought you disregarded relative risks.
bigvince
> bigvince <Vince.Mirag...@gmail.com> wrote in part:
>
> >A study published in the New England Journal of Medicine said
> >Avandia increased the risk of cardiac-related deaths by 64 percent and
> >heart attacks by 43 percent. Dr. Robert Meyer, head of the FDA office
> >that reviews diabetes drugs, said other data contradicted those
> >I guess my point is the regulatory process for these drugs is broken.
> >Thanks Vince
>
> How would you know? I thought you disregarded relative risks.
> --
> Jim Chinnis Warrenton, Virginia, USA
>>> No but its important to have a context to evaluate .If I have a risk of .04 of an event and it is increased to .06 well thats a 50% increase and also a very small increase .To make choices you need both numbers. No I don' t disregard relative risk. I just think it's important to
label things accurately . The article says the risk is raised by 64%
and if you read the entire article it showed clearly it was relative
risk . If the article had said it increased cardiac deaths by 64% i
would find that misleading . The fact that the drug approved to reduce
mortality in diabetes actually increased it is evidence enough for me
that the system is broken; perhaps you disagree. I prefer that drugs
show proven clinical benefits another such as reducing mortality
rather then such surrogate marker as were used to get this drug
approved. To not require that type in my opinion allows theses
disasters to happen Dr.Nissen who wrote the study estimates thousands
of unnecessary heart attacks from this .Not a day goes by that a drug
or family of drugs is not recalled their use limited or a black box
warning placed on them . Within the last month so Zelnorm has been
removed ,the use of anemia drugs has been questioned, and now this. I
believe the system needs to be changed so that end results not
markers. Thanks Vince
bigvince
> bigvince <Vince.Mirag...@gmail.com> wrote in part:
As I am unaware of the studies which show this benefit in primary
prevention please cite a couple for me. And the linkage I was
refering to is not the reduction of LDL and CHD which are both in
relative numbers. But rather what does a relative reduction of 50%
mean in tearms of events. If you move from ..02 to .03 50% increase
is much more impressive than the small change actually occuring. In
this case I feel it exagerates the change. I think information needs
to be complete. Do you still think that Dr. Wilkes article is not
referring to statins .Thanks Vince
Jim Chinnis
>The fact that the drug approved to reduce
>mortality in diabetes actually increased it is evidence enough for me
>that the system is broken; perhaps you disagree. I prefer that drugs
>show proven clinical benefits another such as reducing mortality
>rather then such surrogate marker as were used to get this drug
>approved. To not require that type in my opinion allows theses
>disasters to happen
There's a tradeoff. To determine whether mortality is increased by a drug
that appears to make risks lower would require decades of tests on a fairly
large test population and placebo population. How long should one deprive
those on the placebo from receiving a drug? Could you even get volunteers
for such a study that would take decades and would prevent half of them from
being on any drug at all? Would there be compliance for more than a short
time?
There are compromise solutions, and one of them is to do tests over a few
years at most looking for problems and markers of problems. That's what
seemed to have happened in the present case.
The system is definitely broken, but perhaps not in the way you imply.
Jim Chinnis
>On May 22, 10:46 am, Jim Chinnis <jchin...@SPAMalum.mit.edu> wrote:
I don't do homework for people except when I have things at hand. I'll
follow up when i have my resources available. You want evidence that statins
reduce coronary artery disease events in primary prevention?!
I for one am glad to only have to deal with relative risk reductions and
then apply them to my own situation. I'd never be able to remember the ream
of absolute risk reductions that occur in all the studies done.
Oh, I think Wilke's article referred to statins, but he played to his
audience by referring to them as cholesterol pills. I think that minimizes
what they do, just as you think using relative risk reductions can distort
the value of them.
Jim Chinnis
>I don't do homework for people except when I have things at hand. I'll
>follow up when i have my resources available. You want evidence that statins
>reduce coronary artery disease events in primary prevention?!
Actually, here's a very recent met-analysis:
+ Arch Intern Med. 2006 Nov 27;166(21):2307-13. Related Articles, Links
+
+
+Primary prevention of cardiovascular diseases with statin therapy: a
meta-analysis of randomized controlled trials.
+
+Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK.
+
+Department of Medicine, University of Toronto, Toronto, Ontario.
+
+BACKGROUND: While the role of hydroxymethyl glutaryl coenzyme A reductase
inhibitors (statins) in secondary prevention of cardiovascular (CV) events
and mortality is established, their value for primary prevention is less
clear. To clarify the role of statins for patients without CV disease, we
performed a meta-analysis of randomized controlled trials (RCTs). METHODS:
MEDLINE, EMBASE, Cochrane Collaboration, and American College of Physicians
Journal Club databases were searched for RCTs published between 1966 and
June 2005. We included RCTs with follow-up of 1 year or longer, more than
100 major CV events, and 80% or more of the population without CV disease.
From each trial, demographic data, lipid profile, CV outcomes, mortality,
and adverse outcomes were recorded. Summary relative risk (RR) ratios with
95% confidence intervals (CIs) were calculated using a random effects model.
RESULTS: Seven trials with 42,848 patients were included. Ninety percent had
no history of CV disease. Mean follow-up was 4.3 years. Statin therapy
reduced the RR of major coronary events, major cerebrovascular events, and
revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI,
2.8%-24.6%) (P = .02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001),
respectively. Statins produced a nonsignificant 22.6% RR reduction in
coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). No
significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P
= .09) or increases in cancer or levels of liver enzymes or creatine kinase
were observed. CONCLUSION: In patients without CV disease, statin therapy
decreases the incidence of major coronary and cerebrovascular events and
revascularizations but not coronary heart disease or overall mortality.
Note the following: "Statin therapy reduced the RR of major coronary events,
major cerebrovascular events, and revascularizations by 29.2% (95% CI,
16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = .02), and 33.8% (95%
CI, 19.6%-45.5%) (P<.001), respectively."
bigvince
> Jim Chinnis <jchin...@SPAMalum.mit.edu> wrote in part:
And studies HAVE shown event reductions in primary prevention. Let's
stop
beating this dead horse.
There are some interesting issues here, but I don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits
in
primary prevention are two of them.
--
Jim Chinnis Warrenton, Virginia, USA
Jim earlier you wrote "There are some interesting issues here, but I
don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits
in
primary prevention are two of them.
Then you cite a meta- analysis that concludes "CONCLUSION: In
patients without CV disease, statin therapy
decreases the incidence of major coronary and cerebrovascular events
and
revascularizations but not coronary heart disease or overall
mortality." I question the fact that statins reduce mortality you
say thats not an issue and cite a study that concludes that statins do
not reduce the incidence of all cause mortality. The article
starts......BACKGROUND: While the role of hydroxymethyl glutaryl
coenzyme A reductase
inhibitors (statins) in secondary prevention of cardiovascular (CV)
events
and mortality is established, their value for primary prevention is"
less "
clear." . Jim this is the question that: if I understand you
correctly , your position is that there effectiveness in primary
prevention has been established. The authors of this and it is the
study you presented find it " less clear'. that's why they did the
analysis.
Jim and I do not want to beat a dead horse
.................but.......,,,,,,1. This study and you presented it
found no decrease in mortality with statin therapy.................2
.Included people with a history of heart disease up 10% there are
other issues . But my question is how can you say " establishing
mortality benefits in
primary prevention " is not worthy of discussion then cite a study
that concludes statin offer no reduction in "coronary heart disease or
overall mortality." to prove your point. Thanks . Vince
David Rind
This meta-analysis has two major problems.
First, the main cause of it finding such a small effect on all-cause
mortality (RRR 8%) was inclusion of the large and badly flawed ALLHAT
trial. Take a look at what the estimated RRR would be if ALLHAT were
excluded and you'll see that the point estimate would be similar to the
RRR in all-cause mortality seen in secondary prevention with statins.
Second, it had no basis to conclude that statins do not decrease
coronary heart disease mortality. The meta-analysis found a point
estimate RRR of 23% for CHD mortality. That this was not statistically
significant is likely a power issue. It certainly isn't evidence of an
absence of benefit, and that RRR is very similar to what is seen in
secondary prevention with statins.
Using statins for primary prevention typically results in such small
absolute risk reductions that they are often clinically unimportant. But
my read of the evidence is that whether in primary or secondary
prevention statins have pretty similar relative risk reductions over a
wide range of baseline risks.
--
David Rind
dr...@caregroup.harvard.edu
William Wagner
David Rind <dr...@caregroup.harvard.edu> wrote:
So your father and mother in law with no heart issues were told to
consider Statins at age 60 +- 10. What would suggest?
Can you answer in less then 10 words?
Bill that values David's words.
David Rind
> So your father and mother in law with no heart issues were told to
> consider Statins at age 60 +- 10. What would suggest?
>
> Can you answer in less then 10 words?
>
> Bill that values David's words.
Depends on their cardiac risk.
(Word count 5)
--
David Rind
dr...@caregroup.harvard.edu
bigvince
>
> - Show quoted text -
This meta-analysis has two major problems.
First, the main cause of it finding such a small effect on all-cause
mortality (RRR 8%) was inclusion of the large and badly flawed ALLHAT
trial. Take a look at what the estimated RRR would be if ALLHAT were
excluded and you'll see that the point estimate would be similar to
the
RRR in all-cause mortality seen in secondary prevention with statins.
If you pick and choise what studies you wish :I guess you conclude
what you wish. But the study included ALLHAT. IF you have concerns
about the design of ALLHAT please be specific The authors felt it
should be included However I expect that the conclusions of the study
are accurate at least the conclusion on mortality statins do not
decrease overall mortality when used in primary prevention. Do not
decrease mortality ; here I will quote you " > Using statins
for primary prevention typically results in such small
> absolute risk reductions that they are often clinically unimportant " My read is what small if any gains there are must be balanced against the risk of side effects. And I do not feel what if any benefits make this an atractive option. You also comment........ > Second, it had no basis to conclude that statins do not decrease
> coronary heart disease mortality. The meta-analysis found a point
> estimate RRR of 23% for CHD mortality. That this was not statistically
> significant is likely a power issue. It certainly isn't evidence of an
> absence of benefit, and that RRR is very similar to what is seen in
> secondary prevention with statins.. Well again I did not make the conclusion but the study " Statins produced a nonsignificant 22.6% RR reduction in
> >>coronary heart disease mortality (95% CI, 0.56-1.08) (P = .13). " Perhaps a power issue but perhaps there were other issues for whatever reason the statement is accurate. Look my point was that there can be a reasoned discussion as to weather statins are usefull in primary prevention and that the benefit from statins at least in overall mortality is far from proven . This study supports both points. The reason for the study ..."statins) in secondary prevention of cardiovascular (CV) events
> >>and mortality is established, their value for primary prevention is less
> >>clear. My secould point was that there lifesaving potential in primary prevention had not been proven the study supports that point. Look you feel that the inclusion of ALLHAT "distorted the study' . I suspect that only those studies that show benefit are much more likely to be published than negative studies. In the last few days a NYT article discusses that in relation to a diabetes treatment. My read is this study has flaws that could enhance the benefit of statins one is publication bias and two about 10% had CHD. Thanks Vince
Jim Chinnis
I thought that bigvince was claiming there were no studies that showed heart
disease event reductions in primary treatment with statins. The cited
meta-analysis seemed like a good one, especially because it found strong
evidence for reductions of all types of events in primary treatment even
though it included the ALLHAT study.
I have to say that the meta-analysis' wording of the conclusion regarding
all-cause mortality is unfortunate and probably muddies the water for those
who do not understand the nature of hypothesis testing.
As Dr. Rind points out, one of the great things about all the studies on
statins is that the relative reduction in events, mortality, etc. seems
pretty constant across populations...
Jim Chinnis
>William Wagner wrote:
>> So your father and mother in law with no heart issues were told to
>> consider Statins at age 60 +- 10. What would suggest?
>>
>> Can you answer in less then 10 words?
>>
>> Bill that values David's words.
>
>Depends on their cardiac risk.
>
>(Word count 5)
If risk equals zero, risk reduction is zero.
If not ...
(Word count 10)
bigvince
that bigvince was claiming there were no studies that showed heart
disease event reductions in primary treatment with statins
>>
but I don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits
in
understood that at least part of my concern about the use of statins
in primary care was that they have not been proven to decrease all
cause mortality the analysis does not change that as it agrees with my
premise.
>The cited
meta-analysis seemed like a good one, especially because it found
strong
evidence for reductions of all types of events in primary treatment
even
though it included the ALLHAT study.
...." CONCLUSION: In patients without CV disease, statin therapy
decreases the incidence of major coronary and cerebrovascular events
and
revascularizations but not coronary heart disease or overall
do not decrease coronary heart dieease or overall or mortality not a
finding that I'd characterise as "strong evidence for reduction of all
types of events"
>I have to say that the meta-analysis' wording of the conclusion regarding
all-cause mortality is unfortunate and probably muddies the water for
those
who do not understand the nature of hypothesis testing
that you do not like this meta -analysis found after looking at many
studies that statins do not decrease mortality or coronary heart
disease. Jim as to the second half of your statement about hypothesis
testing well I have to believe that the Doctors who conducted the
study and their peers who reviewed it understood it Dr.Rind
understands it and if you do not understand it you areasily confused.
Jim my understanding is you start with your hypothesis for example
Statins when used in primary prevention reduce mortality rates then
you collect your evidence all the studies reviewed in this meta
analysis than you draw conclusions. Statins do not reduce mortality
rates. If the evidence supports your hypothesis good if not you must
change your hypothesis or look for better evidence.Jim at these stage
the evidence does not support the hypothesis.
>.As Dr. Rind points out, one of the great things
about all the studies on
statins is that the relative reduction in events, mortality, etc.
seems
pretty constant across populations...
they do not all even point in the same direction on some parameters
one study shows an increase one shows a decrease Dr. Rind comments
speak for themselves
Jim Chinnis
>On May 24, 11:24 pm, Jim Chinnis <jchin...@ > I thought
I can't follow your post, maybe just can't see who wrote what. I don't know
your issues. Let's call it a misunderstanding.
We disagree on the appropriate mortality conclusion for the meta-analysis i
cited. The authors mis-state the lack of effect. It is not possible to
accept the null hypothesis.
Keep in mind that it is extremely difficult to demonstrate a reduction in
mortality when you treat people preventatively. The size of study and the
length of time needed for the study are just too large. When you start
demanding evidence of decreased mortality in specific subgroups, it gets
even crazier.
bigvince
> bigvince <Vince.Mirag...@gmail.com> wrote in part:
>
> - Show quoted text -
I' d like to see good evidence on any subgroup in terms of mortality
in primary prevention. Actually I accept the findings from this study
as correct on both issues . In your statement earlier you made the
claim that statins decrease over all mortality when in fact I have
seen very little evidence to support that . Have you modified your
position now you seem to be saying that to prove such an effect is
difficult. The mortality issue was settled by the authors I accept
their findings you disagree not so much with me but with the authors.
They also concluded that there was not a significant diffeerence in
rates of heart diesease.Again this is accurate it may be because
technical reasons but it is an accurate desciption of the evidence
published in a peer reviewed journal. .Basically I agree with the
position of Dr. Wilkes that given the lack of proff in some cases .and
the fact that the absolute reduction in risk is small that this class
of drugs is overused in primary prevention. Thanks Vince
bigvince
Jim said > I thought that bigvince was claiming there were no
studies that showed heart
disease event reductions in primary treatment with statins.
Vince said >>>> Jim your earlier comments " There are some
interesting issues here,
but I don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits
in
primary prevention are two of them." Led me to believe that you
understood that at least part of my concern about the use of statins
in primary care was that they have not been proven to decrease all
cause mortality the analysis does not change that as it agrees with my
premise.
Jim said>>The cited
meta-analysis seemed like a good one, especially because it found
strong
evidence for reductions of all types of events in primary treatment
even
though it included the ALLHAT study
Vince said>>>
Jim your statement is not backed up by the facts; from the study
...." CONCLUSION: In patients without CV disease, statin therapy
decreases the incidence of major coronary and cerebrovascular events
and
revascularizations but not coronary heart disease or overall
mortality. " - If fact the study concludes statins in this setting
do not decrease coronary heart dieease or overall or mortality not a
finding that I'd characterise as "strong evidence for reduction of all
types of events"
Jim said ><>>>> I have to say that the meta-analysis' wording of
the conclusion regarding all-cause mortality is unfortunate and
probably muddies the water for those
who do not understand the nature of hypothesis testing
Vince said >>>Jim it is not the wording that troubles you it is
the conclusion
that you do not like this meta -analysis found after looking at many
studies that statins do not decrease mortality or coronary heart
disease. As far as hypothesis testing Jim my understanding is you
start with your hypothesis for example
Statins when used in primary prevention reduce mortality rates . Then
you collect your evidence:all the studies reviewed in this meta
analysis than you draw conclusions.
. If the evidence supports your hypothesis good if not you must
change your hypothesis or look for better evidence.Jim at these stage
the evidence does not support the hypothesis.
Jim said >> As
Dr. Rind points out, one of the great things
about all the studies on
statins is that the relative reduction in events, mortality, etc.
seems
pretty constant across populations...
Vince said>>>
Jim all the studies on statins do not say the same thing sometimes
they do not all even point in the same direction on some parameters
one study might show an increase another shows a decrease Dr. Rind
comments
speak for themselves
Dr. Rind said.>> Using statins for primary prevention typically
results in such small
absolute risk reductions that they are often clinically unimportant.
But
my read of the evidence is that whether in primary or secondary
prevention statins have pretty similar relative risk reductions over a
wide range of baseline risks.
I 've went over this for clarity. Thanks Vince
Jim Chinnis
>> We disagree on the appropriate mortality conclusion for the meta-analysis i
>> cited. The authors mis-state the lack of effect. It is not possible to
>> accept the null hypothesis.
>>
>> Keep in mind that it is extremely difficult to demonstrate a reduction in
>> mortality when you treat people preventatively. The size of study and the
>> length of time needed for the study are just too large. When you start
>> demanding evidence of decreased mortality in specific subgroups, it gets
>> even crazier.
>> --
>> Jim Chinnis Warrenton, Virginia, USA- Hide quoted text -
>>
> I' d like to see good evidence on any subgroup in terms of mortality
>in primary prevention.
I know you would, but it doesn't exist. For any drug, as far as I know.
But I think that if you look at properly done studies, even though they
aren't big enough to show mortality differences in, say, women at a
significance level of 0.5, there are resons to think the mortality benefit
exists. These include the fact that secondary treatment studies find no
difference between the relative risk reductions for women and the group as a
whole, that mortality is reduced in secondary treatment, and some other
things.
>Actually I accept the findings from this study
>as correct on both issues . In your statement earlier you made the
>claim that statins decrease over all mortality when in fact I have
>seen very little evidence to support that .
I assume you mean in primary rather than secondary treatment. I interpret
the evidence differently, as stated above.
>Have you modified your
>position now you seem to be saying that to prove such an effect is
>difficult.
No, I believe the evidence supports reduced mortality in primary prevention.
And, yes, it will be very expensive and slow to "prove."
>The mortality issue was settled by the authors I accept
>their findings you disagree not so much with me but with the authors.
Actually, no. I think I disagree with the way you interpret their
conclusion. They didn't show a statistically significant reduction in
mortality. Even though they included a large defective study (ALLHAT) that
biased the result away from a significant reduction in mortality, they still
had a reduction in mortality, but their studies weren't large enough or long
enough for it to exceed the p<=0.05 threshold.
>They also concluded that there was not a significant diffeerence in
>rates of heart diesease.
No. They were referring to mortality from heart disease. Same issue as
above.
>Again this is accurate it may be because
>technical reasons but it is an accurate desciption of the evidence
>published in a peer reviewed journal. .Basically I agree with the
>position of Dr. Wilkes that given the lack of proff in some cases .and
>the fact that the absolute reduction in risk is small that this class
>of drugs is overused in primary prevention. Thanks Vince
--
bigvince
> Actually, no. I think I disagree with the way you interpret
their
conclusion. They didn't show a statistically significant reduction in
mortality. Even though they included a large defective study (ALLHAT)
that
biased the result away from a significant reduction in mortality, they
still
had a reduction in mortality, but their studies weren't large enough
or long
enough for it to exceed the p<=0.05 threshold.
MarilynMann
disease, http://www.cmaj.ca/cgi/reprint/176/6/S1
A series of articles that may be of interest.
Marilyn
bigvince
in your mind ;as opposed to the authors of the meta- analysis
study.Make it (ALLHAT) defctive enough that it should not be given
David Rind
I've made this point in smc in the past, though not recently or in this
thread:
In general, once an analysis has shown or not shown something, the
burden of proof in a subset analysis is to show that the subset is
different from the group as a whole, not just that the effect is or is
not seen in a particular subset.
So, if drug X seems to have no effect in a large study, but a subset
analysis suggests it is harmful in elderly women and beneficial in young
men, we should be very wary of believing that the effect in the subsets
is real unless we had a very good reason a priori to suspect these
differences would exist.
Similarly, if drug Y is beneficial in a large study, but a subset
analysis suggests it works in men but does not work in women we should
be similarly wary. In particular, the statistical burden of proof is to
show, at a minimum, that it is likely that the effect in women is
different from the effect in men.
In any study, purely because of chance we can always find subsets where
the drug appears to work better or worse than it worked in the group as
a whole.
This, by the way, applies only to effects of drugs on the relative risks
of outcomes which are typically pretty similar across subsets. We would
all expect that given that women are at lower risk for cardiovascular
disease than men that a drug that lowered cardiovascular risk would have
smaller absolute benefits in women than men.
--
David Rind
dr...@caregroup.harvard.edu
Jim Chinnis
>
Just one thing: The subjects in the "usual care" group in many cases took
more powerful statins than the statin "treatment" group did. It was a long
term study and "usual care" subjects tended to get newer, more powerful
statins as time went by.
MarilynMann
> MarilynMann wrote:
> > A comprehensive view of sex-specific issues related to cardiovascular
David, Your post looks like you were replying to me, but were you
replying to Vince?
Also, what do you think about the findings in the Women's health study
on cognitive effects of low dose aspirin? There were more benefits in
women who smoked or had dyslipidemia (there were benefits on an
executive function test in the general group).
Marilyn
MarilynMann
> of outcomes which are typically pretty similar across subsets. We would
> all expect that given that women are at lower risk for cardiovascular
> disease than men that a drug that lowered cardiovascular risk would have
> smaller absolute benefits in women than men.
>
In that study on oxidative stress in children I was looking at, the
effect of gender was not significant. That seems odd to me, because
in kids with FH you can see differences by gender early on (e.g., in
CIMT). Perhaps it was due to the small sample size (41
hypercholesterolemic children, 40 normocholesterolemic children).
Marilyn
David Rind
I was replying to the general thread and the posting of the CMAJ
article. It's just a basic point that we should hesitate to believe that
drugs works differently in men/women, blacks/whites, tall people/short
people without strong evidence showing such different effects.
--
David Rind
dr...@caregroup.harvard.edu
David Rind
Sorry, didn't answer the other half of this. Are you talking about the
study published a couple of weeks ago in BMJ? My recollection is that it
showed no overall effect of aspirin on cognition.
--
David Rind
dr...@caregroup.harvard.edu
MarilynMann
> Sorry, didn't answer the other half of this. Are you talking about the
> study published a couple of weeks ago in BMJ? My recollection is that it
> showed no overall effect of aspirin on cognition.
>
Yes, that is the study I am talking about. The aspirin group
performed better than the placebo group in category fluency but not in
the other tests. In the subsets of women who were current smokers or
who had hyperlipidemia, the aspirin group experienced significantly
less cognitive decline than the placebo group. Intuitively, those
results make sense if women at CVD risk are also at risk of dementia.
It is also worth noting that the dose was only 100 mg every other
day. Obviously, more research is needed, but those results didn't
seem like proof of no effect to me. It is possible the result would
have been more impressive at, say, 81 mg/day and/or starting at a
younger age.
Marilyn
David Rind
I'd have to look more carefully at the actual study, but this seems like
the sort of issue of subgroup analysis I was mentioning.
Overall the treatment had no effect on cognition, but on one subset
measure of cognition (fluency) it was beneficial, and in a couple of
subsets of patients (smokers, hyperlipidemia) it was beneficial.
Even though the latter subset results may be biologically plausible in
some way, you need to be very suspicious that all those subset results
could be due entirely to chance. It's just the nature of what happens
when lots of statistical tests are performed on lots of subsets.
--
David Rind
dr...@caregroup.harvard.edu
MarilynMann
>
> - Show quoted text -
Yes, I see your point. I certainly would not expect many doctors to
start recommending low dose aspirin to patients who were not already
taking it for possible cardiovascular benefits on the basis of this
study. After all, there are gastrointestinal and other risks with
aspirin that you have to be mindful of. I do think the issue of
whether there is a cognitive benefit deserves further study.
I started taking low dose aspirin recently myself, although not on a
doctor's recommendation. I mentioned it to my internist and she was
sort of noncommittal, although she did not try to talk me out of it.
But what I might choose to do myself and what doctors should recommend
to their patients are totally different things.
Thanks,
Marilyn
MarilynMann
>
> - Show quoted text -
Also, I have a family history of early stroke.
William Wagner
MarilynMann <ma...@comcast.net> wrote:
Perhaps, but you got another four years for sure. Live it like your
last day. ;))
http://www.xpn.org/listen_live/listen.php
Bill
MarilynMann
wrote:
> > Also, I have a family history of early stroke.
>
> Perhaps, but you got another four years for sure. Live it like your
> last day. ;))
>
> http://www.xpn.org/listen_live/listen.php
>
> Bill
>
> --
Thanks, I will try to do so.
Marilyn
David Rind
I wasn't trying to suggest that there aren't cardiovascular benefits to
taking aspirin, just that this particular study didn't seem to show this
particular benefit.
The flip side of what I was discussing with subgroup analyses is
actually pretty well illustrated by aspirin for primary prevention. We
have the PHS suggesting that aspirin is good for heart disease but not
strokes in men, and WHS suggesting that aspirin is good for strokes but
not heart disease in women.
While it's possible that aspirin really has differential cardiovascular
effects in men and women this seems unlikely. At least one meta-analysis
of all the studies suggested that aspirin reduces vascular events in men
and women to a similar degree and these conflicting results are just
random variation around the true effect. These random differences are
exacerbated by the lower baseline risk of events in women than men.
--
David Rind
dr...@caregroup.harvard.edu
MarilynMann
>
> The flip side of what I was discussing with subgroup analyses is
> actually pretty well illustrated by aspirin for primary prevention. We
> have the PHS suggesting that aspirin is good for heart disease but not
> strokes in men, and WHS suggesting that aspirin is good for strokes but
> not heart disease in women.
>
> While it's possible that aspirin really has differential cardiovascular
> effects in men and women this seems unlikely. At least one meta-analysis
> of all the studies suggested that aspirin reduces vascular events in men
> and women to a similar degree and these conflicting results are just
> random variation around the true effect. These random differences are
> exacerbated by the lower baseline risk of events in women than men.
>
> --
Interesting. Thanks.
Marilyn
Tony Wesley
> bigvince <Vince.Mirag...@gmail.com> wrote in part:
> I can't follow your post, maybe just can't see who wrote what.
Vince, in your posts, it is difficult for me to determine when you are
quoting and what text is yours.
bigvince
studies that showed heart
disease event reductions in primary treatment with statins.
Vince said >>>> Jim your earlier comments " There are some
interesting issues here,
but I don't think relative vs
absolute numbers or the difficulty of establishing mortality benefits
in
primary prevention are two of them." Led me to believe that you
understood that at least part of my concern about the use of statins
in primary care was that they have not been proven to decrease all
cause mortality the analysis does not change that as it agrees with
my
premise.
Jim said>>The cited
meta-analysis seemed like a good one, especially because it found
strong
evidence for reductions of all types of events in primary treatment
even
though it included the ALLHAT study
Vince said>>>
Jim your statement is not backed up by the facts; from the study
...." CONCLUSION: In patients without CV disease, statin therapy
decreases the incidence of major coronary and cerebrovascular events
and
revascularizations but not coronary heart disease or overall
mortality. " - If fact the study concludes statins in this setting
do not decrease coronary heart dieease or overall or mortality not a
finding that I'd characterise as "strong evidence for reduction of
all
types of events"
Jim said ><>>>> I have to say that the meta-analysis' wording
of
the conclusion regarding all-cause mortality is unfortunate and
probably muddies the water for those
who do not understand the nature of hypothesis testing
Vince said >>>Jim it is not the wording that troubles you it is
the conclusion
that you do not like this meta -analysis found after looking at many
studies that statins do not decrease mortality or coronary heart
disease. As far as hypothesis testing Jim my understanding is you
start with your hypothesis for example
Statins when used in primary prevention reduce mortality rates . Then
you collect your evidence:all the studies reviewed in this meta
analysis than you draw conclusions.
. If the evidence supports your hypothesis good if not you must
change your hypothesis or look for better evidence.Jim at these stage
the evidence does not support the hypothesis.
Jim said >> As
Dr. Rind points out, one of the great things
about all the studies on
statins is that the relative reduction in events, mortality, etc.
seems
pretty constant across populations...
Vince said>>>
Jim all the studies on statins do not say the same thing sometimes
they do not all even point in the same direction on some parameters
one study might show an increase another shows a decrease Dr. Rind
comments
speak for themselves
Dr. Rind said.>> Using statins for primary prevention
typically
results in such small
absolute risk reductions that they are often clinically unimportant.
But
my read of the evidence is that whether in primary or secondary
prevention statins have pretty similar relative risk reductions over
a
wide range of baseline risks.
malco...@doctors.org.uk
Dear people,
This is Dr Kendrick writing. I was pointed to this discussion group by
a colleague, and I think it is lively and well-informed. Please excuse
me butting in like this.
I would like to make a couple of points
Firstly, I do not doubt that statins reduce the risk of cardiovascular
events in both primary and secondary prevention, and in both men and
women (although the effect is less in women generally, and this should
be no surprise as men and women clearly are different with regard to
CVD - for reasons that are a bit complex to go into here)
Secondly, I do not believe that statins reduce the risk of
cardiovascular events through LDL lowering. Any benefits are created
by other well-known mechanisms of action that statins also have e.g.
anti-coagulatant and plaque stabilisation. This 'non-lipid lowering'
conjecture is, I believe, supported by the fact that statins reduce
the risk of stroke, yet a raised LDL level is not a risk factor for
stroke. Also statins improve median survival in heart failure, despite
the fact that a low LDL level is a powerful risk factor for death in
heart failure and a high LDL level is protective.
Finally, for this post, people do not take drugs to prevent themdying
from one particular fatal disease e.g. a heart attack. People take
drugs to live longer. In primary prevention trials, statins have NOT
been shown to reduce the risk of overall mortality - in either men or
women. In some studies e.g. AFCAPS and TEXCAPS, mortality went up. In
ALLHAT (the horribly flawed study that was not, actually flawed)
mortality was unchanged. In ASCOT-LLA (stopped early due to 'massive'
benefits) mortality was unchanged etc. etc. And whilst 'clever'
epidmiologists will say that the trials were not sufficiently powered
to detect significant differences in mortality, this rather begs the
question, how big can the difference possibly be if you need (as I
have read) thirty thousand people over five years to disprove the null
hypothesis. Does this not rather suggest that any difference is going
to be so small as to be - cliniclaly - worthless. And, on the other
side of the equation are side-effects, costs, and the horribly
unhealthy concept that health comes out of a bottle.
Regards
Malcolm Kendrick
David Rind
> Secondly, I do not believe that statins reduce the risk of
> cardiovascular events through LDL lowering. Any benefits are created
> by other well-known mechanisms of action that statins also have e.g.
> anti-coagulatant and plaque stabilisation. This 'non-lipid lowering'
> conjecture is, I believe, supported by the fact that statins reduce
> the risk of stroke, yet a raised LDL level is not a risk factor for
> stroke. Also statins improve median survival in heart failure, despite
> the fact that a low LDL level is a powerful risk factor for death in
> heart failure and a high LDL level is protective.
Sorry, but I don't think the epidemiologic reasoning here (around HF or
stroke) is particularly helpful. It's unlikely that none of the benefits
of statins have to do with LDL reduction, since other classes of drugs
that reduce LDL also seem to reduce cardiovascular events.
Unfortunately those other classes don't typically reduce CV events by
all that much and they have a worrisome tendency to increase all-cause
mortality. It certainly seems likely that some of the benefits of
statins are unrelated to their effects on LDL.
> Finally, for this post, people do not take drugs to prevent themdying
> from one particular fatal disease e.g. a heart attack. People take
> drugs to live longer. In primary prevention trials, statins have NOT
> been shown to reduce the risk of overall mortality - in either men or
> women.
Really? What was the result in WOSCOPS and why aren't you including it
in the list of primary prevention studies of statins?
> In some studies e.g. AFCAPS and TEXCAPS, mortality went up.
(For other readers, this is a single study.) There's no reasonable look
at the data that would conclude an increase in mortality in
AFCAPS/TexCAPS. There were 77 deaths in the placebo arm and 80 in the
statin arm. This isn't just something that was nearly statistically
significant: 2 dead patients switching arms would change your conclusion.
> In
> ALLHAT (the horribly flawed study that was not, actually flawed)
> mortality was unchanged.
ALLHAT had so much noncompliance with assigned treatment that it is
uninterpretable.
> In ASCOT-LLA (stopped early due to 'massive'
> benefits) mortality was unchanged etc. etc.
You are willing to state that AFCAPS/TexCAPS showed "an increase in
mortality", but that ASCOT-LLA showed unchanged mortality? In ASCOT-LLA,
the HR for mortality was 0.87 (95% CI 0.71-1.06); that is, it fell
slightly short of statistical significance at a 0.05 level. The absolute
numbers and rates were 185 deaths (3.6%) in the statin arm and 212
deaths (4.1%) in the placebo arm. Why would you believe a 3 death
difference in mortality in AFCAPS/TexCAPS and reject a mortality benefit
of 0.5% in ASCOT-LLA?
> And whilst 'clever'
> epidmiologists will say that the trials were not sufficiently powered
> to detect significant differences in mortality, this rather begs the
> question, how big can the difference possibly be if you need (as I
> have read) thirty thousand people over five years to disprove the null
> hypothesis. Does this not rather suggest that any difference is going
> to be so small as to be - cliniclaly - worthless. And, on the other
> side of the equation are side-effects, costs, and the horribly
> unhealthy concept that health comes out of a bottle.
I mostly agree with the sentiments of this, but not as presenting the
information as "statins have no mortality benefit in primary
prevention". It's not true and it's misleading.
It's better to recognize that statins do have relative mortality
benefits in primary prevention that look a lot like their relative
mortality benefits in secondary prevention. This allows people at a
given risk of CHD mortality without known CHD to make reasonable choices
about whether to take a statin for primary prevention.
As I've said before in this thread, for most people the mortality
benefits in primary prevention will be so small as not to be clinically
meaningful, but this won't be true for everyone. Some people, even in
primary prevention, will have a fairly high baseline risk, and others
will be interested in tiny reductions in mortality because of personal
preferences.
--
David Rind
dr...@caregroup.harvard.edu
MarilynMann
> Secondly, I do not believe that statins reduce the risk of
> cardiovascular events through LDL lowering. Any benefits are created
> by other well-known mechanisms of action that statins also have e.g.
> anti-coagulatant and plaque stabilisation. This 'non-lipid lowering'
> conjecture is, I believe, supported by the fact that statins reduce
> the risk of stroke, yet a raised LDL level is not a risk factor for
> stroke. Also statins improve median survival in heart failure, despite
> the fact that a low LDL level is a powerful risk factor for death in
> heart failure and a high LDL level is protective.
>
Dr. Kendrick,
My 14-year-old daughter has very high LDL and a family history of very
early MI, consistent with heterozygous familial hypercholesterolemia.
It has been suggested to us that she start taking a statin. I asked
Dr. Ravnskov what he would suggest in a situation such as my
daughter's. He was not willing to give a recommendation, but he made
the following observations about FH:
"I can understand your concern. However, the prognosis is not as bad
as most
doctors think. The salient point is that it is not the high
cholesterol that
causes the problem, but most likely another characteristic in some FH
individuals, they have a higher tendency to blood clotting. But again,
this
is only seen in some.
Large studies of FH individuals have found that those who get heart
attack
have smoked much more often than those who survive to old age, their
body
weight is a little higher, and they have more often diabetes."
If I understand what he is saying here correctly, he concedes that
there is early heart disease in some individuals with FH, but argues
it is not due to high LDL but to some other cause (e.g., higher
tendency to blood clotting). Even if that is true, I do not see how
that argues against taking a statin for primary prevention in FH, even
in women. (Whether one should start a 14-year-old on a statin is a
different issue.) You yourself argue that statins have anti-coagulant
effects.
Second, I agree that traditional risk factors have an influence in
determining who among individuals with FH will develop early heart
disease. However, people with FH do not have a higher tendency to
have these risk factors than normal individuals. So the higher
tendency toward early heart disease in FH still seems like a concern
to me.
Marilyn Mann
bigvince
malcolm...@doctors.org.uk wrote:
> Secondly, I do not believe that statins reduce the risk of
> cardiovascular events through LDL lowering. Any benefits are created
> by other well-known mechanisms of action that statins also have e.g.
> anti-coagulatant and plaque stabilisation. This 'non-lipid lowering'
> conjecture is, I believe, supported by the fact that statins reduce
> the risk of stroke, yet a raised LDL level is not a risk factor for
> stroke. Also statins improve median survival in heart failure, despite
> the fact that a low LDL level is a powerful risk factor for death in
> heart failure and a high LDL level is protective.
Sorry, but I don't think the epidemiologic reasoning here (around HF
or
stroke) is particularly helpful. It's unlikely that none of the
benefits
of statins have to do with LDL reduction, since other classes of drugs
that reduce LDL also seem to reduce cardiovascular events.
Unfortunately those other classes don't typically reduce CV events by
all that much and they have a worrisome tendency to increase all-cause
mortality. It certainly seems likely that some of the benefits of
statins are unrelated to their effects on LDL.
>> It seems to me that if lowering LDL was the major component of
whatever benefit statins convey than similar benefits would follow LDL
lowering by other drugs they do not.There seems to be a protective
aspect to LDL levels in certain populations. And the fact that
lowering them with other classes of drugs increased mortality seems to
indicate that. I seems reasonable that most of whatever benefit
statins provide is not directly provided by LDL.
> .Finally, for this post, people do not
take drugs to prevent themdying
> from one particular fatal disease e.g. a heart attack. People take
> drugs to live longer. In primary prevention trials, statins have NOT
> been shown to reduce the risk of overall mortality - in either men or
> women.
> Finally, for this post, people do not take drugs to prevent themdying
> from one particular fatal disease e.g. a heart attack. People take
> drugs to live longer. In primary prevention trials, statins have NOT
> been shown to reduce the risk of overall mortality - in either men or
> women.
Really? What was the result in WOSCOPS and why aren't you including it
in the list of primary prevention studies of statins?
> In some studies e.g. AFCAPS and TEXCAPS, mortality went up.
(For other readers, this is a single study.) There's no reasonable
look
at the data that would conclude an increase in mortality in
AFCAPS/TexCAPS. There were 77 deaths in the placebo arm and 80 in the
statin arm. This isn't just something that was nearly statistically
significant: 2 dead patients switching arms would change your
conclusion.
>> The above study also did not show any decrease in overall
mortality. The study from Canada that started this discussion found no
decrease in overall mortality. Many studies have found the same. Some
the opposite . My reading is that it is not proven and in real terms a
very small benefit .
As I've said before in this thread, for most people the mortality
benefits in primary prevention will be so small as not to be
clinically
meaningful, but this won't be true for everyone. Some people, even in
primary prevention, will have a fairly high baseline risk, and others
will be interested in tiny reductions in mortality because of personal
preferences.
>> It seems that you would agree that for most people the mortality
benefits in primary prevention are clinically meaningless But there
was another part to Dr. Kendricks comments "And, on the other
side of the equation are side-effects, costs, and the horribly
unhealthy concept that health comes out of a bottle. " As I think you
both feel that part or more of statins effect comes from anticoagulant
,and other effects would it not be prudent to investigate statins as
opposed something as simple as omega 3 fatty acids fish oil which have
been shown to be of benefit. These are healthy options that actually
increase well being on several levels cause no side effects and need
more emphasis than they get. The American Heart Association has
recommendations on fish oils it is widely ignored. Statins are in my
opinion vastly over used why the disconnect. Thanks Vince
Joe Doe
MarilynMann <ma...@comcast.net> wrote:
I asked
> Dr. Ravnskov what he would suggest in a situation such as my
> daughter's. He was not willing to give a recommendation, but he made
> the following observations about FH:
>
> "I can understand your concern. However, the prognosis is not as bad
> as most
> doctors think. The salient point is that it is not the high
> cholesterol that
> causes the problem, but most likely another characteristic in some FH
> individuals, they have a higher tendency to blood clotting. But again,
> this
> is only seen in some.
> Large studies of FH individuals have found that those who get heart
> attack
> have smoked much more often than those who survive to old age, their
> body
> weight is a little higher, and they have more often diabetes."
Ravnskov is an idiot on this. Brown & Goldsteins original impetus to
study LDL came from children with FH who were getting heart attacks at
before age 5!!! Diabetes and weight and smoking have little chance of
being issues in these kids.
See:
http://www4.utsouthwestern.edu/moleculargenetics/pages/brown/past.html
I am sorry you have to face these difficult choices but I personally
would choose to be on a statin.
Roland
MarilynMann
>
>
> I am sorry you have to face these difficult choices but I personally
> would choose to be on a statin.
>
Thanks.
Marilyn
David Rind
Vince, I'm not sure if this is a problem with your newsreader or how you
are using it, but your posts are very confusing about who has written
what. It makes it hard to respond to things you say or ask.
--
David Rind
dr...@caregroup.harvard.edu
bigvince
>
> Sorry, but I don't think the epidemiologic reasoning here (around HF or
> stroke) is particularly helpful. It's unlikely that none of the benefits
> of statins have to do with LDL reduction, since other classes of drugs
> that reduce LDL also seem to reduce cardiovascular events.
>
> Unfortunately those other classes don't typically reduce CV events by
> all that much and they have a worrisome tendency to increase all-cause
> mortality. It certainly seems likely that some of the benefits of
> statins are unrelated to their effects on LDL.
populations along with the fact that lowering LDL levels with non
statin drugs tends to increase mortalty rates both indicate that much
of the benefit of statin theraphy is from non lipid lowering
mechanisms. As something as simple as fish oil ,Omega 3 Fatty acid has
also been shown to influence CV events and I believe overall mortality
is it not important to determine what is really causing whatever
benefit is being observed.
Here the evidence is really confusing to me . My feeling is that
statins reducing overall mortality has not been proven. I base this on
the fact that many studies have found no significant decrease in
mortality , others have found a small but significant decrease. It
really seems to boil down to the allhat study. Two recent meta-
analysis had the same disagreement about allhat that you had with Dr.
Kendrick one that excluded Allhat found a significant difference. The
other mentioned earlier in this thread included ALLHAT and found no
difference. The fact that this is still being looked at and disagreed
on seems to me that it has not been proven.
> As I've said before in this thread, for most people the mortality
> benefits in primary prevention will be so small as not to be clinically
> meaningful, but this won't be true for everyone. Some people, even in
> primary prevention, will have a fairly high baseline risk, and others
> will be interested in tiny reductions in mortality because of personal
> preferences.
>
We agree that in most cases clinical benefits in terms of mortality
may be meaningless.However people do not only take medicines to
prevent dying but also to feel better.Also they need to be informed of
there options. The American Heart association has recommendations
about fish oil consumption ,diet and exercise all of which are
beneficial in this population. So rather than tell a person statins
will reduce you risk by 15% I think he needs to understand that lets
use the numbers from WOSCOPS all male population and a lot of risk
factors a very good group to show benefit. To prevent 1 mortality 111
people needed to be treated 5 years. Thats about as good as it gets
for benefits . Many in that group will have muscle pain and other side
effects. That's a quality of life issue. Some may not be able to
tolerate statins . If I put that same group on fish oil' ,exercise,
diet ,stress reduction ect.. I believe the data says that the results
would be about the same or better. I know that group would feel
better. I do feel there is a real danger in viewing health as coming
out of a pill bottle. Thanks Vince
MarilynMann
primary prevention, they generally are not thinking about people with
heFH. So I do not know Dr. Kendrick's position on whether statins
should be prescribed for women with heFH. If anyone has read his book
perhaps they can tell us.
Also, I want to note that Dr. Ravnskov is correct that some doctors
overestimate the risks from heFH. The reason for this is that many
studies that were done over the years drew patients from lipid
clinics. People with heFH who are referred to lipid clinics are not a
random sample. One study in the Netherlands estimated that 40% of
people with heFH live a normal lifespan even if untreated. However,
this currently does not help us too much because we are not able yet
to predict who those people will be. Consequently, all people with
heFH are currently put on statins.
Marilyn
MarilynMann
>
> >>>I'd have to look more carefully at the actual study, but this seems like
>
> >>>Overall the treatment had no effect on cognition, but on one subset
> >>>measure of cognition (fluency) it was beneficial, and in a couple of
> >>>subsets of patients (smokers, hyperlipidemia) it was beneficial.
>
> >>>Even though the latter subset results may be biologically plausible in
> >>>some way, you need to be very suspicious that all those subset results
> >>>could be due entirely to chance. It's just the nature of what happens
> >>>when lots of statistical tests are performed on lots of subsets.
>
> >>>--
> actually pretty well illustrated by aspirin for primary prevention. We
> have the PHS suggesting that aspirin is good for heart disease but not
> strokes in men, and WHS suggesting that aspirin is good for strokes but
> not heart disease in women.
>
> While it's possible that aspirin really has differential cardiovascular
> effects in men and women this seems unlikely. At least one meta-analysis
> of all the studies suggested that aspirin reduces vascular events in men
> and women to a similar degree and these conflicting results are just
> random variation around the true effect. These random differences are
> exacerbated by the lower baseline risk of events in women than men.
>
>
I see there is a discussion of subgroup analyses in bmj: John
Fletcher, Subgroup analyses: how to avoid being misled, BMJ
2007;335:96-7.
Marilyn
Po...@nospam.invalid
>I see there is a discussion of subgroup analyses in bmj:
What/where is bmj?
Port