What am I missing here? Has it not been proven that Statin + Niacin combo is like 90% affective in stopping plaque progression in its tracks? Why does that not say that LDL reduction AND particle size reduction,(Niacin for LP(a),works best? Its not just LDL, I developed heart disease with a 90-100 LDL before my Dr discovered  high LP (a). Treated with 10mg statin,1500 Niacin, diet,I am at a30/30 count. OVER&OUT

Let's just summarise. First there was Keys with his total cholesterol. This turned out to be garbage. Then there was LDL vs HDL. But LDL is calculated and, as we know from this site, tells us nothing about anything. Then we have LDL particle size. Small dense is bad, big fluffy is good, noting that big fluffy contains lots of cholesterol per particle and can increase your calculated, or even absolute, LDL. Two factors, most studies use calculated LDL. The bin is there, file promptly.

The second is that something controls your LDL particle size. How, on a practical basis, does Dr Davis control LDL size and density? No wheat and no sugar. Does wheat and sugar elimination alter anything in the body? Wheat contains both an insulin mimetic and two insulin potentiators, plus starches and sugars both increase blood insulin levels per se. Perhaps there is a message here. It's been known for decades that insulin drives the proliferation of the arterial media we call arteriosclerosis.

If insulin also controls LDL particle size (I have no information on this, but I'm willing to bet it does) then Yudkin and Stout are correct, Keys is wrong and the cholesterol hypothesis, what remains of it, describes the effects of insulin on blood lipids. While insulin and glucose do the damage to the arteries.

Just a cholesterol skeptic view.

Peter

Statins are anti-inflammatory, antioxidant, anti-proliferative and probably anti other things too. Unfortunately they drop cholesterol levels (in humans anyway). Zetia, like torcetrapib and clofibrate, does the cholesterol dropping thing without the anti everything else that statins bring along. No wonder they killed so many people in the clinical trials. Clofibrate. Torcetrapib.

If a drug company develops a drug which converts small dense LDL to light fluffy LDL without affecting insulin sensitivity or glucose, I predict it will go the way of clofibrate and torcetrapib. There's the bin.

I especially find it interesting that, among the so-called pleiotropic, or non-lipid, effects of statin drugs is a modest rise in 25-OH-vitamin D3 levels.

I think this just once again shows that statins DO reduce heart disease but NOT because of the reduction in LDL. I'm always amazed at the Dr. who say you don't need to be on a statin your LDL is fine. Statins have been proven to reduce death rates in cardiovascular disease by 30 to 40% and yes with niacin by 90%!!!!!!!! Anybody worried about heart disease should be taking them. And save me the "side effects" alarm of statins that is so over blown. The fact is we invented a drug to reduce LDL, it does that but thats not why it reduces heart attacks and we're still not sure why they do. We accidently created a great class of drugs.

I remember in Taubes reading that small LDL are the result of particles being formed in a high-triglyceride environment--if so there is a more direct link to diet than through insulin.

About the merits of statins, can't we at least say that through reducing the number of all LDL particles and hence the number of small particles arteries are protected?

Keith

The drug company slanted this study so that they'd get a wonderful result, that they didn't and the lengths that they went to hide or misrepresent the data that came out of the study has to make you suspicious of what ELSE they have learned.

Did you catch that they also suppressed other study results showing liver damage from Zetia?

Also, did you catch the BMJ story today about the calcium supplementation trial that lowered LDL raised HDL and increased cardiac and stroke events in older women?

While that too isn't a death blow to the LDL hypothesis, it certainly doesn't bolster it.

Peter,

Good post; you have an impressive grasp of the literature on this!  I have a question for you, though:  Besides the epidemiology (which I know you don't buy), aren't there still tons of animal studies linking atherosclerosis to dietary saturated fat?  In fact, to promote atherogenesis in lab animals so they can study it, don't they feed them a diet rich in palmitic, stearic, myristic and lauric acids from animal and tropical plant fats, which works predictably?

Drug companies are actually scrutinized fairly closely, though plenty of shenanigans still go on.

What scares me even more is what may have been going on BEFORE the intensified scrutiny began a few years ago.

Nowadays, the return on investment for treatment of chronic diseases like cholesterol, osteoporosis, and hypertension are so substantial that it is causing them to see a blur between right and wrong.

Yes. I believe that the evidence for that effect of statin drugs is quite confident.

When I question the Lipid Hypothesis, what I really mean is that I question the wisdom of the simple "high cholesterol means more atherosclerosis" philosophy, a belief that is clearly oversimplified, though it contains a germ of truth.

For anonymous,

Of course statins reduce cardiac mortality and obviously it's nothing to do with LDL cholesterol lowering. But before you pop one on the off chance (they are available OTC in the UK) go very carefully through this paper.

You need the full text, the abstract tells you nothing, so here's a summary:

There were 2913 patients in the placebo group. A total of 306 died during their 3 years of not taking a statin. That is 10.5% died. In the treatment group there were 2891 patients and 298 died, that's 10.3%. Bear in mind that these were high risk cardiovascular patients, the sort for whom statin therapy is supposed to be effective in saving lives.

There was undoubtedly a significant improvement in cardiac mortality WITHOUT improvement in overall mortality. To sum up the PROSPER trial, you can have the cause of death changed from heart attack to cancer, but not the date on the death certificate. You choose. Perhaps you're too young to be in the PROSPER trial, but live long enough and you won't be!

PS if you EVER see a statin trial without the overall mortality figures, just assume there was no benefit or worse. If there is even a miniscule benefit it will be broadcast far and wide.

Keith,

Thanks for the pointer. Obviously high triglycerides are a classic marker of hyperinsulinaemia and insulin resistance. I'll follow that one when I get that far in to Taubes' book. Seems it's looking good for Yudkin.

bad_crc,

Yes, there are thousands of papers like that. They usually use D12451 or something like it. High fat alright, 45% calories from lard. As the rest is? A bit of corn starch, a mass of maltodextrin and an even bigger mass of sucrose!!!!! But of course it's the lard that kills....

Whereas using a real high fat diet you get this paper. I would suggest the 60% of calories from fat us a little low for a rodent. Choosing for themselves they can go to around 80%, get plump but don't develop insulin resistance.

Peter

My understanding is that studies show that statins are effective in reducing heart attacks ONLY in people who have already HAD heart attacks. Not in the general population.

This would confirm the growing suspicion that statins work by limiting the inflammation associated with heart disease. Not through their effect on lipids.

To get back to Zetia/Vytorin, what Dr. Nissen pointed to, which IS in my mind worth noting, was that while the variation in individual endpoints did not rise to statistical significance every single endpoint measured went in the wrong direction. That argues against random effects in my mind.

Beyond that, we know that in most people heart disease develops over a longer period than that spanned by this study, which only lasted 2 years. If all these parameters measured were trending negatively at 2 years, what happens at 5? Or 10? This is one of those drugs that once they put on on it, you take them forever. So the 5 or 10 year result could be devastating if this turns out to be a significant finding.

My suggestion would be continue testing this drug in small studies involving people who are very well informed of the risks, but end the writing of the current 1 million prescriptions a month. That's a LOT of guinea pigs, and if there turned out to be an accelerating pace of problems with it, a lot of people could die unnecessarily.

Statins reduce the number of LDL particles, which is very poorly represented by the conventional (Friedwald)calculated LDL cholesterol.

More importantly, when someone with heterozygous hypercholesterolemia (as in this Vytorin study) has a high number of SMALL LDL particles, then statin drugs, in my view, do provide benefit. But a superior effect would be to specifically reduce the number of small LDL particles, best accomplished with such strategies as elimination of wheat, weight loss via low carbohydrate diet, fish oil, vitamin D, and niacin.

This raises the question of how well the two groups in this study were matched for the number of small LDL particles. To my knowledge, this was not measured.

Let me also remind everybody that the measure obtained and used for comparison was carotid IMT, not carotid plaque.

I'm certain I'm not alone in feeling bewildered that such a dominant theory of the disease could turn out to have been so wrong for so long at such great cost in lives and treasure.

Just as a question of historical interest, how far back in the history of science do we have to look to find this kind of reversal of understanding of what the facts are with such broad and great consequence?

Hi, WC--

I'm not sure, but it's not the first time.  

Is the earth still flat?

Hi Dr. D.

I was thinking of Galileo also and his remarkable discovery that the earth orbits the sun.

But then I thought "surely we don't have to go that far back do we to get to such a broad and consequential paradigm shift?"

Maybe we do.

Could zetia be interfering with the absorption  of simvastatin?

Hi wccaguy,

You may enjoy this discussion article from PLoS. The authors intend it to be provocative, put it does pose the question "on which day did medicine stop making mistakes?"

Peter

In response to Jenny, not all studies on reducing heart attack death havwe been done on people who already had a heart attack. The reduction of 30 to 40% is whether you've had one or not.

Our saturated fat question keeps coming up, but the current common wisdom is that saturated fats are "neutral" in the sense that they raise both LDL and HDL. But do we know what they do to the number of small particles? Of course, if LDL is raised by making particles fluffy then saturated fats are clearly protective.

Keith

Hi, Richard-
No, there was indeed a substantial further drop in LDL with Vytorin over simvastatin.

There is a very modest shift from small to large LDL.

Zetia dropped my very high, inherited LDL to normal, BUT I afer a couple months on Zetia my post-menopausal body stopped making estrogen--my gynecologist remarked on it.  

I also started having a problem with persistent visual afterimages which the ophthalmologist said might also be from having too little cholesterol.

Both problems went away when I stopped the Zetia. I have very high LDL but I also have the "longevity" cholesterol gene which makes for big fluffy LDL as well as very low Apo(b). My doctors--including the cardiologist I saw--are ignorant about the implications of both findings and just obsess about the high LDL.

Since naturally produced estrogen seems to be protective for heart disease, I wonder if some people with inherited high LDL are like me have the large fluffy LDL molecules which give a deceptively high LDL value on tests. For them lowering it with Zetia drops LDL TOO low, so that the body doesn't have the cholesterol it needs for important functions, like making the naturally produced female hormones that may be protective against heart disease.

Hi, Jenny-
Keep in mind that conventional LDL is a flagrantly inaccurate number. In my experience, LDL of 150 when accurately measured (we use the NMR LDL particle number as the "gold standard"), the true number is between 80 and 270 mg/dl.

In my view, conventional LDL is a silly number. It is also the basis of a $23 billion (annual revenue) industry.

In Dec 05 I had a heart scan score of 145.  I went from 10 mg of Lipitor to 80mg of Vytorin and 1000 Niacin, 1 fish oil.  At that time my particle number was 1325 and small particle # 977.  A year later it went to 1503/1277.

In Nov 07 my heart scan went to 291. I then went to 2000 mg of Niacin and 150 COQ10,4 fish oil, 500 mg C, Vitamin D.

My new liposcience profile taken Dec 27 07 shows small particle down to 249 and particle number down to 279.

I dont know why my plaque increased so much but the new lipo profile is impressive in reduction.

Is there anything here that seems weird or is it just the plaque grew fast and is likely now under control with the much improved scores?  All other factors on the profile were great and my Vitamin D is very good and CRP excellent too.  My homosistine was 15.7 is the only thing a bit high.

Thanks!!

Sorry, but I do not assess entire programs on this blog.

I would invite you to participate in the conversations in the Track Your Plaque Forum for detailed discussions like this. There is also a free report on "10 steps to take if your heart scan score increases" on the www.trackyourplaque.com website.

I would not automatically conclude that Zetia causes carotid plaque. This is absurd. And I am definitely not one to come to the rescue of a drug or drug manufacturer. I am simply after understanding and truth.

Probably probably the most helpful in addition to up-to-date info I came across on this topic. I am positive fortunate that I noticed your article by chance. I¡¯ll be subscribing to your individual rss feed in order that I can have the most recent posts. Take pleasure in all the pieces here.

Probably probably the most helpful in addition to up-to-date info I came across on this topic. I am positive fortunate that I noticed your article by chance. I¡¯ll be subscribing to your individual rss feed in order that I can have the most recent posts. Take pleasure in all the pieces here.

This is very well written.  Great perspective.

And how many of these procedures are ABSOLUTELY necessary after they get you into the hospital?  

I recently changed cardiologists.  The new doctor, after reviewing my history and talking with him (yeah, a dialog!), he made the comment that he wonders why I even had a pacemaker installed (keeps heart rate from dropping below 60)!!  Talk about being left speechless!!  

You see, I had passed out.  It was discovered that I had severe blockage of the left descending artery.  A stent was inserted.  Then the doctor said that if a pacemaker were not installed I could experience sudden death due to low heart rate.  I can still hear his booming voice that could be heard on the entire floor stressing the words "sudden death."  What would you do?  

Hey, is the thinking that if it is not really necessary it is at least innocuous, then cha-cling . . . $65,000?  Scary.    

Anyway, my new doctor said that it is something that needs more study, etc.   I know the "control unit" can be changed out for new batteries but I've never heard of the wiring being removed from the heart muscles.  Geeez.

Ignatius Semmelweiss had the same problem;  He railed against the conventional wisdom that 'knew' there was no reason for handwashing before surgeries.

"A much more familiar scenario is the man or woman who undergoes two or three heart catheterizations, receives 3,4, or 6 stents, followed a few years later by a heart bypass, pacemaker, defibrillator, as well as the tests performed for catastrophe management, such as nuclear stress test, echocardiogram, laboratory blood analysis, and consultation with several specialists. "

I think you have been following me around. I am glad to say that I did not go on to pacemaker/defibrillator, but I had all the rest. The day I got my first stent, my doctor told my husband "I fixed her" and proudly handed us a before and after picture. Funny, I did not get any pictures when I had more angioplasies.

I am so tired of band-aid medicine. Finally, I think that I am on the right track of lifestyle changes, thanks to information here and other forward thinking websites.

Agreed, great perspective... but my goodness! Pardon this slightly off topic comment, but you just described word for word what a good friend of mine is going through with pneumonia -  except she was sent home from a doctor's office twice. By the time she was admitted to hospital, her blood pressure was about 60/40 and she was in agony from a collapsed lung.

Brilliant. Where is your monthly column in the Wall Street Journal?

"Perhaps it's excessively cynical to label it "disease engineering." But, whether from benign neglect or purposeful failure to diagnose, the fact remains: Heart disease is, all too often by the standard path, undiagnosed and neglected for years until the procedural payoff strikes."

What an incredibly ballsy statement!  My hat is off to you.  

I have been a Respiratory Therapist for 23 years.  To hear a cardiologist make such a statement is the most validating thing I have heard in all these years.

I have almost been fired more times than I can count, for trying to address a low oxygen level.

Shoot some docs take everything personally!  I'm not trying to save anyone, just make them feel better while they're on the planet.

You and I both know that they can save themselves.  It is just a matter of education.

Many blessings

Dr. Davis,

What makes you think that people who show up with all the symptoms of serious infection get antibiotics?

One of my kids is permanently deaf in one ear because the pediatrician gave us that speech about how antibiotics just cause bacterial resistance and refused treatment.

And there have been quite a few stories in the press recently of young people dying of pulmonary MRSA because their initial symptoms were ignored.

You're a cardiologist so you see this problem in the context of heart disease. But the problem of only treating complications is widespread through all medical specialties.

Years ago when my blood sugars were routinely going into the 200s after every meal I visited the guy who was supposed to be the "best" endo in our area, who offered me no treatment and told not to come back to see him until I'd spent a year with an A1c over 8%--an A1c high enough to guarantee complications. He told me he didn't bother treating people whose blood sugar wasn't that bad.

My guess is that this attitude grows out of the way physicians are trained with hospital-based residencies that concentrate on heroic medicine.

This makes people who are not in the throes of a massive complication look "fine" and keeps them from getting proper preventative treatment.

Your post and Jenny's comment make the point that people can't be lax about their own care; they need to be willing to learn, be informed, get second and third (or even 4th) opinions sometimes, and to be assertive when the recommended care doesn't seem to match with their intuition or condition.

There's a continuum between throwing all the available treatments at a condition and waiting to let nature take care of it, and there are cases to be made for approaches on either end and those in between, but it takes good judgement to know when and how to apply the appropriate approach.  Too many people have abdicated their own responsibility in the decision and judgement process.

You could also include thyroid disease in there as a problem that doctors routinely ignore, until it gets to the state where the patient has major problems (full blown hypo/nodules, etc).

And prevention, for many health problems, seems to be a dirty word to doctors. The system is very flawed across all specialties.