Another interview with Livin' La Vida Low Carb's Jimmy Moore

I recently provided another interview for Livin' La Vida Low Carb's Jimmy Moore.

You may remember Jimmy as the irrepressible host of the Livin' La Vida Low Carb Show who lost around 200 lbs, dropping from 410 to 230 lbs on a low-carbohydrate diet.

In this hour-long interview, we discussed some of the dietary strategies that we use in the Track Your Plaque program.

Jimmy's website is definitely worth exploring. It's loaded with great interviews, including with Good Calories, Bad Calories author, Gary Taubes.

"Millions of needless deaths"

"Millions of needless deaths" is the title of an editorial by Life Extension Magazine's Bill Faloon.

". . . If vitamin D’s only benefit was to reduce coronary heart attack rates by 142%, the net savings (after deducting the cost of the vitamin D) if every American supplemented properly would be around $84 billion each year. That’s enough to put a major dent in the health care cost crisis that is forecast to bankrupt Medicare and many private insurance plans."

Although I don't agree with all the over-the-top commentary that issues from Mr. Faloon or Life Extension (although I sit on their Medical Advisory Board), I agree with virtually all of the issues he raises with vitamin D.

Despite the enormously compelling observations of vitamin D potential effects in populations, the medical community's reluctance comes from the lack of treatment data. In other words, what we lack are long-term data on vitamin D supplementation vs. placebo on rate of heart attack, vitamin D vs. placebo on risk of colon cancer, etc.

The data that exists connecting vitamin D levels with cardiovascular risk originate from three population observations:

1) The NHANES data in 16,000 participants showed 20% increased risk of cardiovascular events in those with vitamin D levels <20>20 ng/ml after factoring in all standard risk factors.

Another NHANES analysis showed the high prevalence of vitamin D deficiency in those with cardiovascular disease.

2) A German study of 2500 participants that showed showed the lowest quartile of vitamin D levels (<13.3>28.4 ng/ml.

3) The Health Professionals' Follow-Up Study of 18,000 males showed a 2.4-fold increase in cardiovascular events in those with vitamin D levels <15>30 ng/ml.

While we lack treatment data (vitamin D vs. placebo) in a large population, we do have data that Suzie Rockway, Mary Kwasny (both from Rush University, Chicago) and I generated on the effect of vitamin D as a part of a broader treatment program on coronary calcium scores:

Effect of a Combined Therapeutic Approach of Intensive Lipid Management, Omega-3 Fatty Acid Supplementation, and Increased Serum 25 (OH) Vitamin D on Coronary Calcium Scores in Asymptomatic Adults.
Davis W, Rockway S, Kwasny M. Amer J Ther 2008 (Dec 15).

The impact of intensive lipid management, omega-3 fatty acid, and vitamin D3 supplementation on atherosclerotic plaque was assessed through serial computed tomography coronary calcium scoring (CCS). Low-density lipoprotein cholesterol reduction with statin therapy has not been shown to reduce or slow progression of serial CCS in several recent studies, casting doubt on the usefulness of this approach for tracking atherosclerotic progression. In an open-label study, 45 male and female subjects with CCS of >/= 50 without symptoms of heart disease were treated with statin therapy, niacin, and omega-3 fatty acid supplementation to achieve low-density lipoprotein cholesterol and triglycerides /=60 mg/dL; and vitamin D3 supplementation to achieve serum levels of >/=50 ng/mL 25(OH) vitamin D, in addition to diet advice. Lipid profiles of subjects were significantly changed as follows: total cholesterol -24%, low-density lipoprotein -41%; triglycerides -42%, high-density lipoprotein +19%, and mean serum 25(OH) vitamin D levels +83%. After a mean of 18 months, 20 subjects experienced decrease in CCS with mean change of -14.5% (range 0% to -64%); 22 subjects experienced no change or slow annual rate of CCS increase of +12% (range 1%-29%). Only 3 subjects experienced annual CCS progression exceeding 29% (44%-71%). Despite wide variation in response, substantial reduction of CCS was achieved in 44% of subjects and slowed plaque growth in 49% of the subjects applying a broad treatment program.


I also summed up the data as of early 2008 in a Life Extension article:

Vitamin D's Crucial Role in Cardiovascular Protection


I do agree with Mr. Faloon: It's time to take the vitamin D issue very seriously. Personally, I think it is foolhardy to not correct vitamin D deficiency, even in the absence of long-term treatment data.

Should we subject people living in tropical climates with vitamin D blood levels of 90 ng/ml to long-term observation? Though that has not yet been done, it has been done--in effect--through observations on the prevalence of diabetes, heart disease, and various cancers by latitude: the farther away from the equator, the greater the prevalence of these diseases.

That's more than good enough for me.

Thiazide diuretics: Treatment of choice for high blood pressure?

Thiazide diuretics are a popular first-line treatment for hypertension among the primary care set.

This practice became especially well-established with the 2002 publication of the ALLHAT Study (Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs Diuretic:The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)).

ALLHAT showed that an inexpensive diuretic like chlorthalidone (a weak diuretic in the thiazide class, similar to hydrochlorothiazide) as first-line treatment for hypertension achieved equivalent reductions in cardiovascular events (cardiovasular death and heart attack) as non-thiazide antihypertensives, lisinopril (an ACE inhibitor) and amlodipine (a calcium channel blocker, better known as Norvasc).

After 7 years of treatment, there was 14% death or heart attack among all three groups--no difference.

This was interpreted to mean that inexpensive thiazide diuretics like chlorthalidone offer as much benefit as other blood pressure medications at reduced cost.

On the surface, that's great. Anything that detracts from the ubiquitous pharmaceutical industry propaganda of bigger, better, more expensive drugs to replace old, inexpensive, generic drugs is fine by me.

But you knew there'd be more to this issue! If we accept that thiazides are equivalent to other single-drug treatments for high blood pressure, what do we do with the following issues:

--Thiazides deplete body potassium-This effect can be profound. In fact, built into the ALLHAT mortality rate is an expected death rate from potassium depletion. When potassium in the body and blood go low, the heart becomes electrically unstable and dangerous rhythms develop.

--Thiazides deplete magnesium--Similar in implication to the potassium loss, magnesium loss also creates electrical instability in the heart, not to mention exaggeration of insulin resistance, rise in triglycerides, reduction in HDL.

--Thiazides reduce HDL cholesterol

--Thiazides increase triglycerides

--Thiazides increase small LDL particles--You know, the number one cause for heart disease in the U.S.

--Thiazides increase uric acid--Uric acid is increasingly looking like a coronary risk factor: The higher the uric acid blood level, the greater the risk for heart attack. Thiazides have long been known to increase uric acid, occasionally sufficient to trigger attacks of gout (uric acid crystals that precipitate in joints, like rock candy). (Fully detailed Special Report on uric acid coming this week on the Track Your Plaque website.)

What about the advice we commonly give people to hydrate themselves generously? Yet we give them diuretics? Which is it: More hydration or less hydration? You can't have both.

Do thiazides exert an apparent cardiovascular risk reduction in a society due to its flagrant sodium obsession?

Thus, there are a number of inconsistencies in the thinking surrounding thiazides. In my experience, I have seen more harm done than good using these agents. While I cannot fully reconcile the reported benefit seen in ALLHAT with what I see in real life, all too often I see people having to take another drug to make up for a side-effect of a thiazide diuretic (e.g., high-dose prescription potassium to replace lost potassium, allopurinol to reduce uric acid, etc.). I have seen many people get hospitalized, even suffer near-fatal or fatal events from extremely low potassium or magnesium levels.

My personal view: ALLHAT or no, avoid thiazide diuretics like the plague. Sure, it might save money on a population basis, but I suspect that the ALLHAT data are deeply misleading.

What's better than a thiazide, calcium blocker, or ACE inhibitor? How about vitamin D restoration, thyroid normalization, wheat elimination?

"High-dose" Vitamin D

I stumbled on one of the growing number of local media stories on the power of vitamin D.

In one story, a purported "expert" was talking about the benefits of "high-dose" vitamin D, meaning up to 1000, even 2000 units per day.

I regard this as high-dose---for an infant.

Judging by my experiences, now numbering well over 1000 patients over three years time, I'd regard this dose range not as "high dose," nor moderate dose, perhaps not even low dose. I'd regard it as barely adequate.

Though needs vary widely, the majority of men require 6000 units per day, women 5000 units per day. Only then do most men and women achieve what I'd define as desirable: 60-70 ng/ml 25-hydroxy vitamin D blood level.

I base this target level by extrapolating from several simple observations:

--In epidemiologic studies, a blood level of 52 ng/ml seems to be an eerily consistent value: >52 ng/ml and cancer of the colon, breast, and prostate become far less common; <52 ng/ml and cancers are far more likely. I don't know about you, but I'd like to have a little larger margin of safety than just achieving 52.1 ng/ml.

--Young people (not older people >40 years old, who have lost most of the capacity to activate vitamin D in the skin) who obtain several days to weeks of tropical sun typically have 25-hydroxy vitamin D blood levels of 80-100 ng/ml without adverse effect.

More recently, having achieved this target blood level in many people, I can tell you confidently that achieving this blood level of vitamin D achieves:

--Virtual elimination of "winter blues" and seasonal affective disorder in the great majority
--Dramatic increases in HDL cholesterol (though full effect can require a year to develop)
--Reduction in triglycerides
--Modest reduction in blood pressure
--Dramatic reduction in c-reactive protein (far greater than achieved with Crestor, JUPITER trial or no)
--Increased bone density (improved osteoporosis/osteopenia)
--Halting or reversal of aortic valve disease

(I don't see enough cancer in my cardiology practice to gauge whether or not there has been an impact on cancer incidence.)

My colleagues who have bothered to participate in the vitamin D conversation have issued warnings about not going "overboard" with vitamin D, generally meaning a level of >30 ng/ml.

I know of no rational basis for these cautions. If hypercalcemia (increased blood calcium) is the concern, then calcium levels can be monitored. I can reassure them that calcium levels virtually never go up in people (without rare diseases like sarcoid or hyperparathyroidism). Then why any hesitation in recreating blood levels that are enjoyed by tropical inhabitants exposed to plentiful sun that achieve these extraordinary health effects?

For the present, I have applied the target level of 60-70 ng/ml without apparent ill-effect. In fact, I have witnessed nothing but hugely positive effects.

Vitamin D Home Test

The ever-resourceful Dr. John Cannell of the Vitamin D Council has announced the availability of an at-home, self-ordered vitamin D test kit for $65. The Vitamin D Council newsletter is reprinted below.

(However, please note that, as wonderful as the advice Dr. Cannell provides, I don't agree on several small points, such as the lack of need for vitamin D if you use a tanning bed or obtain "sufficient" sun; I have seen many people with dark tans, virtually all over 40 years old, who are still severely deficient. I attribute this to the lost capacity for vitamin D activation as we age.)

I have not used this service. Should anyone choose to try it, please let us know how it goes.



The Vitamin D Newsletter
December 28, 2008

The Vitamin D Council is happy to announce that we have partnered with ZRT Laboratory to provide an inexpensive, $65.00, in-home, accurate, vitamin D [25(OH)D] test. The usual cost for this test is between $100.00 and $200.00.

If you read this newsletter, you know about our interest in accurate vitamin D testing. In the next few weeks, you may read about the Vitamin D Council's quest for accurate vitamin D blood tests in the national media. Before we partnered with ZRT, we verified, repeatedly, that ZRT provides accurate and reliable vitamin D tests and that their method corresponds very well to the gold standard of vitamin D blood tests, the DiaSorin RIA.

Our ZRT service is not just inexpensive, it means no more worrying about your doctor ordering the right test or interpreting it correctly. You buy the test kit on the internet or by phone, a few days later the kit comes in the mail, you or a nurse friend do a finger stick, collect a few drops of blood, and send the blotter paper back to ZRT in the postage paid envelope provided with the kit. A week later you get results back in the mail and know accurate 25-hydroxy-vitamin D levels of you and your family.

For every test you order, ZRT will donate $10.00 to the Vitamin D Council. Please read the new page hyperlinked below on our website as it both explains the procedure and how to order the test.

http://www.vitamindcouncil.org/health/deficiency/am-i-vitamin-d-deficient.shtml

Executive summary: keep your family's 25-hydroxy-vitamin D blood test above 50 ng/ml, year around. Most adults need at least 5,000 IU per day, especially this time of year. Most children need at least 1,000 IU per day per every 25 pounds of body weight. Bio Tech Pharmacal provides high quality and inexpensive vitamin D. Currently Bio Tech Pharmacal is providing vitamin D for numerous scientific studies. To see their prices and for ordering, click the hyperlink below.

http://www.bio-tech-pharm.com/catalog.aspx?cat_id=2

As a gift to our readers for the New Year, Thorne publications have provided a free download to a basic paper about vitamin D. I wrote it earlier this year for educated lay people as well as health care practitioners. Please read this paper carefully, your family's well-being, even lives, may depend on you understanding it.

http://www.thorne.com/altmedrev/.fulltext/13/1/6.pdf

Seasons Greetings
John Cannell, MD
vitamindcouncil.org

Where do Track Your Plaque membership revenues go?

People pay about $90 per year to become Members on the Track Your Plaque website. This provide access to our in-depth Special Reports, guides, webinars, and our proprietary software data tracking tools. Members can also participate in online discussions, such as those in the Track Your Plaque Forum and chats.

Why is there a charge for membership in the program and where does the money go?

Money raised from membership fees goes towards:

1) The costs of doing business, e.g., server fees, software purchases, legal fees. Hosting webinars, for instance, costs us about $99 per month for the GoToWebinar software service.

2) Software development--Our most recent round of software data tracking tools, for instance, cost us nearly $30,000. That may not be a lot from big business standards, but it is onerous enough that obtaining membership dues really helps.

3) Graphics development--A website without graphics would be awfully dull, regardless of the quality of the textual content. Some of the newest tools on the Track Your Plaque website require photography and graphics work, which can add up very quickly.


Where membership fees do NOT go:

1) In our pockets--In fact, except for the various contractors who are paid for their services (e.g., software developers), NOBODY on the Track Your Plaque staff are paid: not me, nor any of the behind-the-scenes staff. Some of the staff overlap with my office staff, but they are paid purely out of the office revenues, not out of Track Your Plaque membership dues.

2) Towards overhead costs beyond those listed above--For example, membership fees do not pay for office lease, utilities, phones, etc.


We rely on membership fees because we have chosen to remain as free of commercial bias as possible. We host no advertising, we have no behind-the-scenes corporate or institutional agendas, we show no favoritism to any business or commercial operation. We believe this permits editorial freedom that few other health websites can enjoy. (In fact, I know of no other that is so free of commercial bias, outside of small blogs or narrow-interest websites.)

If you want to see what damage commercial bias can create, just go to a health website like WebMD. I challenge you to find information that is not flagrantly biased by commercial influence, namely that of the drug industry. (According to the WebMD SEC filings, in fact, the great majority--approximately 80%--of their $331 million revenues (2007) were derived directly or indirectly from the drug industry.) This commercial bias reaches into all of WebMD's related businesses, including MedicineNet.com, RxList.com, Medscape.com, and several others.

Preventing heart disease is not a money maker, sad to say. It is, from the perspective of conventional heart care, a big money loser. Undergo a heart catheterization, hospitalization, stent or bypass for anywhere from $14,000 to well over $100,000---or pay $90 for in-depth health information that dramatically reduces the potential need for the hospital and its procedures, minimizes need for prescription medication (statins alone, of course, are a $27 billion annual revenue phenomenon), and achieves all this by maximizing nutrition, self-purchased nutritional supplements, and inexpensive heart scans. Nobody is going to make a bundle off of this approach.

So that is why we charge a membership fee. I often get a laugh from some of the comments of people on this blog or even in my office who believe that we are rolling in money from the website from membership dues. The opposite is true: We don't pay ourselves. Virtually every penny is reinvested back into the website to better serve the Members.

Getting your dose of fish oil right

Confusion often stems from the simplest of calculations: dose of fish oil.

Actually, you and I don't take fish oil for fish oil. We take fish oil for its content of omega-3 fatty acids, the dominant ones being EPA and DHA. The contents of fish oil outside of its EPA + DHA content likely exert little or no benefit (beyond that of other dietary oils).

To determine what you are currently taking, simply examine the back of your fish oil bottle and look for the EPA + DHA composition. This should be clearly and prominently labeled. If not, don't buy that brand again. Add up the EPA + DHA content per capsule, then multiply by the number of capsules you take per day. That yields your daily EPA + DHA intake.

The only other substantial source of omega-3 fatty acids is fish. Other food sources, such as non-fish meats, eggs, etc., contribute little or none. Processed foods that bear health claims of "contains heart healthy omega-3" often contain linolenic acid or flaxseed oil, which contributes very little to total EPA + DHA, or contain relatively trivial quantities of DHA. What are you doing eating processed foods, anyway?

What should the total daily dose of EPA + DHA dose be? That depends on what your goals are.

If your goal is to modestly reduce the risk of dying from heart attack, then just eating fish a couple of times per month will begin to exert an effect, or just taking a dose of 300 mg EPA + DHA per day from a low-potency capsule will do it. However, that's an awfully unambitious goal.

Our starting omega-3 dose in the Track Your Plaque program has, over the years, increased and now stands at 1800 mg EPA + DHA per day. However, the dose for 1) full reduction of triglycerides and/or triglyceride-containing abnormal lipoproteins, 2) reduction of Lp(a), and 3) the ideal dose for coronary and carotid plaque control are substantially higher.

But once you know your desired daily target of total EPA + DHA, you can easily determine the quantity of capsules to take by doing the above arithemetic, totaling the EPA + DHA per capsule. For example, if you have been instructed to take 6000 mg per day EPA + DHA, and your capsule contains 750 mg EPA + DHA, then you will need to take 8 capsules per day (6000/750).

Flat tummy . . . or, Why your dietitian is fat

When I go to the hospital, I am continually amazed at some of the hospital staff: 5 ft 4 inch nurses weighing over 200 lbs, etc.

But what I find particularly bothersome are some (not all) hospital dietitans--presumably experts at the day-to-day of healthy eating--who waddle through the halls, easily 40, 50, or more pounds overweight. It is, to say the least, credibility-challenging for an obese dietitian to be providing nutritional advice to men or women recovering after bypass or stent while clearly not in command of nutritional health herself.

What's behind this perverse situation? How can a person charged to dispense "healthy" nutritional information clearly display such clear-cut evidence of poor nutrition?

How would you view a success coach dressed in rags? Or a reading coach who can barely read a sentence?

Easy: She follows her own advice.

Hospital dietitians are essentially forced to adhere to nutritional guidelines of "official" organizations, such as the American Heart Association and the USDA. There is some reason behind this. Imagine a rogue dietitian decides to advocate some crazy diet that yields dangerous effects, e.g., high-potassium diets in people with kidney disease. There is a role for oversite on the information any hospital staff member dispenses.

The problem, of course, doesn't lie with the dietitian, but with the organizations drafting the guidelines. For years, the mantra of hospital diets was "low-fat." More recently, this dated message has begun--only begun--to falter, but now replaced with the "healthy, whole grain" mantra. And that is the advice the hapless dietitian follows herself, unwittingly indulging in foods that make us fat.

Sadly, the "healthy, whole grain" message also contributes to heart disease via drop in HDL, increased triglycerides, a huge surge in small LDL, rise in blood sugar, increased resistance to insulin, tummy fat, and diabetes. Yes, the diet provided to survivors of heart attack increases risk.

The "healthy, whole grain" message also enjoys apparent "validation" through the enormous proliferation of commercial products cleverly disguised as healthy: Cheerios, Raisin Bran, whole grain bread, whole wheat pasta, etc. The "healthy, whole grain" message, while a health disaster, is undoubtedly a commercial success.

I'll bet that our fat dietitian friend enjoys a breakfast of healthy, whole grains in skim milk, followed by a lunch of low-fat chicken breast on two slices of whole grain bread, and ends her day with a healthy meal of whole wheat pasta. She then ascribes her continually climbing weight and size 16 figure to slow metabolism, lack of exercise, or the once-a-week piece of chocolate.

Wheat has no role in the Track Your Plaque program for coronary plaque control and reversal. In fact, my personal view is that wheat has no role in the human diet whatsoever.

More on this concept can be found at:

What's worse than sugar?

The Wheat-Deficiency Syndrome


Nutritional approaches: Large vs. Small LDL

Are you wheat-free?

Statin drug revolt

I sense a growing revolt against the intrusion of statin drugs into our lives.

No doubt, the statin drug industry is, at least from an economic perspective, a huge success: $27 billion annual revenues at last accounting. The latest big plug for more and more statins was the JUPITER trial that showed reduced cardiovascular events on Crestor in people with "normal" LDL cholesterol levels and increased c-reactive protein.

It seems that not one day passes that doesn't include some news story about the "benefits" of statin drugs: reduction in heart attack, stroke, colon cancer, osteoporosis, heart failure, etc.

Ironically, the overwhelming economic success of the statin drug industry also seems to be encouraging a grassroots revolt.





More and more people are coming to the office, more people commenting on the web over how they want to avoid statin drugs, stop a drug they are already taking, or at least reduce the dose of an ongoing drug.

My day-to-day experience with coronary plaque control and reversal is that, while statin drugs are helpful tools, they are not necessary tools for full benefit of a prevention program. "Need" for statin drugs can differ by the patterns measured, though not the usual patterns suggested by the drug industry. For instance, using C-reactive protein, a la JUPITER, as justification for statin prescription is, in my view, totally absurd and makes no sense whatsoever, since inflammatory responses can be effective reduced with plenty of other strategies besides statin drugs. Conventional LDL, likewise, is a fictitious number that often bear little or no resemblance to the true and genuine measured value (apoprotein B or LDL particle number).

So here are a number of strategies that can help reduce or eliminate the "need" for a statin drug:

--Elimination of wheat and cornstarch--This is no namby-pamby dietary strategy, as low-fat diets were. This is a powerful, enormously effective strategy, particularly if LDL is in the small category. Small LDL drops like a stone when these foods are eliminated. This means no breads, pasta, breakfast cereals, pretzels, crackers, chips, tacos, wraps, etc.
--Non-wheat fibers--Especially raw nuts, ground flaxseed, and oat bran.
--Vitamin D restoration
--Fish oil
--Weight loss
--Niacin

There are additional strategies that focus on specific subsets of LDL cholesterol (e.g., Lp(a) masquerading as LDL). But the above list can reduce LDL cholesterol substantially, reducing the apparent "need" for a statin drug.

You will notice that there are few money makers in the above list, compared to the billions of dollars reaped by the statin drug industry. There is therefore little incentive to allow a pretty sales rep to go to your doctor and pitch the use of over-the-counter vitamin D or make changes in diet.

Statin drugs in my view need to be shoved back into their more limited role as drugs to be used on occasion when necessary (e.g., heterozygous familial hypercholesterolemia with LDL cholesterol values of 250 mg/dl in a person with measurable coronary plaque). These should never have achieved the "celebrity" status they enjoy, complete with gushing endorsements by TV personalities, daily news stories, and back-to-back TV commercials.

Join the revolt!

Lovaza Rip-off

Lovaza is GlaxoSmithKline's prescription fish oil, an ethyl ester modification to allow higher concentration of omega-3 fatty acids, EPA + DHA, per capsule. Each capsule contains 840 mg EPA + DHA.

It is FDA-approved for treatment of high triglycerides (>500 mg/dl). In their marketing, they claim "Unlike LOVAZA, dietary supplements are not FDA approved to treat any disease." They also highlight the "patented five-step" purification process that eliminates any concerns over mercury or pesticide residues.

What does Lovaza cost? In Milwaukee, it costs about $70 per capsule per month (PCPM). Most people are taking four capsules per day: $280 per month, or $3360 per year to obtain 3360 mg of EPA + DHA per day. (Funny coincidence with the numbers.)

Did you catch that? $3360 per year, just for one person to take Lovaza.

What if I instead went to Costco and bought their high-potency fish oil. This is also an ethyl ester form. It costs $14.99 for 180 capsules, or $2.50 PCPM; each capsule contains 684 mg EPA + DHA. I would therefore have to take five capsules per day to obtain the same 3360 mg EPA + DHA per day. This would cost me 5 x $2.50 = $12.50 per month, or $150 per year.

$3360 per year vs. $150 per year to obtain the same dose of omega-3 fatty acids, or a 22.4-fold difference.

Lovaza is FDA-approved for treatment of high triglycerides. But I am seeing more and more people take it for other reasons at this four-capsule-per-day dose. Regardless, this "drug" is adding $3360 per year costs to our healthcare. A school teacher, for instance, recently commented to me that she didn't care about the costs, since her insurance (in Milwaukee county, teachers have unbelievably generous healthcare coverage) covers Lovaza. I've heard this from others: insurance covers it, so they don't care how much it costs.

Guess who eventually has to pay the $3360 per year per person costs? Yup, you and me. We all bitch and moan about the costs of healthcare and health insurance, but many of us are more than willing to shift the costs to our friends and neighbors to save a few bucks. You think Lipitor makes a bundle of money for Pfizer at about $120 per month? Lovaza is making a bundle of money for GlaxoSmithKline, and all because people are cheap and willing to selfishly shift costs to other people.

Keep in mind that $3360 per year is just for fish oil. It's not for surgery, it's not for hospital care, it's just for stinking fish oil.
Is an increase in heart scan score GOOD?

Is an increase in heart scan score GOOD?

In response to an earlier Heart Scan Blog post, I don't care about hard plaque!, reader Dave responded:

Hello Dr Davis,

Interesting post about hard and soft plaque. I recently had a discussion with my GP regarding my serious increase in scan score (Jan 2006 = 235, Nov 2007 = 419).

After the first scan we started aggressively going after my LDL, HDL and Trig...196,59,221

And have them down to 103, 65, 92 - we still have a way to go to 60/60/60 [The Track Your Plaque target values]-

So the increase is a surprise, but my doctor said that the increase could in part be cause some of the soft plaque had been converted to hard plaque and the scan would show that conversion.



Dave's doctor then responded to him with this comment:

"Remember that although your coronary calcium score has gone up, this does not mean that you are at greater risk than you were a year ago. Remember that the most dangerous plaque is the not-yet calcified soft plaque, which will not show up on an EBT [i.e., calcium score]. It is only the safe, calcified plaque that can be measured with the EBT. [Emphasis mine.] For your score to go up like it did, while your lipids came down so much, what had to happen was that lots of dangerous unstable plaque was converted to stable, calcified plaque. There are no accepted guidelines for interpreting changes in calcium scores over time, because the scores tend to go up as treatment converts dangerous plaque to safer plaque. We do know that aggressively lowering LDL reduces both unstable and stable plaque, and we know that risk can be further lowered by adjuvant therapy such as I listed above."


Huh?

This bit of conventional "wisdom" is something I've heard repeated many times. Is it true?

It is absolutely NOT true. In fact, the opposite is true: Dave's substantial increase in heart scan score from 235 to 419 over 22 months, representing a 78% increase, or an annualized rate of increase of 37%. This suggests a large increase in his risk for heart attack, not a decrease. Big difference!

Dr. Paulo Raggi's 2004 study, Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy in 495 participants addresses this question especially well. Two heart scans were performed three years apart, with a statin drug initiated after the first scan, regardless of score.

During the period of study, heart attacks occurred in 41 participants. When these participants were analyzed, it was found that the average annual increase in score over the three year period was 42%. The average annual rate of increase in those free of heart attack was 17%. The group with the 42% annual rate of increase--all on statin drugs--the risk of heart attack was 17.2-fold greater, or 1720%.

The report made several other important observations:

--20% of the heart attack-free participants showed reduction of heart scan scores, i.e., reversal. None of the participants experiencing heart attack had a score reduction.
--Only 2 of the 41 heart attacks occurred in participants with <15% per year annual growth, while the rest (39) showed larger increases.
--The intensity of LDL reduction made no difference in whether heart attacks occurred or not. Those with LDL<100 mg/dl fared no better than those with LDL>100 mg/dl.

Dr. Raggi et al concluded:

"The risk of hard events [heart attack] was significantly higher in the presence of CVS [calcium volume score] progression despite low LDL serum levels, although the interaction of CVS change and LDL level on treatment was highly significant. The latter observation strongly suggests that a combination of serum markers and vascular markers [emphasis mine] may constitute a better way to gauge therapeutic effectiveness than isolated measurement of lipid levels."

This study demonstrates an important principle: Rising heart scan scores signal potential danger, regardless of LDL cholesterol treatment. Yes, LDL reduction does achieve a modest reduction in heart attack, but it does not eliminate them--not even close.

These are among the reasons that, in the Track Your Plaque program, we aim to correct more than LDL cholesterol. We aim to correct ALL causes of coronary plaque, factors that can be responsible for continuing increase in heart scan score despite favorable LDL cholesterol values.

So, Dave, please forgive your doctor his misunderstanding of the increase in your heart scan score. He is not alone in his ignorance of the data and parroting of the mainstream mis-information popular among the statin-is-the-answer-to-everything set.

Just don't let your doctor's ignorance permit the heart attack that is clearly in the stars. Take preventive action now.

Comments (30) -

  • Anonymous

    11/20/2007 5:41:00 PM |

    Dr Davis,

    What should Dave do?  He appears to have improved his LDL:HDL ratio as well as his total C to HDL ratio substantially, but his CAC score jumped significantly.  Maybe look at other risk factors?

    The info here gives no indication of median blood pressure for Dave.  LP(a)?  No indication of particle sizes. But, which of these or others would be most likely to be Dave's downfall in attempting to mitigate a future hard endpoint?

    I don't ask this lightly, I myself am trying to follow the TYP program and keep my high-for-my-age 29 CAC score from growning.  But, I'm frankly not looking forward to my rescan in about a year.  I'm a bit worried about the, "What if my scan shows a dramatic increase?  What then?"

    Thank you for the valuable information you provide.

    :LaughingCT

  • Dr. Davis

    11/20/2007 11:17:00 PM |

    I would urge Dave to follow all the principles of the Track Your Plaque program, including:

    1) Fish oil to provide minimum 1200 mg EPA + DHA per day

    2) Correction of all concealed lipoprotein patterns such as IDL and Lp(a)

    3) Vitamin D raised to 50 ng/ml--crucial!

    4) Normalization of blood pressure, including during exericse.

    5) Normal blood sugar (<100 mg/dl).

    Further efforts might be required, depending on the long-term effects on rate of plaque growth.

  • Ross

    11/21/2007 3:41:00 AM |

    My question is: how repeatable do you think the scores are on the CT scan?  Are they bulletproof (+/- 5% no matter where measured), consistent by analyst (+/- 5% with the same doctor analyzing the scan), or...?  

    I am currently visiting my brother in law, who is an FP doctor with a private practice.  One of his professional friends, a cardiologist who seems a cut above (thinks stenting is a cop-out), recently told him that he only trusted two centers in the mid-Ohio region to score a 16-slice CT scan accurately, and that even then, the variability was still too high for his taste.  Two numbers within 20% were within his expected error bars and weren't different enough to indicate any change to him.  Two different scan centers?  He wouldn't even compare the two scan scores.

    In my own job (software), I've had to manage human-measured numbers over and over again.  One observation keeps coming up: a single value doesn't mean much without an understanding of the accuracy of that value.  I really am curious about how you estimate confidence intervals on CT scan scores.

  • Dr. Davis

    11/21/2007 3:55:00 AM |

    Hi, Ross--

    Excellent questions.

    Several thoughts:

    1) 16-slice scanners are, unfortunately, prone to wider error in heart scan scoring, perhaps as much as 20%. The variation in scoring on an EBT or 64-slice device is far less.

    2) Variation from scan to scan, when expressed as percent, depends to a great degree on the score itself. Lumping all scores together, variation should be no more than 8-9%. However,a low score of, say 2, then repeated at 4 means 100% variation. However, the same absolute difference of 2 but with a score of 1002 and repeated at 1004 is <1% variation. Therefore, higher scores assume much less percent variation, usually <5%.

    3) Variation among different reading physicians tends to be a minor issue, since much of the scoring is done by standard criteria determined by software, not the human eye. The only real source of human variation comes from disputable areas, such as the mitral valve (which can sometimes encroach into the coronary area and appear like plaque) and the mouth of arteries, which can be debated as being in the aorta or in the coronary arteries themselves. However, these disputable areas are issues in <5% of scans.

  • Tom

    11/21/2007 4:30:00 AM |

    It's interesting that a 29 year old is able to track his plaque. I'm in my 60's now and recently found your site AFTER bypass surgery and a calcium score >700 via a 64 slice scan.
    In reading past comments, those of us having had the heart procedure are now unable to follow our progress via the cac score. Until this post I had hoped to use your recommended blood tests for indication of progress, but if LDL reduction achieves a modest risk reduction, we are left without a specific guide.
    Question: Was the progress in blood tests in dave's case a result of statins ?

  • Dr. Davis

    11/21/2007 12:46:00 PM |

    That's why lipoproteins are so important--they provide other indicators. In my experience, people who have LDL cholesterol as the sole cause of heart disease are a very small minority. The vast majority of people have multiple causes beyond LDL.

    Also, about 50% of people can still get a heart scan score after bypass surgery if you find a center willing to do a detailed analysis. You will need to ask.

    Also, I don't know what Dave did, since he is a reader and everything he posted is above. Are you there, Dave?

  • Dr. Davis

    11/21/2007 5:41:00 PM |

    Hi, Paul--

    I think your doctor might be confusing heart scans with CT coronary angiograms. She is right in saying that CT angiograms (using X-ray dye) require a lot of radiation; 100 chest x-rays worth with present technology.

    However, a plain heart scan to generate a heart scan score requires 4 chest x-rays worth on an EBT device, 8-10 on an 64-slice multi-detector device.

    See the Track Your Plaque Special Report, Radiation and Heart Scans: The Real Story at http://trackyourplaque.com/library/fl_06-021radiation.asp.

  • Anonymous

    11/21/2007 6:01:00 PM |

    Regarding repeatability, there is a 2005 study by Serukov, Bland, and Kondos that shows that the repeatability is a function of the square root of the calcium score, and that volume score is more repeatable than Agatston score. The reference is

    “Serial Electron Beam CT Measurements of Coronary Artery Calcium: Has Your Patient's Calcium Score Actually Changed?” Alexander B. Sevrukov, J. Martin Bland and George T. Kondos, American Journal of Roentgenology 2005; 185:1546-1553
    http://www.ajronline.org/cgi/content/full/185/6/1546

    In this report, the standard deviation of the difference between two sequential calcium scored is

    SDAG130 = 2.515 *sqrt(avg score)
    SDVol130 = 1.758 *sqrt(avg score)

    This results in the following values, where SDA is the standard deviation for the Agatston score and SDV is the standard deviation for the volume score.

    Score-SDA--%SDA--SDV--%SDV
    5-----5.62---112%---3.93--79%
    10----7.95---79%----5.55--56%
    20----11.2---56%----7.86--39%
    50----17.7---35%----12.4--25%
    100---25.1---25%----17.5--18%
    200---35.5---17%----24.8--12%
    300---43.5---14%----30.4--10%
    400---50.3---12%----35.1---9%
    500---56.2---11%----39.3---8%
    600---61.6---10%----43.0---7%
    700---66.5----9%----46.5---7%
    1000--79.5----7%----55.5---6%

    These values show why many people use 15% as a breakpoint - only if the score has changed by more than 15% can it be said that the change is real. And this is only true for scores above 200 or so.

    Harry

  • Anonymous

    11/21/2007 7:17:00 PM |

    My cardiologist told me that EBT scanning is not recommended for anyone under the age of 30. Is this true? If so, how do I (29 years) reliably know that I am at risk?

    I discovered your blog recently. Since I have a very bad family history of diabetes, high blood pressure, and cholesterol, I decided to visit a cardiologist last month so that I can request for an EBT scan. He said that I'm too young for that, and has instead asked me to take a Carotid IMT and Stress test - are these tests reliable enough to provide insight on my risk? Could these tests return "false positive" values?

    I had found during a blood test I did this July only to find that my triglycerides were at 600!! The other cholesterol values were bad too - totalC-HDL-LDL-Tri (255-31-Not measurable-600)

    Since then I have found your blog, lost around 25 lbs and did a VAP recently (I asked for NMR and all I got from doctors - what? What the heck is that?) So I settled for a VAP, since they knew about it.

    I did a VAP along with a comprehensive blood test and the measures that came up high were.

    LIPID related:
    Total LDL-C Direct:130 (Normal<130)
    Real LDL-C:110 (N<100)
    Sum Total LDL-C: 130 (<130)
    Remnant LIPO (IDL+VLDL3): 30 (<30)
    HDL-2:9 (>10)
    VLDL3: 14 (<10)

    Non-LIPID related high values:
    Uric Acid: 8.3  (4.0-8.0)
    Fasting Glucose: 104 (65-99)
    Creatine Kinase Total: 631 (<=200)


    LP PLA2 is normal: 164 (115-245)
    HBA1C suggests prediabetic: 5.7 (Normal <6%)


    Due to my very high value of CK Total, I researched online and found that this can increase due to high exercise, and I had it repeated after taking rest, and it returned normal results. My doctor was really surprised about this and initially hesitant to fractionise my CK. I feel empowered that I am able to take charge of my health and preventative care with the
    information that is available online (of course, one needs to tread that carefully and make an informed decision due to various conflicting opinions out there).

    Sorry for the long post, Doc. I have a newfound awareness of my health thanks to your blog, and am very much interested in knowing your inputs. I just hope that more physicians in our country follow your noble path and understand the true value and empowerment of preventive care.

    - Philip

  • Dr. Davis

    11/21/2007 8:09:00 PM |

    Hi, Philip--

    In general, 29 is very young, perhaps too young, unless there is an outstanding family history (e.g., father with heart attack at age 37). Although your lipid/lipoproteins are concerning, it would be highly unusual to have anything but a zero heart scan score at your age.

  • Dr. Davis

    11/21/2007 8:14:00 PM |

    Hi, Harry--
    Thanks for the help!

  • Neelesh

    11/22/2007 4:51:00 AM |

    Hi Dr. Davis,
      I've just bought the Track Your Plaque book, waiting for its arrival. I've had a heart attack a year back.I'm 30 years old with no family history, non-alcoholic, non-smoker and vegetarian.
    The event was attributed to ectatic arteries(Type-III) and a very high level of LP(a)- between 120-130. The standard lipid profile was also marginally higher. If I had not insisted for an LP(a) test after reading Dr Agatston's South Beach Heart Program, I would have never found the LP(a) factor.
       I was stented during the hospitalization and now I'm wondering how effective the heart scan will be, given that the accuracy reduces  with stented arteries (http://circ.ahajournals.org/cgi/content/meeting_abstract/114/18_MeetingAbstracts/II_692-a)

    Thanks!
    -Neelesh

  • Dr. Davis

    11/22/2007 2:35:00 PM |

    Hi, Neeleesh--

    I do advocate heart scanning in people with stents, but I generally suggest that only the unstented arteries be scored. It's imperfect, excluding the most diseased artery, but it's proven a useful compromise, leaving you with two "scorable" arteries.

    The study you cite, however, is not about heart scans, it's about CT coronary angiography, a study that yields "percent blockage" sort of information, not an index of plaque.

    Beyond Lp(a), you should strongly consider vitamin D normalization.  By your first name, I take it you are from India/Pakistan or similar background, an ethnic origin that is associated with severe vitamin D deficiency.

  • Neelesh

    11/22/2007 3:00:00 PM |

    Thanks Dr. Davis. And yes, I'm from India.

  • wccaguy

    11/22/2007 3:13:00 PM |

    Dr. Davis,

    I found your answer to Neeleesh to be interesting in the extreme.  I have a  follow up question to it.

    I don't have specific references for the two facts I have heard but couldn't reconcile:

    1   India has high coronary artery disease incidence.

    2   Your answer to Neeleesh states that vitamin d levels are low in India and Pakistan.  And that would help much to explain the high rate of coronary artery disease in these countries.

    3   And yet India is close to the equator and so vitamin d levels should be relatively high because of sun exposure right?

    The question then is this:  What is the cause of the low vitamin d level in those countries?

    Thanks!

  • Dr. Davis

    11/22/2007 4:00:00 PM |

    It is interesting, isn't it?

    I believe part of the explanation is that, the darker your skin complexion, the more you are "protected" from intense and prolonged sun exposure. But, activation of 7-hydrocholesterol to 25-OH-vitamin D3 may require many hours more exposure. Thus, a fair skinned person might activate D within minutes, while a dark skinned individual might require hours.

    Another factor that has not been thoroughly explored but has potential for yielding enormous insights: Vit D receptor genotypes. That is, vitamin D deficiency may express itself in different ways in different populations. Some might get colon cancer, others multiple sclerosis, others coronary disease.

    I believe that the dark-skinned phenomenon becomes especially an issue when migrating to sun-deprived climates such as the northern U.S.

  • wccaguy

    11/22/2007 6:12:00 PM |

    Hi Doc,

    Your explanation makes sense.

    I did a quick google search and found experts on the problem in India attributing it to the increasing extent to which Indians were staying indoors and not "being active."

    But the vitamin D issue throws the whole question of "activity" into question doesn't it?  It might not be the activity per se but instead the amount of sunlight reduction.

    And if, per your explanation, darker skinned people need more time in the sun than lighter skinned people for Vitamin D3 to be "activated" then than a decrease in sunlight would have more effect on darker skinned people than lighter skinned people.

    Very interesting...  And perhaps INCREDIBLY good news!!!

    Because it means that there might be a cheap effective treatment for the coronary disease epidemic in India.

    Does all that make sense?

  • wccaguy

    11/22/2007 6:19:00 PM |

    Just to follow up one more point on this D3 question...

    I guess what we need to do is find a study which shows a correlation between degree of skin pigmentation and Vitamin D3 activation?

    (I'm not sure if the word "degree" is the right word, but perhaps the question is understood anyway?)

    Answering that question would certainly set up the basis for a scientific study right?

  • Dr. Davis

    11/23/2007 12:56:00 AM |

    Yes, it does. It could serve as the basis for a tremendously interesting study.

  • Dr. Davis

    11/23/2007 1:09:00 AM |

    There are indeed a few studies that document this effect, e.g., Factors that influence the cutaneous synthesis and dietary sources of vitamin D (abstract viewable at Arch Biochem Biophys. 2007 Apr 15;460(2):213-7.)

    However, I am not aware of any study that examines the effect of vitamin D supplementation specifically in this population that tracks coronary atherosclerosis. One British study  in Bangladeshi adults did demonstrate dramatic reduction in inflammatory markers with vit D replacement (Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? at http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=12454321&ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum  ).

  • Dave K

    11/24/2007 12:21:00 AM |

    Hi Dr Davis,

    Sorry - I have been offline for a couple of days.  Interesting discussion.  I will try and add some detail lipid info.

    July 2007 Blood work showed

    My Lp(a) is 7
    IDL = 10
    VLDL=11
    HDL-2 = 15
    HDL-3 = 50
    VLDL C = 18
    VLDL1+2 = 7

    Currently taking fishoil 1700 mg of DHA+EHA
    Vitamin D 800mg - just incresed to 2000
    Baby Aspirin
    Multivitamin
    Crestor
    Just started Zetia after getting this last scan result
    Eat basic South Beach phase 3
    BMI - 27
    Glucose is 105
    Exercise 4X week...
    Lp-PLA2=120

    Blood pressure high-normal but I don't know about during exercise.  Cardilogist scheduled me for a stress test after this volume increase.

    I have not has a blood test for Vit D.

    Also - I had an angiograham after the first scan because I was having chests pains .... it turned up that I had no blockages whatsoever.  So we judged the chest pains as non cardiac.

    So I am following your list pretty close.  I guess I just have to wait to see how these changes do.  How long would you wait for another scan?

    Not sure what else to add - your website says to consider L-arginie...


    I do have a specific question.  In the scan report it shows where the calcium was found.  Don't know the software, but there was one spot where it showed in the early report that it didn't show in this report (of course there was several new areas) - could that have actually been a reversal at that spot?

  • Dr. Davis

    11/24/2007 1:25:00 AM |

    Small LDL and a deficiency of large HDL, along with modest excess weight, high blood sugar, high blood pressure all suggest you are (or were) likely over-dependent on processed carbohydrates like wheat products. Your pattern would likely respond vigorously to reduction or elimination of these foods and weight loss. Niacin can help this pattern. In our experience, normalization of vitamin D is crucial.

  • Dave K

    11/26/2007 5:51:00 AM |

    Dr Davis,

    Few more data ....

    Some of the treatments have only been for the last 6 months or so.  The Statin was first (of course) and it took almost a year to get something I could tolerate.  The we talked about Vit D (700) and fish oil (800 Omega 3).  After a full Lipid scan around 9 months ago - we decided to add more fish oil.  So the full dosage I listed is only 6 months old or so.

    Also - I love my red wine and I know the number says two glasses and i rarely do two - so its three or four ... which might be my next step....

    From your last response, I assume the VLDL and IDL levels are the ones you would target hardest at this point.

    Don't do a lot of sugar or wheat... Do eat Oatmeal everyday with rasins or blueberries.

    Oh and my other question was with this kind of increase how long would you wait for the next scan?

  • Dr. Davis

    11/26/2007 12:08:00 PM |

    Dave-

    I generally recommend waiting a year after all identifiable causes have been corrected. However, given your minimal doses of vit D, I usually have my patients wait at least six month after vitamin D blood levels are corrected.

  • Dave

    11/26/2007 8:01:00 PM |

    Dr Davis,

    Thank you ... keep up the great work and I'll keep reading... and tracking.

    Dave

  • G

    11/27/2007 12:39:00 AM |

    Neeleesh and DR. D,

    This Canadian physician appears to have a lot of indepth awareness of the diff phenotypes. He suggests (in the author's response) that D2 may not work as well in East Indians (may worsen glycemic control) versus D3 (the more biologically active vitamin D). Very fascinating!!

    http://www.cfp.ca/cgi/reprint/53/9/1435
    Repletion of vitamin D with vitamin D2 is common
    practice, and vitamin D2 can be used safely when monitored
    to achieve normal levels of 25(OH)D. This might
    take 2 to 3 months, as discussed in your letter and in my
    paper, because the half-life is about 2 weeks. Using vitamin
    D3 (1000 to 5000 IU) daily, depending on the level
    of deficiency, will also achieve this goal. I also agree
    that the goal is to achieve levels of 25(OH)D higher than
    100 nmol/L, preferably 100 to 125 nmol/L.
    My concern regarding vitamin D2 is that it is a synthetic
    analogue and might interact with the vitamin D
    receptor differently in various cell systems. It has been
    reported that vitamin D3 might improve glycemic control.
    7 Vitamin D2 has been reported to cause worsening
    of glycemic control in people of East Indian descent.8
    Is this because of vitamin D receptor polymorphism, or
    because of enhanced 24-hydroxylase enzyme activation,
    or is it due to how vitamin D2 interacts with the receptor?
    Until this has been sorted out, I feel safest using
    vitamin D3. There are about 2000 synthetic analogues
    of vitamin D. The search is on for one that can cross the
    blood-brain barrier to treat certain types of brain cancers
    without causing hypercalcemia.9 But then again,
    what other effects would this compound have? There
    are still so many unknowns.
    The first step is to recognize that most Canadians
    do not get enough vitamin D, especially in the winter
    months, because of where we live. This recognition
    might reduce the need for expensive drugs to treat
    various conditions and might improve the well-being of
    many Canadians.
    An ounce of prevention is worth a pound of cure.
    —Gerry Schwalfenberg MD CCFP
    Edmonton, Alta
    by e-mail

    here's the orig article which is one of the most excellent summaries I've seen so far -- great minds think alike -- they advise > 50ng/ml like DR. Davis as well!
    http://www.cfp.ca/cgi/reprint/53/5/841

  • Neelesh

    11/27/2007 4:05:00 AM |

    D,
    Interesting study indeed. Thanks for the information. I guess I have a lot of things to discuss with my cardiologist next week. Smile
    -Neelesh

  • chickadeenorth

    12/2/2007 11:16:00 PM |

    Hi to Gerry Schwalfenberg MD CCFP, do you know any Dr In Edtmn who practices Track your Plague, if so could you suggest names to help me. I live out by Jasper and need a skilled Dr in this treatment program, I would travel to Edtmn.Many thanks.
    chickadeenorth
    (hope its ok for me to ask this here)

  • cadoce66

    4/5/2008 8:37:00 PM |

    hi my aunts 63 yrs and she underwent an angioplasty with a medicated stent .. Shes on PLAVIX and her artery was 90% blocked and she had an evolving AWMI...
    Please advise what she should taketo prevent another blockage or heart attack!
    Thanks!

  • buy jeans

    11/3/2010 10:34:10 PM |

    So, Dave, please forgive your doctor his misunderstanding of the increase in your heart scan score. He is not alone in his ignorance of the data and parroting of the mainstream mis-information popular among the statin-is-the-answer-to-everything set.

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