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.

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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.

I offset the cost of my self-directed testing by making sure I fund my Medical Savings Account sufficiently (deducted from my paycheck in equal installments).

October/November is the benefit enrollment period for many folks, so if you have a MSA available to you, you need to enroll or re-enroll now.  Maximum IRS allows one to elect is $8000/year I believe.

I calculate mine to cover my total estimated self-directed testing and all doctor/rx copays for the upcoming year.

Although you are paying with your own $$$, at least it comes out of pre-tax dollars, which makes it a very good deal.

One of the things I love about reading these blog comments is that I get ideas.
Now I will set up a Medical Savings Account for myself.
Fortunately for me, Group Health subsidizes the cost of blood glucose home testing.
Jeanne
(I'd register, if Google Blogger could remember my password.

I get yearly tests done through lef.org. I've been happy with the service they provide, and the prices seem reasonable.

StephenB

I answered "Do it but express reservastions" but the real answer is that some of my doctors have "refused outright" and some "Do it without question".

When I asked to be tested for celiac disease, two doctors refused. Both told me I did not have this problem as I was not losing weight and did not have diarrhea. Their refusal may have been my good luck as that made me turn to alternative testing(Enterolab) that looks for gluten sensitivity and not just celiac disease.

More recently I was told by my PCP I did not need a winter vitamin D test as my level was 46ng/ml at the end of summer. I changed PCP's and got my vitamin D level tested - it had dropped to 24ng/ml(same lab).

I am glad there are labs that I can access without a doctor. I still use Enterolab to follow my gluten antibody levels. I now have doctors who seem to be willing to work with me and help me optimize my health.

I think you missed #5, which is true for the large numbers of people in HMOs, where their doctor is a direct employee of the patient's insurer:

5) The doctor receives a bonus for ordering fewer tests.

Even though self testing through LE, Direct Labs, etc. requires that the user pay (i.e. no insurance payment), I have found that even then they are cheaper than doctor ordered tests because of outrageous prices for hospital initiated lab tests with large dedutible/coypayment charges.

I am not impressed by all the wondrous diagnostic techniques developed for detecting common chronic conditions like heart disease. We already know what causes these chronic diseases. They are lifestyle diseases. Proper diet and exercise being the primary components of good health.

Knowing the cause, we also know the cure for most chronic diseases: improve your lifestyle. People who have followed this plan usually make an amazing discovery. Lifestyle changes act almost like the proverbial universal cure. It is not just heart disease, but a whole range of other chronic conditions get reversed or effectively managed. Lifestyle diseases require lifestyle cures.

How many more technologically advanced tests should you undergo before you adopt the cure? Really, why should you wait? Most people in the USA will die of or at least suffer from one or more avoidable chronic conditions in their lifetime. You can undergo testing until you are finally and definitively diagnosed, or you can proactively adopt the cure and more likely avoid all of the unpleasant consequences of modern chronic diseases.

I don't oppose testing for anybody who wants it. But I see that an obsession with testing operates as an excuse to put off addressing necessary lifestyle treatments.

After reading Jenny Ruhl's Diabetes 101 I decided I wanted to more closely monitor my blood sugar. My a1c is 5.5, which my doctor tells me is "fine" but it is on the high side of normal, and after learning that even small elevations of blood sugar can be damaging,(new information that my doctor may not be aware of)  I want to be monitoring my BSs closely.
I've asked my doctor how to get a blood sugar monitor. I voted that he usually allows me to have tests I want, but I'm afraid he's going to think I'm a hypochondriac for wanting the BS monitor.

I know my internist is unfamiliar with the tests; he told me "I'm not into the minutiae of lipid testing". So I went to LEF to get it done myself.

There is no need to ask your doctor about a glucose monitor and risk acquiring the image of a hypochondriac.  

Anyone can buy a glucose monitor and testing strips at any pharmacy in the US without a prescription, no questions asked.  There are free meter offers online at testing supply businesses, but they usually require a Rx.  I bought my meter and test strips OTC for nearly a year at Costco.  

Without that diet diary and data already, I know my doctor wouldn't have taken me seriously, despite my Gestational Diabetes History (my A1c was 5.5%, too and my FBG was 92).  A it was, he still humored me by ordering a 3 hr GTT when I insisted, then later apologized to me when he called with the results (I already knew the results, as I used my meter during the GTT - what I wanted were the simultaneous insulin levels, which the lab screwed up!).

Often there is a mail-in rebate for the meter, making the cost very low or free (check around and review the various meters for the features you want).  The simpler (fewer memory and analysis features), smaller meters are often below $20.   The major downside of any meter is the cost of the strip.  But for your own information, the out-of-pocket costs may well be worth it.  Plus, you've kept your privacy and avoided potentially problematic notes on your medical record, which could well be priceless if you can keep your BG normal and controlled on your own with diet, exercise, and the self-testing meter.

BTW, I'm NOT recommending hiding diabetes from your doctor if that's what you're dealing with.  But for your own curiosity and ability to figure out what is going on with your own health,  especially if you don't have a cooperative physician, learning how to self-test on your own can be very useful.

From what I understand not all states allow direct to consumer lab tests. Is that true?
Anne

As of 3/11/10 I've eliminated sugar, eat only grass fed ruminants cooked in coconut oil, eliminated all grains, grain and seed derived oils, almost daily 30 mins of midday sun, limit my fruit to 1/2 cup wild blueberries 3x/week and have kept my carbs under 50g/day.  39y.o. Male.  BP went from 140/90 to 120/81.  BW 270lb to 227lb.  I saw an internist for a physical at a major teaching hospital in a large U.S. city (he's a  professor at the associated medical school).  He called me with my lipid panel with a tone of concern.  TC 226, HDL 67, LDL 160, Trig 43.  He said I have to go on a "low cholesterol diet"  and follow up with him in 6 months to see.  I asked him to order a VAP.  "No, I don't do that.  Watch your chol intake and will look at other options in six months,"