Heart Scan Blog Redux: Cheers to flavonoids

Because in Track Your Plaque we've been thinking a lot about anthocyanins, here's a rerun of a previous Heart Scan Blog post about red wine. (Anthocyanins are among the interesting flavonoids in red wine, along with resveratrol and quercetin.)


The case in favor of healthful flavonoids seems to grow bit by bit.

Flavonoids such as procyanadins in wine and chocolate, catechins in tea, and those in walnuts, pomegranates, and pycnogenol (pine bark extract) are suspected to block oxidation of LDL (preventing its entry into plaque), normalize abnormal endothelial constriction, and yield platelet-blocking effects (preventing blood clots).

Dr. Roger Corder is a prolific author of many scientific papers detailing his research into the flavonoids of foods, but wine in particular. He summarizes his findings in a recent book, The Red Wine Diet. Contrary to the obvious vying-for-prime-time title, Dr. Corder's compilation is probably the best mainstream discussion of flavonoids in foods and wines that I've come across. Although it would have been more entertaining if peppered with more wit and humans interest, given the topic, its straightfoward, semi-academic telling of the story makes his points effectively.

Among the important observations Corder makes is that regions of the world with the greatest longevity also correspond to regions with the highest procyanidin flavonoids in their wines.




Regarding the variable flavonoid content of wines, he states:

Although differences in the amount of procyanidins in red wine clearly occur because of the grape variety and the vineyard environment, the winemaker holds the key to what ends up in the bottle. The most important aspect of the winemaking process for ensuring high procyanidins in red wines is the contact time between the liquid and the grape seeds during fermentation when the alcohol concentration reaches about 6 percent. Depending on the fermentation temperature, it may be two to three days or more before this extraction process starts. Grape skins float and seeds sink, so the number of times they are pushed down and stirred into the fermenting wine also increases extraction of procyanidins. Even so, extraction is a slow process and, after fermentation is complete, many red wines are left to macerate with their seeds and skins for days or even weeks in order to extract all the color, flavor, and tannins. Wines that have a contact time of less than seven days will have a relatively low level of procyanidins. Wines with a contact time of ten to fourteen days have decent levels, and those with contact times of three weeks or more have the highest.

He points out that deeply-colored reds are more likely to be richer in procyanidins; mass-produced wines that are usually "house-grade" served at bars and restaurants tend to be low. Some are close to zero.

Wines rich in procyanidins provide several-fold more, such that a single glass can provide the same purported health benefit as several glasses of a procyanidin-poor wine.

So how do various wines stack up in procyanidin content? Here's an abbreviated list from his book:

Australian--tend to be low, except for Australian Cabernet Sauvignon which is moderate.

Chile--only Cabernet Sauvignon stands out, then only moderate in content.

France--Where to start? The French, of course, are the perennial masters of wine, and prolonged contact with skins and seeds is usually taken for granted in many varieties of wine. Each wine region (French wines are generally designated by region, not by variety of grape) can also vary widely in flavonoid content. Nonetheless, Bordeaux rate moderately; Burgundy low to moderate (except the village of Pommard); Languedoc-Roussillon moderate to high (and many great bargains in my experience, since these producers live in the shadow of its northern Bordeaux neighbors); Rhone (Cote du Rhone) moderate to high, though beware of their powerful "barnyard" character upon opening; decanting is wise.

Italy--Much red Italian wine is made from the Sangiovese grape and called variously Chianti, Valpolicella, and "super-Tuscan" when blended with other varietals. Corder rates the southern Italian wines from Sicily, Sardinia, and the mainland as high in procyanidins; most northern varieties are moderate.

Spain--Moderate in general.

United States--Though his comments are disappointingly scanty on the U.S., he points out that Cabernet Sauvignon is the standout for procyanidin content. He mentions only the Napa/Sonoma regions, unfortunately. (I'd like to know how the San Diego-Temecula and Virginian wines fare, for instance.)

The winner in procyanidin content is a variety grown in the Gers region of southwest France, a region with superior longevity of its residents. The wines here are made with the tannat grape within the Madiran appellation; wines labeled "Madiran" must contain 40% or more tannat to be so labeled (such is a quirk of French wine regulation). Among the producers Dr. Corder lists are Chateau de Sabazan, Chateau Saint-Go, Chateau du Bascou, Domaine Labranche Laffont, and Chateau d'Aydie. (A more complete list can be found in his book.)

How does this all figure into the Track Your Plaque program? Can you succeed without red wine? Of course you can. I doubt you could do it, however, without some attention to flavonoid-rich food sources, whether they come from spinach, tea, chocolate, beets, pomegranates, or red wine.

Though my wife and I love wine, I confess that I've never personally drank or even seen a French Madiran wine. Any wine afficionados with some advice?

Can wheat elimination cure ulcerative colitis?

Tammy is a 36-year old mother of three young children. Since age 20, she has suffered with the debilitating symptoms of ulcerative colitis: constant, gnawing abdominal pain; frequent diarrhea, often bloody.



Tammy has had to take several medications, some with significant side-effects, all of which provided only partial relief from the pain and diarrhea. Her gastroenterologist and surgeon were planning a colectomy (removal of the colon) with creation of an ileostomy (rerouting of the small intestine to the abdominal surface, which would require Tammy to wear an ileostomy bag under her clothes for the rest of her life).



Although Tammy had previously tested negative for celiac disease (an allergic sensitivity to the gluten in wheat products), I urged her to attempt a trial of a wheat-free diet. Having witnessed many people experience relief from irritable bowel syndrome, acid reflux, and other common gastrointestinal complaints, all while trying to reduce blood sugar and small LDL, I'd hoped that Tammy would obtain at least some small improvement in her terrible symptoms.



I therefore urged Tammy to try it. After all, what was there to lose? Tammy grudgingly agreed.



She returned 6 months later. Her report: She had lost 38 lbs, virtually all of it within the first 6-8 weeks. Her diarrhea and cramping were not better, but gone. She was down to a single medicine from her former list of drugs.



I am unsure what proportion of people with ulcerative colitis or other inflammatory bowel diseases like Crohn's will experience a result like Tammy's. Perhaps it's only a minority. But I take this another piece of evidence that this enormously destructive thing called wheat has no place in the human diet.



We have no facts or figures on the prevalence of various forms of wheat intolerance in the U.S. When I contacted the Celiac Disease Foundation, they had no figures on the number of fatalities per year in the U.S. from celiac disease. But if there are 2-3 million Americans with celiac disease, there are probably 100 times that many people with various forms of wheat intolerance.



Postprandial pile-up with fructose

Heart disease is likely caused in the after-eating, postprandial period. That's why the practice of grazing, eating many small meals throughout the day, can potentially increase heart disease risk. Eating often can lead to the phenomenon I call triglyceride and chylomicron "stacking," or the piling up of postprandial breakdown products in the blood stream.

Different fatty acid fractions generate different postprandial patterns. But so do different sugars. Fructose, in particular, is an especially potent agent that magnifies the postprandial patterns. (See Goodbye, fructose.)

Take a look at the graphs from the exhaustive University of California study by Stanhope et al, 2009:



From Stanhope KL et al, J Clin Invest 2009. Click on image to make larger.

The left graphs show the triglyceride effects of adding glucose-sweetened drinks (not sucrose) to the study participants' diets. The right graphs show the triglyceride effects of adding fructose-sweetened drinks.

Note that fructose causes enormous "stacking" of triglycerides, meaning that postprandial chylomicrons and VLDL particles are accumulating. (This study also showed a 4-fold greater increase in abdominal fat and 45% increase in small LDL particles with fructose.)

It means that low-fat salad dressings, sodas, ketchup, spaghetti sauce, and all the other foods made with high-fructose corn syrup not only make you fat, but also magnifies the severity of postprandial lipoprotein stacking, a phenomenon that leads to more atherosclerotic plaque.

Track Your Plaque: Safer at any score

Imagine two people.

Tom is a 50-year old man. Tom's initial heart scan score was 500--a concerning score that carries a 5% risk for heart attack per year.

Harry is also 50 years old. His heart scan score is 100--also a concerning score, but not to the same degree as Tom's much higher score.

Tom follows the Track Your Plaque program. He achieves the 60:60:60 lipid targets; chooses healthy foods, including elimination of wheat; takes fish oil at a therapeutic dose; increase his blood vitamin D level to 60-70 ng/ml, etc. One year later, Tom's heart scan score is 400, representing a 20% reduction from his starting score.

Harry, on the other hand, doesn't understand the implications of his score. Neither does his doctor. He's casually provided a prescription for a cholesterol drug by his doctor, a brief admonition to follow a low-fat diet, and little else. One year later, Harry's heart scan score is 200, a doubling (100% increase) of the original score.

At this point, we're left with Tom having a score of 400, Harry with a score of 200. That is, Tom has twice Harry's score, 200 points higher. Who's better off?

Tom with the score of 400 is better off. Even though he has a significantly higher score, Tom's plaque is regressing. Tom's plaque is therefore quiescent with active components being extracted, inflammation subsiding, the artery in a more relaxed state, etc.

Harry's plaque, in contrast, is active and growing: inflammatory cells are abundant and producing enzymes that degrade supportive tissue, constrictive factors are released that cause the artery to pinch partially closed, fatty materials accumulate and trigger a cascade of abnormal responses.

So it's not just the score--the quantity of atherosclerotic plaque present--but the state of activity of the plaque: Is it growing, is it being reduced? Is there escalating or subsiding inflammation? Is plaque filled with degradative enzymes or quiescent?

Following the Track Your Plaque program therefore leads us to the notion that it's not the score that's most important; the most important thing is what you're doing about it. We sometimes say that Track Your Plaque makes you safer at any score.

Triglyceride and chylomicron "stacking"

Continuing the comments started in Grazing is for cattle, here's an interesting study from the Oxford Center for Diabetes, Endocrinology and Metabolism.

Volunteers were fed a test meal breakfast of Rice Krispies, a banana, and a chocolate milkshake (76.4 grams carbohydrates, 51.9 grams fat, 12.2 grams protein). Lunch was served 5 hours later and consisted of a cheese sandwich and a second chocolate milkshake 43.4 grams carbohydrates, 49.6 grams fat, 24.0 grams protein). Frequent blood samples were then assessed over the day. (Don't try this at home: These are obviously very dangerous foods!)

Here's the pattern of triglycerides that was observed (1st dotted vertical line = breakfast, 2nd dotted vertical line = lunch):



Note that triglycerides only begin to decline 3-4 hours after breakfast, only to peak higher after lunch.


Here's the pattern observed for chylomicrons, the "granddaddy" of lipoproteins that derives from intestinal absorption of fatty acids:



Both graphs from Heath RB et al Am J Phyiol Endocrinol Metab 2006.


With chylomicrons, note a similar pattern to triglycerides: Chylomicrons begin to decline at 3-4 hours, only to peak higher after lunch.

This is the first study to examine the effect of sequential meals on such postprandial (after-eating) patterns. But it makes the graphic point that, if insufficient time is permitted between meals, both triglycerides and chylomicrons will "stack" themselves higher and higher. (Chylomicrons are subjected to processing by the enzyme, lipoprotein lipase, to form highly atherogenic, or plaque-causing, chylomicron remnants.)

While not examined in this study, my bet is that "grazing," i.e., eating small meals or snacks frequently, is an extreme instance of triglyceride, chylomicron, and chylomicron remnant stacking. That can only lead to one thing: accelerated heart and vascular plaque.

What is a healthy vitamin D blood level?

When measuring blood levels of vitamin D (as 25-hydroxy vitamin D), what constitutes a desirable level?

There's no study that directly examines this question, no study that enrolled thousands of people and assigned a placebo group and groups receiving escalating doses of vitamin D and/or achieved higher levels of vitamin D, then observed for development of cancer, diabetes, depression, heart disease, multiple sclerosis, osteoporosis, osteoarthritis, etc. Such a study would requires many thousands of participants (particularly to observe cancer and multiple sclerosis incidence), many years of observation, and many tens of millions of dollars. Nope, only a drug company could afford such costs.

So we have to piece together various observations and extrapolate what we believe to be the ideal level of vitamin D. Epidemiologic observations in several cancers (breast, colon, prostate, and bladder) suggest that a 25-hydroxy vitamin D level of 30 ng/ml or higher is desirable (with less cancer incidence above this level). Other data suggest a level of 52 ng/ml or greater is desirable. Unfortunately, much cancer research looked at intake of vitamin D from food and supplement sources, rather than actual blood levels. We also have to factor in the great individual variation in vitamin D metabolism, with a single dose yielding variable blood levels (as much as a 10-fold difference). There's also the variation introduced by vitamin D-receptor variation (genetic polymorphisms).

A new study using vitamin D administration helps chart the desirable levels of vitamin D.

Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial.

In this New Zealand study, 42 women (23 to 68 years old) were given 4000 units vitamin D, 39 women given placebo. Median 25-hydroxy vitamin D levels increased from 21 nmol/L (8.4 ng/ml) to 75 nmol/L (30 ng/ml). Both HOMA (a measure of insulin sensitivity) and fasting insulin levels improved, with greatest improvement seen at 25-hydroxy vitamin D levels of 80-119 nmol/L (32-47.6 ng/ml) or greater.

We also know that a vacation on a Caribbean beach in a bathing suit will increase vitamin D blood levels to the 80-110 ng/ml range without ill-effect (at least in young people who maintain the capacity to activate vitamin D in the skin, a phenomenon that declines as we age).

So do we really know the truly ideal level of vitamin D to achieve? I believe that, given the above observations, it is reasonable to extrapolate that the ideal vitamin D blood level likely lies somewhere above 50 ng/ml. We also know that vitamin D toxicity (i.e., hypercalcemia) is virtually unheard of until vitamin D blood levels approach 150 ng/ml, and even then is inconsistent. The health benefits of vitamin D supplementation are so tremendous, that I am not willing to wait for the prospective data to explore this question fully. For now, I aim for a blood level of vitamin D of 60-70 ng/ml (150-175 nmol/L).

Grazing is for cattle

Many dietitians and nutritionists advise many people today to "graze," i.e., to eat small snacks every couple of hours. They argue that it blocks the drop in insulin and blood sugar that can trigger greater appetite and claim it can facilitate weight loss.



This is an absurd notion. Humans are not meant to graze. Humans are meant to find a wild boar or other animal, kill it, gorge on the meat, organs, and fat, then revert to berries, roots, leaves, and other foraged foods until the next kill. A human living in the wild does not have a cupboard or refrigerator full of ready-to-eat snacks to graze on.

The several hours after a meal is the most dangerous for creating coronary atherosclerotic plaque, i.e., the post-prandial period. In other words, eat dinner and, for the next 6-12 hours, your intestinal tract degrades the food; food byproducts are absorbed into the blood or lymph system. The blood is literally flooded with the byproducts of your meal.

Postprandial abnormalities are emerging to be a potent, and much underappreciated, means of causing heart disease and atherosclerosis in other vascular territories (especially carotid arteries and thoracic aorta).

Not eating--i.e., the fasting state--for extended periods is good for you. Encouraging people to graze amplifies atherosclerotic risk, since it creates an abnormal prolonged postprandial state.

The disastrous results of a low-fat diet

Rob was never that committed to following the program in the first place.

I met Rob because of a modest heart scan score and consultation for a cholesterol abnormality. Rob had been cycled through all the statin agents by his primary care physician, all of which resulted in terrible muscle aches that he found intolerable.

I started out, as usual, characterizing his cholesterol abnormality with lipoprotein testing (NMR):

LDL particle number 1489 nmol/L
LDL cholesterol (Friedewald calculation) 143 mg/dl
Small LDL 52% of total LDL
HDL 50 mg/dl
Triglycerides 82 mg/dl

(LDL particle number is the emerging gold standard for LDL quantification, superior to calculated or Friedewald LDL cholesterol for prediction of cardiovascular events.)

Rob is a busy guy. After only a couple of brief visits, life and work got in the way and Rob let his attentions drift away from heart health. Since the information I provided made little impact on his thinking, he reverted to the low-fat diet his primary care doctor had originally prescribed and that he read about in magazines and food packages. He also ran out of the basic supplements I had advised, including fish oil and vitamin D, and just never restarted them.

A couple of years passed and Rob decided that just poking around on his own might not cut it. So he came back to the office. We repeated his NMR lipoprotein analysis:

LDL particle number 2699 nmol/L
LDL cholesterol (Friedewald calculation) 229 mg/dl
Small LDL 81% of total LDL
HDL 53 mg/dl
Triglycerides 78 mg/dl


Two years of a low-fat diet had caused Rob's LDL particle number to skyrocket by 81%, nearly all due to an explosion of small LDL. Recall that small LDL is more susceptible to oxidation, more inflammation-provoking, more adhesive--the form of LDL particles most likely to cause heart disease.

Also, note that, despite the enormous increase in small LDL, HDL and triglycerides remained favorable. This counters the popular rule-of-thumb offered by some that small LDL is not present when HDL is "normal."

Low-fat diets as commonly practiced are enormously destructive. In Rob's case, a low-fat diet caused both calculated Friedewald LDL as well as LDL particle number to increase dramatically. In many other people, low-fat diets increase calculated Friedewald LDL modestly or not at all, but cause the more accurate LDL particle number to increase significantly, all due to small LDL.

I'm happy to say that, once Rob witnessed how far wrong he could go on the wrong program, he's back on Track. (Sorry, pun intended.) He has resumed his supplements and eliminated the food triggers of small LDL--wheat, cornstarch, and sugars.

Dr. David Grimes reminds us of vitamin D

In response to the Heart Scan Blog post, Fish oil makes you happy: Psychological distress and omega-3 index, Dr. David Grimes offered the following argument.

Dr. Grimes is a physician in northwest England at the Blackburn Royal Infirmary, Lancashire. He is author of the wonderfully cheeky 2006 Lancet editorial, Are statins analogues of vitamin D?, questioning whether the benefits of statin drugs simply work by way of increased vitamin D blood levels.


There is a fashionable interest in Omega-3 fatty acids, and these become equated with fish oil.

But fish oil is much more. Plankton synthesise the related squalene (shark oil) which, in turn, is converted into 7-dehydrocholesterol (7-DHC). The sun now comes into play and it converts 7-DHC into vitamin D (a physico-chemical process).

Small fish eat plankton, large fish eat small fish, and we eat large fish. So vitamin D passes through the food chain.

This has been a vital source of vitamin D for the the Inuits and also for the Scots and other dwellers of northwest Europe. (Edinburgh is on the same latitude as Hudson Bay and Alaska, further north than anywhere in China). In these locations there is not adequate sunlight energy to guarantee synthesis of adequate amounts of vitamin D, again by the action of sunlight on 7-DHC in the skin.

When the Scots moved from coastal fishing villages to industrial cities such as Glasgow, they became seriously deficient in vitamin D, and so the emergence of rickets. This was followed by a variety of other diseases resulting from vitamin D deficiency: tuberculosis, dental decay, coronary heart disease, and even multiple sclerosis and depression (the Glasgow syndrome).

And so it was with the Inuits. When their diet changed from fish for breakfast, fish for lunch, fish for dinner, they became deficient of vitamin D and they developed diseases characteristic of industrial cities, where there is indoor work for long hours, indoor activities, and atmospheric pollution.

It is the vitamin D component of fish and fish oils that is important.

I recently saw an elderly lady from Bangladesh living in northwest England. I would have expected her to have a very low blood level of vitamin D, as her exposure to the sun was minimal. However the blood level was 47ng/ml, not 4 as expected. She eats oily fish from Bangladesh every day, showing its value as a source of vitamin D with subsequent good health. I expect her blood levels of omega-3 fatty acids would also be high.

But it is unfashionable vitamin D that is important, not fashionable omega-3.

David Grimes
www.vitamindandcholesterol.com


Excellent point. The health effects of omega-3 and vitamin D are intimately intertwined when examining populations that consume fish.

In this study of Inuits, it is indeed impossible to dissect out how much psychological distress was due to reduced vitamin D, how much due to reduced omega-3s. My bet is that it's both. Thankfully, we also have data examining the use of pure omega-3 fatty acids in capsule (not intact fish) form, including studies like GISSI Prevenzione.

Nonetheless, Dr. Grimes reminds us that both vitamin D and omega-3 fatty acids from fish oil play crucial roles in mental health and other aspects of health, and that it's the combination that may account for the extravagant health effects previously ascribed only to omega-3s.

Why does fish oil reduce triglycerides?

Beyond its ability to slash risk for cardiovascular events, omega-3 fatty acids from fish oil also reduce triglycerides.

There's no remaining question that omega-3s do this quite effectively. After all, the FDA approved prescription fish oil, Lovaza, to treat a condition called familial hypertriglyceridemia, an inherited condition in which very high triglycerides in the 100s or 1000s of milligrams typically develop.

The omega-3 fraction of fatty acids are unique for their triglyceride-reducing property. No other fraction of fatty acids, such as omega-6 or saturated, can match the triglyceride-reducing effect of omega-3s.

But why does fish oil reduce triglycerides?

First of all, what are triglycerides? As their name suggests, triglycerides consist of three ("tri-") fatty acids lined up along a glycerol (sugar) "backbone." Triglycerides are the form in which most fatty acids occur in the bloodstream, liver, and other organs. (Fatty acids, like omega-3, omega-6, mono- or polyunsaturated, or saturated, rarely occur as free fatty acids unbound to glycerol.) In various lipoproteins in the blood, like LDL, VLDL, and HDL, fatty acids occur as triglycerides.

Of all lipoproteins, chylomicrons (the large particle formed through intestinal absorption of fatty acids and transported to the liver via the lymph system) and VLDL (very low-density lipoprotein, very low-density because they are mostly fat and little protein) particles are richest in triglycerides. Thus, we would expect that omega-3s exert their triglyceride-reducing effect via reductions in either chylomicrons or VLDL.

Indeed, that seems to be the case. The emerging evidence suggests that omega-3 fatty acids from fish oil reduce triglycerides through:

--Reduced VLDL production by the liver (Harris 1989)
--Accelerating chylomicron and VLDL elimination from the blood
--Activation of peroxisome proliferator-activated receptor gamma (PPAR-gamma)--Omega-3s ramp up the cellular equipment used to convert fatty acids to energy (oxidation) (Gani 2008)

Combine omega-3 fatty acids from fish oil with wheat elimination and you have an extremely potent means of reducing triglycerides. Read a previous Heart Scan Blog post here to read how a patient reduced triglycerides 93.5% from 3100 mg/dl to 210 mg/dl in just a few weeks using fish oil and wheat elimination.

Heart disease reversal a big "No No"

I dare you: Ask your doctor whether coronary heart disease can be reversed.

My prediction is that the answer will be a flat "NO." Or, something like "rarely, in extraordinary cases," kind of like spontaneous cure of cancer.

There are indeed discussions that have developed over the years in the conventional scientific and medical literature about reversal of heart disease, like Dean Ornish's Lifestyle Heart Trial, the REVERSAL Trial of atorvastatin (Lipitor) and the ASTEROID Trial of rosuvastatin (Crestor). Reversal of atherosclerotic plaque in these trials tends to be small in scale and sporadic.

Of course, the medical literature is swamped with studies that have nothing to do with reversal, like what stent is best, what platelet-inhibiting intravenous drug is best, when should angioplasty or stents be used and when, do implantable defibrillators save lives, improvements in coronary bypass techniques, etc. There are tens of thousands of these studies for every study that focuses on the question of atherosclerotic plaque reversal.

The concept of reversal of heart disease has simply not gained a foothold in the lexicon nor in the thinking of practicing physicians. Heart disease is a relentlessly, unavoidably, and helplessly progressive disease in their way of thinking. Perhaps we can reduce the likelihood of cardiovascular events like heart attack and death with statin drugs and beta blockers. But reverse heart disease ? In your dreams!

We need to change this mentality. Heart disease is a reversible phenomenon. Atherosclerosis in other territories like the carotid arteries is also a reversible pheneomenon. Rather than throwing medicines and (ineffective) diets at you (like the ridiculous American Heart Association program), what if your doctor set out from the start not just to reduce events, but to purposefully reduce your heart's plaque? While it might not succeed in everyone, it would certainly change the focus dramatically.

After all, isn't this the theme followed in cancer treatment? If you had a tumor, isn't cure the goal? Would we accept an oncologist's advice to simply reduce the likelihood of death from cancer but ignore the idea of ridding yourself completely of the disease? I don't think so.

Then why accept "event reduction" as a goal in heart disease? We shouldn't have to. Heart disease reversal--elimination--should be the goal.

Demystification

Once upon a time, remember how medical information was mysterious, hospitals were places where frightening, inscrutable things happened, diseases were strange maladies that struck without reason, and obtaining information about health was like hunting for buried treasure? The full extent of many peoples' understanding of health came through relatively anemic sources like Readers' Digest. (Remember "I am Joe's Colon"?)

Compare this to what we have now. If I wanted to obtain information about ankylosing spondylitis (a rare genetic disease of the spine), a Google search yields 1.46 million citations. Not all the information, of course, is helpful or relevant, but there's certain to be a bounty of information that far exceeds what you could have uncovered 40 years ago.




Suppose you enter the search phrase "antithrombin III" into your Google search. Citations: over 900,000. (The number of search citations, in fact, exceeds the number of Americans with a deficiency of this blood clotting protein!)

The same is true with heart disease. There was a time, not more than 30-40 years ago, when information about the heart and heart disease was hard to come by. The most you would find were superficial discussions about heart attacks, what chest pain means, descriptions of bypass surgery. Ask your doctor, you'd likely receive a brief, cursory response about how you probably shouldn't worry it.

Even during medical school in the 1980s, I remember struggling to get answers to my questions from faculty during medical school and medical training. It was as if providing too much information would eliminate the advantage superiors wielded over trainees.

The same selfish sentiment, the "I know something you don't know" mentality reminiscent of a schoolboy's "naa na na naa naa!" unfortunately persists. But it is rapidly disintegrating. Soon it will join the junk heap of medical mis-information accumulated over the years (a big pile, to be sure). The internet and, I'll admit (grudgingly), the media, have been responsible for demystifying the formerly mysterious and indecipherable world of health.

You now have, at a moment's disposal, access to an extraordinary array and breadth of health information that was inconceivable just a few years ago.

Times are changing. Doctors no longer hold the monopoly over health information. The public--YOU--are rapidly becoming the arbiters of health, the informed consumers of a soon-to-be retail product called health care, and the increasingly savvy judges of what should join the mainstream path of health. It is all part of this wave of change that I've been advocating: the emerging concept of self-empowerment in healthcare.

Added to the junk heap of health-mistakes-of-years-past will be medical protectionism over health information, heart procedures, drug industry excesses, nutritional mis-information, among others. The demystification of health information will open the floodgates of individual insight into health. It delivers control over your own health destiny straight into your own lap.

Everything has omega-3

Walking the supermarket aisles, you may have lately noticed that numerous new products are appearing sporting "omega-3s" on the label.

Some products simply contain alpha-linolenic acid, a tiny amount of which is converted to the biologically active omega-3s, EPA and DHA. Natural Ovens' Brainy Bagel, for instance, carries a claim of "620 omega-3."



I find this confusing and misleading, since people will often interpret such a claim to mean that it contains 620 of EPA and DHA, similar to two capsules of standard fish oil (1000 mg capsules). Of course, it does NOT. I find this especially troublesome when people will actually stop or reduce their fish oil, since they've been misled into thinking that products like this bread contain active omega-3 fatty acids that yield all the benefits of the "real stuff."


Other products actually contain the omega-3, DHA, though usually in small quantities. Breyer's Smart with DHA is an example, with 32 mg DHA per container.


I find products with actual DHA (from algae) a more credible claim. However, the Center for Science in the Public Interest (CSPI) has looked at the actual contents of DHA in some of these products and found some discrepancies, including amounts of DHA less than the labeled amount and claims of omega-3 wihtout specifying DHA vs. linolenic acid. (It's probably linolenic acid, if it's not specified.)

All in all, the addition of DHA to food products is a nice way to boost your intake of this healthy omega-3. However, keep in mind that these are processed, often highly processed, foods and you will likely pay a premium for the little boost. For now, stick to fish oil, the real thing.

For a brief summary of the CSPI report and a link to the Nutrition Action Newsletter, see Omega-3 Madness: Fish Oil or Snake Oil.

Are cardiologists the enemy?

I'm sitting at dinner with two colleagues. One is a cardiology colleague, another an internist who, in addition to practicing general internal medicine, also takes heart disease prevention very seriously. He has, in fact, participated in the Track Your Plaque program and dropped his heart scan score substantially.

"Why don't we see you in the cath lab much?" my cardiology colleague asked me. He was puzzled, since he knew my background in cath lab work from years before, spending day and night doing procedure after procedure. He spends virtually all his days there.

"Well, my patients simply don't have events any more. Heart attacks and angina among people in my program are just about non-existent. They don't have symptoms and they don't have to go to the hospital. I can't remember the last time that I was woken up in the middle of the night for an urgent procedure for one of my patients."

The internist across the table smiled and expressed his agreement. "That's the same thing I'm seeing: No heart attacks, very few if any referrals to cardiologists for procedures. I remember when it was a several times a week thing. Now, almost never. "

Looking at my cardiology colleague, I saw the usual cardiologist reaction: Eyes searching left and right and behind us for something more interesting. Certainly, talking about a virtual cure for coronary heart disease was just too damn dull.

Such is the attitude of 98% of my colleagues: If it doesn't generate a revenue-producing procedure, why bother? Prevention is for general practitioners, the line of thinking goes. "And anyway, I'm too busy doing procedures! I don't ahve time to talk about prevention and health!" Of course, the poor general practitioner is already overloaded with caring for arthritis, flu, diabetes and all the new drugs for diabetes, headaches, vaccinations, diarrhea, and . . .oh, yes, heart disease prevention.

Are cardiologists the enemy? No, of course they are are not. But they often act like they are. Talking to cardiologists is like going to the car dealer with your checkbook out, pen in hand. The salesman gets to write the check himself and you just sign it. Talk to a cardiologist and more often than not you will end up with a heart procedure--whether or not you need it.

Unfortunately--tragically--they often forget what they are supposed to be doing: Taking care of a disease by preventing it. Putting in a defibrillator is not preventing a disease. Putting in three stents, laser angioplasty, and thrombectomy are not ways of preventing a disease.

I'm thankful for my internist friend who sees the light. Coronary heart disease is a an easily measurable, quantifiable, preventable, and REVERSIBLE process for many, if not most, people when provided the right tools. But don't ask your neighborhood cardiologists to give you those tools.

Are CETP inhibitors kaput?

Was torcetrapib’s crash and burn fatal for this class of drug?

At the 2007 American Heart Association meetings in Orlando, Florida, Dr. Philip Barter of Sydney, Australia, presented an update of the ILLUMINATE drug trial for the once-promising drug, torcetrapib, the billion-dollar bet that Pfizer made on its first entry into the new drug class.

You may recall that the crash and burn of Pfizer’s torcetrapib in December 2006 made headlines and prompted enormous disappointment for many patients and doctors who had hoped for a new drug choice to raise HDL cholesterol. Pfizer executives (heads flew!) and investors were also disappointed, anticipating release of a drug that might have become the number one biggest selling drug in the world—ever, surpassing even Lipitor's® $13 billion annual sales.

Torcetrapib is the first among the “cholesteryl-ester transfer protein inhibitors,” or CETP-inhibitors, drugs that block the exchange of cholesterol and triglycerides between HDL and VLDL particles and prevent formation of the unwanted small LDL particles. Preliminary efforts suggested that effects were positively enormous.

However, the 15,000-participant trial was abruptly terminated after 550 days when an excess of deaths were identified among the group taking the experimental drug: 59 deaths in control group; 93 deaths in the torcetrapib group.

In addition, cardiovascular events were 24% greater in the torcetrapib group, numbering 373 compared to 464 in the no-torcetrapib group, including a substantially greater number of heart attacks and hospitalizations. Another surprise came in the way of cause of death among some of the torcetrapib patients, with an excess of deaths due to cancers (twice as many in the torcetrapib group), strokes, and infections.

Why the divergence: enormous improvements in cholesterol values, yet increase in adverse effects including more heart attack? Deeper digging by the principal investigators uncovered unexpected distortions of electrolytes like sodium and potassium. They then re-analyzed blood samples from participants on both sides of the trial and discovered that participants taking torcetrapib experienced significant rise in the blood pressure hormone, aldosterone. This, they surmised, also likely accounted for the 4 mmHg average rise in blood pressure among those taking the experimental drug. (This is the same pathway blocked by blood pressure drugs like ACE inhibitors lisinopril and enalapril, ARBs like losartan.)

Simultaneously (what a coincidence!) with the torcetrapib data, investigators at competing drug manufacturer, Merck, reported encouraging data with their version of CETP inhibitor, anacetrapib. In a phase II FDA trial of 589 patients, anacetrapib reduced LDL-C levels by up to 40% and increased HDL-C up to 139%.


Spokesman Daniel Bloomfield, M.D., of Merck Research Laboratories reported that "The favorable lipid effects seen in this study with multiple doses of anacetrapib were significant, and confirm the continued evaluation of the clinical benefits of CETP inhibitors in the treatment of dyslipidemia." Quick to distinguish this drug from torcetrapib’s track record of dangerous effects on blood pressure, he added that "the decreased LDL-C concentrations, increased HDL-C concentrations and no demonstrable increase in blood pressure seen with anacetrapib are particularly encouraging results of this study."

However, the data reported only an 8 week expereince. Given the experience with torcetrapib, longer term data will obviously be required to assess safety. After Pfizer spent over $1 billion and sacrificed lives to obtain this experience, Merck will need to tread carefully.

It will clearly be many years before we have a confident answer on whether the CETP-inhibitor class of drugs will be a safe choice for correction of cholesterol abnormalities, especially low HDL. Are we helpless until then?

Though CETP inhibitors offer the potential for a one-stop opportunity to raise HDL substantially, there are still many strategies available to raise HDL.

Strategies that raise HDL and are available today include:
• Weight loss—to your ideal weight. A very effective strategy.
• Reduction in processed carbohydrates—like breads, pasta, cookies, pretzels, etc. Note that very low-fat diets reduce HDL. Often a huge effect.
• Fish oil—A small effect, more dramatic when triglycerides are high.
• Niacin—Vitamin B3, the best we have at present. Doses of 500-1500 mg per day raise HDL 20–50%; work with your doctor if you are contemplating niacin. We use this agent everyday and have had great success; good hydration is key to minimize the annoying “hot-flush” effect.
• Dark chocolate—40 grams, or about 2 inches square, a delicious way to squeeze out a little rise in HDL.
• Alcoholic beverages—Red wines are almost certainly the preferred route, rich in flavonoids.
• Exercise—HDL-raising effects vary, but can sometimes be as much as 10–20 mg.
• Other drugs—Though not commonly used for this effect, drugs like pioglitazone (for diabetes and pre-diabetes); fibrates (Tricor® or fenofibrate; Lopid® or gemfibrozil); and Pletal® or cilostazol are occasionally prescribed.
• Vitamin D—You won’t find validation of this effect in any scientific study, but our emerging experience in our heart disease reversal program is suggesting that this neglected nutrient can exert powerful HDL-raising effects. In fact, supplementing vitamin D has made my life much easier.


And, last I checked, none of these HDL-raising strategies are ever fatal.

Roto Rooter for plaque




Joe, a machinist, was frightened and frustrated.

With a heart scan score of 1644 at age 61, his eyes bulged when I advised him that, if preventive efforts weren't instituted right away, his risk for heart attack was a high as 25% per year. Joe had "passed" a stress test, thus suggesting that, while coronary plaque was present--oodles of it, in fact--coronary blood flow was normal. Thus, there would be no benefit to inserting three stents, say, or a bypass operation.


(Illustration courtesy Wikipedia)

"I don't get it, doc. Why can't you just take it out? You know, like Roto-Rooter it out? Or give me something to dissolve it!"

Of course, if there were such a thing, I'd give it to him. But, of course, there is not. It doesn't mean that there haven't been efforts in this direction over the years. Among the various attempts made to "Roto-Rooter" atherosclerotic plaque have included:

Coronary endarterectomy
This is a drastic procedure rarely performed anymore but enjoyed some popularity in the 1980s and 1990s. Coronary endarterectomy was performed during coronary bypass surgery, but few thoracic surgeons performed it. Milwaukee's Dr. Dudley Johnson was the foremost practitioner of this procedure (retired a few years ago after his own bypass operation) with a mortality in excess of 25%. A very dangerous procedure, indeed. The technical hurdle, beyond the tedium and length of time required to remove plaque that had a tendency to fragment, was blood clot formation after tissue was exposed upon plaque removal. I saw many lengthy hospital stays and deaths following this procedure.

Coronary atherectomy
This is an angioplasty-type procedure that has gone through several variations over the years.

In the early 1990s, transluminal extraction atherectomy (TEC) was a technique involving low-rpm drill bits with a suction apparatus that was used to clear soft debris, usually from large coronary arteries or, more commonly, bypass grafts. Then came direction atherectomy, in which a steel housing contained a sharp drill bit that captured atherosclerotic plaque in an aperture along the housing length and stuffed it into a nosecone, retrieved once the device was removed.

Then came high-speed rotational atherectomy in which a diamond-tipped drill bit rotated up to 200,000 rpm and essentially pulverized plaque to flow downstream and, presumably, eventually captured by the liver for disposal. Rotational atherectomy is still in use on occasion. Laser angioplasty, usually using the excimer wavelength, vaporizes plaque. I did plenty of all of these back in the early and mid-1990s.

While all atherectomy procedures sound clever, they are all plagued by the same problem: vigorous return of plaque. Remove plaque, it grows back. There are few instances today in which atherectomy is still performed.

Chelation
This involves a metal-binding, or "chelating," agent like EDTA normally used in conventional practice for lead poisoning. Usually administered IV, some have also advocated oral use. People who use chelation also tend to believe in faith healing and other practices based on faith, not science. There is an international trial that is nearing completion that should provide the final word on whether there is any role to intravenous chelation.

There are numerous other oral treatments that claim a Roto-Rooter-like effect. Nattokinase, for example--an outright, unadulterated, and unqualified scam.

Unfortunately, the helpless, ignorant, and gullible are many. When frightened by the specter of heart disease, there are plenty of people who will willingly pay for the hope provided by clever ads, fast-talking salespeople, and unscrupulous practitioners.

So, Joe, there is no Roto-Rooter for coronary atherosclerotic plaque, at least one that is safe, doesn't involve a life-threatening effort, provides results that endure beyond a few months, and truly works.

The Track Your Plaque program may not be easy. There are obvious common hurdles to adhering to these concepts: obtaining lipoprotein testing, getting intelligent interepretation of the results, persuading your doctor to measure vitamin D blood levels, battling the onslaught of prevailing food propaganda that confuses and misleads. The Track Your Plaque program also requires time, at least a year.

But it's the best program there is. Do you know of anything better?

"Beware nutritional supplements"



In our effort to expand the reach for the nationwide conversation on heart disease reversal, I'd like to welcome the newest contributor to the Track Your Plaque family, a new Member blogger, Heart Cipher.

We first came to appreciate the insights of Heart Cipher on our Member Forum. His curiousity and ability to cut through the bull--- have won over our hearts and minds. I think you will appreciate his unique perspective as someone who has experienced first hand the inadequacies of the present procedure-focused, drug-obsessed standard of medical care that dominates, yet has the intelligence and worldliness to recognize that there are better ways.

Read his post about meeting a new cardiologist for the first time and the reaction he receives when he describes the Track Your Plaque program here.

http://www.heartcipher.com/

The rules of reversal


For the last few years, most practicing physicians have followed a rough blueprint for cholesterol management provided by the Adult Treatment Panel-III “consensus” guidelines, or ATP-III, a lengthy document last released in 2001, updated in 2004.

For instance, ATP-III suggests reducing LDL cholesterol to 100 mg/dl or less for those deemed to be at high risk for future heart disease, arbitrarily defined as a risk of 20% over a 10-year period. It also suggests that a desirable triglyceride level is no more than 150 mg/dl. The ATP-III guidelines have been the topic of discussion in thousands of medical meetings, editorials, and reports. They have served as the basis for many dinners at nice restaurants, weeks in Vegas or Honolulu, many, many lunches catered by pharmaceutical representatives. For most internists, family doctors, cardiologists, and lipid clinics, ATP-III is the Bible for cholesterol management.

AT-III has also become the de facto standard that could conceivably held up as the prevailing "standard of care" in a court of law in cases of presumed negligence to treat cholesterol values. “Doctor, would you agree that the consensus guidelines issued by the National Institutes of Health and endorsed by the American Heart Association state that LDL cholesterol should be reduced to 100? You do? Then why was Mr. Jones’ LDL not addressed according to these guidelines?”

Who was on the ATP-III panel and on what scientific evidence were the guidelines based? Several problems:

1) Of the 9 physician members of the panel, 8 had ties to industry, some of them quite intimate.

2) The studies upon which the guidelines were based and figure prominently, such as the Heart Protection Study, PROVE IT, and 4S, were all funded by the pharmaceutical industry. Of course, it would be unreasonable to expect anyone other than the pharmaceutical industry to fund drug studies. But prominently neglected or understated in the guidelines are all the other insights and treatments for coronary atherosclerotic risk available that were NOT funded by industry.

Of course, there’s money to be made in reducing LDL cholesterol. Lots of it--$23 billion last year alone, in fact. Just keeping that fact in mind makes the ATP-III guidelines make far better sense.

ATP-III is really not a blueprint for heart disease prevention. It is a blueprint--by industry, for industry--on how and when to treat LDL cholesterol.


But what if ATP-III had been a map for navigating coronary plaque reversal instead? What if it were not obsessed with just reducing LDL cholesterol, but was focused on providing the corner internist, family doctor, or cardiologist a roadmap for navigating the highways and byways of reversal?

That would be interesting. Mainstream reversal. Imagine that.

Among the difficulties is that the path to reversal is not lined with deep pockets. Treat LDL and who gains? That's easy. Reverse heart disease and who gains? Beyond LDL reduction, very few (beyond you and me, of course).

That’s why the call for a new Age of Self-Empowerment in healthcare is necessary now more than ever. In my view, in the foreseeable future, we will not have an ATP-III-like blueprint for heart disease control or reversal, nor will we witness a boom of nationwide appreciation that coronary atherosclerosis is a reversible process.

It’s time to take the control back and put it in our own hands. Don't expect the American Heart Association to do it. Don't expect the pharmaceutical industry to do it. If there's anyone who's going to do it, it's YOU.

Incurable wheataholics

Greg slumped back in his chair.

"I'm sorry, doc. I feel like the world's biggest schlump!"

He was referring to the fact that he had gone wheat-free for two months--eliminated all breads, bagels, donuts, pasta, breakfast cereals, crackers, pretzels--and promptly lost 30 lbs. He felt great, discovered new levels of energy he thought he'd lost long ago.

Then some friends convinced him to have some cheeseburgers at a fast food restaurant.

"After that, it was downhill. I couldn't get enough. My wife made chile and I had to have four slices of bread with it. Then I'd have two more. I just couldn't stop."

Now, having regained the 30 lbs in the space of another two months, Greg was expressing his disgust.

And it's not the first time. Greg has struggled with his wheat-alholism for as long as I've known him. I've tried motivating him by showing him the flagrant lipoprotein patterns that his wheat habit and excess weight caused: markedly elevated LDL particle number, severe small LDL, low HDL, high triglycerides, high C-reactive protein, high blood sugar, high blood pressure. Greg has received a total of 7 stents over the past 5 years. His next stop is the operating room for a bypass if he can't bring his patterns and impulses under control.

But for some reason, Greg seems to always return to the wheat trough, gorging on breads, pretzels, cake, often in great quantities.

I'm not entirely sure what to do with someone with Greg's severe degree of wheat-aholism. I view wheat-aholism as similar to alcoholism. For some, it can be as addictive.

The only strategy that I know can work is to make a clean break and drop wheat products altogether. Just as an alcoholic cannot just satisfy him/herself with a drink or two a day, so a wheataholic can't be satified with just a couple of wheat crackers. It inevitably leads to the avalanche of wheat indulgences.

Perhaps we should form a new group: Wheataholics Anonymous. "Hi. My name is Greg and I'm a wheataholic."

The battle for asymptomatic disease

The heart disease revenue pie is shrinking. So is the "serving size" being shared by competing hospitals.

In other words, as more hospitals open heart programs, there is more competition for the same heart patient. Throw into the mix the drop in "acute" presentations of disease, probably due to the now widespread prescribing of statin drugs. When I first started cardiology practice 15 years ago, for instance, days and nights spent taking care of heart attacks coming through the emergency room was a common event. It still happens, but far less frequently. (I don't mean to suggest that the actual prevalence of coronary heart disease has decreased, just the acute, catastrophic version of it.)

Throw into this mix the results of the COURAGE Trial that has put a damper on the value of stents and angioplasty vs. "optimal" medical therapy in people with stable anginal symptoms, since there was little advantage of procedures. Though it has not stopped the practice, it has reduced the enthusiasm for procedures. Though data are hard to come by, I've heard talk of 10% or greater drops in total procedural volume over the past year.

It's not uncommon for hospitals to have overbuilt heart facilities in anticipation of continued growth of this--until recently--growth industry called heart disease. However, factors are converging that may provide a new profit opportunity for hospitals.

One such opportunity is CT coronary angiography. The usual scenario: Man or woman without symptoms is persuaded somehow--an ad, primary care physician, next door neighbor with a scary event, Dr. Mehmet Oz gushing about this sexy new technology on yet another Oprah episode--to undergo a CT coronary angiogram. A "severe" blockage is found, despite the lack of symptoms, and voila! A stent patient or bypass patient is created out of nothing! Do this repeatedly and systematically, and a hospital can regain its former high-procedural volume glory.

Heart scans, though I believe deeply in them and they are the basis for the Track Your Plaque prevention and reversal program, can also be used and abused this way. Asymptomatic person has a score 150. Concerned, they go to their physician who orders a nuclear stress test. An "inferior perfusion defect" is seen, presumably representing poor flow through the right coronary artery (but often just means that the diaphragm overlaps the heart muscle and yields this apparition, a "false positive" or misleading result). "But--wink--we've got to find out if there's a severe blockage, don't we? You don't want to end up in an early grave!"

Thus, the battle for new patients with asymptomatic disease is getting underway in earnest. The scramble for cardiologists to learn how to use CT coronary angiograms is proceeding at breakneck speed, with new training courses being offered nationwide several times and places every month. CT coronary angiography is a useful test, but it is also subject to enormous abuse. It also provides the ticket for the unscrupulous physician and the revenue-hungry hospital eager to expand its patient volume.

Many people believe that this cannot happen commonly in 2007, given scrutiny of practices, litigiousness, and the expectation of a moral sense in medicine. However, I've witnessed such incidents several times this month alone. If you need graphic proof of just how far this can go before action is taken, read Coronary, Stephen Klaidman's chilling tale of a cardiologist and cardiothoracic surgeon in small-town northern California who built an enormous heart center based on fabricated heart disease diagnoses. You'll also find their story in Shannon Brownlee's recently released Overtreated: Why Too Much Medicine Is Making Us Sicker and Poorer.





Of course, the Track Your Plaque program is meant principally for people without symptoms, also. But we are advocating that asymptomatic disease is a reason for prevention, not procedures. There's a difference.

By the way, the two practitioners who engineered the escapade detailed in these books, cardiologist Chae Hyun Moon and cardiac surgeon Fidel Realyvasquez, walked away with a monetary fine and suspension of their California medical licenses. It is likely that many people died because of their abusive practices, but the state struggled to make a sufficiently persuasive case for reasons that I still don't understand.