Wednesday, August 29, 2012

There Is No Such Thing As Bad Cholesterol

Putting The Myth To Rest: There Is No Such Thing As Bad Cholesterol
Perhaps one of the biggest health myths propagated in western culture and certainly in the United States, is the correlation between elevated cholesterol and cardiovascular disease (CVD). Unfortunately, despite dozens of studies, cholesterol has not been shown to actually cause CVD. To the contrary, cholesterol is vital to our survival, and trying to artificially lower it can have detrimental effects, particularly as we age.

Cholesterol seems to be one of those things that strikes fear into the hearts of many, so to speak. We have become obsessed with eating foods low in cholesterol and fat. Ask almost anyone, and they can tell you their cholesterol levels.

What is certain is that the 'little knowledge' that the media often imparts means many folks assume cholesterol is simply a 'bad' thing. Alternately, a good number of us may have heard the terms 'good' cholesterol and 'bad' cholesterol bandied about without knowing much about what this really means. In fact it is a fairly safe bet that if you asked anyone on the street for his or her instinctive response, if asked about cholesterol, they would probably say that we simply need to 'reduce it'.

The 'noddy-science' offered by marketing men to a generally scientifically-naive public has led many people to believe that we should replace certain food choices with specially developed products that can help 'reduce cholesterol'. Naturally this comes at a price and requires those who can afford it to pay maybe four or five times what a 'typical ordinary' product might cost. But is this apparent 'blanket need' to strive towards lowering our cholesterol justified? And, indeed, is it healthy?

For anyone who has had the official diagnosis of 'high cholesterol' in their bloodstream, they may even have embarked upon a program of medicinal intervention. In fact it is quite likely that they may have joined the legions of long-term pill-poppers who are already lining the pockets of the profit-oriented pharmaceutical giants.

But let's take a moment, now, to review some of the facts and fallacies about the much-maligned substance: cholesterol.

Cholesterol is needed to make hormones. Without it we would not produce estrogen, progesterone or testosterone. It is vital for the functioning of nerve synapses and provides the structural integrity for our cell membranes. Cholesterol is used by the skin to help prevent water evaporation and to make our skin waterproof. Vitamin D is synthesized from cholesterol. And bile, used for fat digestion, consists mostly of cholesterol. The liver produces about 90 percent of the cholesterol in our bodies; only 10 percent comes from diet. If we eat too much cholesterol, the liver decreases the output of cholesterol.

Cholesterol is a naturally occurring lipid. This means it is a type of fat or oil and it is in fact an essential component in creating and sustaining the membranes of the cells of all bodily tissues. So this alone means we need cholesterol to survive! Most of the cholesterol that is found in our bodies is actually naturally manufactured within our own cells. However there is also an additional contribution that we get from external 'nutritional' sources - the foods we consume. In a typical diet providing around 400mg of cholesterol per day from food sources, about half to two-thirds of this amount is actually absorbed through the process of digestion. The body will normally secrete about a gram (1000mg) of cholesterol per day into the bile via the ducts, and approximately three-fifths of this is then re-absorbed.

Where our tissues or organs are a particularly dense complex of cells, which have closely packed cell membranes, there will naturally be higher levels of cholesterol. The key organs that need, and contain, these higher amounts of cholesterol include the liver, the brain and the spinal cord - none of which would work well if we reduced cholesterol too much!

In effect cholesterol plays an essential role in the development and maintenance of healthy cell walls. It is also a critical factor in the synthesizing of steroid hormones, which are a key factor in our natural physical development.

Being a lipid, cholesterol is fat-soluble, but it is not soluble in blood. However it needs to be transported around the body to the places where it can be utilized. This is why, in order to be moved around, it must become 'associated' with certain lipoproteins which feature a water-soluble (therefore 'blood transportable') coat of proteins. There are two key types of lipoproteins that transport cholesterol around the body: low-density and high-density variants. The essential cellular function of cholesterol requires that sufficient amounts are manufactured by specialized sub-systems (or organelles) within the body's cells called the endoplasmic reticulum. Alternatively, the cholesterol we need must be derived from our diet. During the process of 'digestion and assimilation' of foods, it is the low-density lipoprotein (LDL) that carries dietary cholesterol from the liver to various parts of the body.

When there is sufficient cholesterol for cellular needs, the other key transport mechanism in this amazing 'logistics system' - high-density lipoprotein (HDL) - can take cholesterol back to the liver from where any unnecessary excess can be processed for excretion.

The 'noddy-science' of the so-called 'functional food' manufacturers would have us believe that there is such a thing as 'bad' cholesterol and 'good' cholesterol. This is, in fact, totally untrue. The cholesterol itself, whether being transported by LDL or HDL, is exactly the same. Cholesterol is simply a necessary ingredient that is required to be regularly delivered around the body for the efficient healthy development, maintenance and functioning of our cells. The difference is in the 'transporters' (the lipoproteins HDL and LDL) and both types are essential for the human body's delivery logistics to work effectively.

Problems can occur, however, when the LDL particles are both small and their carrying capacity outweighs the transportation potential of available HDL. This can lead to more cholesterol being 'delivered' around the body with lower resources for returning excess capacity to the liver.

LDL can vary in its structure and occur in particles of varying size. It is the smaller LDL particle sizes that can easily become 'trapped' in the arteries by proteoglycans, which is, itself, a kind of 'filler' found between the cells in all animal and human bodies. This can then cause the cholesterol the LDL carries to contribute to the formation of fatty deposits called 'plaques' (a process known as atherogenesis). As these deposits build up, they restrict the arteries' width and flexibility. This causes an increase in blood pressure and can also lead to other cardiovascular problems such as heart attacks or strokes.

The LDL itself is consequently sometimes referred to as 'bad cholesterol', but you can now appreciate the fact that this is simply incorrect. In fact LDL, HDL and cholesterol are all essential to our health. However, it seems that it has become common for humans to have a preponderance of 'unhealthily' small LDL particles, which can become a precursor to heart and arterial disease due to the mechanisms described. It is apparently healthier to have a smaller number of larger LDL particles carrying the same quantity of cholesterol than a large number of small LDL particles might transport, but for some reason this is less common. This is an interesting area that demands more research.

When LDL becomes retained by the glycol-proteins in the arteries it is subject to being oxidized by 'free radicals'. This is when the process can become health threatening. It has therefore been suggested that increasing the amount of antioxidants in our diet might effectively 'mop up' free radicals, and consequently reduce this harmful oxidation. Although the idea of consuming foods rich in antioxidants, or even using supplements, is now widely promoted, the scientific evidence for their efficacy still remains to be fully established.

Another point to consider is the occurrence of substances called 'very-low-density-lipids' or VLDL, also known as triglycerides. VLDL is converted to LDL in the bloodstream and therefore contributes towards increased levels of LDL and to subsequent potential cholesterol-related health problems. This is why triglycerides are usually measured when a cholesterol test of your blood is undertaken.

The production of VLDL in the liver - which amounts to a combination of cholesterol and low-density apolipoprotein - is exacerbated by the intake of fructose. Fructose is the type of sugar found in many fruits, it is also a component of sucrose and of the widely used food ingredient high-fructose corn syrup. This implies that anyone whose LDL or triglyceride levels are unduly high should cut back on those sweet sugary snacks, and even on the sweeter, fructose laden fruits; not simply reduce their intake of fatty foods!

Vitamin B3, otherwise known as niacin, on the other hand, actually lowers the amount of VLDL, and therefore also LDL. In addition, niacin helps to stimulate the production of helpful HDL, the lipoprotein that carries excess cholesterol back to the liver for excretion. However, in keeping with the best traditions of consuming 'all things in moderation', currently recommended upper limits for daily intake of niacin is 35mg, given that it can have toxic effects in larger amounts. Even so, medical professionals have been known to prescribe niacin in doses as high as 2g, up to three times a day, for treatment of those with dangerously high blood cholesterol levels. Naturally you should never self-medicate with high doses of niacin without taking appropriate medical advice.

Niacin in the diet is typically derived from high protein foods including liver and other meats, as well as significant amounts being found in certain nuts and whole grains.

However one of the fashionable types of pharmaceutical drugs of recent times, introduced to treat the apparently increasing incidence of high cholesterol levels particularly in the West, are Statins. Most likely you have a friend or relative taking these useless drugs (Lipitor, Mevecor, Crestor, etc.) to lower cholesterol. Statin medications are the number-one-selling drugs in the world.
They work by interfering with the liver function and reducing the production of LDL. But Statins are a questionable innovation on at least a couple of accounts. Firstly they are not without side-effects: they can, for example, lead to the breakdown of major muscular material, which can ultimately overwhelm the kidneys and even cause acute renal failure.

Statins also appear to reduce the body's natural levels of the vitamin-like, cellular protection agent known as Co-enzyme Q10. This benzoquinone plays an important role in cellular energy release, particularly in hard worked areas like the lungs, liver and heart. CoQ10 (as it is sometimes called) has also been shown to protect the brain against neurological degeneration. But perhaps most interestingly, with respect to cholesterol, CoQ10 also acts as an antioxidant, particularly active in protecting the system against LDL oxidation and the potential problems associated with this as described above. So whilst Statins might provide a reduction in LDL per se, they might also be causing more problems in the long-term. Naturally, as with many modern drugs, they generally have to be taken for the long-term by anyone who has been prescribed them.

What is particularly disturbing about Statins is, perhaps, the fact that they may be seen as a 'quick fix' for unhealthily high LDL, and consequently cholesterol levels throughout the body. They need to be taken over a long period - which makes them very profitable for drugs manufacturers. But they may also be prescribed without the over-arching message that in order to address any cholesterol problem 'naturally', the sufferer must change their lifestyle and diet. Statins can seem an easy option but may indeed merely be the beginning of a process where the 'negative health pay-off' is simply delayed rather than actively defused! That is not to say that in extreme cases of high blood cholesterol, or hypercholesterolemia, there may not be a useful role for Statin therapy when natural strategies fail or do not prove effective, or feasible.

In truth, and in summary, cholesterol is an important and essential substance that we need for health at a cellular level. It is most likely that any imbalance in our cholesterol transport system comes down to long-term poor dietary and exercise habits. Ensuring that we consume some extra anti-oxidant foods, along with including niacin rich foods, might well be of benefit. But it is perhaps most important to recognize that deliberate and continued levels of activity and the consumption of a healthful diet is a better solution than questionable quick-fix drugs, if we ever are diagnosed with levels of cholesterol and triglycerides that might give cause for concern.

Reference Sources 114, 136, 151, 158
Read the full article here.

The Straight Dope on Cholesterol: 10 Things You Need to Know - Attia

The Straight Dope on Cholesterol: 10 Things You Need to Know

This is a guest post by Peter Attia and is a summary based on a 10-part series of the same name that you can find at The Eating Academy
To put this summary post and, more importantly, this 10-part series in perspective, let’s examine one of the most pervasive pieces of dietary advice given to people worldwide:

“Eating foods that contain any cholesterol above 0 mg is unhealthy.”
- T. Colin Campbell, PhD, author of The China Study.

No summary of this length can begin to fully address a topic as comprehensive as cholesterol metabolism and the pathogenesis of atherosclerosis. In fact, those of us who challenge conventional wisdom often find ourselves needing to do exactly what Frederic Bastiat suggested:

“We must admit that our opponents in this argument have a marked advantage over us. They need only a few words to set forth a half-truth; whereas, in order to show that it is a half-truth, we have to resort to long and arid dissertations.”

So, at the risk of trying to minimize the “long and arid” part of this process, below are the 10 things you need to know to be the judge – for yourself – if the conventional advice about cholesterol is correct.

1. The sine qua non of atherosclerosis is the presence of a sterol in an artery wall. How it gets there is the only thing we should be worrying about.

Contrary to popular belief, atherosclerosis is not caused by many of things we think of, such as smoking, high blood pressure, diabetes, high LDL (the so-called “bad” cholesterol), or low HDL (the so-called “good” cholesterol). Some of these are certainly markers of risk – low HDL, for example – while others accelerate the process – smoking, for example – but none of these are the direct cause of atherosclerosis.

The sine qua non of atherosclerosis is the presence of sterols (cholesterol or phytosterol) in arterial wall macrophages. Sterols are delivered to the arterial wall by the penetration of the endothelium by an apoB-containing lipoprotein, which transport the sterols. In other words, unless an apoB-containing lipoprotein particle violates the border created by an endothelium cell and the layer it protects, the media layer, there is no way atherogenesis occurs. If this is a bit confusing, don’t worry. It’s all made clear below.

2. Cholesterol is vital for life; no cholesterol = no life.

Cholesterol is a 27-carbon molecule shown in the figure below. Each line in this figure represents a bond between two carbon atoms. That’s it. Mystery over.

All this talk about “cholesterol” and most people don’t actually know what it is. So, there you have it. Cholesterol is “just” another organic molecule in our body.

I need to make one distinction that will be very important later. Cholesterol, a steroid alcohol, can be “free” or “unesterified” (“UC” as we say, which stands for unesterified cholesterol) which is its active form, or it can exist in its “esterified” or storage form which we call a cholesterol ester (“CE”). The diagram below shows a free (i.e., UC) molecule of cholesterol. An esterified variant (i.e., CE) would have an “attachment” where the arrow is pointing to the hydroxyl group on carbon #3, aptly named the “esterification site.”
Cholesterol 1
One of the biggest misconceptions is that cholesterol is “bad.” This could not be further from the truth. Cholesterol is very good! In fact, there are (fortunately rare) genetic disorders in which people cannot properly synthesize cholesterol. One such disease is Smith-Lemli-Opitz syndrome (also called “SLOS,” or 7-dehydrocholesterol reductase deficiency) which is a metabolic and congenital disorder leading to a number of problems including autism, mental retardation, lack of muscle, and many others.

Cholesterol is absolutely vital for our existence. Every cell in our body is surrounded by a membrane. These membranes are largely responsible for fluidity and permeability, which essentially control how a cell moves, how it interacts with other cells, and how it transports “important” things in and out. Cholesterol is one of the main building blocks used to make cell membranes (in particular, the ever-important “lipid bilayer” of the cell membrane).

Beyond cholesterol’s role in allowing cells to even exist, it also serves an important role in the synthesis of vitamins and steroid hormones, including sex hormones and bile acids. Make sure you take a look at the picture of steroid hormones synthesis and compare it to that of cholesterol (above). If this comparison doesn’t convince you of the vital importance of cholesterol, nothing I say will.
One of the unfortunate results of the eternal need to simplify everything is that we (i.e., the medical establishment) have done the public a disservice by failing to communicate that there is no such thing as “bad” cholesterol or “good” cholesterol. All cholesterol is imperative for life to exist!

The only “bad” outcome is when cholesterol ends up inside of the wall of an artery, most famously the inside of a coronary artery or a carotid artery, AND leads to an inflammatory cascade which results in the obstruction of that artery (make sure you check out the pictures in the links above). When one measures cholesterol in the blood we really do not know the final destination of those cholesterol molecules!

3. The cholesterol we eat has little to do with the cholesterol we measure in our bloodstream.

We ingest (i.e., take in) cholesterol in many of the foods we eat and our body produces (“synthesizes”) cholesterol de novo from various precursors. About 25% of our daily “intake” of cholesterol – roughly 300 to 500 mg – comes from what we eat (called exogenous cholesterol), and the remaining 75% of our “intake” of cholesterol – roughly 800 to 1,200 mg – is made by our body (called endogenous production). To put these amounts in context, consider that total body stores of cholesterol are about 30 to 40 gm (i.e., 30,000 to 40,000 mg) and most of this resides within our cell membranes. Nearly every cell in the body can produce cholesterol, and thus very few cells actually require a delivery of cholesterol. Cholesterol is required by all cell membranes and to produce steroid hormones and bile acids.

Of this “made” or “synthesized” cholesterol, our liver synthesizes about 20% of it and the remaining 80% is synthesized by other cells in our bodies. The synthesis of cholesterol is a complex four-step process (with 37 individual steps) that I will not cover here, but I want to point out how tightly regulated this process is, with multiple feedback loops. In other words, the body works very hard (and very “smart”) to ensure cellular cholesterol levels are within a pretty narrow band (the overall process is called cholesterol homeostasis). Excess cellular cholesterol will crystalize and cause cellular apoptosis (programmed cell death). Plasma cholesterol levels (which is what clinicians measure with standard cholesterol tests) often have little to do with cellular cholesterol, especially artery cholesterol, which is what we really care about. For example, when cholesterol intake is decreased, the body will synthesize more cholesterol and/or absorb (i.e., recycle) more cholesterol from our gut. The way our body absorbs and regulates cholesterol is really amazing, so I want to spend a bit of time discussing it.

  • The blue circle in this figure represents something called a Niemann-Pick C1-like 1 protein (NPC1L1). It sits at the apical surface of enterocytes and it promotes active influx (i.e., bringing in) of gut luminal unesterified cholesterol (UC) as well as unesterified phytosterols into the enterocyte. Think of this NPC1L1 as the ticket-taker at the door of the bar (where the enterocyte is the “bar”); he lets most cholesterol (“people”) in. However, NPC1L1 cannot distinguish between cholesterol (“good people”) and phytosterol (“bad people” – for reasons I won’t discuss here) or even too much cholesterol (“too many people”).

  • The pink circle in this figure represents a structure called the adenosine triphosphate (ATP)-binding cassette (ABC) transporters ABCG5 and ABCG8. This structure promotes active efflux (i.e., kicking out) of unesterified sterols (cholesterol and plant sterols – of which over 40 exist) from enterocytes back into the intestinal lumen for excretion. Think of ABCG5/G8 as the bouncer at the bar; he gets rid of the really bad people (e.g., phytosterols, as they serve no purpose in humans) you don’t want in the bar who snuck past the ticket-taker (NPC1L1). Of course, in cases of hyperabsorption (i.e., where the gut absorbs too much of a good thing) they can also efflux out un-needed cholesterol. Along this analogy, once too many “good people” get in the bar, fire laws are violated and some have to go. The enterocyte has “sterol-excess sensors” (a nuclear transcription factor called LXR) that do the monitoring, and these sensors activate the genes that regulate NPC1L1 and ABCG5/G8.
There is another nuance to this, which is where the CE versus UC distinction comes in:
  • Only free or unesterified cholesterol (UC) can be absorbed through gut enterocytes. In other words, cholesterol esters (CE) cannot be absorbed because of the bulky side chains they carry.
  • Much (> 50%) of the cholesterol we ingest from food is esterified (CE), hence we don’t actually absorb much, if any, exogenous cholesterol (i.e., cholesterol in food).
  • Furthermore, most of the unesterified cholesterol (UC) in our gut (on the order of about 85%) is actually of endogenous origin (meaning it was synthesized in bodily cells and returned to the liver), which ends up in the gut via biliary secretion and ultimately gets re-absorbed by the gut enterocyte. The liver is only able to efflux (send out via bile into the gut) UC, but not CE, from hepatocytes (liver cells) to the biliary system. Liver CE cannot be excreted into bile. So, if the liver is going to excrete CE into bile and ultimately the gut, it needs to de-esterify it using enzymes called cholesterol esterolases which can convert liver CE to UC.

4. The cholesterol in our bloodstream has little to do with the cholesterol in our artery walls (i.e., atherosclerosis).

To understand how cholesterol travels around our body requires some understanding of the distinction between hydrophobic and hydrophilic. A molecule is said to be hydrophobic (also called nonpolar) if it repels water, while a molecule is said to be hydrophilic (also called polar) if it attracts water. Think of your veins, arteries, and capillaries as the “waterways” or rivers of your body. Cholesterol is precious “cargo” that needs to move around, but it needs a “boat” to carry it.
The proteins that traffic collections of lipids are called apoproteins. Once bound to lipids they are called apolipoproteins, and the protein wrapped “vehicle” that transports the lipids are called lipoproteins. Many of you have probably heard this term before, but I’d like to ensure everyone really understands their important features. A crucial concept is that, for the most part, lipids go nowhere in the human body unless they are a passenger inside a protein wrapped vehicle called a lipoprotein. As their name suggests, lipoproteins are part lipid and part protein. They are mostly spherical structures which are held together by a phospholipid membrane (which, of course, contains free cholesterol). The figure below shows a schematic of a lipoprotein.
You will also notice variable-sized proteins on the surface of the lipid membrane that holds the structure together. The most important of these proteins are called apolipoproteins, as I alluded to above. The apolipoproteins on the surface of lipoprotein molecules serve several purposes including:
  1. Assisting in the structural integrity and solubility of the lipoprotein;
  2. Serving as co-factors in enzymatic reactions;
  3. Acting as ligands (i.e., structures that help with binding) for situations when the lipoprotein needs to interact with a receptor on a cell.
Apolipoproteins come in different shapes and sizes which determine their “class.” Without getting into the details of protein structure and folding, let me focus on two important classes: apolipoprotein A-I and apolipoprotein B. ApoA-I is the apolipoprotein that wraps HDL particles. ApoB is the apolipoprotein that wraps VLDL, IDL, and LDL particles.

5. The only way sterols end up in artery walls – the one place we don’t want them to be – is if the sterols are carried there by an apoB-containing lipoprotein particle.

So what drives a LDL particle to do something as sinister as to leave the waterway (i.e., the bloodstream) and “illegally” try to park at a dock (i.e., behind an endothelial cell)? Well, it is a gradient driven process which is why particle number is the key driving parameter.

As it turns out, this is probably a slightly less important question than the next one: what causes the LDL particle to stay there? In the parlance of our metaphor, not only do we want to know why the boat leaves the waterway to illegally park in the dock with its precious cargo, but why does it stay parked there? This phenomenon is called “retention” in lipidology-speak.

Finally, if there was some way a LDL particle could violate the endothelium, AND be retained in the space behind the cell (away from the lumen on the side aptly called the sub-endothelial space) BUT not elicit an inflammatory (i.e., immune) response, would it matter?

I don’t know. But it seems that not long after a LDL particle gets into the sub-endothelial space and takes up “illegal” residence (i.e., binds to arterial wall proteoglycans), it is subject to oxidative forces, and as one would expect an inflammatory response is initiated. The result is full blown mayhem. Immunologic gang warfare breaks out and cells called monocytes and macrophages and mast cells show up to investigate. When they arrive and find the LDL particle, they do all they can to remove it. In some cases, when there are few LDL particles, the normal immune response is successful. But, it’s a numbers game. When LDL particle invasion becomes incessant, even if the immune cells can remove some of them, it becomes a losing proposition and the actual immune response to the initial problem becomes chronic and maladaptive and expands into the space between the endothelium and the media.

The multiple-sterol-laden macrophages or foam cells coalesce, recruit smooth muscle cells, induce microvascularization, and before you know it complex, inflamed plaque occurs. Microhemorrhages and microthrombus formations occur within the plaque. Ultimately the growing plaque invades the arterial lumen or ruptures into the lumen inducing luminal thrombosis. Direct luminal encroachment by plaque expansion or thrombus formation causes the lumen of the artery to narrow, which may or may not cause ischemia.

Read more: http://www.marksdailyapple.com/the-straight-dope-on-cholesterol-10-things-you-need-to-know-part-1/#ixzz24wyQCVFe
Read the complete article here.

Friday, August 24, 2012

Triglycerides: Mother of Meddlesome Particles - Davis

Triglycerides: Mother of Meddlesome Particles

Triglycerides are a crucial risk factor for coronary plaque growth, even at levels previously thought to be normal. Dr. Davis discusses why and how this oft-neglected factor can be harnessed to strengthen your program.

While the world obsesses over cholesterol, a potent stimulator of plaque growth is frequently ignored—triglycerides. A subject of controversy in past, the data are now clear: triglycerides spawn unwanted lipoprotein particles that trigger plaque growth. Track Your Plaque members are advised that control of triglycerides is essential to everyone’s plaque control program.

Triglyceride control is crucial if you are interested in gaining control over coronary plaque. Triglycerides should be brought under control at the start of your program. If you are experiencing plaque growth (increasing heart scan scores), seriously reining in triglycerides should be considered.
How important are triglycerides?
For years, the relationship between coronary heart disease and triglycerides remained muddled by the confounding effects of low HDL. In other words, increased triglycerides tend to occur alongside low HDL. This caused many to dismiss the importance of triglycerides. To make matters even murkier, high triglycerides in some situations generated high risk for heart disease, while in others it appeared unrelated to heart disease, even when markedly elevated (in the thousands!).

Thanks to the evolving science of lipoproteins, the issues are crystallizing. One important fact has emerged: triglycerides are a critical risk factor for coronary plaque growth, even at levels previously thought to be normal. Yes, high triglycerides frequently occur with low HDL, but they also behave independently. High triglycerides are a common cause of heart disease, even in people with low or normal cholesterol values. It is crucial that you (and your doctor) pay close attention to triglycerides if you are to succeed in controlling your plaque. We urge Members to make triglyceride control a priority in their program.
Where do triglycerides come from?
The liver produces a particle called “very low-density lipoprotein”, or VLDL, packed full of triglycerides. The higher your triglycerides, the more VLDL you will have. Sometimes triglycerides are increased due to genetic factors. More commonly, triglycerides are high due to excess weight, indulging in processed carbohydrates, and resistance to insulin (metabolic syndrome).

VLDL is like that bad kid on the block you want your kids to avoid. VLDL particles in the blood come into contact with LDL and HDL particles and they’re never quite the same. When a LDL or HDL particle meet VLDL, the triglycerides of VLDL are passed on. The result: LDL and HDL become bloated with triglycerides. Triglyceride-loaded LDL and HDL are a ready target for a set of enzymes in the blood and liver that reconfigure these particles into smaller versions, small LDL and small HDL. Recall that both small LDL and HDL are highly undesirable particles that stimulate plaque growth.

Although “official” (ATP-III) guidelines suggest that triglycerides over 150 mg are undesirable, we regard any value over 60 mg as high. An ideal level for an intensive Track Your Plaque approach is <45 font="font" mg.="mg.">
How will I know if I have this pattern?
On a conventional cholesterol panel, increased triglycerides and low HDL are tip-offs that excess VLDL are available to contribute to coronary plaque growth. At what triglyceride level does this cascade begin to take effect and create this collection of particles? Levels of 45 mg/dl or greater. In the Track Your Plaque program, we aim for zero plaque growth or reduction, and so we target triglyceride levels of 60 mg/dl or less.

You’ll notice that low HDL and increased triglycerides are also patterns that characterize the metabolic syndrome. In our experience, over 50% of adults show at least some of the characteristics of the metabolic syndrome. In our society of inactive, sedentary lifestyles and packaged, processed foods, metabolic syndrome is rampant. That means increased triglycerides from VLDL are also running rampant. The result: a 3 to 7-fold increase in risk for heart attack. Eliminating the metabolic syndrome is another battle we need to fight to conquer plaque. (See Shutting Off the Metabolic Syndrome.)
How can triglycerides be reduced?
Our triglyceride target of 60 mg or less dramatically reduces triglyceride availability. Without triglycerides, LDL and HDL can’t be processed into undesirable small particles. Among the strategies we use to reach our triglyceride target of 60 mg or less:

  • Fish oil—The omega-3 fatty acids in fish oil are our number one choice for substantially reducing triglycerides. Fish oil, 4000 mg per day, is a good starting dose (providing 1200 mg EPA+DHA); higher doses should be discussed with your physician, though we commonly use 6000–10,000 mg per day without ill-effect. Flaxseed oil, while beneficial for health, does not correct lipoprotein patterns. Consider a concentrated fish oil preparation (e.g., Omacor™, a prescription preparation, or “pharmaceutical grade” preparations from the health food store) if you and your doctor decide a high dose is necessary.
  • Weight loss to ideal weight or ideal BMI (25). If achieved with a reduction in processed carbohydrates, the effect will be especially significant. Exercise will compound the benefits of weight loss, triggering an even larger drop in triglycerides.
  • Reduction in processed carbohydrates—especially snacks; wheat-flour containing foods like breads, pasta, pretzels, chips, bagels, and breakfast cereals; white and brown rice; white potatoes. The reduction of high- and moderate-glycemic index foods is the factor that reduces triglycerides. High triglycerides are therefore a pattern that develops when someone follows a low-fat diet. For this reason, we do not advocate low-fat diets like the Ornish program. Reducing your exposure to wheat-containing snacks and processed foods is an especially useful and easy-to-remember strategy that dramatically reduces triglycerides.
  • Elimination of high-fructose corn syrup—This ubiquitous sweetener is found in everything from beer to bread. High-fructose corn syrup causes triglycerides to skyrocket 30% or more.
  • Niacin in doses of 500–1500 mg is an effective method of reducing triglycerides. Niacin also raises HDL, increases large HDL, reduces the number of small LDL particles, reduces VLDL, and modestly reduces total LDL. The preferred forms are over-the-counter Slo-Niacin® and prescription Niaspan®, the safest and best tolerated. Immediate-release niacin (just called niacin or nicotinic acid on the label) can also be taken safely, provided it is taken no more frequently than twice per day. Total daily doses of >500 mg should only be taken under medical supervision. Avoid nicotinamide and “no-flush niacin” (inositol hexaniacinate), neither of which have any effect whatsoever.
  • Green tea—The catechins (flavonoids) in green tea can reduce triglycerides by 20%. Approximately 600–700 mg of green tea catechins are required for this effect, the equivalent of 6–12 servings of brewed tea. (Tea varies widely in catechin content.) Nutritional supplements are also available that provide green tea catechins at this dose. The weight loss accelerating effect of green tea may add to its triglyceride-reducing power.
  • The thiazolidinediones (Actos®, or pioglitazone, and Avandia®, or rosiglitazone), usually prescribed for pre-diabetes or diabetes, can reduce triglycerides by 30%; Actos may be more effective than Avandia in this regard. However, these agents are accompanied by weight gain.
  • The fibrate class of prescription drugs (fenofibrate, or Tricor®, and gemfibrozil®, or Lopid) reduce triglycerides 30–40%, i.e., almost as effectively as fish oil.

The evil influences of VLDL and triglycerides are therefore erased from your risk profile by achieving the Track Your Plaque target of triglycerides 60 mg/dl or less. One or more of these strategies are usually required to bring your triglycerides to target. 

        William Davis, MD

Selected references:

Packard CJ. Understanding coronary heart disease as a consequence of defective regulation of apolipoprotein B metabolism. Curr Opin Lipidol 1999; 10:237–244.

Otvos J. Measurement of triglyceride-rich lipoproteins by nuclear magnetic resonance spectroscopy Clin Cardiol 1999;22 (Suppl II) II-21–II-27.

Grundy SM. Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome. Am J Cardiol 1998;81(4A):18B–25B.

Zilversmit DB. Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins. Clin Chem 1995;41(1):153–158.

Academic takes a well-aimed swipe at cholesterol drug ezetimibe - Briffa

Academic takes a well-aimed swipe at cholesterol drug ezetimibe
I am not particularly enthusiastic about cholesterol management. I don’t believe that the role cholesterol has in cardiovascular disease is as is popularly stated. But more importantly, when we use drugs to manage cholesterol the results are, by and large, disappointing. For example, treatment with statins does not save lives in people without a prior history of heart attack or stroke. Even in people at higher risk of cardiovascular disease, the great majority of treated individuals over a few years will not benefit. And then we have the problems of side effects.

The popularity of cholesterol management strategies in many way hinges on the idea that (LDL) cholesterol is bad, and lowering it is good. Yet, the scientific literature is littered with evidence that does not support either of these contentions. For example, we have evidence linking higher cholesterol levels with improved health outcomes and longevity in the elderly. We also have plenty of evidence which shows that cholesterol reduction will not always benefit health, and may in fact pose hazards here.

A case in point here concerns the drug ezetimibe. This medication reduces cholesterol, but unlike statins (which reduce cholesterol production in the liver), ezetimibe blocks the absorption of cholesterol from the gut. It’s generally very effective at reducing cholesterol levels, and because of this, the Food and Drugs Administration (FDA) licensed ezetimibe for use in the treatment of raised cholesterol in 2002. Since then, ezetimibe has gone to rack up sales in the order of $4 billion dollars annually.

Ezetimibe was licensed on the basis of its ability to lower cholesterol. At this time, no study has been published that it had benefits on health. So, what’s happened since? Well, there’s been a few studies that have looked at ‘clinical’ endpoints or disease processes (such as the build-up of plaque in the arteries), and the results have been far from encouraging.

For example, 2008 saw the publication of the so-called ENHANCE study which found that adding ezetimibe to simvastatin (a statin) led to an increase in the thickness of artery walls in the neck compared to simvastatin alone (though the difference was not statistically significant). The results of this trial were delayed by 2 years and had to be forced out of the manufacturers by the US Government.

Other studies have not only found no benefit, they’ve revealed worsening outcomes. In one study, treatment with ezetimibe was associated with (statistically significant) worsening of the narrowing of the arteries in the legs [1]. And then we have the inconvenience of the trials which link ezetimibe use to an increased risk of dying from cancer [2], which some researchers (in the pay of ezetimibe’s manufacturers) put down to ‘chance’, even though the data shows that the association is highly unlikely to be due to chance, and in all likelihood is a real effect.

Casual conversations with members of the medical profession reveal to me that the issues with ezetimibe are largely unrecognised, though there have been signs in the scientific literature that we are at last seeing some awareness of the issues. I came across a piece published recently in the journal Expert Opinion in Pharmcotherapy written by Dr Sheila Doggrell of the University of Queensland in Australia [3]. Dr Goggrell has reviewed the evidence and concludes this:

“…ezetimibe alone or in the presence of simvastatin has not been shown to have any irrefutable beneficial effects on atherosclerosis or cardiovascular morbidity and mortality. Thus, until/unless the use of ezetimibe is clearly shown to improve clinical outcomes, its use should be largely restricted to clinical trials investigating clinical outcomes and should not be used routinely in everyday practice.”

It is perhaps relevant that Dr Doggrell is an academic, which perhaps gives her the tools to take a cool hard look at the data and come to her own conclusions. Despite not being a clinician she is acutely aware that the only important thing is the impact ezetimibe has on health (not cholesterol levels). It’s an approach that I think more clinicians could do with adopting.

1. West AM, et al. The effect of ezetimibe on peripheral arterial atherosclerosis depends upon statin use at baseline. Atherosclerosis. 2011;218(1):156-62
2. Peto R, et al. Analyses of cancer data from three ezetimibe trials. NEJM 2008;359(13):1357-66
3. Doggrell SA. The ezetimibe controversy – can this be resolved by comparing the clinical trials with simvastatin and ezetimibe alone and together? Expert Opin Pharmacotherapy 2012;13(10):1469-80
Emphasis of bold text added by me - bd. Read thecomplete article here.

Wednesday, August 22, 2012

Coronary artery calcium bests other risk markers.. - O'Riordan

Coronary artery calcium bests other risk markers for CVD risk assessment

August 22, 2012 Michael O'Riordan

Winston-Salem, NC - A comparison of multiple risk markers suggests that coronary artery calcium (CAC) provides the most improvement in the assessment of cardiovascular disease risk in patients at intermediate risk for future events [1]. Ankle-brachial index, high-sensitivity C-reactive protein (CRP), family history, and CAC were all independent risk predictors for incident coronary heart disease and cardiovascular disease, but CAC provided superior discrimination and risk reclassification compared with the other risk markers.
"If you go to any cardiologist, all that they're doing while you're sitting in front of them is trying to put you into one of three risk categories," lead investigator Dr Joseph Yeboah (Wake Forest University School of Medicine, Winston-Salem, NC) told heartwire. "We know what we should do for low-risk people. We just emphasize lifestyle changes, and most of the time over 10 years nothing happens to them. We know that in high-risk patients, in addition to lifestyle, certain medications work. What we don't know how to do is treat people who fall into the intermediate group. They're in no-man's land. Yet we know a chunk of the people who have heart attacks are within this group. This tells us that there are people who are wrongly put into this category based on current risk tools."
In an editorial accompanying the study [2], Dr J Michael Gaziano (Brigham and Women's Hospital, Boston, MA) and Dr Peter Wilson (Atlanta Veteran Affairs Medical Center, GA) agree that a CAC scan might help guide clinical decisions, but radiation exposure and costs remain important considerations. "Coronary artery calcium findings also are somewhat resistant to change even in the face of improvement in risk factors and may be useful as a single measure for assessment, especially when refinement of a risk estimate is important, but might not be useful for tracking risk over time," according to the editorialists.
The study and editorial are published in the August 22, 2012 issue of the Journal of the American Medical Association.

Data from the MESA study
Using data from the Multiethnic Study of Atherosclerosis (MESA), the researchers identified 1330 intermediate-risk patients without diabetes mellitus who had data available for all six of the following cardiovascular risk markers: CAC, carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), and CRP, as well as family history of coronary heart disease. The purpose of the study, explained Yeboah, was to test the effectiveness of these "top-tier" risk markers for cardiovascular risk stratification when added to conventional risk scores in the same group of patients.
After a median follow-up of 7.6 years, there were 123 cardiovascular events. CAC, ABI, high-sensitivity CRP, and family history of coronary heart disease were independently associated with incident coronary heart disease, defined as a composite of MI, angina followed by revascularization, resuscitated cardiac arrest, and coronary heart disease death.
Association of risk markers with incident coronary heart disease*

Risk markerHazard ratio (95% CI)
Ankle-brachial index0.79 (0.66-0.96)
Brachial flow-mediated dilation0.93 (0.74-1.16)
Coronary artery calcium 2.60 (1.94-3.50)
Carotid intima-media thickness1.17 (0.96-1.45)
Family history2.18 (1.38-3.42)
High-sensitivity CRP1.28 (1.00-1.64)

*Adjusted for age, sex, race/ethnicity, systolic blood pressure, total cholesterol, HDL cholesterol, smoking status, body-mass index, use of blood-pressure medication, and use of statins

For coronary and cardiovascular disease events, which included stroke and cardiovascular death, the addition of each of the six markers to the Framingham risk score significantly improved the discrimination of clinical events compared with the Framingham score alone. The area under the curve (AUC) improved for all the risk markers but improved the most with CAC scoring. With the addition of CAC, the AUC improved from 0.623 to 0.784.
Similarly, CAC fared best when assessed by net reclassification improvement (NRI), a measure of the relative improvement in the classification of risk with the additional variable. The researchers note that 25.5% of the events were reclassified correctly to the high-risk category, while 40.4% of nonevents were reclassified into the low-risk group. The NRI for the addition of CAC to the Framingham risk score, plus race/ethnicity, was 0.659, the highest reported NRI of the six risk markers.

CAC fares best, but there are caveats
While CAC performed the best of the six markers, Yeboah said that there are important caveats to the results. Echoing the editorialists, he told heartwire that only CAC scoring exposes patients to a small, but not trivial, amount of radiation. He said the long-term effects of radiation on patients remain unknown and will need to be determined before widespread screening using CAC can be used to help the decision-making process.
There would be no benefit to society if we drastically reduce the number of heart attacks only to find out that everybody is developing cancer.
"There would be no benefit to society if we drastically reduce the number of heart attacks only to find out that everybody is developing cancer," said Yeboah.
In addition, there are no outcome studies showing that adding CAC screening to traditional risk scoring systems in intermediate-risk patients reduces the risk of cardiovascular events. If these caveats are addressed, said Yeboah, then CAC screening should be used for the 28 million US adults who fall within the intermediate-risk category. Currently, the American Heart Association and the European Society of Cardiology say it is "reasonable" to use CAC as a screening method for intermediate-risk patients.
In their editorial, Gaziano and Wilson note that research into general cardiovascular disease prevention is timely, given that the National Cholesterol Education Program (NCEP) Adult Treatment Panel 4 treatment guidelines are expected this year, and the addition of novel risk markers to Framingham or the Reynolds risk score might help physicians make a decision about whether or not to start a patient on lifelong statin therapy.
They note, however, that if a patient is near a boundary for lipid-lowering therapy, the doctor can simply choose to see the patient again in a few months rather than order a costly CAC imaging test. Reassessing vascular risk with a patient visit to repeat tests might improve accuracy and reveal trends that could help guide treatment decisions, according to Gaziano and Wilson. While CAC scores can help augment the risk-assessment process, they have limited utility in tracking a patient's progress, as the test is not likely to be repeated over time.
Read the full article here.

Effects of low carbohydrate diets on cardiovascular risk factors.

Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors.


Centro Hospitalar Vila Nova Gaia/Espinho, Gaia, Portugal Centro Hospitalar do Porto, Porto, Portugal Faculdade de Medicina da Universidade do Porto, Porto, Portugal Veteran Affairs Medical Center, Durham, NC, USA Duke University Medical Center, Durham, NC, USA.


A systematic review and meta-analysis were carried out to study the effects of low-carbohydrate diet (LCD) on weight loss and cardiovascular risk factors (search performed on PubMed, Cochrane Central Register of Controlled Trials and Scopus databases). A total of 23 reports, corresponding to 17 clinical investigations, were identified as meeting the pre-specified criteria. Meta-analysis carried out on data obtained in 1,141 obese patients, showed the LCD to be associated with significant decreases in body weight (-7.04 kg [95% CI -7.20/-6.88]), body mass index (-2.09 kg m(-2) [95% CI -2.15/-2.04]), abdominal circumference (-5.74 cm [95% CI -6.07/-5.41]), systolic blood pressure (-4.81 mm Hg [95% CI -5.33/-4.29]), diastolic blood pressure (-3.10 mm Hg [95% CI -3.45/-2.74]), plasma triglycerides (-29.71 mg dL(-1) [95% CI -31.99/-27.44]), fasting plasma glucose (-1.05 mg dL(-1) [95% CI -1.67/-0.44]), glycated haemoglobin (-0.21% [95% CI -0.24/-0.18]), plasma insulin (-2.24 micro IU mL(-1) [95% CI -2.65/-1.82]) and plasma C-reactive protein, as well as an increase in high-density lipoprotein cholesterol (1.73 mg dL(-1) [95%CI 1.44/2.01]). Low-density lipoprotein cholesterol and creatinine did not change significantly, whereas limited data exist concerning plasma uric acid. LCD was shown to have favourable effects on body weight and major cardiovascular risk factors; however the effects on long-term health are unknown.
Emphasis added by bd.
Read the full article here.


Tuesday, August 21, 2012

Heart Calcium Scan Most Effective in Predicting Risk of Heart Disease

Released:8/20/2012 10:45 AM EDT
Source:Wake Forest Baptist Medical Center

Newswise — WINSTON-SALEM, N.C. – Aug. 21, 2012 – Heart calcium scans are far superior to other assessment tools in predicting the development of cardiovascular disease in individuals currently classified at intermediate risk by their doctors, according to researchers at Wake Forest Baptist Medical Center.

The test, known as coronary artery calcium (CAC), uses a CT scan to detect calcium build-up in the arteries around the heart. The study findings are presented in the Aug. 22 issue of the Journal of the American Medical Association.

Current medical guidelines recommend classifying individuals as high, intermediate or low risk using the Framingham Risk Score (FRS), a cardiovascular risk-prediction model. However, doctors realize that the model isn’t perfect and that the intermediate group actually includes some individuals who could benefit from more aggressive drug therapy, as well as individuals who could be managed solely with lifestyle measures.

“We know how to treat patients at low and high risk for heart disease, but for the estimated 23 million Americans who are at intermediate risk, we still are not certain about the best way to proceed,” said Joseph Yeboah, M.D., assistant professor of cardiology at Wake Forest Baptist and lead author of the study.

The Wake Forest Baptist study, which was funded by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health, evaluated which of the top-tier assessment tools best identified people within the intermediate group who were actually at higher or lower risk.

Determining the relative improvements in prediction afforded by various tests, especially when used in conjunction with the FRS, could help identify intermediate-risk people who may benefit from more aggressive primary prevention interventions, including the use of aspirin and the setting of lower targets for drug treatment of LDL cholesterol and blood pressure, Yeboah said.

Using data from the NHLBI’s Multi-Ethnic Study of Atherosclerosis (MESA) study, the researchers did a head-to-head comparison of six top assessment tests for cardiovascular risk prediction in intermediate-risk people: CAC score, ankle-brachial index, brachial flow mediated dilation, carotid intima-media thickness, high sensitivity C-reactive protein and family history of heart disease.
Of the 6,814 total MESA participants from six communities across the country, 1,330 were considered at intermediate risk and were included in this study. The researchers determined that the CAC score proved the best in predicting which among the intermediate-risk people would go on to have heart disease in the ensuing 7.5 years (average) of follow-up observation.

“If we want to concentrate our attention on the subset of intermediate-risk patients who are at the highest risk for cardiovascular disease, CAC is clearly the best tool we have in our arsenal to identify them. However, we have to look at other factors such as costs and risks associated with radiation exposure from a CT scan before deciding if everyone in the intermediate group should be screened,” Yeboah said.

Additional research is needed to explore the costs, benefits and risks of widespread use of CAC screening in people at risk of heart disease, he said.

The study’s co-authors are: Robyn L. McClelland, Ph.D., University of Washington, Seattle; Tamar S. Polonsky, M.D., University of Chicago; Gregory L. Burke, M.D., Jeffery J. Carr, M.D., and David M. Herrington, M.D., Wake Forest Baptist; Christopher T. Sibley, M.D., National Institutes of Health; Daniel O’Leary, M.D., Tufts Medical Center; David C. Goff Jr., M.D., Ph.D., University of Colorado; and Philip Greenland, M.D., Northwestern University
Read the full article here.

Ask Your Doctor for a Complete Lipid Evaluation - Watson

Ask Your Doctor for a Complete Lipid Evaluation Sent Saturday, March 10, 2012

Diet Heart News, volume 2, number 3
Heart disease is the #1 cause of death. About 50 percent of people who die suddenly from heart disease have low or normal cholesterol. To protect yourself from heart disease, ask your doctor for a complete lipid evaluation. Fast 10-12 hours before blood is drawn (you can drink water). Because Total Cholesterol (TC) and LDL cholesterol are not the most reliable predictors of heart disease, they are not posted in the following chart.
QUICK SUMMARY: Focus on Fasting Glucose, HDL, Triglycerides (TG) and the all important TG:HDL ratio. Keep in mind that before the advent of cholesterol-lowering statin drugs, the normal range for Total Cholesterol (TC) was: 180 mg/dl to 340 mg/dl. Also, it's important to note that LDL is actually a family of particles. A discussion about LDL subclasses and LDL subclass testing follows in the summary of this article.

1. C-reactive protein (CRP) is produced by the liver in response to inflammation in the body. If monitored early enough, elevated CRP can be an early warning of a heart attack several years in advance. Optimum levels are below 1 mg/l. (You will have to request this test with most doctors.)

2. Fasting Glucose (FG) measures fasting blood sugar. Lowest all-cause mortality is associated with fasting glucose in the range of 80-89 mg/dl. According to the clinical experience of Dr. Robert Atkins, the risk of heart disease increases in linear manner as your Fasting Glucose goes over 100 mg/dl. (Specifically ask for this inexpensive test.)

3. Fibrinogen is a protein that in excess promotes blood clots. Elevated fibrinogen = thicker blood. Thicker blood flows less easily through partially blocked arteries. Consistent elevated fibrinogen (over 350 mg/dl) conveys a 250 percent increased risk of heart disease compared to people with fibrinogen levels below 235. (People who have recently suffered a heart attack will have elevated fibrinogen levels.)

4. Homocysteine is normally rapidly cleared from the bloodstream. Elevated homocysteine is a result of B-vitamin deficiencies, particularly folic acid, B-6 and B-12. Elevated homocysteine is associated with increased risk of heart attack, stroke, and all cause mortality. Levels less than 8 mmol/L are associated with longevity. (Again, you may have to request this test.)

5. Lipoprotein(a) has been called the "heart attack cholesterol." Lipoprotein(a) is a sticky protein that attaches to LDL and accumulates rapidly at the site of arterial lesions or ruptured plaque. Readings of 30 mg/dl or more indicate serious increased risk of heart disease, especially in the presence of elevated fibrinogen (>350). While the Lp(a) level is largely genetically determined, it can be influenced by nutritional factors, such as high blood sugar and trans fatty acid consumption. (This test may not be as important as the rest and is seldom done routinely.)

6. HDL is made in the liver and acts as a cholesterol mop, scavenging loose cholesterol and transporting it back to the liver for recycling. HDL is associated with protection from heart disease. You want as much HDL as possible. HDL of 60 or more is associated with protection for men--70 or more for women.

7. Triglycerides (TG) should be under 100 mg/dl. Triglycerides are blood fats made in the liver from excess energy - especially carbohydrates. Risk is linear--the higher the number, the greater the risk, especially for women. While doctors may insist that a reading up to 150 is okay, Dr. Atkins' clinical experience suggested otherwise.

8. TG:HDL ratio is the most reliable predictor of heart disease. Calculate your ratio by dividing TG by HDL. As an example, if TG = 80 and HDL = 80, your ratio is 1:1 representing low risk of heart disease. If your TG = 200 and your HDL = 50, your ratio is 4:1 representing serious risk of heart disease.

9. VLDL - Increasingly, Very Low Density Lipoprotein is measured/calculated. VLDL is sent out from the liver to deliver those liver made fats (Triglycerides) - as opposed to a Chylomicron that delivers dietary fat from the gut. Generally, VLDL is one fifth of your triglyceride level, although this is less accurate if your triglyceride level is greater than 400 mg/dl. (Beyond the scope of this article, LDL is the offspring of VLDL - they are closely-related.)

LDL particle size: Small dense Pattern B/Large fluffy Pattern A
LDL - low density lipoprotein - is a family of particles. A lot of people with elevated LDL do not develop coronary artery disease, while individuals with low or modest levels often develop serious disease. This can be explained by the LDL particle number and size. Routine cholesterol testing only reveals the amount of LDL; not the quality of LDL.
We now know (my doctor didn't) that there are different subclasses of LDL (and HDL). Under an electron microscope, some LDL particles appear large and fluffy; others small and dense. The big, fluffy particles are benign, while the small dense particles are strongly associated with increased risk of heart disease.

In excess, small dense LDL is toxic to the artery lining (the endothelium), and much more likely to enter the vessel wall - become oxidized - and trigger atherosclerosis. It's becoming consensus medical opinion that only oxidized LDL can enter the macrophages in the lining of the arteries and contribute to plaque buildup.

How Do You Know What Size LDL You Have?
Certain clinical factors predict the presence of small dense LDL. These markers include HDL below 40 in men; below 50 in women - and Triglycerides (TG) higher than 120 mg/dl. Diabetes or pre-diabetes also predicts small dense LDL (Pattern B).
To determine LDL particle size, ask your doctor for a VAP (Vertical Auto Profile) test, which separates lipoprotein particles using a high speed centrifuge. The VAP test measures the basic information provided by a routine cholesterol test, but also identifies lipoprotein subclasses, LDL and HDL. (Go to http://thevaptest.com for more information.)

There are other tests as well. The NMR LipoProfile analyzes the number and size of lipoprotein particles by measuring their magnetic properties (http://theparticletest.com). Also Berkeley HeartLab's LDL Segmented Gradient Gel Electrophoresis test measures all seven subclasses of LDL. (http://bhlinc.com).

If you don't have insurance, request the inexpensive fasting glucose test. Any number over 100 - over 95 according to the late Dr. Atkins - is an early warning of diabetes, metabolic syndrome, and heart disease. If you have insurance or can afford a complete lipid panel, consider additional testing to determine the size and number of LDL particles. Remember, "A stitch in time saves nine."
Read the full article here.

The UCLA Study: Elevated LDL Not Associated With Heart Attack Risk

The UCLA Study: Elevated LDL Not Associated With Heart Attack Risk Sent Wednesday, November 23, 2011

Diet Heart News, volume 1, number 8

The UCLA Study: Elevated LDL Not Associated With Heart Attack Risk

Since the early 1950s, mainstream researchers have been seeking the cause of atherosclerosis and heart disease spearheaded early on by University of Minnesota professor and American Heart Association board member Ancel Keys. The result - the 50 year old Diet Heart or Cholesterol Hypothesis:

If you eat too much food containing cholesterol and/or saturated fat, the level of cholesterol in your blood will rise. The excess cholesterol will be deposited in artery walls, causing them to thicken and narrow. In time, this will block blood supply to the heart or brain causing a heart attack or stroke.
According to this still unproven but enduring hypothesis, high blood cholesterol is caused by an atherogenic diet high in cholesterol and saturated fat - found mainly in animal products such as red meat, whole milk, eggs, butter - and the tropical saturates coconut and palm. In this scenario, high blood cholesterol is the main cause of atherosclerosis and heart disease.

The medical and nutrition communities and various government agencies have been behind Diet Heart ever since. If animal fat and high blood cholesterol are the chief villains, then cholesterol-lowering diets and cholesterol-lowering drugs would appear to be wise choices. But 50 years later - after a lengthy test of time - the incidence of heart disease has not gone down as promised, and researchers like science writer Gary Taubes have uncovered a great deal of their evidence that is unsupportable, contradictory, and hopelessly wrong.

A look at the recent five year UCLA/AHA Study
The UCLA research team used an American Heart Association database that included 541 hospitals across the country. The database provided detailed information on 136,905 patients hospitalized for cardiovascular disease whose lipid levels upon hospital admission were documented.
The results after five years: 75 percent of patients hospitalized for a heart attack had LDL cholesterol below 130 mg/dl - in the so called safe range. Even more astounding, 50 percent of patients had LDL below 100 mg/dL - considered optimal. (21 percent of the patients were taking a statin cholesterol-lowering drug.)

Now don't you think that the UCLA researchers would have concluded that there was no association between elevated LDL and risk of heart attacks? After all, this was a five year study of heart attacks suffered by 136,905 patients in an American Heart Association database that included records from 541 hospitals.

Yes - this should have been the nail in the coffin for the Diet Heart or Cholesterol Hypothesis, but not according to study director Dr. Gregg C. Fanarow, Professor of Cardiovascular Medicine and Science, David Geffen School of Medicine, UCLA, who concluded:

"Almost 75 percent of heart attack patients fell within recommended targets for LDL cholesterol, demonstrating that the current guidelines may not be low enough to cut heart attack risk... "
May not be low enough!

Low cholesterol is already associated with depression and death by accidents, cancer and violence. According to the American Heart Association's journal Circulation, 1992; 86:3, the all cause death rate increases when total cholesterol drops below 180. Isn't there sufficient evidence now to conclude that elevated LDL and total cholesterol are not the cause of heart attacks and that the cholesterol hypothesis should be discarded along with official low fat diets and cholesterol-lowering drugs?
Don't hold your breath! UK cardiologist Dr. Malcolm Kendrick:

"I have come to realize that there is, literally, no evidence that can dent the cholesterol hypothesis... The effect of this study on the cardiovascular research community was....as you would expect...nothing at all, a deafening silence..."

Dr. Fonarow disclosed that he has conducted research for GlaxoSmithKline and Pfizer and serves as a consultant and has received honorarium from the following drug companies: Abbott, AstraZeneca, GlaxoSmithKline, Merck, Pfizer and Schering Plough.

Dr. H. Bryan Brewer, a physician-scientist at the National Heart, Lung and Blood Institute, failed to disclose his ties to AstraZeneca. Brewer had previously written a glowing report in a medical journal about Crestorwithout disclosing that he is a paid consultant and had presided over a company-sponsored symposium."

He and the others forgot!

Earlier in 2004, the doctors in the National Cholesterol Education Program (NCEP) who wrote the current cholesterol guidelines and, in effect, control cardiology, failed to disclose that six of the nine authors had direct financial ties to the makers of statin drugs, including: Pfizer's Lipitor, Bristol-Myers Squibb's Pravachol, Merck's Lovastatin, and AstraZeneca's Crestor.

The new more stringent cholesterol-lowering guidelines boosted statinsales from $15 billion in 2004 to over $23 billion in 2005. And now the UCLA study provides more proof that lowering cholesterol with drugs or diet will not reduce cardiovascular disease or the risk of heart attack.

But as Winston Churchill said: "Men occasionally stumble over the truth, but most of them pick themselves up and hurry off as if nothing had happened." [especially if there is money to be made].
Read the complete article here.

Monday, August 20, 2012

One more credible article on the yoke about egg yokes - Kock

The 2012 Atherosclerosis egg study: Plaque decreased as LDL increased with consumption of 2.3 eggs per week or more

 August 20, 2012 Ned Kock Health Correlator
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A new study by David Spence and colleagues, published online in July 2012 in the journal Atherosclerosis ( 1), has been gaining increasing media attention (e.g., 2). The article is titled: “Egg yolk consumption and carotid plaque”. As the title implies, the study focuses on egg yolk consumption and its association with carotid artery plaque buildup.

The study argues that “regular consumption of egg yolk should be avoided by persons at risk of cardiovascular disease”. It hints at egg yolks being unhealthy in general, possibly even more so than cigarettes. Solid critiques have already been posted on blogs by Mark Sisson, Chris Masterjohn, and Zoe Harcombe ( 3, 4, 5), among others.

These critiques present valid arguments for why the key findings of the study cannot be accepted, especially the finding that eggs are more dangerous to one’s health than cigarettes. This post is a bit different. It uses the data reported in the study to show that it (the data) suggests that egg consumption is actually health-promoting.

I used the numbers in Table 2 of the article to conduct a test that is rarely if ever conducted in health studies – a moderating effect test. I left out the “egg-yolk years” variable used by the authors, and focused on weekly egg consumption (see Chris’s critique). My analysis, using WarpPLS ( 6), had to be done only visually, because using values from Table 2 meant that I had access only to data on a few variables organized in quintiles. That is, my analysis here using aggregate data is an N=5 analysis; a small sample indeed. The full-text article is not available publicly; Zoe was kind enough to include the data from Table 2 in her critique post.

Below is the model that I used for the moderating effect test. It allowed me to look into the effect that the variable EggsWk (number of eggs consumed per week) had on the association between LDL (LDL cholesterol) and Plaque (carotid plaque). This type of effect, namely a moderating effect, is confusing to many people, because it is essentially the effect that a variable has on the effect of another variable on a third. Still, being confusing does not mean being less important. I should note that this type of effect is similar to a type of conditional association tested via Bayesian statistics – if one eats more eggs, what is the association between having a high LDL cholesterol and plaque buildup?

You can see what is happening visually on the graph below. The plot on the left side is for low weekly egg consumption. In it, the association between LDL cholesterol and plaque is positive – eating fewer eggs, plaque and LDL increase together. The plot on the right side is for high weekly egg consumption. In this second plot, the association between LDL cholesterol and plaque is negative – eating more eggs, plaque decreases as LDL increases. And what is the inflection point? It is about 2.3 eggs per week.

So the “evil” particle, the LDL, is playing tricks with us; but thankfully the wonderful eggs come to the rescue, right? Well, it looks a bit like it, but maybe other foods would have a similar effect. In part because of the moderating effect discussed above, the multivariate association between LDL cholesterol and plaque was overall negative. This multivariate association was estimated controlling for the moderating effect of weekly egg consumption. You can see this on the plot below.

The highest amount of plaque is at the far left of the plot. It is associated with the lowest LDL cholesterol quintile. (So much for eggs causing plaque via LDL cholesterol eh!?) What is happening here? Maybe egg consumption above a certain level shifts the size of the LDL particles from small to large, making them harmless. (Saturated fat consumption, in the context of a nutritious diet in lean individuals, seems to have a similar effect.) Maybe eggs contain nutrients that promote overall health, leading LDL particles to "behave" and do what they are supposed to do. Maybe it is a combination of these and other effects.
Reade the complete article here.