Healthy Decisions for the Love of Health

 Atherosclerosis

Symptoms and Diagnosis of Atherosclerosis

Symptoms associated with atherosclerosis depend on the stage of the disease. In the early stages, which may last for decades, it rarely has any symptoms. In the later stages, the symptoms are caused by the obstruction of blood flow.

In the coronary arteries, the most common symptoms of atherosclerosis in men are chest pain (angina) and shortness of breath. In the arteries of the legs (peripheral arterial disease), the most common symptoms are leg pain (claudication). Unfortunately, atherosclerosis that occurs in the brain often has no symptoms; the first indication of serious vascular disease in the brain is often a stroke. So-called mini strokes, which have temporary symptoms similar to those of full-blown strokes, are sometimes an important warning sign of an impending stroke.

If a plaque deposit in an artery ruptures, the symptoms are likely to be acute, often in the form of a heart attack, stroke, or pulmonary embolism. Each of these is a critical condition that requires immediate medical supervision. People who suspect they may be suffering from one of these conditions should call 911 immediately. Symptoms include fainting, seizures, breathlessness, pain, and cognitive impairment.

 

Blood testing is recommended for all adults. A comprehensive blood test will measure levels of LDL, HDL, VLDL, and triglycerides, as well as levels of C-reactive protein, homocysteine, and fibrinogen. HealthSmart Nutrition recommends blood testing at least annually. More frequent testing might be recommended to monitor progress after a patient begins a heart-healthy supplementation program.

People who have suffered a heart attack or stroke or who have symptoms indicative of coronary artery ischemia (such as chest pain) should see a physician. They may be required to undergo additional testing to determine the health of their coronary arteries.

Additional tests include the following:

Angiography. During this test, a catheter is inserted through a large artery, usually in the groin, and guided into the heart, where it is used to deliver contrast material into the coronary arteries. This contrast material is visible under x-ray. The test allows physicians to identify the location and degree of vascular occlusion.

Electrocardiogram. This is an electronic readout of heart function that can reveal ischemic damage as a result of restricted blood flow.

 

Intima-media thickness. This test uses ultrasound imaging to estimate the thickness of the intima, or inner layer of the arteries. An increase in intima-media thickness over time indicates that atherosclerotic vascular disease is worsening. This technique can also be used to measure the effectiveness of cardiovascular intervention therapies.

Computed tomography scanning. This technique can assess the degree of calcification in the coronary arteries, which correlates strongly with atherosclerosis. Because of the risks associated with radiation exposure, HealthSmart Nutrition advisors do not recommend computed tomography scanning unless absolutely necessary.

The National Institutes of Health, together with the National Cholesterol Education Program, also offers an easy-to-use online test to help people determine their risk of a major cardiovascular event. The test relies on commonly used parameters such as age and weight to determine a 10-year Coronary Risk Profile. The Coronary Risk Profile can be accessed at http://www.nhlbi.nih.gov/guidelines/cholesterol/.


Atherosclerosis is perhaps the single most deadly disease in the United States, yet there is a good chance that most people, even those at high risk for heart disease, don’t really understand how it develops. The fact is, long before any symptoms are clinically evident, atherosclerosis begins as a malfunction of specialized cells that line our arteries. Called endothelial cells, they are the key to atherosclerosis, and underlying endothelial dysfunction is the central feature of this dreaded disease.

Not every person who suffers from atherosclerosis have the risk factors we commonly associate with the disease, such as elevated cholesterol, but every single person with atherosclerosis has endothelial dysfunction. It is the uniting concept through which coronary artery disease must be understood. Atherosclerosis begins with inflammation and immune cell activation at the endothelial level, and they lead to endothelial dysfunction and eventually damage to the artery and formation of plaque. This process is hastened by high cholesterol, smoking, obesity, high blood pressure, and other risk factors for coronary heart disease.

Atherosclerosis takes a huge toll on our society. According to the American Heart Association, more than 64 million Americans suffer from some form of cardiovascular disease, making it the leading cause of death in the country. In 2001, cardiovascular disease was responsible for more than 39 percent of all deaths in the United States (American Heart Association: Heart Disease and Stroke Statistics 2004).

 

In the world of conventional medicine, atherosclerosis is a widely misunderstood disease, perhaps because of a fundamental misconception about the nature of the arteries themselves. In this antiquated view, the arteries have been thought of as stiff pipes that gradually become clogged with excess cholesterol floating around the bloodstream. The solution recommended most often has been to reduce the dietary consumption of fats in order to lower levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) in the blood. Conventional medicine’s preferred method of re-establishing blood flow in clogged arteries is through surgery (coronary artery bypass graft surgery) or by insertion of catheters bearing tiny balloons that crush the plaque deposits against the arterial walls (angioplasty), followed by the implantation of tiny mesh tubes (stents) to keep the arteries open.

 

There are problems with this view, however. For one thing, the grafts used to re-establish blood flow can also develop atherosclerotic plaque deposits. The same was true for balloon angioplasty; in their early years, up to half of all angioplasty procedures “failed” when the arteries gradually closed again. Even today, with the use of improved stents, the failure rate is between 10 and 15 percent, and many people have to undergo repeat angioplasty or even surgery.

Today, our understanding of atherosclerosis has literally redefined the disease. We now understand atherosclerosis as a chronic inflammatory disease that affects the way arteries function at the most basic level. Instead of viewing the arteries as pipes through which blood flows, we now understand that arteries are muscular organs that change and adapt to their environment and contract and expand in response to multiple factors, helping to raise and lower blood pressure and distribute blood throughout the body. Finally, we have begun to unravel the biochemical processes that underlie atherosclerosis.

 

This new understanding of atherosclerosis has yet to filter into mainstream medicine, but the most progressive and forward-thinking researchers are already developing novel ways to correct the endothelial dysfunction that underlies coronary heart disease.

See the following excerpt:

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

Oldgren J, Wallentin L, Grip L, Linder R, Norgaard BL, Siegbahn A. Eur Heart J. 2003 Jan;24(1):86-93

Department of Medical Sciences, Cardiology, University Hospital, Uppsala, Sweden.

AIM: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METHODS AND RESULTS: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01. CONCLUSION: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acute phase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.

 

Endothelial Dysfunction: Underlying Arterial Disease

The cause and progression of atherosclerosis are intimately related to the health of the inner arterial wall. Arteries are composed of three layers. The outer layer is mostly connective tissue and provides structure to the layers beneath. The middle layer is smooth muscle; it contracts and dilates to control blood flow and maintain blood pressure. The inner lining consists of a thin layer of endothelial cells (the endothelium) that provides a smooth, protective surface. Endothelial cells prevent toxic, blood-borne substances from penetrating the smooth muscle of the artery. They also respond to changes in blood pressure and release substances into the cells of the smooth muscle that help change the muscle tone of the artery. Furthermore, endothelial cells secrete chemicals that provoke a protective response in the artery after an injury. This protective response includes signaling smooth muscle cells and white blood cells to congregate at the site of an injury.

As we age, however, the endothelium becomes leaky, allowing lipids and toxins to penetrate the endothelial layer and enter the smooth muscle cells. As a result, smooth muscle cells gather at the site of the injury, and the artery loses some flexibility. In response, the endothelium signals white blood cells to congregate along the cell wall. These white blood cells produce pro-inflammatory substances, such as leukotrienes and prostaglandins, as well as damaging free radicals that attack the endothelium (Touyz RM 2005). Toxins soon begin to penetrate into the arterial wall, where lipids such as LDL, cholesterol, and triglycerides accumulate and become oxidized.

 

At this point, the atherosclerotic process has begun in earnest. In response to the oxidized lipids, the body mounts an intensive immune response that causes more white blood cells to attack the fats, producing more inflammation within the arterial wall. In an attempt to heal the injury, smooth muscle cells begin to produce collagen to form a cap over the injury site. The mixture of oxidized lipids, white blood cells, and smooth muscle cells forms a plaque deposit. Over time, calcium accumulates on the deposit and forms a brittle cap. If this calcified plaque ruptures, a blood clot can form, and the clot may result in a heart attack or stroke.

 

All the processes described above, in which the inner arterial wall is damaged and normal endothelial function is compromised, are collectively referred to as endothelial dysfunction. Evidence of endothelial dysfunction can even be found in adolescents who are genetically prone to atherosclerosis. While this process occurs naturally to some degree in all people, it is aggravated by the traditional risk factors for heart disease, such as smoking and obesity (two of the leading modifiable risk factors for coronary artery disease). The following are additional risk factors:

Oxidized LDL cholesterol .

Oxidized LDL

Before we continue, it's important to distinguish between 'standard' LDL cholesterol, and 'modified' LDL cholesterol. The former is the type of LDL that your body produces each and every day as a part of perfectly normal and healthy metabolic function. Modified LDL, in contrast, has undergone some sort of deleterious alteration; the most widely studied example is 'oxidized' LDL. This is LDL that has been subject to free radical damage.

During the eighties, some researchers began to wake up to the fact that LDL itself was not a reliable independent risk factor for CHD. After all, half of those who suffer CHD have LDL levels within the normal limit. Among the 28,000-plus participants of the Women's Health Study, for example, forty-six percent of first cardiovascular events occurred in women with LDL cholesterol levels under 130 mg/dL--the 'desirable' target for primary prevention set by the NCEP.(5)

Research in both animals and humans has shown that oxidized LDL is a far better predictor of atherosclerosis and cardiovascular disease than regular LDL cholesterol. This would indicate that a person's antioxidant status, rather than their LDL levels, is a more important determinant of whether or not they will develop advanced plaques.

That, of course, is not how the medical orthodoxy interpreted the findings. The discovery of oxidized LDL cholesterol, they insisted, simply gave further support to the importance of lowering LDL cholesterol. Lower LDL, they claimed, and you will also lower oxidized LDL levels.

Wrong again.

In animal studies, administration of antioxidant drugs like probucol impairs LDL oxidation and arterial plaque formation, even when there is no change in blood cholesterol levels.(6-10)

In fact, administration of the antioxidant butylated hydroxytoluene (BHT) significantly reduces the degree of atherosclerosis on the aortic surface of rabbits even though it raises LDL cholesterol levels!(9)

A similar phenomenon is observed in humans. Among elderly Belgians, higher levels of oxidized LDL were accompanied by a significantly increased risk of heart attack, regardless of overall LDL levels.(11,12)

In Japanese patients undergoing surgery to remove plaque from their carotid arteries, blood levels of oxidized LDL were significantly higher than those measured in healthy controls. Advanced carotid plaques extracted from the patients showed far higher levels of oxidized LDL than neighbouring sections of artery that were disease-free. Elevated oxidized LDL was also associated with an increased susceptibility of plaque rupture. However, there was no association between oxidized LDL concentrations and overall LDL levels.(13)

The irrelevance of total LDL levels was further underscored when patients given aggressive LDL cholesterol-lowering treatment were compared with those receiving less aggressive treatment. Despite greater LDL reductions in the former group, there were no differences in calcified plaque progression as detected by electron beam tomography.(14)

It's the Antioxidants!

In 1997, Swedish researchers published a comparison of CHD risk factors among men from Vilnius in Lithuania and Linkoping in Sweden. These two groups were selected because the former had a four-fold higher death rate from CHD than the latter. Very little difference in traditional risk factors existed between the two groups, except that the men from CHD-prone Vilnius had lower total and LDL cholesterol levels!

 

According to common wisdom, the lower total and LDL cholesterol of the Lithuanian men should have placed them at reduced risk of heart disease. When the researchers probed further, they discovered that the men from Vilnius had significantly higher concentrations of oxidized LDL.(15) They also displayed significantly poorer blood levels of important diet-derived antioxidants such as beta carotene, lycopene, and gamma tocopherol (a form of vitamin E).(16,17) Blood levels of these particular nutrients are largely determined by dietary intake, especially from the consumption of antioxidant-rich fruits, nuts, and vegetables. So while the Lithuanian men had lower LDL levels, they had a greater susceptibility to oxidized LDL due to what appeared to be a poorer intake of antioxidant-rich foods.

This may well have explained their greater susceptibility to cardiovascular disease; in tightly-controlled clinical trials, individuals randomized to increase their intake of fruits and vegetables have experienced significant reductions in cardiovascular and all-cause mortality.

 

The LDL Theory on Trial

Speaking of tightly-controlled clinical trials, none have ever conclusively demonstrated that LDL cholesterol reductions can prevent cardiovascular disease, nor increase longevity.

In the massive GISSI-Prevenzione trial in Italy, the mortality benefits of omega-3-rich fish oil appeared early on in the study--as did an increase in LDL cholesterol levels! Mean LDL levels in the subjects given fish oil rose from 136mg/dl at baseline to 150mg/dl after six months, before gradually returning to initial levels at 42 months. A similar pattern was observed in the control group. This extended period of elevated LDL levels did not in any way prevent the fish oil patients from experiencing significantly more favorable cardiovascular and mortality outcomes.(18)

In the Lyon Diet Heart Study, an experimental group advised to increase consumption of root vegetables, green vegetables, fish and fruit, and omega-3 fatty acids also experienced greatly improved cardiovascular and survival outcomes. The study was originally intended to follow the patients for 4 years, but death rates diverged so dramatically early on that researchers decided it would be unethical to continue and called an end to the trial. After an average follow-up of 27 months, the overall death rate of the control group was more than twice that of the experimental group.

One little publicized finding from this well-known trial was that the total and LDL cholesterol levels of the treatment and control groups were virtually identical throughout the entire study. Those in the treatment group, however, did show significantly higher blood levels of omega-3 fatty acids and antioxidants (19).

Research on the oxidation of low density lipoproteins (LDL), the so called "bad cholesterol," led to the discovery by Salomon, professor of chemistry, of isolevuglandins and other toxic oxidized lipids that form this graffiti on proteins. (isoprostanes are believed to be valuable indicators of oxidative stress in animal tissues, i.e. when there is an excessive production of lipid peroxidation products, which may be involved in the development or exacerbation of cancer, and cardiovascular and neurological diseases for example.)

 

Pure samples of isolevuglandins and other oxidized lipids prepared synthetically in Salomon's research provide doctors at the Cleveland Clinic (John Crabb, Stanley Hazen, Henry Hoff, Joe Hollyfield and Eugene Podrez), with valuable tools and information for studies of heart disease, macular degenerative disorders and other diseases brought on by oxidative damage of lipids.

He credits the research link between CWRU and the Clinic as making the connection between the chemistry lab and biological processes.

The clinical groups suspected the involvement of oxidized lipids in pathological processes they were studying, he said, but the amounts of these lipids in biological specimens were so minute that progress was stymied until methods were developed for making virtually unlimited amounts of pure oxidized lipids in the chemical laboratory.

The National Institutes of Health recognized Salomon's ground-breaking research with a new four-year, $1.4 million research grant for the study, "Preprostaglandin Endoperoxides." The grant continues 23 years of NIH support and expands upon research that has resulted in patents on detecting a variety of these "fingerprints" of lipid oxidation that can be used to read the "graffiti" on oxidatively damaged proteins in the blood.

Through the development of antibodies that recognize the modified proteins, the researchers can measure the accumulation of them in human blood that may occur over days, weeks or even months.

The quantity of the modified proteins correlates with cardiovascular disease, Salomon said. While many people have high levels of LDL, only a small fraction of them will develop heart disease. Salomon found that the "graffiti" resulting from oxidized lipids sticking to proteins is a better indicator of cardiovascular disease than the classical risk factors, high LDL or total cholesterol levels in the blood.

Salomon also found that some people have an allergic reaction to the "graffiti" because their immune system responds to the altered proteins as if they were alien invaders.

Preprostaglandin endoperoxides are unstable intermediates, produced throughout the body, from which hormone-like oxidized lipids are formed to promote blood clotting or thinning, depending upon the needs of the organism. Other endoperoxide-derived oxidized lipids produce pain and inflammation. The medicinal actions of aspirin and other nonsteroidal antiinflammatory drugs such as Celebrex, result from their ability to block the enzyme responsible for generating the endoperoxides.

"We stumbled onto a non enzymatic process that transforms endoperoxides into toxic oxidized lipids, levuglandins, that stick to proteins and DNA," Salomon said.

Similar endoperoxides are produced by nonenzymatic oxidation of lipids caused by free radicals. Salomon realized that when these endoperoxides are transformed into isolevuglandins they become "very reactive materials that act like a magnet that sticks to everything, including the protein in LDL particles."

Macrophage cells, described as the garbage trucks of the blood, try to carry away oxidatively damaged LDL. When macrophages get gummed up with oxidized lipids, they "become bloated with partially digested lipoprotein and globules of cholesterol" and form "foam cells," Salomon said.

Eventually foam cells develop into the atherosclerotic plaque found in cardiovascular disease.

 

"Macrophages are supposed to clean up oxidatively damaged LDL but are covered with these toxic oxidized lipids that bring the whole process to a grinding halt," Salomon said.

 

Isolevuglandins "spoil" the protein, according to Salomon, who added that antioxidants, like vitamin E, help protect the body against this bad chemistry. When the antioxidants fail, the damage from free radical oxidation occurs.

What about Statins?

What about statin drugs? According to medical 'opinion leaders' (those who tell the rest of the unthinking masses what to believe), recent trials with statin drugs have proven once and for all that LDL reduction is beneficial. Allegedly, these trials have also shown that the greater the LDL reductions, the better.

Again, this is completely false.

Statins Do a Whole Lot More Than Just Lower LDL

Statin drugs exert their lipid-lowering effect by blocking an enzyme in the liver that is involved in the early stages of cholesterol synthesis. Statins inhibit the synthesis of mevalonate, a precursor not only to cholesterol, but also to a substance known as geranyl-geraniol. Inhibition of geranyl-geraniol produces beneficial effects on levels of nitric oxide (NO), a substance with anti-inflammatory and artery-dilating properties.(20,21) The consequences of this dual action are widespread:

In research with mice, statins markedly reduce measures of both inflammation and atherosclerosis, even though there is little change in serum cholesterol levels.(22)

 

Statins reverse or impede the progression of atherosclerosis in rabbits, without any accompanying change in serum cholesterol.(23,24)

 

In human volunteers with slightly elevated cholesterol, researchers found that four weeks of simvastatin therapy significantly enhanced forearm blood flow, a measure of arterial function. The amount of improvement was unrelated to the degree of cholesterol reduction.(25)

 

In elderly diabetic patients, cerivastatin increased dilation of the brachial artery after only 3 days, before any change in cholesterol levels had occurred.(26)

 

Statins have been shown to reduce blood platelet production of thromboxane, an eicosanoid that encourages blood-clotting. This effect was not seen with the older drugs that lowered total or LDL cholesterol such as cholestyramine, cholestipol, and fibrates.(27)

 

Statins have also been observed to inhibit the migration of smooth muscle cells seen in atherosclerotic plaque formation.(28,29)

 

Statins may prevent advanced atherosclerotic plaques, or atheromas, from rupturing. Plaque rupture is believed to be the instigating factor in a significant portion of coronary events.(30)

 

Clearly, the effects of statins go far beyond merely lowering cholesterol. The multi-faceted nature of statins is no doubt why almost all of the major controlled, randomized trials with statin drugs have shown no association between the degree of total or LDL cholesterol lowering and the CHD survival rate. In most of these studies, the risk of a fatal heart attack was similarly reduced whether total or LDL cholesterol levels were lowered by a small or large amount.(31-37)

There are two exceptions--the PROSPER trial, which recorded the highest survival rates in both the treatment and control groups among those with the highest LDL levels.(38)

 

In the Japanese Lipid Intervention Trial (J-LIT), a six-year study of over 47,000 patients treated with simvastatin, those with a total cholesterol level of 200-219 mg/dL had a lower rate of coronary events than those whose levels were above or below this range. The lowest overall mortality rate was seen in the patients whose total and LDL cholesterol levels were between 200-259 mg/dL and 120-159 mg/dL. The highest death rate in the study, by the way, was observed among those whose cholesterol levels were below 160 mg/dL.(39)

The Establishment Method of Dealing With Contradictory Evidence

 

When confronted with non-supportive evidence, the medical establishment usually does what any good purveyor of profitable misinformation would do--ignores it. Additionally, it simultaneously seeks out supportive evidence, no matter how flimsy, and then embarks on an aggressive propaganda campaign to 'educate' as many people as possible to this allegedly supportive evidence. The end result is that the public receives a highly distorted version of events that, while far from the truth, is nonetheless far more palatable to the reigning orthodoxy.

A perfect example of this phenomenon occurred in April 2004, when the results of the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial (PROVE-IT) were published.

 

The PROVE-IT researchers randomized patients who had recently been hospitalized for an acute coronary event to either 40 milligrams of pravastatin (Pravachol) or 80 milligrams of atorvastatin (Lipitor) daily. Not surprisingly, median LDL cholesterol levels were lowered to a greater extent on high dose atorvastatin.

After an average follow-up of two years, the high dose atorvastatin group enjoyed a 30 percent reduction in CHD mortality and a 28 percent decrease in overall mortality(40). Establishment spokespeople could barely hide their euphoria; after a continual stream of non-supportive major trials, they finally had a study in which LDL reduction appeared to be correlated with improved clinical outcomes! According to the barrage of publicity awarded to the trial by an ever compliant media, PROVE-IT finally 'proved' that the lower the LDL level, the better!

Actually, PROVE-IT proved no such thing.

 

Neither did TNT, the highly-hyped study published in March 2005 which also supposedly proved the value of aggressive LDL-lowering. In this study, 10,001 CHD patients with LDL cholesterol levels of less than 130 mg/dl were randomly assigned to either 10 or 80 milligrams of atorvastatin (Lipitor) daily. TNT was sponsored by Pfizer, the manufacturer of Lipitor (currently the world's best-selling drug).

 

Those receiving low-dose atorvastatin reduced their mean LDL cholesterol levels to 101 mg/dl, while those taking the high dose brought their LDL readings down to 77 mg/dl. After a median follow-up of 4.9 years, 2.5 percent of the low-dose group had died from coronary causes, compared to 2 percent in the high dose group, a twenty percent relative risk reduction.(41) Glowing media reports enthusiastically hailed these results as triumphant confirmation of the PROVE-IT findings. According to the hype, the "lower is better" era of LDL reduction had officially arrived.

 

Wait Just a Minute…

That statins exert a whole host of biochemical effects beyond mere lipid-lowering is beyond question. In light of this inescapable fact, how can anyone confidently conclude that it was LDL reduction--and not amplification of one or more of these other effects--that produced the favorable cardiovascular outcomes seen in PROVE-IT or TNT?

 

The answer, of course, is that they can't.

Cut the CRP

 

C-reactive protein (CRP) is a substance that serves as a marker for inflammatory activity inside the body. CRP has attracted a great deal of attention ever since a large study published in 2002 suggested that this protein was a significantly better predictor of future cardiovascular events than LDL cholesterol.

In January 2005, the New England Journal of Medicine published two studies examining the interplay between statin use, CRP levels, and subsequent coronary event rates. The first of these, using data from the aforementioned PROVE IT study, found that: "Patients who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol."(42)

In the second study, researchers used intravascular ultrasonography to examine the association of LDL and CRP with the continued development of atherosclerosis in 502 CHD patients. They found that "Atherosclerosis regressed in patients with the greatest reduction in CRP levels, but not in those with the greatest reduction in LDL cholesterol levels."(43)

These results reinforce what is already obvious to those whose minds have not been thoroughly dulled by the massive anti-cholesterol offensive--namely, that the favorable results seen in PROVE-IT were due to the non lipid-lowering actions of statins. The strong correlation between CRP and improved clinical outcomes indicates that the anti-inflammatory effects of statins played a key role.

Of course, the CRP analysis of the PROVE-IT trial was published almost a year after the initial paper that focused on LDL. This was more than enough time to milk the LDL publicity machine for all it was worth, and to use the PROVE-IT results as primary justification for a further reduction in the official NCEP cholesterol-lowering guidelines.

The Charade Continues

With the sole exception of two selectively interpreted trials (PROVE-IT and TNT), decades of dietary and drug intervention trials have repeatedly shown a complete disconnect between total and LDL cholesterol reduction and clinical outcomes.

 

As such, there exists no proof that LDL cholesterol causes cardiovascular disease, nor that LDL reduction can lower the incidence of CVD events. So how much longer will the medical mainstream keep up the LDL cholesterol charade?

 

A long, long time, if comments by one of the leading proponents of this nonsensical paradigm are anything to go by.

Commenting on recent research that questions a causal role for C-reactive protein in cardiovascular disease, Dr Steven Nissen, a cardiologist at Ohio's Cleveland Clinic, says the debate "reminds him of the resistance experienced 20 years ago when the importance of cholesterol was first discovered."

 

According to Nissen, "Many nihilists fought vociferously against the concept of LDL as a causative agent in atherosclerosis. A few of them still don't accept the concept."(44)

 

Planet Earth to Steve Nissen…

 

Nissen's response to critics of the cholesterol agenda is a classic textbook example of the kind of dismissive, evasive arguments used by those who propagate scientifically untenable nonsense. Orthodoxy knows full well that it can't rationally address all of the numerous contradictions and fallacies inherent in its pet hypothesis, so it instead attempts to portray dissenting commentators as lone quacks who are out of step with scientific reality.

 

For those tempted to believe such rot, I would strongly suggest you first visit the home page for The International Network of Cholesterol Skeptics. This is a worldwide network of researchers, doctors, and science writers who are highly critical of the anti-cholesterol campaign. It includes such highly esteemed researchers as Dr. Uffe Ravnskov, MD, PhD, (who has published dozens of papers on kidney disease and the cholesterol hypothesis), Kilmer McCully, MD, (the pioneer researcher who uncovered the link between homocysteine and cardiovascular disease), Peter Langsjoen, MD, (foremost authority on the interaction between statin drugs and coenzyme Q10), and Mary Enig, PhD, (the renowned biochemist who first raised the alarm on trans fatty acids).

 

While Nissen would have his colleagues and the public believe that opposition to the cholesterol hypothesis is limited to a handful of disgruntled "nihilist" crackpots, the truth is that a growing number of highly esteemed and accomplished individuals are joining the campaign to alert the public to the fact that this hypothesis is a total sham.

 

Linus Pauling's Unified Theory and Therapy for Heart Disease

Linus Pauling claimed that specific non-toxic substances called Lp(a) binding inhibitors taken orally will prevent and may even dissolve existing atherosclerotic plaque build-ups.

 

This work is based on at least 2 Nobel Prizes in Medicine and the efforts of countless medical researchers. The theory and conclusions offered represent the final contribution of an American scientific giant.

 

The fact that you have not heard about this discovery in the mainstream media is disturbing. It speaks volumes about how powerful interests can somehow suppress vital information that would be detrimental to their financial interests.

In 1989, the eminent American scientist Linus Pauling and his associate Matthias Rath MD, unlocked a medical mystery.

 

They found the reason human beings suffer heart disease.

Then in 1991, Linus Pauling invented a non-prescription cure. The twice Nobel prize winning genius, chemist, and medical researcher made the strong (and so far unreported) claim that heart disease can be controlled, even cured, by a specific "mega-nutrient" therapy.

 

Heart patients using the Pauling Therapy routinely avoid angioplasty and open heart surgery. Not by lowering cholesterol, as the media would have us believe, but by attacking the root cause. Rapid recovery has been the rule, not the exception. Strangely, there are no known adverse side effects, yet the medical profession ignores Pauling and Rath.

You Must Unlearn What You Have Learned
Atherosclerotic plaques deposit in response to injury. This major finding led to the 1985 Brown-Goldstein Nobel prize in medicine. The confusion in the media is cause and effect. The fallacy is that cholesterol causes heart disease, but plaque build-ups are the effect of heart disease.

 

G. C. Willis, MD, made the crucial observation in the early 1950s. A Canadian doctor, he noticed that atherosclerotic plaques in his patients kept forming in the same places. Usually near the heart where the blood vessels are stretched and bent.

Willis was the first to implicate high blood pressures and the mechanical stress caused by the heart beat.

The Pauling and Rath theory relies on this observation that plaque does not form randomly throughout the blood stream. (Note: In a heart bypass, veins from the leg are used which are without plaque.) Accordingly, it is unlikely that the primary cause of the lesions leading to heart disease are "poisons" circulating in the blood.

 

What causes the stress fractures in the walls of blood vessels that leads to heart disease?

 

The Pauling/Rath unified theory blames a lack of a specific protein caused by a specific vitamin deficiency. Visualize a garden hose being continually stepped on 70-80 times per minute. A fate similar to the coronary arteries feeding the heart. Like the garden hose, the arteries lose their strength and stability over time from wear and tear.

 

According to Pauling, the atherosclerotic plaques of coronary heart disease form only after cracks or stress fractures appear. This healing process begins with one very important "sticky" form of cholesterol.

 

What is Lp(a) and why is it important?

Lipoprotein(a) "small a" or Lp(a) is a variant of the so called "bad" LDL cholesterol. Lp(a) is "sticky" substance in the blood that Pauling and Rath believe is the lipid that begins the process of forming atherosclerotic plaques in heart disease. The 1985 Nobel prize in medicine was awarded for the discovery of the cholesterol binding sites. The so-called Lysine Binding Sites. We now know that it is Lp(a) and not ordinary cholesterol which binds to form plaque.

 

Briefly, Lp(a) has lysine (and proline) receptors. You can think of a chemical receptor as a simple lock and key. Only one key (e.g. lysine) will fit into the lock (receptor on the Lp(a) molecule.) There may be multiple receptors on the molecule, but once they are all filled up with keys (lysine or proline) the Lp(a) molecule looses its ability to bind with any more "keys."

 

When all the Lp(a) locks have keys, Lp(a) will no longer be able to create plaque.

Once Linus Pauling learned that Lp(a) has receptors for lysine, he knew how to counter the atherosclerosis process chemically.

His invention, the Pauling Therapy, is to increase the concentration of this essential and non-toxic amino acid (and proline) in the blood serum.

Lysine and proline supplements increase the concentration of free lysine and proline in the blood. The higher the concentration of the free lysine (and proline) in the blood, the more likely it is that Lp(a) molecules will bind with this lysine, rather than the lysine strands that have been exposed by cracks in blood vessels, or the other lysine that has been attracted to the Lp(a) already attached to the blood vessel wall.

 

According to Pauling, a high concentration of free lysine can destroy existing plaques.

It is important to keep all this in perspective using the Pauling/Rath Unified theory. If you are not getting enough vitamin C to produce collagen, and your blood vessels are wearing down, then the Lp(a) plaque is of great benefit to you. Simply removing plaque without restoring the vein or artery to health is like tearing a scab off a wound. You do not want to remove the scab until after the tissue underneath has started healing. Your body needs sufficient vitamin C so your veins and arteries can heal.

 

The Unified Theory blames mechanical stresses (high blood pressures, stretching and bending, etc.) on the blood vessels for exposing lysine that Lp(a) is attracted to. This explains why plaque doesn't always form. Atherosclerosis is a healing process. Like a scab, plaques form after a lesion or injury to the blood vessel wall.

 

There is an awesome elegance that these binding inhibitors (vitamin C/lysine) are completely non-toxic.

 

They are also the basic building blocks of collagen. The unified theory blames poor collagen production for the entire problem of heart disease. Therefore, the Pauling Therapy not only melts plaque, but it attacks the root cause by stimulating the bodies' production of collagen.

 

With enough collagen, arteries remain strong and plaque free.

 

The Pauling and Rath theory postulates that the root cause of atherosclerotic plaque deposits is a chronic vitamin C deficiency which limits the collagen our bodies can make.

 

A surprising body of experimental research supports the Pauling/Rath view. Careful studies with animals that do not make their own endogenous vitamin C prove that when the dietary intake of the vitamin is low, collagen production is limited, and blood vessels tend to become thinner and weaker from wear and tear. Plaque deposits then form to compensate for this weakness. Such animals are rare.

 

Large population studies also support the view that increased vitamin C intake results in lower incidence of cardiovascular disease and lower death rates.

Heart Disease is Chronic Scurvy

 

If you suffer plaque deposits, it is likely you owe your life to this material that narrows your arteries. Without plaques, your weakened blood vessels would rupture or leak causing a slow death from internal bleeding. A slower version of scurvy, the disease long dreaded by ancient sailors. (James Lind discovered around 1753 that eating fruit prevents this disease.

 

Acute scurvy can be prevented by a mere 10 mg vitamin C per day.

This process by itself rarely kills people, but plaque lined arteries make heart attack more likely from a blood clot or blockage. (Plaque lined arteries can not easily dilate in response to a clot.) It is currently unknown what amount of vitamin C prevents the atherosclerotic plaques of chronic scurvy, but Linus Pauling often recommended 3000 mg.

 

Many experts think something circulating in the blood must cause these cracks in our blood "pipes." For many years, ordinary LDL cholesterol has been blamed because elevated levels have been correlated with heart disease. Other scientists correlated elevated homocysteine and oxidized cholesterol.

Again, the confusion is cause and effect. If cholesterol causes cracks or lesions, plaque should be more randomly distributed throughout the blood stream. According to the Pauling/Rath unified theory, both elevated homocysteine and oxidized cholesterol are symptoms of scurvy.

Is the mainstream finally catching up with Pauling?

Before teaming with Pauling, Dr. Rath's German research team examined plaque from human aortas (blood vessels near the heart) post-mortem. They discovered that atherosclerotic plaques are composed primarily of Lp(a), not ordinary LDL cholesterol.

Mainstream medical science has known since 1989 that Lp(a) binds to form plaque, not ordinary LDL.

Dr. Rath, realized that Lp(a) was connected somehow with vitamin C and joined the Linus Pauling Institute of Science and Medicine. Together, Pauling and Rath developed their unified theory which holds that increased Lp(a) acts as a surrogate for low vitamin C and hardens weak blood vessels. Their experiments to test their theory proved that low vitamin C intake will increase blood levels of Lp(a) in test animals compared to controls.

An important finding is that this sticky Lp(a) (an LDL-like cholesterol substance) has only been found in the very few animal species that do not make their own vitamin C, including humans. Today, most animals: Make vitamin C in their livers or kidneys, in large "mega" amounts (9,000 mg to 12,000 mg adjusted for body weight - which is high by current medical standards), do not have Lp(a) in their blood, and rarely suffer cardiovascular disease.


We humans are almost unique among life on Earth in that we must get our vitamin C entirely from the diet.

 

The Cause Of Heart Disease

Science has known for almost two decades that damage to the walls of blood vessels (or lesions) are a necessary precondition for the formation of atherosclerotic plaques in human beings. The most popular competing theories as to why these lesions occur include:

 

  • Oxidized cholesterol in the blood,
  • Elevated levels and oxidized homocysteine in the blood, and
  • Vitamin deficiencies


(It is safe to say that few researchers believe that high levels of fat or cholesterol in the diet are the primary cause of heart disease. An exception may be researchers working for companies that offer high priced cholesterol lowering medications. ) In our view, all competing theories must be able to explain:

Why occlusive cardiovascular disease does not occur in animals, and

Why infarction's in humans usually occur in the arteries at locations where the mechanical stress (blood pressure, arterial bending and stretching, etc.) is a factor, rather than more randomly distributed throughout the body.
These two observations are the cornerstones of the vitamin C theory.

 

Furthermore, the early findings of Canadian doctors Patterson and Willis should not be forgotten. Their research indicated that arterial tissue levels of ascorbate (vitamin C) are much lower in heart patients when compared with controls, and that ascorbate supplementation could reduce arterial deposits. This pioneering work should have been immediately followed up.

www.paulingtherapy.com

 

 

 

 

Hypertension. High blood pressure is known to aggravate endothelial dysfunction, and leading researchers have identified the endothelium as an “end organ” for damage caused by high blood pressure. Many studies have shown that high blood pressure is dangerous, and HealthSmart Nutrition suggests a target optimal blood pressure of 119/75 mmHg (or lower).

C-reactive protein. Inflammation is central to the endothelial dysfunction that underlies coronary artery disease. One good way to measure inflammation is through levels of C-reactive protein (CRP). Studies have shown that higher levels of CRP increase the risk of stroke, heart attack, and peripheral vascular disease (Rifai N 2001; Rifai N et al 2001). Stroke patients with the highest CRP levels (greater than 33 mg/L) are two to three times more likely to die or experience a new vascular event within a year than are patients with low levels (less than 5 mg/L) (Di Napoli M et al 2001).

Metabolic syndrome and diabetes. Metabolic syndrome is a cluster of abnormalities that, when they occur in the same person, dramatically elevate the risk of heart disease. These abnormalities include elevated triglyceride levels, insulin resistance, abdominal obesity, elevated blood pressure, and low high-density lipoprotein (HDL). According to recent data, this condition affects about 20 percent of adult Americans. Diabetes is also a significant risk factor for coronary artery disease. High circulating levels of blood glucose (and insulin) cause microvascular damage that accelerates the atherosclerotic process, partly by accelerating endothelial dysfunction (Beckman JA et al 2002).

Metabolic Syndrome  (Syndrome X)

 

During the past 50 years, dietary changes have accelerated, pushing us even further from our evolutionary baseline diet. Refined carbohydrates-pastas, breads, cereals, and breakfast bars-now dominate the diet. Many foods are breaded and fried, merging refined grains with refined and often oxidized oils. People did not consume pressed oils until relatively recently. In addition, many foods also contain large amounts of varying forms of sugar, along with partially hydrogenated oils (vegetable oils processed to have some of the characteristics of saturated fats). These foods, even with fortification, contain relatively few micronutrients such as vitamins, minerals, carotenoids, and flavonoids.

 

Such a diet wreaks havoc on glucose and insulin levels. For example, refined sugars and carbohydrates rapidly boost glucose levels. To reduce high glucose levels (and to prevent kidney damage), the pancreas then secretes large amounts of insulin, which helps transport glucose into cells where it is burned for energy (chiefly in muscle cells) or stored as glycogen (in the liver) or fat (in adipose cells).

 

Over time, elevated insulin levels overwhelm a finite number of insulin cell receptors. As a consequence, these cells become "resistant" (or insensitive) to insulin, and blood levels of glucose and insulin increase-hyperinsulinemia-setting the stage for Syndrome X, diabetes, heart disease, and other disorders. High glucose levels also generate large numbers of cell-damaging free radicals, which appear to cause or exacerbate many of the complications of diabetes such as eye and nerve diseases, and also increase antioxidant requirements.

 

Mohanty P, et al. Glucose challenge stimulates reactive oxygen species (ROS) generated by leucocytes. J Clin Endocrinol Metab 2000;85:2970-3.

 

 

Homocysteine. High homocysteine levels contribute to inflammation and the production of free radicals that attack endothelial cells and raise thrombotic risk (Riba R et al 2004). Mild elevations in serum homocysteine (homocysteinemia) can be caused by nutrient deficiencies, including deficiencies in folate and vitamin B12. Homocysteine, like cholesterol, is strongly associated with risk of heart disease (Haynes WG 2002; Guilland JC et al 2003).

 

Elevated fibrinogen. Fibrinogen is involved in the blood clotting process. When a blood clot forms, fibrinogen is converted to fibrin, which forms the structural matrix of a blood clot (Koenig W 1999). Fibrinogen also facilitates platelet adherence to endothelial cells (Massberg S et al 1999). People with high levels of fibrinogen are more than twice as likely to die of a heart attack or stroke as people with normal fibrinogen levels (Wilhelmsen L et al 1984; Packard CJ et al 2000). This risk goes up even more in the presence of hypertension (Bots ML et al 2002).    

 

Other studies found that individuals who had suffered heart attacks had significantly higher fibrinogen levels than healthy individuals (Ma J et al 1999) and that fibrinogen levels have a stronger association with cardiovascular deaths than cholesterol levels (Thompson SG et al 1995).

 

Atherosclerosis: Not Just a Man’s Disease

For years, many people believed that atherosclerosis primarily affected men. In reality, however, heart disease is the leading killer of women in the United States. Atherosclerosis tends to affect men and women differently and at different times in their lives. Before menopause, women suffer less from heart disease than men of comparable age. After menopause, however, the gap closes with age until eventually women become more likely than men to suffer from heart disease (Sans S et al 1997; LaRosa JC 1992).

Heart disease in women is often undiagnosed because its symptoms are often different from the symptoms men experience. Women are less likely to suffer from the chest pain traditionally associated with coronary artery disease in men (McSweeney JC et al 2003), and their heart attacks tend to be atypical (Sannito N et al 2002). Among women, the pain associated with reduced blood flow (ischemia) may be felt in the upper abdomen or back instead of the chest, and the symptoms of an actual heart attack (myocardial infarction) may also be different from those typically experienced by men.

 

The issue of women and heart disease is further complicated by conflicting messages about hormone replacement therapy sent by conventional medical research. For many years, doctors prescribed conventional hormone replacement therapy to reduce the risk of heart disease among menopausal women. In recent years, however, the wisdom of this approach has been called into question. Two arms of the large Women’s Health Initiative study were stopped early when researchers discovered that women on conventional hormone replacement therapy were at a higher risk for coronary artery disease, heart attack, stroke, and breast cancer than other women. As a result of these findings, which were reported around the world, many women stopped using hormone replacement therapy, despite the possible benefits of estrogen therapy in reducing cardiovascular risk (Rosano GM et al 2003; Benagiano G et al 2004). Unfortunately, this study examined women using conjugated equine estrogens, which are estrogens derived from the urine of pregnant mares (Rossouw JE et al 2002).



Conventional Treatment of Atherosclerosis

The treatment of atherosclerosis depends on the stage of the disease. Severe disease, in which an artery has significant blockage or unstable plaque deposits, may require intensive care. In most cases, however, less severe disease is treated with a combination of lifestyle changes (including dietary changes) and medication. The following dietary and lifestyle changes have been shown to slow, or even reverse, the effects of atherosclerosis:

  • Reduce dietary polyunsaturated oils, food that contain oxidized cholesterol (for example anything with freeze dried eggs or milk), and trans-fatty acids.
  • Increase intake of fibre to at least 10 g daily. Soluble fibre is best too much insoluble fibre lowers minerals.
  • Consume fruits and vegetables daily.
  • Ensure adequate intake of folic acid (400 to 1000 mg daily) to reduce homocysteine levels.
  • For obese people, lower weight and increase physical activity to reduce the risk factors for metabolic syndrome (Syndrome X) and to help control blood pressure and reduce cardiac workload.
  • For people with hypertension, limit sodium intake and maintain adequate intake of potassium, calcium, and magnesium.
  • Stop smoking. This is essential.

 

In conventional medicine In addition to lifestyle changes, a number of medications may be prescribed to control individual risk factors. These include the following:

 

Cholesterol-lowering drugs. When cholesterol levels remain high despite adequate dietary changes, weight loss, and regular exercise, cholesterol-lowering drugs are often prescribed. The drugs most commonly used to lower LDL are the statin drugs: pravastatin (Pravachol®), simvastatin (Zocor®), and atorvastatin (Lipitor®). A new drug, Vytorin®, has recently gained popularity. Vytorin® is a combination pill containing ezetimibe (Zetia®) and simvastatin. It has been shown to lower cholesterol more effectively than either Lipitor® or Zocor® alone. Bile acid sequestrants are another class of drugs prescribed for reducing LDL. These include cholestyramine (Locholest®, Questran®) and colestipol (Colestid®). Other drugs used to lower cholesterol include gemfibrozil (Lopid®), clofibrate (Atromid-S), and probucol (Lorelco) (American Heart Association: Cholesterol-Lowering Drugs 2005).
Antihypertensive drugs. Drugs used to lower high blood pressure include beta blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers, and diuretics.

Antithrombotic drugs. These drugs reduce the blood’s ability to clot, thus reducing the risk of heart attack and stroke. The most common antiplatelet drug today is aspirin. Clopidogrel (Plavix®) is a popular antiplatelet prescription medication. However, many other drugs are prescribed to prevent thrombosis. Some are indicated for preventing stroke, deep vein thrombosis following surgery, or blood clots following arterial revascularization. The leading antithrombotic drugs include adenosine-diphosphate-receptor inhibitors, anticoagulants such as warfarin, thrombin inhibitors, glycoprotein IIa/IIIb inhibitors, phosphodiesterase inhibitors, and Pentoxifylline.

People with advanced coronary artery disease may be recommended for a surgical or “minimally invasive” procedure. In general, there are two main interventional treatments aimed at re-establishing blood flow in diseased coronary arteries: coronary artery bypass grafting and catheter-based procedures such as angioplasty and coronary artery stenting. Unfortunately, neither surgery nor catheter-based procedures can stop the underlying disease progression, and patients might end up needing additional procedures, plus the use of expensive pharmaceuticals for life. Obviously, early intervention through dietary supplementation, exercise, and careful monitoring of risk factors is preferable. Even if surgery or angioplasty is necessary, patients should do everything possible to slow the progression of the disease and support a healthy endothelial layer.

One important note for patients about to undergo coronary artery bypass surgery is the use of coenzyme Q10. It has been shown to improve heart function if taken before surgery (Rosenfeldt F et al 2005).

 

Nutritional Therapy

By the time surgery or angioplasty is recommended for atherosclerosis, preventive medicine has already failed. Because atherosclerosis is such a slow process, there is ample time for intervention before symptoms develop. Dozens of clinical studies have shown that reduction of individual risk factors can help slow or even reverse the damage caused by atherosclerosis, and reversing or slowing endothelial dysfunction should be a cornerstone of therapy.

 

Any program aimed at reducing the risk of heart attack or slowing the progression of atherosclerosis begins with comprehensive blood testing. This step is vital to designing a program that targets an individual’s risk factors. For example, a person with high cholesterol might benefit more from a healthy nutritional program than someone with elevated risk of thrombosis. Similarly, people with high homocysteine levels should follow a program aimed at reducing homocysteine. That said, it is also important that all possible risk areas be addressed and adequate antioxidants consumed to protect against oxidant stress inside the arteries.

HealthSmart Nutrition’s Metabolic Biotyping Advisor can make the appropriate nutritional recommendations.  Talk this over with your advisor.

Copyright © 2005 HealthSmart Nutrition. All rights reserved.
Revised: June 23, 2007

 

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