Preventing and Reversing Heart Disease - DACH

Preventing and Reversing Heart Disease, Part Three

Preventing and Reversing Heart Disease
Part Threeby Jeffrey Dach MD
This Article is Part Three.
For Part One Click Here,
and for  Part Two Click Here.

A Man with Progressive Coronary Artery Disease Unresponsive to Statins
62 year old Jim came just had his third cardiac stent.  A year ago, Jim noticed a “tight feeling” in his chest radiating to his throat, was rushed to the ER, and doctors found he was having a heart attack. A coronary angiogram showed extensive coronary artery disease with irregular plaque formation.

Progressive Coronary Artery Plaque in Spite of Low Cholesterol
For 12 years now, Jim’s cholesterol level had been driven down into the 140 area by the “top cardiologist in the area”, who prescribed a hefty dose of a statin anti-cholesterol drug.  In spite of the lowest cholesterol level on the planet,  Jim’s heart disease progressed relentlessly with worsening calcium scores, worsening angiograms, and worsening symptoms of chest pain.   His disease progression was obviously not caused by an elevated cholesterol level.  For a discussion of how elevated cholesterol is NOT the Cause of Heart Disease, see my article on patients with familial hypercholesterolemia who have very high cholesterol, yet have no heart disease, proving the hypothesis that cholesterol levels are not necessarily a risk factor for heart disease, and reducing cholesterol levels with drugs may be a fruitless endeavor.

Doctors advise Jim to Stop Testosterone
Jim had been taking topical testosterone for the past 5 years, and recently stopped it because of advice from his cardiologist who pointed a finger and said, “You should stop the testosterone….The testosterone is bad for your heart and probably caused your heart attack“.  Jim came to see me for a second opinion.

Jim’s Doctor is Right About That
Jim’s doctor is right in that a number of recent studies have shown a small increase in heart attack rate in men starting testosterone.   This is caused by increased hematocrit (red blood cell count) and increased iron stores which thicken the blood and make it more susceptible to blood clot formation, all risk factors for heart attack.  See  my article on this.  The simple solution is to monitor blood count and iron levels, and donate blood at the blood bank every 4 to 6 weeks to reduce iron and red cells.

Our Approach to Preventing Heart Disease
I must preface these remarks with our approach to prevention and reversal of heart disease which is outlined in Part One  and Part Two  of this series.  We credit and rely heavily on the  “Track Your Plaque Program ” by William Davis MD.  We also use the Linus Pauling Protocol.

Bioidentical Hormones For Prevention and Reversal of Heart Disease
In this article we will revisit the role of the testosterone and estradiol in prevention and reversal of heart disease, looking at the latest research.  Firstly, let’s try to answer the question:

” Is low testosterone a risk factor for heart diease, and is normal testosterone level protective of heart disease?” 

 

Here we assume red cell count and iron levels are kept under control with monthly trips to the blood bank, so there is no short term increase in heart attack rate from hypercoagulability, as noted in a few recent studies of men started on testosterone.

Low Testosterone is Predictive for Increased Mortality from Heart Disease
If testosterone was causative of heart disease,  one would expect men with high testosterone to have more heart disease, and men with low testosterone to have less heart disease.  This is exactly opposite of four major studies showing men with low testosterone have both increased all-cause mortality and increased heart disease mortality.(1-4)

Testosterone Levels in Men With Heart Disease
A recent study by Malkin looked at Testosterone levels in men with known underlying heart disease.  He showed that low Testosterone is common in men with underlying heart disease, and this is associated with almost double the mortality rate.(5)  Again these findings suggest that higher Testosterone is protective and prevents progression of heart disease.  The assumption that Testosterone causes progression of atherosclerosis plaque has been shown false.(6-9).
Above image: Cross section of arteries (left to right) showing development of fatty streak which enlarges into the atherosclerotic plaque.   Animal Studies on Mechanism of Protection
A number of elegant animal studies have been done to elucidate the mechanism by which testosterone is protective of heart disease.  A 1999 study by Alex Andersen in rabbits showed that testosterone reduced aortic atheroscleosis.(10)  Castrated rabbits had low testosterone levels and doubled the  aortic atherosclerosis plaque formation, suggesting that testosterone has a strong preventive effect on male atherosclerosis. In the groups receiving testosterone or DHEA they found marked inhibition of atherosclerosis compared with placebo. The mechanism was not clearly defined.  They speculated on a non-lipid mediated mechanism, possibly related to aromatase conversion of testosterone to estrogen.(10 )

Mouse Model- It’s Really the Estrogen That’s Protective
In an elegant 2001 study published in PNAS, Nathan et al used a mouse model of accelerated atherosclerosis to show that testosterone inhibits atherosclerosis by its conversion to estradiol by the aromatase enzyme.  Similar protection from atherosclerosis was obtained by administering estradiol.  In addition, blocking conversion of testosterone to estradiol with the aromatase inhibitor, anastrazole, eliminated the protective effect, and these animals had progressive atherosclerosis.(11)  Dr Nathan says:

“Testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall”.(11)

 

This information suggests that men with heart disease should NOT take arimidex (anastrazole) along with their testosterone replacement therapy.

Genetically Altered Mouse Model Provides Answers
These findings were confirmed  by Nettleship  in a 2007 study published in Circulation using the Tfm genetically modifired mouse.  This is a mouse genetically altered to have a defective androgen receptor.  In these mice,  testosterone cannot work through its normal pathway, since there is no receptor.  In spite of the lack of androgen receptor, Nettleship found that testosterone replacement in these mice attenuated atherosclerotic changes (fatty streak formation), suggesting the protective effect of testosterone was independent of the testosterone receptor.  The authors concluded that the protective benefits of testosterone were through aromatase conversion to estradiol, and then via the estrogen receptor pathways.(12)

Dr Nettleship’s findings were confirmed by Bourghardt  in a Nov 2010 study published in Endocrinology which using ”ARKO” mice, genetically modified to “knock out” the Androgen Receptor, modified to be Apo-E deficient (to accelerate atherosclerosis).  The authors showed that testosterone therapy administered to the ARKO mice inhibited atherosclerosis.  However inhibition of atherosclerosis was more profound in the wild type mice that still had intact androgen receptors.  The authors concluded the mechanism of protection of testosterone was due to both mechanisms, through the Androgen Receptor as well as through aromatase conversion to estradiol.(13 )

Conclusion:
These genetically modified mouse studies suggest that testosterone’s cardio-protective benefits are due to conversion to estrogen, and that estrogen is the cardioprotective agent.  Both estrogen and testosterone are bioidentical hormones.   Clearly the message here is Testosterone Replacement Therapy should be an important part of any heart disease prevention program,  in those patients who have low Testosterone levels.

Why Do Men Have More Heart Disease Than Women ?
Men and women are quite different when it comes to heart disease.  Men have more than twice the risk of dying from coronary disease than women. (14)  In women, coronary artery disease (CAD) develops on average 10 years later than in men.(15)  Could higher levels of estrogen (estradiol) in women explain the protection enjoyed by women?

Estrogen is Protective
Dr Xing from the University of Alabama would say, yes of course.  In a 2009 article, Dr Xing names a number of mechanisms by which estradiol protects both men and women from heart disease. He says:

“Estrogens have antiinflammatory and vasoprotective effects.  Natural endogenous estrogen 17β-estradiol (bioidentical) has been shown to cause rapid endothelium-independent dilation of coronary arteries of men and women, to augment endothelium-dependent relaxation of human coronary arteries, and improve endothelial function…Observational studies have shown substantial benefit (50% reduction in heart disease) of hormone therapy in women who choose to use menopausal hormones.”(15 )

 

Estrogen is Protective of Heart Disease
A 2010 study in European Heart by Kitamura et al  compared males to female heart attack rates. They found 61% fewer heart attacks in women of reproductive age with high estrogen levels compared to males of the same age.  The authors conclude that estrogen confers cardioprotective benefits.(16)
A review of the Nurse Health Study published in the 2000 Annals  showed 40% reduction in heart disease in hormone replacement users and that “postmenopausal hormone use decreases risk for major coronary events.” (17-18)

See my article on how estrogen protects women from heart disease: Bioidentical Hormones Prevent Heart Disease.

Comparing Three Treatment Modalities
There are three mainstream treatment modalities for coronary artery disease.
1) Surgery with coronary artery bypass.
2) Balloon angioplasty with stenting.
3) Medical Therapy with drugs such as calcium channel blockers and beta blockers.
Which one of these treatment modalities confers the most benefit? The answer is:  None of Them.
Medical Management with Drugs Provides the Same Benefit as Cardiac Angioplasty, Stenting or Bypass
Eleven randomized studies reviewed 3,000 patients with stable coronary artery disease.  Treatment with  angioplasty and stenting showed the same mortality and heart attack rate as drug treatment (also known as medical management).  They both offer the same benefit.(19)(20)
The MASS II study  published in the 2007 Circulation showed medical managment with drugs to have similar outcome to stent or bypass. (21)    A troubling fact remains that after all these studies have been completed,  there is no conclusive evidence that intervention with CABG (coronary artery bypass graft) or coronary stent  is superior to medical therapy (drugs) for treating multivessel coronary artery disease with stable angina and preserved ventricular function.(21 )  Sorano attempts to sort out the fine points of selecting between treatment modalities in her 2009 report. (22)

How Can Drugs Provide the Same Outcome as Surgery or Stenting?
The EPC, the Endothelial Progentor Cell.
Now we have an important question to ask.  How is it possible that the humble country doctor with a few drugs can provide similar outcomes when compared to the high and mighty cardiac surgeon and the interventional cardiologist?  How can drug treatment do as well or better than the cardiac stent or surgical bypass procedure?

I suggest the answer resides in the phenomenon known as “collateral vessel formation”.  The heart has the ability to grow new blood vessels which provide blood flow around the blocked artery.  Medical treatment gives the heart time to grow new collateral vessels. The key to understanding this new vessel formation is the endothelial progenitor cell, also known as the EPC. The EPC is a special type of stem cell found in the bone marrow that circulates to injured myocardium where they promote local angiogenesis, making new blood vessels. (23)

Turning On The Endothelial Progenitor Cell – How to Do It?
A previous article on telomeres and anti-aging discussed the role of estrogen as an activator of telomerase which serves as an anti-aging therapy.  Recent research shows that estrogen  activates the telomeres on endothelial progenitor cells and improves the EPC functional capacity. (24)  Another study showed reduced numbers of EPC cells in the peripheral blood of men with low testosterone levels. (25)

Estradiol Enhances Recovery After Myocardial Infarction – Collateral Vessels
An elegant mouse study was published by Isakura in 2006 Circulation .  They used a mouse model in which myocardial infarction (heart attack) was induced by ligation of the left coronary artery.  The estradiol treated mice showed increased circulating EPC’s and greater capillary density in the recovering myocardium.  This indicates enhanced recovery in the estradiol treated mice by regrowth of collateral vessels. (26)(27)(28)

A study from Bolego in Italy showed that the cardio protective benefits of estrogen could be duplicated with an estrogen receptor drug called PPT. They found that:

“myocardial ischemia-reperfusion injury was exacerbated by ovariectomy (which reduced estrogen levels).   This injury returned to baseline following treatment with estrogen-like drug PPT.”

The protective effects were linked to increased levels of endothelial progenitor cells (EPCs).(29)

Conclusion
Recent research shows the cardioprotective benefits of the bioidentical hormones, testosterone and estrogen.  Testosterone benefit appears mediated by conversion to estradiol via the aromatase enzyme.  Estradiol’s benefits appear related to activation of Endothelial Progenitor Cells which invoke new collateral circulation in areas of injury.

Another treatment modality called EECP also creates new collateral vessels.  Read my article on EECP here.
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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.

Dr. Ron Rosedale On The Facts About Cholesterol Dr. Ron Rosedale talks about common cholesterol myths, and exposes the deceptions and misconceptions that most people have been told. (Interview with Dr. Mercola).

More articles on Cholesterol

Reference Sources 114, 136, 151, 158

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