CRP and the Jupiter study~impressive!

Like many, I resent the pharmaceutical companies marketing techniques w/r to statin drugs. This Jupiter study shows very impressive stat/results. High CRP levels were used as guidelines? Was trying to imagine that related to persons with LAF. What do you think?


[www.theheart.org]

Hello Pam ,

Is this the same study?

[news.bbc.co.uk]


Best wishes,

Ritze

Just remember this is BIG business --- US$35,000,000,000.00 ---; can we really believe the study? see Financial Ties Between Big Pharma and the Medical Establishment

Many things have been written on this forum discussing the dangers of statins; see Jackie's with all the links: Statins for children?

I'd stick with the fish oils, as George Eby keeps reminding us :-) [www.afibbers.org]

Pam - if you have any doubts about whether or not statins are beneficial... be sure to go to Duane Graveline MDs website and read some of the links. www.spacedoc.net

My theory is that they's pushed statins on just about all the general population and now in order to keep up revenues, they need a new target market and it's deplorable mainstream medicine would consider messing up children's biochemistry with such a powerful drug.... we already know the many devastating side effects in adults but long-term, statins for children is unknown.

Jackie

Just an initial impression: If I heard right the study was funded by the company which makes the CRP test.

So the take away message is that the extraordinary rise in heart disease in the western industrialized world is caused by a statin deficiency. (?) This is madness.

Trent

Anybody thought about looking into why the CRP is high to begin with & addressing that (instead of just prescribing a statin).

Pam

I think this is a really interesting study. It was sponsored by Astra Zeneca, the makers of Rosuvastatin, but was carried out independently with an independent data monitoring board.

It shows that elevated levels of CRP and inflammation are probably the main factor behind heart attacks and strokes. Many lone AF-ers have elevated CRP (including myself). Rosuvastatin reduces CRP and inflammation and led to a 20% lower death rate from all causes in the statin group compared with placebo.

There are 2 possible side effects identified - more patients taking the statin developed new diabetes, and they also had significantly higher glycated hemoglobin levels (whatever this might do).

I think it is a great shame that the trial was terminated early after only 1.9 years and not allowed to run its full term of 4 years. Other side effects might have been forthcoming.

Mark

mark wrote:

>
> I think it is a great shame that the trial was terminated early
> after only 1.9 years and not allowed to run its full term of 4
> years.


I agree.


>Other side effects might have been forthcoming.
>

Yes such as more cancers and others issues related to coQ10

Must have been very good reasons for short term!

Joyce

Glycated hemoglobin levels are an indication of how much sugar has been in a person's blood during the past two to four months. Higher levels mean higher blood sugar.

Believe me, I am against statin drugs as much as anyone here. I have always wondered about EPs putting post ablation patients on them and can only think that it is for reduction of inflammation.?? I was also repulsed by the recommendations of testing children and putting them on statins!!!

Ritze, that looks like the study in question to me. They just don't name it.

Christof - I'm with you. I just don't know how to argue the study results, considering that it was done by an independent company........and not a drug company.

Trent - "If I heard right the study was funded by the company which makes the CRP test. " Where did you find this information? and you said ~ "So the take away message is that the extraordinary rise in heart disease in the western industrialized world is caused by a statin deficiency. (?) This is madness." I think it means the presence of inflammation, or is a marker of inflammation. I would hope that is an unbiased test, unless you consider that the marketers of the test of CRP would see dollar signs at the thought of every adult in the world getting CRP tested!!

GeorgeN ~ you said "Anybody thought about looking into why the CRP is high to begin with & addressing that (instead of just prescribing a statin)."
********A lovely thought indeed..........Do you think AstraZeneca is going to fund such studies? In the mean time..........

Mark ~ you said, "I think it is a great shame that the trial was terminated early after only 1.9 years and not allowed to run its full term of 4 years. Other side effects might have been forthcoming."
*************I agree. I came away with the thought that the study was aborted because the results became so obvious, making it unfair for the placebo group?

I was just amazed at the results. What a rotten trick if it was somehow rigged, although I don't know that I would put it past them (see Jackie's post).

If it WAS true, then thinking that many LAFFERS have elevated CRP levels??

Thanks for your thoughts everyone...................I'm still puzzled:~)

Higher blood sugar would tie in with the higher levels of diabetes.

As someone who could have benefited from this treatment if it had been fully tested, I'm really angry it was terminated early. I don't buy the conspiracy theory, I think it is much more likely to be an over reaction to the preliminary results that is unfortunately rather typical of the safety first culture that we now have in our society.

Mark

George - they already know many reasons that drive up CRP (silent inflammation) and one prevalent cause is intestinal hyperpermeability (leaky gut) which allows all sorts of molecules to enter the blood stream - (some of that ws covered in the silent inflammation post and also the one on No More Heartburn.) "They" just aren't interested in determining the source of the problem.... no money in that.

I've just heard an interesting interview by a well known gastroenterologist who is also enlightened and uses integrative medicine. I'll be posting some of highlights soon.

Jackie

Mark, do you mean early termination of the study because of elevated blood sugars?

pam

Pam

No - sorry if that was confusing, the comment about elevated blood sugar was in response to Susan's post when we were discussing possible side effects of the statin.

The study, as you said in your previous post, was terminated because of the perceived unfairness to the placebo group. I think they are too quick to terminate these trials. Basically what they are saying is that the placebo group should also be put on Crestor. I don't think the trial was long enough to drive out all possible side effects.

Mark

Mark - You're right of course ~ ideally ~ but I wouldn't want to be on the losing end of a drug study myself:>(

The study was designed to assess whether statin therapy should be given to apparently healthy individuals with normal LDL cholesterols but elevated C-reactive protein levels (CRP >2.0 mg/L).

The results would certainly suggest that one consider statin use if CRP is high (for reasons other than infection or injury), even if other markers/risk factors for stroke or heart events are low .… unless you have evidence that the results of this study were fudged or that a lot of studies showing different results have not been reported.

Here are a couple of ways to results are reported:

If you are a person “with low LDL cholesterol but elevated C-reactive-protein (CRP) levels, investigators showed that rosuvastatin (Crestor, AstraZeneca) 20 mg reduced the risks of various outcomes as follows:

“After 1.9 years of follow-up, treatment with rosuvastatin significantly reduced the primary composite end point 44% compared with placebo. This reduction was observed among nearly all of the individual end points, including a 55% reduction in nonfatal MI, a 48% reduction in the risk of nonfatal stroke, and a 47% reduction in the risk of hard cardiac events (a composite of MI, stroke, and death from cardiovascular causes). "

"In terms of absolute benefits, the proportion of patients who had an MI, stroke, revascularization, or hospitalization for unstable angina or died from cardiovascular causes was 1.6% in the rosuvastatin arm and 2.8% in the placebo arm, an absolute risk reduction of 1.2%. Similarly, the proportion of patients with hard cardiac events—cardiovascular death, MI, and stroke—was reduced from 1.8% in the placebo arm to 0.9% in the rosuvastatin arm, an absolute reduction of 0.9%.”

"The absolute risk reduction for an individual may not seem like much, but is statin use for the population studied a sensible public health measure?

“The JUPITER investigators … calculated the number needed to treat (NNT) based on the primary-end-point event and report that the NNT with rosuvastatin for two years to prevent one primary end point is 95 and just 31 need to be treated for four years to prevent one primary-end-point event.”

This means that for every 1000 people (with normal LDL but CRP>2.0) treated for four years, 1000/31=32 events will be prevented, and so forth. Is this level of prevention worth the risk of statin side effects in those on statins (http://www.rxlist.com/crestor-drug.htm) ?

In this study, “in terms of side effects, significantly more patients in the rosuvastatin arm developed new diabetes, and they also had significantly higher glycated hemoglobin levels (poor blood sugar control), report investigators. Any reported serious adverse events were similar between the placebo and statin-therapy arms.”

If this were the only population for whom statins might be prescribed, the answer might well be “No”, but this study cannot answer that question.

The fact is that there are many factors what could lead one to consider statin use. This study does emphasize that a low LDL level by itself does not indicate low risk for an “event” … but this is nothing new .

I think that the best strategy is to take as many risk factors as possible into consideration and to do the best one can to determine the probablity of problems in each individual case.

I think this is best accomplished by the use of the Berkeley HeartLab (http://www.bhlinc.com/) or the VAP test (http://www.atherotech.com/aboutus/faq.asp) which measures many factors in addition to those in the usual lipid profile.

The other strategy (as noted by GeorgeN and Jackie) is to compare statin vs other measures to reduce CRP. The individual can of course try various approaches and see what effects these have on his CRP (and lipid profile).

I was struck by this statement at the end of the article:

“[CRP] summarizes a myriad of metabolic problems that individually are not bad enough to treat but collectively indicate increased risk. Increased CRP tells you that. It is one number, and explaining and implementing it may be easier for physicians and patients than trying to explain why 'borderline' high blood pressure and being 'a little overweight' are bad. They damage and inflame blood vessels, and high CRP shows it."

Is the converse true … that is one has borderline blood pressure and is a little overweight but has a low CRP that these factors are having no negative effect?
-- Dick

There is something I read yesterday, which made me very angry about these drug companies and really suspicious about statin drugs. Read this horrifying story of Former NASA Astronaut and doctor, Duane Graveline MD:

[www.spacedoc.net]
[www.spacedoc.net]

Other stories: <[www.spacedoc.net];

It reminded me of the many times, that me and my wife have been prescribed harmful pharmaceuticals by well meaning doctors, marketed as SAFE and EFFECTIVE, which ended up killing or injuring tens of thousands of people. Years later these same drugs were withdrawn from the market. Many drugs long banned in western countries are still marketed in the Philippines and elsewhere in Asia. --- I'm just thankful to God, that he has protected us!

This trial showed that Crestor is very effective at reducing CRP. A number of other treatments (such as fish oils etc.) have also been mentioned on this board as reducing CRP. But are there any trials showing what really does work of a similar nature to the Crestor trial?

I'm taking fish oil supplements anyway as the evidence seems overwhelming to their general benefit.

Mark

Christof,

You may also be interested in this thoroughly researched article by Professor Bill Ware about statins.

You can find it here:

[www.yourhealthbase.com]

Also for those interested in the relationship between heart disease and CRP this article is a must:

[www.yourhealthbase.com]

Hans

Mark,

Although Crestor did lower CRP, the question still must be, "What good does that do?" I would not call absolute reductions of 1.2% and .9% for "soft" and "hard" CV events (see my post above), respectively, strong evidence of effectiveness in actually reducing harm.

Perhaps the reason for this is that there are other factors that contribute to these events that were not covered in the study (some of which may be included in the Berkeley or VAP tests -- see <[www.bhlinc.com])?

Of course, statins may affect these other factors as well (http://www.atherotech.com/HealthcareProfessionals/treatmentguide.asp)

Along with you I would hope for more research comparing the cost/benefit ratios of various approaches to reducing CPR (see the second article cited by Hans above for a few suggestions, and references to more by Drs Sinatra and Willett.)

Hans,

Unless I have overlooked something, the material on statins in your first linked article is aimed at showing that statins may have positive effects that have little to do with their effects on cholesterol (as opposed to evaluating their benefits)...

"To put it another way, if the beneficial effects of cholesterol lowering drugs, which today are mostly statins, is due to actions of the drug that do not involve lowering levels of cholesterol, then the cholesterol lowering itself is irrelevant in this context, even if a dose dependence is observed. That is, the non-lipid lowering mechanism could be dose dependent as well and responsible for all the observed benefits (see p 3 for more)."

The second article is really interesting and includes the pro's and con's of a few ways to lower CRP (see section entitled "Reduction of CRP").

It concludes with this:

"High CRP levels have been associated with an increased risk of future heart attacks, ischemic stroke, and peripheral arterial disease. However, there is no clear consensus as to whether a single screening test for CRP is useful as a diagnostic tool. The diagnostic value of CRP screening can be improved by performing two tests a month or so apart and by including both CRP and the cholesterol level ratio (TC/HDL) in the final risk assessment, perhaps in conjunction with a Framingham risk calculation."

I would substitute the use of the Berkeley Panel or VAP test for his suggested diagnostic combo because either one would include those tests and more...

-- Dick

Hello Dick,

This is my "take" on the Jupiter trial - As the myth that lowering cholesterol, LDL in particular, is protective against heart disease is gradually debunked, the purveyors of statin drugs clearly needed a different marketing approach. They decided to exploit the observation that statins have an anti-inflammatory effect, or at least an effect in reducing the level of the inflammatory marker CRP (C-reactive protein). They enrolled a group of "apparently healthy" patients in a 2-year trial. Very conveniently, they defined "apparently healthy" as having a low LDL cholesterol level. What they did not emphasize is that the average CRP level in the group was 4.2 to 4.3 mg/L. This level has been associated with an increased risk of heart attacks, ischemic stroke, and peripheral arterial disease. So, I guess it comes down to whether you would consider such a group "apparently healthy". I would not, and if you accept my reasoning, then there is absolutely no reason why healthy people with a CRP at 1 mg/L or below should start taking statin drugs because of the hoopla created by the Jupiter trial!! Especially as there are many far safer and less expensive means of dealing with the systemic inflammation indicated by high CRP levels. Regular exercise, reduction of excess weight, smoking cessation, stress avoidance, and supplementation with vitamin E all significantly reduce CRP levels. Several afibbers, myself included, have found beta-sitosterol and Zyflamend to be highly effective in reducing CRP and there is evidence that curcumin on its own is a highly effective anit-inflammatory. Unfortunately, these highly effective, inexpensive natural supplements are unlikely to ever be tested in a study comparable to the Jupiter one.

The treatment with Crestor increased the risk of diabetes and rhabdomyolysis (a serious, sometimes fatal muscle disorder). Was the trial really stopped early so that all the trial participants could "benefit" from taking statin drugs? Or, was it stopped early to avoid the embarrassing situation where adverse effects would outweigh the benefits?????

Nobody knows what halving a normal LDL level will do in the long term. Cancer and depression comes to mind as possible long-term adverse effects. Of course, statin use has also been associated with transient global amnesia, but I don't know if any cases of this were reported in the Jupiter (Crestor) trial.

Hans

There seems to me to be something particularly sinister about this whole business (and I use the word "business" advisedly). And no, I don't mean the fact the Astra-Zeneca, the maker of Crestor (the drug used in the study) sponsored the research. Nor do I mean the fact that apparently the hospital involved gets a kick-back on CRP tests.

Just recently, as reported in the New England Journal of Medicine, a Danish study concluded that, while CRP can be a "marker" of inflammation, it does not, in itself, seem to cause cardiovascular problems.

I quote: "Nordestgaard and his colleagues turned to the ultimate source for the variety between individuals' blood levels of CRP -- genetics. Some people are genetically programmed to have high levels of CRP, while others have genes giving them low levels of the protein.

The Danish researchers performed genetic studies on more than 10,000 people, looking at four variant forms of the CRP genes.

In theory, people whose genetic profile gave them high levels of CRP should have an increased incidence of ischemic diseases such as heart attack and stroke -- if the causal theory was true.

But no such relationship was found, Nordestgaard said.

'So, we cannot say that high CRP levels per se lead to ischemic vascular disease,' he said."

If I understand correctly, a high CRP level indicates that a marker of inflammation (CRP) is circulating in the blood, not necessarily that the vascular system is, itself, inflamed. The source of the inflammation could be from any number of "metabolic problems" (or not) having, per the Danish study, no measurable effect whatsoever on cardiovascular health.

In the Jupiter study, they speak of a 44% reduction of cardiovascular events (heart attack, stroke, etc.) among otherwise healthy people with no typical indicators of heart disease. So, initially, these peoples' risk of CV disease is already relatively low: 14 per 1,000 according to the study. By giving a presumably lifelong treatment of statins, they propose to be able to reduce that number from roughly 14 in 1,000 to 8 in 1,000 (over the same very short period at least). I'm not going to do the math since I'm bad at it, but that seems to be where they're getting their 44%, translatable to 6 fewer events in 1,000.

So, even though they are unable to identify the subset of people whose elevated CRP is due to cardiovascular (and not genetic, arthritic, infectious etc.) conditions; and even though CRP apparently is incapable of itself "causing" cardiovascular disease; and even though the reduction in CV events in otherwise healthy populations on statins is an underwhelming 6 per 1,000, they are proposing to put millions of otherwise healthy individuals on a life-long regimen of a pharmaceutical some of whose very significant problems are known, and others which can only be assumed and projected given the serious biological activity of the drug. (For instance, if the patients' cholesterol is already low as in the study, what happens to the cardioprotective action of cholesterol when it's lowered even further?)

This study seems to be leading otherwise serious people to propose a massive medical experiment on huge numbers of otherwise unsuspecting people which can, perhaps, have a statistically significant effect on lowering the incidence of CV disease in a given population, but which may lead to possibly grimmer outcomes for the overall health of the same population and almost certainly for a large number of individuals involved. This, of course, doesn't take into account the felicitous effect it would have on Big Pharma's bottom line.

I repeat: this is madness.

Trent

I wish the excellent Cholesterol/CRP articles by Ph.D. William Ware, which Hans referred to, would be published in the New England Journal of Medicine, to bring some balance to this statin hype.

It is alarming to what extend pharmaceutical research has become an extended arm of the marketing departments of pharma corporations over the last decade. I think this study shows obvious signs of this trend. The uncritical reporting in the mainstream media about these kind of studies is another worrisome trend. All checks and balances are slowly being eroded to the detriment of patients.

Dr. Michael R. Eades has posted a sensible analysis of the Jupiter study on his blog, "Truth versus hype in the Jupiter study":

"Let’s take a look at what the study really shows. But before we do, let’s psychoanalyze the people putting the study together. What do you think they wanted out of this study.

Typically a study starts with an hypothesis, say, zinc cures the common cold. The study then involves giving people suffering from colds zinc or a placebo to see what happens. The researchers then say that the data confirms the hypothesis or refutes it. It’s not good to go into a study with a predetermined idea of what you want. You just need an hypothesis. Your hypothesis could be that zinc has no effect on the common cold. You wouldn’t go into a study with the idea that we’re by God going to prove zinc cures the common cold. It just doesn’t work that way.

But what about the Jupiter study? Know what Jupiter stands for? It stands for Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin. Which translates to by God we’re going to prove that statins prevent something. We certainly know the mindsets of the people running this study."
[...]
"Let’s look at the sort of fishy aspects of this study. First, the patient population is most unusual. How many subjects are there out there who have both normal LDL-cholesterol levels (defined as 130 mg/dl or below) AND elevated C-reactive protein levels. Not very many. Especially if you eliminate anyone with any history of inflammatory disorders, which the researchers did. Most people who have an inflammation arising from the metabolic syndrome, obesity or other common inflammatory disorders will have both elevated lipids AND elevated C-reactive protein levels. They are typically found together. The authors of this study had to use 1315 sites in 26 different countries to get the 17,802 subjects involved. Simple division tells us that there were an average of about 13 subjects per center. Not many. To paraphrase F. Scott Fitzgerald who said “the rich are different from you and me.” Well, these subjects are different from you and me. And what may work for them may not necessarily work for you and me.

Second, when you look at Table 1 showing the baseline characteristics of the participants, you can see that in virtually all respects the two groups of subjects look identical, which is as it should be in a randomized study. But closer evaluation indicates that there not identical in a couple of parameters. In the category Family history of premature CHD (coronary heart disease) we see that there are 51 more subjects with a family history of premature CHD in the placebo group than in the Crestor group. Since a family history of premature CHD is probably the strongest risk factor for developing premature CHD, do you think a few more of the subjects in the placebo group may have developed it? And maybe died as a result?

Third, looking at this same table and checking the very next category, Metabolic syndrome, we find that 71 more patients in the placebo group with metabolic syndrome than we do in the Crestor group. Since the metabolic syndrome is another strong risk factor for development of CHD, do you think some of that difference in deaths could have come from this disparity in the groups? As I say, not conclusive, but fishy."

You can read the whole blog post, which also links to the original text of the Jupiter study here:
[www.proteinpower.com]

Good job, Christof, thank you. And for the vit-C-&-E-study debunking post also.
PeggyM

Trent and Hans, when i replied to Christof's post i had not yet read either of yours. Together all 3 posts effectively debunk this deceptive study.

1] Figures don't lie, but liars can figure.
2] Lies, damned lies, and statistics.

PeggyM

Well done, Hans!

Crikey! We seem to have a lot of fans of alternative medicine on this forum! There seems to be an inbuilt assumption - mainstream medicine - bad, alternative medicine - good.

I've had a look at some of the sites mentioned and I only wish the claims made as gospel truth would be subject to the same criticism as applied to drug trials.

There is criticism of the Jupiter trial because it is funded by Astra Zeneca, makers of Crestor, even though it was carried out independently. The alternative sites mentioned all seem to be flogging books, supplements etc. whose sales would dry up if the mainstream trials are accepted. Not much independence there!

I clicked on a link on one of the sites and my anti-virus software detected a particularly nasty virus hidden away.

Let's try and maintain a sense of balance. There are justified criticisms of the Jupiter trial, like its early termination and the cost per death prevented were it to be rolled out more widely, but also lessons to be learnt such as the role of CRP. I would venture to guess that an awful lot of people on this board are in the low LDL, high CRP category this trial was directed at.

Mark

Is it a fact that the test was carried out by the makers CRP testing?

A new article on the Jupiter trials:

[www.theheart.org]

Mark - typically, our body is not deficient in a prescription drug, that's why we like to look for the source of the problems and attempt to restore what nutritional deficiencies exist. Such is the case with statins. Elevated CRP can be managed very nicely with natural products that have no downside or do not interfere with other important functions such as found with statin drugs. I see nothing wrong with testing for CRP; in fact, it would be negligent not to, but I do have a problem with testing so that patients can then be prescribed a statin drug.

You may recall, my post which was a review of the book, "Overdo$ed America" written by John Abramson, MD, who also is on Harvard Medical School Faculty, that the problem with most studies today is that very often the results are biased, authored by paid ghost writers to convey just what the sponsor of the study intended, and really can't be relied on to be truthfully reported unless the entire study (which is often hundreds of pages) is thoroughly reviewed by a reader with experience looking for study flaws.
[www.overdosedamerica.com]
<[www.afibbers.org];

It doesn't pay to become all worked up over a published study these days because most don't tell the whole story. But, as a general rule, you can be pretty confident that the results favor the sponsors of the study and their outcome intent. This fact has been noted by many editors of well known medical journals. Another book on the same topic is by former author of the New England Journal of Medicine, Marcia Angell -

[content.nejm.org]
[articles.mercola.com]

Jackie

I love that book, "Overdosed America"! It gives tremendous insight into what's really behind the many studies done, and how they are so often skewed to support whatever drug is being promoted. T. Colin Campbell also writes about this topic in his book, "The China Study", which is an excellent book on nutrition and it's implications for diet, weight loss and long term health". On a related topic, he says this:
"When nutrition education is provided in relation to public health problems, guess who is supplying the "educational" material? The Dannon Institute, Egg Nutrition Board, National Cattlemen's Beef Association, National Dairy Council, Nestly Clinical Nutrition, Wyeth-Ayerst Laboratories, Bristol-Myers Squibb Company, Baxter Healthcare Corp. and other have all joined forces to produce a Nutrition in Medicine program and the Medical Nutrition Curriculum Initiaitive" Do you think that this all-star team of animal foods and drug industries representatives is going to objectively judge and promote optimal nutrition...? etc.

Too many foxes watching the hen house, wouldn't you say? I'm sure there are some grains of truth in some of these things, but I dont' take any of these studies on face value anymore.

Barb