I frequently see patients in my practice who have cholesterols above 200mg/dL and have either been advised by a physician to take a statin drug to lower their cholesterol, or they are concerned on their own that their cholesterol level may be too high. In this newsletter I will share information on controversies in cholesterol therapy and whether the current guidelines to lower cholesterol are evidence-based. 

Our society’s obsession with cholesterol goes back to the famous Framingham Heart Study initiated in 1948, where a correlation between heart attacks and high cholesterol turned up when studying diets, lifestyles and environments of a large number of families. The high cholesterol correlation was found in men, but not women.  In 1956, the American Heart Association drew on the conclusions of the Framingham study and Ancel Keys, a famous pubic health scientist of the time, stating that butter, lard, beef and eggs were the cause of coronary heart disease.   Because lowering cholesterol did not reduce the risk of death from heart disease, the Cholesterol Consensus Conference in 1984 developed the guideline that a lower “acceptable” level of cholesterol (the magic 200mg/dL number) was needed.  When lowering total cholesterol levels below 200 did not translate into saving lives from heart attacks, the focus was then turned to LDL cholesterol levels.  The unfortunate patient who had an LDL cholesterol level of above 130 was now condemned to a lifetime of expensive drugs.  In addition, when a person with a completely normal LDL cholesterol level suffered a heart attack, he would still be placed on a cholesterol-lowering drug.

In 1977, Dr. Michael DeBakey, the internationally renowned heart surgeon, pointed out that only 30-40% of people with blocked arteries and heart disease had elevated blood cholesterol levels.  He asked “how do you explain the other 60 – 70%?” 

Looking at non-US populations such as Crete or France, average cholesterol levels of their populations are well above 200 mg/dL with diets rich in butter, cheese, creamy sauces, and, of course, red wine.  These populations have less heart disease than the US population.  One famous French investigation, the Lyon Diet Heart Study, published in the late 1990s, showed heart attack survivors following a Mediterranean diet were far less likely to experience a second heart attack or heart failure that individuals on the typical low-fat diet endorsed by the American Heart Association.  The Mediterranean diet, rich in anti-oxidant foods such as fresh vegetables and fruits, fish and fish oil clearly protected participants from heart disease.  What was also found was that people with higher cholesterols had less deaths from cancer, respiratory failure, suicides, and automobile accidents.  Why accidents and suicides?  You need cholesterol to make brain cells and for memory!

Although high cholesterol is only a finding on a blood test, the medical establishment and pharmaceutical industry, backed by the government in the 20th century made it into an actual disease.  Unlike most other diseases, the most common symptom of high cholesterol is feeling normal.  According to most experts, the only treatment for this new disease is to use cholesterol-lowering drugs.  In over 4 decades of use of these drugs heart disease and stroke still remain the number one cause of death in both men and women, where one out of two men and women will die of atherosclerosis related disease.

HDL cholesterol is responsible for clearing out the LDL cholesterol that sticks to the arterial walls.  Exercise, anti-oxidant minerals and vitamins, and omega-3 fish oils increase the amount of HDL cholesterol. LDL cholesterol is not bad.  As a matter of fact, it is critical to maintain life. LDL transports cholesterol and triglycerides from the liver to peripheral tissues. LDL also regulates cholesterol synthesis at these sites. It only becomes harmful when it is oxidized by free radicals.  The oxidized form of LDL cholesterol sticks to the arterial walls and initiates the formation of plaque.  This is a very important point for our readers to understand.

For example, we know cigarette smoking increases the risk of many diseases such as heart disease, stroke and cancer.  Smokers with normal levels of LDL cholesterol have a greatly increased risk of developing heart disease compared to non-smokers with the same LDL level.  Of course the reason why a smoker with normal levels of LDL cholesterol is at greater risk is because his LDL cholesterol gets oxidized at an incredible rate.  Homocystine levels are also increased by cigarette smoking which further oxidizes LDL cholesterol and the arterial lining itself.  The degree of oxidation directly corresponds to the risk of developing heart disease, not the level of LDL cholesterol.  But statin drugs do not address the true bad cholesterol, the oxidized LDL cholesterol.

Atherosclerosis (or ateriosclerosis) is damaged, hardened and possibly clogged arteries throughout the body due to plaque formation.  Plaque can be of two types.  Stable plaque, covered with fibrous tissue, slowly expands inward and shrinks the diameter of arteries.  Unstable, vulnerable plaque is much more dangerous.  It can rupture, spilling its contents into the arteries and shut off blood flow, causing a heart attack or stroke. When a stroke occurs, either there is a lack of blood to an area of the brain or the blood vessel has leaked, spilling blood into the brain.  Interestingly enough, plaque is only about 5% cholesterol and 95% calcium. 

Although plaque can develop slowly, it can also develop within 6 months.  Many cardiologists have seen this.  Stress can speed things up.  For a cardiac patient, emotional stress is deadly, and blood vessels can spasm and tighten up, further reducing blood flow.  If plaque develops slowly, the body can form natural bypasses called collaterals.  A patient may have a slowly closing coronary artery and not have a heart attack or require surgery or stents.

In 2000, doctors at Harvard University published the first of a series of landmark research studies showing heart disease was an inflammatory disease, just as we think of rheumatoid arthritis as an inflammatory disease.  I was privileged to hear one of the Harvard cardiologists at a medical conference I was attending present this dramatic finding.  He made a point that he could do a cardiac catheterization on a patient, not find significant blockage or hardening of the arteries, and within 6 months this same patient could return with plaque formation or a heart attack.  This concerned him.  What was going on?  The Harvard researchers found that it was the vascular inflammation that caused the oxidized LDL cholesterol to stick in the arteries.  They found C reactive protein to be a key biochemical substance that indicated the presence of vascular inflammation.  Like a silent smoldering fire, low-grade inflammation leads to weakening and eventual rupture of arterial plaques that directly trigger heart attacks and strokes.  This explains why more than half of heart attack and stroke victims have normal cholesterols. 

At the Center, all new adult patients have screening high sensitivity C reactive protein and homocystine (another inflammation causing substance) levels checked in addition to cholesterol levels. 

The National Cholesterol Education Program is part of the National Heart, Lung, and Blood Institute, meaning it is part of our federal government.  In 2004 it selected a panel of nine “experts” to review statin drug use and make recommendations as to guidelines doctors should follow to reduce cardiovascular disease.  Their findings were published in the journal Circulation in July 2004.  It was recommended that individuals at high cardiovascular disease risk attain levels of LDL less than 100mg/dL and for individuals at very high risk, the LDL target was less than 70mg/dL.  This is very difficult to do because these targets create an unnatural physiological condition.  This requires very high doses of statin drugs, doubling or tripling the dose, oftentimes in combination with other drugs. 

What Circulation failed to do was disclose that six of the nine “experts” had direct financial ties to the makers of statin drugs.  Even though this conflict of interest was disclosed in the media at the time, no action was taken to review the credibility of their conclusions by other less biased researchers. These guidelines immediately boosted the sales of statins from 15 billion dollars per year to over 22 billion dollars in 2005.  Statins are the number one selling medication in the United States.

On October 3, 2006, after extensive review of all studies relating to cholesterol-lowering statin drugs, scientists reported in the Annals of Internal Medicine that “current clinical evidence does not demonstrate that titrating lipid therapy to achieve proposed low LDL cholesterol levels is beneficial or safe.”  This shocking review also exposed the deceitful manipulation of statistics.

In November 2007 I attended the ACAM conference in Phoenix, Arizona.  One of the speakers was James Wright M.D., PhD, CRCP(C).  He is a professor in the Departments of Anesthesiology, Pharmacology & Therapeutics and Medicine at the University of BC, Vancouver, Canada.  He is also the Managing Director of the Therapeutics Initiative, a government funded organization with a mandate to provide evidence-based practical information about drugs and other therapies to health professionals in BC.  He gave an eye-opening lecture on whether the lipid lowering guidelines are evidence based.  Just because a major medical journal publishes a study doesn’t mean the data or statistical analysis is accurate, or the study design was the way it was supposed to be, or the conclusions of the authors factual.  Due to space considerations, I am greatly condensing his lecture points, but Dr. Wright’s website www.ti.ubc.ca can be viewed and includes therapeutics letters and drug assessment reports.

The first issue he addressed was that there are 7 different guidelines for treatment of high cholesterol, depending upon which country you live in, even though the guidelines are based on the identical evidence presented in published reports. The USA had the strictest guidelines.  Dr. Wright pointed out that the guidelines make unproven assumptions and extrapolations.  For example, in the MEGA trial published in the medical journal Lancet, Pravostatin (Pravachol) plus diet versus diet alone in a primary prevention population of 8214 randomized patients was looked at. However 382 patients were for some unknown reason excluded from the analysis.  He asked what happened to these people.  Did they die?  No one knows, so the data and study conclusions cannot be accepted as accurate.

When a doctor or drug company proposes a treatment the question “Do the benefits exceed the risks?” should be asked.  In other words, all therapies have both benefits and harms, and patients should be made aware of them. This is called informed consent. The best measure of treatment risk is what is called a “serious adverse event” or SAE.  This is any event that leads to death, hospitalization, prolongation of hospitalization, permanent disability, or is considered threatening by a physician.  SAEs must be reported and documented in clinical trials.  But they weren’t in most cases.  Do the therapies proposed reduce SAEs?  Again, what Dr.Wright found was a bias in reporting. 

He repeatedly requested in writing the data from all the primary prevention trial authors from all major statin drug trials.  In some cases he received no response.  In other cases he received pages of data.  In nocase did he receive the SAE data requested!! Of course, the question that comes up is if these drugs are truly showing the benefits outweigh the risks of taking the drug, why aren’t the drug manufacturers or authors of the studies sending the SAE data?  What are they hiding?

What Dr. Wright did find reported was “total mortality,” not cardiovascular mortality.  This gets a bit more complicated, but I’ll simplify his conclusions.

Drug companies evaluated the use of their statin drugs in two different populations.  The first population contained patients that had an event -- heart attack, stroke, leg amputation, TIA, or if a patient had documented peripheral vascular disease or heart disease.  These are called secondary prevention populations. In the statin trials that had to do with secondary preventionpopulations, statins were found to reduce total mortality.  But by how much?  If 50 people were treated for 5 years, one death would be prevented.  If 20 people were treated for 5 years one cardiovascular event would be prevented.  In other words, taking a statin drug reduces the chance of heart attack or stroke by about 5% and death by about 2% over 5 years if you have documented atherosclerosis.  So if you are reading this and have documented atherosclerosis and are taking a statin drug, you need to ask yourself if the benefits to you outweigh the risks and side effects of the treatment.

The other group of patients he looked at was the primary prevention populations.  This accounts for 80% of the patients taking statin drugs today.  These are people who have risk factors such as diabetes or high cholesterol levels, but no documented heart or peripheral vascular disease.  Statins did not reduce mortality in this population.  His conclusion was that people with diabetes, hypertension, smokers, hypercholesterolemia, etc. but who have no proven occlusive vascular disease, should not be taking statin drugs because there was no evidence of a net health benefit in this population. And Dr. Wright is not alone in this opinion.

Dr. Stephen Sinatra is one of a minority of cardiologists who incorporate nutritional therapies as the mainstay of treatment of heart disease. In his book Reverse Heart Disease Now, he points out that one third of the patients on statin drugs have side effects, and he doesn’t prescribe statins to lower cholesterol or in patients without evidence of cardiovascular disease.  This class of medications has a long list of potentially serious side effects that are not clearly explained to the patients taking them or even to the doctors prescribing them. 

I agree with Dr. Wright and Dr. Sinatra and do not prescribe statins to lower cholesterol. I realize this opinion does not reflect what most cardiologists or primary care physicians believe or how they are prescribing statin drugs. This does not mean that risk factors shouldn’t be treated in some manner. A healthy diet and exercise is the foundation for any person’s health program, and for many this approach is adequate.  Unfortunately, nutritional supplements that lower cholesterol and oxidative stress, and have virtually no side effects are considered by the FDA (Food and Drug Administration) to be an illegal health claim.  Instead, the FDA expects Americans to use statin drugs to accomplish this goal. 

In the next issue of the Newsletter, I will discuss statin drug side effects and nutritional therapies that can be used to reduce risk factors for heart disease.

Success Story – Patient with Endometrial Hyperplasia treated with Bio-identical Hormonal Therapy

Mrs. S is a 47 year old patient who initially saw me in 2006.  Two years after her periods stopped she began spotting and went to her gynecologist who subsequently found her to have endometrial hyperplasia after performing a D&C. Endometrial hyperplasia is a condition that occurs when the lining of the uterus (endometrium) grows too much. It is a benign condition in and of itself, but is associated with hormonal imbalance that can be a risk factor for the development of uterine or breast cancer. Mrs. S was also experiencing anxiety, sleep disturbance, and fatigue which is common for some women in menopause.

Her gynecologist suggested she go on Prometrium in a high dose for the first 10 days of the month.  This is one of the traditional treatments for this condition.  Some women undergo a D&C procedure where the lining of the uterus is scraped out.  Mrs S. wanted to be placed on bio-identical hormonal therapy but her gynecologist did not agree.  After a comprehensive evaluation at the Center, the patient was found to have to have multiple nutritional deficiencies on Spectracell testing, hormonal imbalance with low progesterone and estradiol as well as an anemia on laboratory testing.  Mrs. S was placed on the appropriate nutritional supplements and her anemia corrected.  She was also placed on bio-identical hormonal replacement with Biestrogen (a combination of human identical estradiol and estriol) mixed in grape seed oil.  This is placed under the tongue via dropper twice daily in a customized dose.  She was also placed on natural micronized progesterone in the form of a trouche that is placed under the tongue where it rapidly dissolves.  The patient’s lab values of hormones normalized, and within several months the patient’s sleep pattern returned to normal.  Her anxiety disappeared and her energy returned to normal.  She went back to her gynecologist recently who did an endometrial biopsy that showed complete resolution of the previous endometrial hyperplasia (she did not tell him she was taking bio-identical hormones).