From: "Steve Harris" <email@example.com>
Subject: Cholesterol Intervention, Heart Disease, and Total Mortality
Date: Thu, 9 Aug 2001 14:21:27 -0600
Cholesterol Intervention Trials
The gold standard for proving causation in medicine is the
prospective randomized controlled human intervention trial. It
doesn't even need to be blinded if the endpoint is MI or death.
Death is hard to fool yourself about. Big MIs also eventually
get objectively detected, one way or the other.
The literature on cholesterol intervention and coronary heat disease
(CHD) and total mortality risk is now so large that it's necessary to
go to the meta analysis level to get anything short enough to be
discussed on a newsgroup. So I'm presenting it at that level below.
My general synthetic take: lowering cholesterol decreases CHD risk
and total mortality risk IF it's done with statins, niacin, or diet, or any
combo of these. It is said that it may take some minimal 5-10 % reduction
to be worth doing mortality-wise, but those figures include fibrate data,
and this should be broken out.
The epidemiologic total mortality news for fibrate (Lopid-type)
drugs is bad, and they're responsible for nearly ALL of the
intervention trial negative TOTAL mortality data. With the
relatively crumby support for their benefits, I'm frankly
surprised they entire class has not been made illegal. It's a
matter of getting into a bad thing slowly, I suppose.
PPARalpha (I suspect) is a signal transduction colon cancer
promoter like PPARbeta and you don't want to mess with it,
with fibrates (we don't yet know about the "glitazone"
PPARgamma agonists, but they may work in the opposite
direction, and be cancer inhibitors). In any case, though,
two old fibrates are implicated in increased mortality, and
nobody yet knows anything epidemiologically about the
relatively new micronized fenofibrate (Tricor). Obviously
somebody's got a new patented drug to shove. I wouldn't
take it if I were you! If you have horrid triglyceride levels,
talk to your doc about fishoil. Salmon every day's not
going to kill you, but a fibrate might.
The data for beneficial fibrate effect on heart disease is mild. The
best argument for them is the gemfibrazole VA-HIT study which
found a reduction in cardiac events. It was probably underpowered
and didn't find any reduction in cardiac mortality. Mention that to
the Lopid drug-rep guy who tells you it had no negative effect on
mortality. If it had no positive effect even on *cardiac* mortality,
the study was definitely too underpowered to comment on *total*
Polyunsaturated fats, interestingly, seem to increase colon cancer
incidence as well (there is animal and human data which is
not quoted below), and there is epidemiologic evidence (posted
in another message) that low-cholesterol is an independent risk
for cecal cancer and it may be that anything that lowers cholesterol
does this. Somebody needs to break the cecal colon cancer risk out of
the statin and niacin trial data, if they haven't already. Perhaps it's
getting diluted in this and other cholesterol lowering trials, by other
cancers on which the treatment has no effect. This would be
good to know. If a single narrow cause of mortality goes up from
a drug, it can still get swamped by all the good things it does.
This data does generally support the idea that LDL is a direct
causal CHD risk-factor. You can argue all you like about the
statins just happening to have some other benefit than the one
they were designed for, but you cannot then explain the diet
and niacin studies, nor even (for that matter) the narrow effect
of certain fibrates on CHD-events alone (if you don't count
the cancer they probably cause). Also, you have to throw out
the familiar hypercholestolemia literature, and a huge amount
of animal CHD model intervention literature, including studies on
primates. Too many strands of evidence from too many
different sources! No, nature doesn't give us coincidences
that large. If you have to explain away results that don't fit
your hypothesis from 10 different kinds of studies, and you
have to do it in ten different kind of post-hoc and ad-hoc
ways, this should be a clue that maybe you're wrong. <g>
So, anyway here are the 8 abstracts everybody who thinks of
treating cholesterol should have read. --Steve Harris, M.D.
1: Circulation 1999 Mar 2;99(8):E1-7
Lowering LDL cholesterol: questions from recent meta-analyses and subset
analyses of clinical trial DataIssues from the Interdisciplinary Council on
Reducing the Risk for Coronary Heart Disease, ninth Council meeting.
Gotto AM Jr, Grundy SM.
Cornell University Medical College, New York, NY 10021, USA.
The benefit of cholesterol-lowering therapy in the prevention of coronary
heart disease (CHD) is well established. The secondary prevention
Scandinavian Simvastatin Survival Study (4S) and the primary prevention
West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated that
lipid lowering with a statin can dramatically and cost-effectively reduce
CHD morbidity and mortality with no increase in noncardiovascular
mortality. The Cholesterol and Recurrent Events (CARE) trial extended
benefit to CHD patients without high cholesterol. Post hoc analyses of
data from these large trials are contributing to speculation, driven by
subset analyses and meta-analyses, about whether cholesterol intervention
should be target based, as current guidelines recommend. Whereas CARE
data support the importance of baseline LDL cholesterol (LDL-C), with
greatest clinical event risk reduction in the upper part of the LDL-C
range in the trial, 4S found no difference in outcome according to
baseline LDL-C in a quartile analysis, and WOSCOPS found no linear
relation between decrease in LDL-C and decrease in relative risk for CHD.
Furthermore, WOSCOPS showed no additional clinical benefit with LDL-C
lowering beyond approximately 24%. Questions raised by such analyses
require answers from prospective, hypothesis-based data, and at present
there is no compelling argument for moving away from LDL-C targets. The
hypothesis-based findings of 4S, CARE, and WOSCOPS support current
clinical guidelines, and lowering LDL-C may reduce risk more
substantially than might have been predicted.
PMID: 10051310 [PubMed - indexed for MEDLINE]
2: Rev Esp Cardiol 1998;51 Suppl 6:23-9
[All mortality by cause of death. The challenge of coronary prevention].
[Article in Spanish]
Servicio de Medicina Interna, Hospital Universitario San Carlos, Universidad
Much debate on the benefits and risks of cholesterol lowering to prevent
coronary heart disease has focused on excess non-CHD mortality rates
reported in some trials. Because of the wide variation in design of
cholesterol-lowering trials and because the non-CHD mortality rate was
not a controlled endpoint of statistical power in most published studies,
it has been difficult to determine whether any excess mortality was due
to certain therapies, to other mechanisms, or to chance. As a result,
some investigators have performed retrospective analyses of pooled trial
data in order to augment statistical power. Some investigators have
hypothesized that the human brain is dependent on a constant supply of
cholesterol from the circulation and that cholesterol loss in neuronal
membranes, with the possible consequences of behavioral disorders and
increased risk of accident and violent death. Indeed Weidner and Griffin
suggest that low cholesterol is a marker for poor underlying health;
physical illnesses are likely to cause depression and other negative
emotional states, which are often accompanied by suppressed appetite and
weight loss causing reduction in cholesterol levels. Such mental states
may also increase the risk of non-CHD death, for example suicide. Rossouw
reviews the evidence concerning non-CHD mortality in cholesterol-lowering
trials and reports metaanalyses carried out for all trials combined. The
findings indicated a significant (15%) increase in non-CHD mortality in
all trials combined. However, this was not related to cholesterol
lowering itself, because there was no increased risk in trials with > 10%
cholesterol reduction, whereas there was a significant (22%) increase in
trials with lesser degrees of cholesterol lowering. The publication of a
large secondary prevention trial (4S) employing Simvastatin for
cholesterol lowering supports the idea that cholesterol reduction itself
does not have adverse effects on non-CHD mortality. The overview of all
published trials demonstrates their effectiveness in reducing cholesterol
and provides clear evidence of benefits on stroke and total mortality. A
10% reduction in cholesterol yielded about a 20% decrease in CHD
mortality, which would be expected to result in about a 6% reduction in
total mortality. Endothelium-dependent relaxations are reduced in
hyperlipidemia and atherosclerosis. Exogenous L-arginine improves or
restores the reduced endothelium-dependent relaxations. Moreover
inflammation is associates with the initiation and progression of
atherosclerosis. The fact of the matter is the Cardiovascular drugs
already in clinical use or in development are able to interfere with
certain aspects of endothelial function and may be useful in protecting
the vessels and, hence, in preventing the development of cardiovascular
PMID: 10050141 [PubMed - indexed for MEDLINE]
3: Angiology 1998 May;49(5):339-48
Perspectives in the treatment of dyslipidemias in the prevention of coronary
Borgia MC, Medici F.
Universita Degli Studi di Roma La Sapienza, Italy.
In this review the indications for the available treatments for
dyslipidemias in the prevention of coronary heart disease (CHD) are
considered, and their efficacy according to the latest studies is
analyzed. As data sources the authors used the main multicenter studies
performed in the last twenty years to evaluate primary and secondary
prevention of CHD by correcting dyslipidemias as well as the results of
meta-analyses of these studies. All treatments considered were found
effective in preventing CHD morbidity and mortality to some extent. In
particular, the combination of diet with niacin or hydroxymethylglutaryl
coenzyme A (HMG CoA) reductase inhibitors seems to give the best results.
These drugs induce a marked reduction of total and low-density
lipoprotein (LDL) cholesterol and an increase of high-density lipoprotein
(HDL) cholesterol concentrations. The use of diet, niacin, and HMG CoA
reductase inhibitors reduces total as well as specific mortality.
Treatment of dyslipidemia to prevent CHD depends on the pattern and
severity of dyslipidemia, the presence of overt CHD, and the patient's
response to diet. Pharmacologic treatment should be started only after
dietary modifications have been tried and must be combined with diet.
Drug side effects must also be considered, for they may affect patient
compliance. High levels of total and LDL and low levels of HDL
cholesterol are major risk factors for coronary atherosclerosis.
Correcting lipid abnormalities can reduce the risk of development or
progression of CHD. Diet and drugs are the main instruments available to
normalize lipid levels. The choice of drug to combine with diet must be
based on its specific effects on lipid metabolism, side effects, and
efficacy in reducing CHD.
PMID: 9591525 [PubMed - indexed for MEDLINE]
4: Circulation 1998 Mar 17;97(10):946-52
Cholesterol reduction yields clinical benefit: impact of statin trials.
Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD.
Merck Research Laboratories, West Point, PA 19486, USA. firstname.lastname@example.org
BACKGROUND: We determined the effect of incorporating the results of
eight recently published trials of Hmg CoA reductase inhibitors
("statins") on the conclusions from our previously published
meta-analysis regarding the clinical benefit of cholesterol lowering.
METHODS AND RESULTS: We used the same analytic approach as in our
previous investigation, separating the specific effects of cholesterol
lowering from the effects attributable to the different types of
intervention studied. The reductions in coronary heart disease (CHD) and
total mortality risk observed for the statins fell near the predictions
from our earlier meta-analysis. Including the statin trial findings into
the calculations led to a prediction that for every 10 percentage points
of cholesterol lowering, CHD mortality risk would be reduced by 15%
(P<.001), and total mortality risk would be reduced by 11% (P<.001), as
opposed to the values of 13% and 10%, respectively, reported previously.
Cholesterol lowering in general and by the statins in particular does not
increase non-CHD mortality risk. CONCLUSIONS: Adding the results from
the statin trials confirmed our original conclusion that lowering
cholesterol is clinically beneficial. The relationships (slope) between
cholesterol lowering and reduction in CHD and total mortality risk became
stronger, and the standard error of the estimated slopes decreased by
about half. Use of statins does not increase non-CHD mortality risk. The
effect of the statins on CHD and total mortality risk can be explained by
their lipid-lowering ability and appears to be directly proportional to
the degree to which they lower lipids.
PMID: 9529261 [PubMed - indexed for MEDLINE]
5: Circulation 1995 Apr 15;91(8):2274-82
Cholesterol reduction yields clinical benefit. A new look at old data.
Gould AL, Rossouw JE, Santanello NC, Heyse JF, Furberg CD.
Merck Research Laboratories, West Point, Pa 19486, USA.
BACKGROUND: There has been a continuing debate about the overall benefit
of cholesterol lowering. We performed a novel meta-analysis of all
randomized trials of more than 2 years' duration (n = 35 trials) to
describe how coronary-heart-disease (CHD), non-CHD, and total mortality
are related to cholesterol lowering and to type of intervention. METHODS
AND RESULTS: The analytic approach was designed to separate the effects
of cholesterol lowering itself from the other effects of the different
types of intervention used. For every 10 percentage points of
cholesterol lowering, CHD mortality was reduced by 13% (P < .002) and
total mortality by 10% (P < .03). Cholesterol lowering had no effect on
non-CHD mortality. Certain types of intervention had specific effects
independent of cholesterol lowering. Fibrates (clofibrates, 7 trials;
gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P < .01)
and total mortality by about 17% (P < .02). Hormones (estrogen, 2 trials;
dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P
< .04), non-CHD mortality by about 55% (P < .03), and total mortality by
about 33% (P < .01). No specific effects independent of cholesterol
lowering were found due to diet (n = 11) or other interventions (resins,
5; niacin, 3; statins, 2; partial ileal bypass, 1). CONCLUSIONS: The
results suggest that cholesterol lowering itself is beneficial but that
specific adverse effects of fibrates and hormones increase the risk of
CHD (hormones only), non-CHD, and total mortality.
PMID: 7697857 [PubMed - indexed for MEDLINE]
6: Cardiovasc Drugs Ther 1992 Apr;6(2):101-2
Cholesterol lowering and the reduction of CHD incidence and total mortality:
results from a meta-analysis of randomized trials.
This editorial reports on a meta-analysis done on cholesterol-lowering
trials. Coronary heart disease incidence is reported for 16 trials and
total mortality for 19 trials. The cholesterol benefit ratio, i.e., the
percent risk reduction divided by the percent cholesterol reduction, was
analyzed in terms of total vs. potential modifying factors. For coronary
heart disease the benefit ratio was 2.8 (95% CL: 1.5, 4.2), and for total
mortality it was 1.2 (95% CL: -0.1, 2.3). Cholesterol reduction had to
be at least 8-9% to outweigh the negative impact of treatment on total
PMID: 1390319 [PubMed - indexed for MEDLINE]
7: Blood Press Suppl 1992;4:29-34
Cholesterol reduction in single and multifactor randomized trials:
relationship to CHD incidence and total mortality as found by meta
analysis of twenty-two trials.
Life Insurance Companies' Institute for Medical Statistics, Ulleval
Hospital, Oslo, Norway.
This paper reports on a meta analysis in twenty-two randomized both
single and multifactor trials regarding the effect of designed
cholesterol reduction on total mortality and CHD incidence. Per cent
reduction in CHD incidence was 2.5 for every per cent associated net
reduction in total cholesterol, but was only 0.74% for total mortality.
Since total net reduction in cholesterol was about 5% in all trials
combined, the number of participants was far too small to demonstrate a
significant expected reduction of 4% in total mortality. However, the 4%
reduction lies just outside the observed 95% confidence limits of the
overall estimate of effect on total mortality (OR = 1.02; CL 0.97, 1.07).
It is concluded that cholesterol reduction must be much larger than 5% to
be able to reduce the relative risk of CHD substantially and total
PMID: 1345332 [PubMed - indexed for MEDLINE]
8: Med J Aust 1991 Nov 18;155(10):665-6, 669-70
Med J Aust. 1992 Feb 3;156(3):222-3
The benefits of reducing cholesterol levels: the need to distinguish primary
from secondary prevention. 1. A meta-analysis of cholesterol-lowering
Silberberg JS, Henry DA.
University of Newcastle, Shortland, NSW.
OBJECTIVE: To use meta-analysis to estimate the benefits of drug
treatment to lower cholesterol levels in the primary and secondary
prevention of coronary heart disease (CHD) events. DATA SOURCES: MEDLINE
search from 1967 to 1990; bibliographies of review articles. STUDY
SELECTION: Nine trials met the entry criteria: they were monofactorial,
randomised and controlled. DATA EXTRACTION: Two independent, unblinded
observers. DATA SYNTHESIS: The odds ratio (and 95% Cl) for death from CHD
was 0.85 (0.64, 1.14) in primary prevention and 0.84 (0.75, 0.95) in
secondary prevention studies when calculated by the method of Peto. The
event rate in the secondary prevention studies was higher than that in
the primary prevention studies, and the absolute risk reduction achieved
by therapy in the former (3.2%) was much higher than that in the latter
(0.1%). The number of subjects needing to be treated to prevent one
death from CHD was 38 in secondary prevention and 675 in primary
prevention. Results with the method of DerSimonian and Laird were
similar. CONCLUSIONS: The benefits of cholesterol lowering to prevent
death from CHD are substantially greater in the secondary prevention
setting than in primary prevention.
PMID: 1834922 [PubMed - indexed for MEDLINE]
From: "Steve Harris" <email@example.com>
Subject: Re: Cholesterol Intervention, Heart Disease, and Total Mortality
Date: Mon, 13 Aug 2001 19:49:36 -0700
CBI <firstname.lastname@example.org_make_it_bigfoot> wrote in message
>"Leon Traister" <email@example.com> wrote in message
>> OK, so I had LFT problems with niacin and my Lp(a) is 32 when not
>> treated. On 134mg Tricor it's 18. What would you do?
>I would keep taking the Tricor. If you go to Pubmed (
>http://www.ncbi.nlm.nih.gov/PubMed/ ) and type in "fibrates AND mortality"
>you will see that the issue is far from settled (change display to
>abstracts). Most of the articles are reviews so you will not have to wade
>through experimental data to understand, the opinions of the authors are
>fairly straight forward. Almost all recommend statins as a first line. Most
>seem to recommend niacin as a second line with fibrates having its share of
>supporters, especially in diabetics. What to do with a person with an
>isolated elevated triglyceride level is the subject of much debate with
>supporters of all three of the therapies mentioned.
Only because of hidebound traditionalism.
Why give or take this drug? You're treating a lab test number.
Nobody has shown that fibrates do anything for anybody.
A meta analysis of 21,000 people in 12 trials over 30 years showed nada.
Two major trials have been done since then: VA-HIT in 6,144 patients
which found a reduction in cardiac events but not cardiac deaths. The
Benzafibrate Infarction Prevention (BIP) Trial with even more patients
(8,200) didn't EVEN show a reduction in cardiac EVENTS, let alone cardiac
deaths or total deaths. The statin drugs in trials of the size and power
of these last two studies have showed not only cardiac death reduction
but all-cause mortality reduction. If fibrates are ever shown to save any
lives, it will take studies larger than those which have ever been done
in the history of cardiology to prove it.
It's time to admit that on the basis of a huge number of patient years of
study, fibrates appear to be CLINICALLY worthless drugs. By "clinically,"
I mean that they fix lab numbers (triglycerides, HDLs) wonderfully, but
have not been proven to anything clinically for patients ("klinikos = at
the bedside, referring to how ill your actual human patient is, judged by
how ill you think he'd be if you hadn't seen his lab results). Any
positive evidence for fibrates is outweighed by far more than an equal
number of patient years showing no effect. And even the positive evidence
is mild. Faced with all this evidence, at once, the FDA would never
approve fibrates as a new class of drugs today. They've been
grandfathered in, and they suck. One hears a sort of wistful but
supportive tone in the review articles, as though a mother were
discussing her children's D+ grade report cards. Sorry, but this is not
the way medicine is supposed to work.
Fibrates may yet prove useful for some subset of patients, but
as of now, NO SUCH SUBSET has been identified. Meanwhile,
these things are expensive, and there's some epidemiological
evidence that they're dangerous. A conservative doctor would
not use them, on the basis of what we know. Their continued
use is on the basis of tradition, which it's time we changed.
Lest you think that standard FDA approved drugs are incapable
of killing patients in search of fixing numbers, before it's been
shown that the drugs actually don't save lives and indeed are
dangerous, I will refer you to the 1993 CAST trial results,
in which the anti-arhythmics (vs. no treatment) killed patients
with a p of 0.003.
Curr Opin Lipidol 2000 Dec;11(6):609-14
Hypertriglyceridemia and the fibrate trials.
Department of Medicine & Cardiology, Aarhus Amtssygehus
University Hospital, Aarhus, Denmark.
Epidemiological studies published since 1996 have established that
hypertriglyceridemia can predict risk of cardiovascular disease in a
manner statistically independent of HDL cholesterol. Nevertheless,
the relationship of concentrations of plasma triglycerides to risk of
cardiovascular disease remains less than straightforward, partly
because triglycerides are carried in lipoproteins of different
atherogenicity, partly because hypertriglyceridemia is
associated with non-lipid atherogenic and thrombogenic processes.
For example, the association of highest risk of cardiovascular
disease to moderate rather than to severe hypertriglyceridemia
can be understood in terms of the distribution of triglycerides
between different classes of plasma lipoproteins. It is counter-intuitive
to most clinicians, however, and hence it can result in the misdirection
of clinical efforts including drug therapy. Fibrates lower plasma
triglycerides, and raise HDL, efficiently and with few immediate
side-effects. Central to their mode of action is activation of certain
nuclear receptors in cells. There is no necessary connection,
however, between that fascinating biochemistry and clinical
benefit as defined by reductions in rates of death by coronary
artery disease. A review of trials of cholesterol-lowering by
diet and drugs, published between 1966 and 1996, included
12 trials of therapy with fibrates or placebo in more than 21000
patients. Overall, these trials indicated no benefit in terms of
reduction in risk of coronary deaths. The period since 1996
has seen the publication of four additional trials of
treatment of 6144 patients with fibrates or placebo. Two of
them were major trials. The VA-HIT was very encouraging,
because treatment with gemfibrozil produced a significant
reduction in the combined incidence of fatal and non-fatal
coronary events. There was no significant reduction in coronary
The results of BIP were frankly disappointing, because they
demonstrated no significant effect of treatment with bezafibrate
on either the primary end-point of the trial or on rates of coronary
death. Clinical indications for the use of fibrates can obviously
not be based on biochemical insights, however intriguing in
their own right, but they have also not been satisfactorily defined
by the randomized clinical trials published to date. Hope
remains, however, that some clarification will result from
ongoing trials of fibrate treatment of patients with type II
PMID: 11086334 [PubMed - indexed for MEDLINE]
From: "Steve Harris" <firstname.lastname@example.org>
Subject: Re: Cholesterol Intervention, Heart Disease, and Total Mortality
Date: Tue, 14 Aug 2001 14:11:00 -0700
pwrlftr wrote in message ...
>"Steve Harris" <email@example.com> wrote in message
>> Only because of hidebound traditionalism.
>> Why give or take this drug? You're treating a lab test number.
>> Nobody has shown that fibrates do anything for anybody.
>After following the link and search strategy recommended by CBI it
>seems pretty clear that his assessment, that the issue is not settled
>and that reasonable experts to do use them, seems to be a reasonable
If you type in "fibrate" and "mortality" in medline you get a lot of junk
you must sort. Including a number of papers in which fibrates are mixed
in with statin results, giving you a sort of stone soup effect. You can
look at fibrates and statins, but not without a parallel control of
fibrate alone. Otherwise how do you know all your good effects aren't
due to the statin?
> If this type of medicine is as worthless and dangerous as
>you say then it would seem that a great many experts have been fooled.
That's quite possible, and I gave you an example of just that kind of thing
happening in cardiology with the CAST trial (which only repeated what
most cardiologists were doing at the time-- and found that the
conventional patient treatment wisdom of the time was killing patients).
Don't tell me it doesn't happen to conservative cardiology. It happens!
I'm not asking you to take this on my authority. I've given you the best
meta-analyses available on medline for why I think it's happening here.
Read them. If you don't believe them, I'll accept any reasonable a
argument from data. If you think gemfibrazole saves lives, let's see
your evidence! I'm a reasonable man. Show me ANY evidence.
I will NOT accept the idea that if these things weren't crumby,
nobody would be using them. CAST that evil spirit of an
idea out right now. CAST it out, I say!
>I also note that searches for fibrates and cancer did not yield the
>results that I would have expected based on your posts. <y fiddling
>with the search engine also turned up a review on the New England
>Journal of Medicine, which I always understood to be quite
>prestigious, that seemd to advocate for their use.
The New England Journal advocated antiarrhythmics for the average
post MI patient, too, if they had some PVDs. But they were wrong.
Reality trumps even the NEJM, I'm afraid.
>I think the choice is clear. We can either take Dr. Harris' word for
>it or look at the more broad spectrum of opinions, many of which seem
I'm not asking you to take my work for it. I'm asking that if you disagree
with me and think that fibrazoles save lives, that you present your
reasons for thinking so. And not from authority. Cite studies.
From: "Steve Harris" <firstname.lastname@example.org>
Date: Thu, 9 Aug 2001 11:23:36 -0600
"Fred Thomas" <email@example.com> wrote in message
> > is what you are saying, that many things are contraindicated (not to be
> > taken), if you are taking a medication that is statin?
> Exactly the opposite. CoQ10 should be taken with it to
Agree, in this case, if only for theoretical reasons. Too bad you can't tell
how MUCH to take, without getting blood levels tested (hard). In the
vicinity of 30-100 mg a day, probably, with your highest fat meals. If you
can afford it.
Note that Baycol (popular cheap high potency statin class drug), has been
pulled from the market for causing deaths, as reported yesterday and today.
It's one of the me-too statins for which there was no long, multi-year
study. Like Lescol, etc. Which cut the price. It may be that this is not
safe. Thus, we may have to stick to the better tested statins like Mevacor,
From: "Steve Harris" <sbharris@ix.RETICULATEDOBJECTcom.com>
Subject: Re: Is there a way to raise HDL with supplements?
Date: Wed, 2 Apr 2003 03:56:04 -0800
"Brandon Berg" <firstname.lastname@example.org> wrote in message
> "Brad Sheppard" <Brad@sheppardsoftware.com> wrote in message
> > Niacin and perhaps a drink a day. Niacine causes flushing, at least
> > at first. See www.drmirkin.com or go to the American Heart Assoc.
> > website for dosage and side effects - it is OTC. I'm on Lipitor and
> > now have a great lipid profile - 139 chol, 55 hdl, 51 trig. Then again
> > I exercise over one hour/day. My profile was 250 chol, 40 hdl, 250
> > trig.
> Why are you taking statins when your cholesterol is at what could
> arguably be considered a dangerously low level?
Obviously because he started out with cholesterol
Consulting his doc and cutting his Lipitor dose in half and
rechecking later is an option. Generally the target has been
LDL of 100.
On the other hand, if there are no side effects or enzyme
abnormalities noted, there is not as yet any evidence that
you can lower cholesterol "too much" with statins. If
anything, the evidence is the reverse-- in secondary
prevention trial in both stroke and MI, those with lower
cholesterols to begin with benefited from statin therapy
nearly as much. And of course they went even LOWER than they
From: Steve Harris <email@example.com>
Subject: Re: Does high chol. promote heart disease?
Date: 7 Jul 2005 13:43:27 -0700
>>I have it also. I'm also still here. I have decided NOT to take chol. pill
to treat the problem due to the dangerous side effects. Since I am a
Christian, I don't fear death. <<
Fine, but would you also not use a seatbelt (if it weren't illegal)?
Familial hypercholesterolemia comes in two varieties-- the one gene
"single dose" and the two gene "double dose" which is worse. The double
dose gives cholesterols over 600 mg/dL (15.5 in SI units). This
usually produces heart attacks before 30.
The single dose variety gives cholesterols around 300 to 400 (roughly 8
to 10 SI). Men have 85% chance of heart attack by age 60, women by age
There is no single "cholesterol pill," but a wide variety of them. We
know enough about the fibrates (Tricor/fenobibrate, gemfibrozil/Lopid,
etc) and the cholesterol binders (Questran) to know they aren't worth
taking. The statins, a third class of drug, work well in people who've
had a heart attack or have diabetes, but haven't yet proven themselves
in people merely at risk from modestly high cholesterol. However, they
haven't been tried to see if they prevent death in people with VERY
high cholesterol and not yet any heart attack, so that's a matter of
guesswork. My guess is yes, and if it had a cholesterol > 300 I'd
certainly be on one. If you try a statin, stick with the old and proven
ones for which there are long clinical trial data available (mevastatin
simvastatin, pravastatin). Refuse Lipitor and Crestor. Any statin can
cause side effects and needs to be stopped instantly at the first sign
of muscle pain, mental problem, numbness, or really ANY symptom of ill
There's a new non-statin drug which is a cholesterol resorption
inhibitor called Zetia (ezetimibe), available both with and without
statin. Mechanistically it is expected not to be too dangerous and so
far looks clean. However, it's new, and one should be wary of new
drugs. It lowers cholesterol well, but there's no data yet to show it
prevents MIs, let alone death. It's an option for those who cannot take
Niacin, for which much more experience is in, prevents MIs but studies
are not large enough to show it prevents death. It has side effects
which are usually more annoying than problematic, but it can cause
liver damage if not carefully followed.
The best of all treatments to start with for those at risk for heart
disease is high dose fishoil EPA/DPA concentrate (5 to 10 grams of 50%
concentrate a day). There is a LONG experience of humans on high fish
fat diets, and the stuff is benign. It lowers triglycerides a great
deal and LDL modestly (at high dose). But it's protective against heart
disease death in ways which have nothing to do with cholesterol levels
(we don't know the mechanism). Most people with major cardiac risk
factors should be taking an aspirin a day, unless they have a reason
See a cardiologist and then get a second opinion. Get on fish oil. Fish
is not enough unless you make sure it's red (sockeye) salmon.
Good luck. And remember finally that you may not be afraid of death,
but if you're afraid of pill side effects, you're not certainly not
fearless. If you're not afraid of being a cardiac cripple in a
wheelchair on chronic oxygen for your congestive heart failure, it's
only because you haven't seen it. That may not be a "dangerous side
effect" but it's certainly a nasty *effect* of heart disease. The worst
thing about heart disease is sometimes you *don't* die. It makes no
sense to fear side effects from a pill when you could be looking a
chronic disability just as awful, from the disease itself.
You can always stop a pill if you're alert to the problems it can
cause. One hears stories of permanent side effects from statin use, but
they are hard to evaluate. And even they don't come from people who
stopped the drug immediately at the first sign of problem. So take them
for what they are worth: stories to pay attention to, but not to bet
your life on.
From: Steve Harris <firstname.lastname@example.org>
Subject: Re: Does high chol. promote heart disease?
Date: 7 Jul 2005 17:34:26 -0700
>>Sorry to jump in the middle of this thread, but the comment on Lopid
being worthless caught my eye as I take Lopid (for very high
triglyceride levels associated with non-diabetic kidney disease). Is it
just worthless for cholesterol control? My triglyclerides have dropped
from over 4,000 mg/dL to 150 mg/dL - not great, but much better. <<
Lopid certainly brings triglycerides down very well. That is the place
where it shines best (rather than as a treatment for high cholesterol
or LDL per se).
Whether this prevents death from heart disease in the small subset of
people who have VERY high triglycerides (like you) is an open question.
Nobody has looked. In the largest studies on Lopid, they gave it to a
broad range of people and did not succeed in showing decrease in
mortality. Perhaps if they'd restricted it to a subset, they might
have. We don't know!
YOU do have an unusual problem, for which no endpoint data from fibrate
treatment are known. 4000 is a VERY high triglyceride level-- high
enough to cause worry of other problems, like pancreatitis. For you, I
think a fibrate is reasonable. However, if I were you, I would
recommend you do the 10 grams of fishoil a day and see if you can then
cut down your fibrate dose.
Here's a very large trial of gemfibrozole in men with coronary disease
where they were unable to show a decrease in heart disease death, or
death from any cause. They had to fold in total non-fatal events to get
anything significant. But since fibrates are carcinogens, a 24%
decrease in non-fatal events is not enough. Note, however, that these
men did not have really high triglycerides and weren't chosen for that.
It's still possible that gemfibrozil would have done better for them,
if they had been. These are NOT the same group as you, though. We
really have no good data for people with your problem, and that's the
N Engl J Med. 1999 Aug 5;341(6):410-8.
Gemfibrozil for the secondary prevention of coronary heart disease in men
with low levels of high-density lipoprotein cholesterol. Veterans Affairs
High-Density Lipoprotein Cholesterol Intervention Trial Study Group.
Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, Faas FH,
Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J.
Center for Chronic Disease Outcomes Research, Veterans Affairs Medical
Center, Minneapolis, MN 55417, USA. email@example.com
BACKGROUND: Although it is generally accepted that lowering elevated
serum levels of low-density lipoprotein (LDL) cholesterol in patients
with coronary heart disease is beneficial, there are few data to guide
decisions about therapy for patients whose primary lipid abnormality is a
low level of high-density lipoprotein (HDL) cholesterol. METHODS: We
conducted a double-blind trial comparing gemfibrozil (1200 mg per day)
with placebo in 2531 men with coronary heart disease, an HDL cholesterol
level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL
cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less.
The primary study outcome was nonfatal myocardial infarction or death
from coronary causes. RESULTS: The median follow-up was 5.1 years. At one
year, the mean HDL cholesterol level was 6 percent higher, the mean
triglyceride level was 31 percent lower, and the mean total cholesterol
level was 4 percent lower in the gemfibrozil group than in the placebo
group. LDL cholesterol levels did not differ significantly between the
groups. A primary event occurred in 275 of the 1267 patients assigned to
placebo (21.7 percent) and in 219 of the 1264 patients assigned to
gemfibrozil (17.3 percent). The overall reduction in the risk of an
event was 4.4 percentage points, and the reduction in relative risk was
22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We
observed a 24 percent reduction in the combined outcome of death from
coronary heart disease, nonfatal myocardial infarction, and stroke (P<
0.001). There were no significant differences in the rates of coronary
revascularization, hospitalization for unstable angina, death from any
cause, and cancer. CONCLUSIONS: Gemfibrozil therapy resulted in a
significant reduction in the risk of major cardiovascular events in
patients with coronary disease whose primary lipid abnormality was a low
HDL cholesterol level. The findings suggest that the rate of coronary
events is reduced by raising HDL cholesterol levels and lowering levels
of triglycerides without lowering LDL cholesterol levels.
Randomized Controlled Trial
PMID: 10438259 [PubMed - indexed for MEDLINE]