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dimanche 4 décembre 2011

The Modern Myth of Cholesterol..Do we need Sherlock Holmes?

While writing this, I was reminded so much of one of my good teachers in Endocrinology, Dr Eric Reiss, I dedicate this to him.
We were Fellows in Endocrinology, very dedicated and so steeped in the biomedicine of Endocrinology. While on a teaching rounds one day with Dr Reiss, one of us presented to him the case of a middle aged black lady whose Primary Care Physicians had wanted an Endocrinology Consultation, while she was an Inpatient at the Teaching Hospital of the University of Miami School of Medicine.
The Endocrine Student made such a good presentation of the “case”, talked about various types of Cholesterols and the proteins that carry them, and the Xanthelesma the lady had around her eyes.
After examining her, Dr Reiss turned to the Young Doctor and asked: I noticed that there is a bandage over her left breast, did you get a history from her about that wound?
Flustered, the buoyant endocrinologist in training said, No, Sir, I did not ask her.
Dr Reiss then exhibited his wisdom by gently asking her the source of the wound in her left breast.
The Lady replied haltingly, I live in a housing project (low income housing) and a rat bit me while I was sleeping.
When is this lady being discharged? Today sir, answered the bright young endocrinologist. How is she getting home? I don't know sir, said the young man.
Do you have the bus fare to go home when they discharge you today?, asked Dr Reiss
The lady looked down and said, No, I don't have the bus fare.
No amount of your knowledge and expertise in cholesterol metabolism and its medical treatment is helpful to this lady. You are proud of your knowledge, but you can help this lady by giving her the bus fare to get home and enquiring how she gets about her eating every day.
Dear friends, I was already very socially conscious but watching that interaction had a deep impression upon me. I didn't want to be an expert in Cholesterol metabolism but I wanted to be able to help that lady..and others in her situation, not only in the USA but in various parts of the world.
In the years following, without a plausible explanation other than the food/exercise, national levels of cholesterol began to go up. People began to look at individual biochemical markers in the blood, and began to wonder what drugs would lower them one by one.
It is incredible to believe that in the eight years between 1994 and 2002, in the USA, in people aged 20 or above, fully 10 per cent of the population had cholesterol levels higher than 200! ( from 3 per cent).If you look at the older population (65+) the prevalence is 27 % in 2003… in 2011, the figure quoted was that 1 in six Americans have unhealthy cholesterol levels.
The first commercially available STATIN drug to treat high cholesterol was introduced in 1987. Since then it has become one of the all time blockbuster drugs. Is there something incongruous with this picture?
Scientific American November 2011 issue had an article, with an attractive title, Cholesterol Conundrum. A science Journalist from NYU continues: Two major clinical trials in the past three years have greatly complicated the scenario of Cholesterol lowering with drugs. The first study, from 2008, shows that lowering LDL does not always lower the risk of having a heart attack. A second study, released in the spring of this year, show that raising HDL levels does not always translate into fewer heart attacks or strokes.
The results have, however, underscored the danger of indulging in a common logical shortcut in medical thinking assuming that artificially producing normal test results in a patient is the same as conferring good health to that patient,
My personal opinion is that cardiovascular disease is an inflammatory process, involving multiple and longstanding pathways and that cholesterol is an indirect measure of that inflammation. The most popular drug called STATINS seems to be excellent at reducing that inflammation.
In a society which is gaining weight with each passing year, where the rate of Diabetes is going up in more than a linear fashion, higher cholesterol levels also demonstrate that all the above related in some fashion to the society itself.
(just the other day, I heard that Inflammatory Bowel Diseases are also on the increasing and much like Diabetes, affecting younger and younger people. Could all these be related? What price this society?)
The three rapidly economically evolving societies, Brasil, China and India have also shown an incredibly steep increase in the rate of cardiovascular diseases in the process, with younger persons affected in disproportionate fashion. In fact, it is not unusual to hear about people in their forties with four vessel by pass surgeries, as if it is a medal earned for their hard work in the buoyant economy.
Is it the inflammation that is being so successfully treated by the expensive Statins? Rather than seeing a benefit of reduction of Cholesterol?
Modulation of C-Reactive Protein–Mediated Monocyte Chemoattractant Protein-1 Induction in Human Endothelial Cells by Anti-Atherosclerosis Drugs
Vincenzo Pasceri, MD, PhD; Jed Chang, BS; James T. Willerson, MD; Edward T. H. Yeh, MD
From the Department of Cardiology (J.C., E.T.H.Y.), University of Texas–MD Anderson Cancer Center; Department of Internal Medicine (V.P., J.T.W., E.T.H.Y.), University of Texas Health Science Center; and the Texas Heart Institute (V.P., J.T.W., E.T.H.Y.), St. Luke’s Episcopal Hospital, Houston, Tex.
Circulation. 2001;103:2531-2534
Conclusions—These results further strengthen the role of CRP in the pathogenesis of vascular inflammation and, likely, atherosclerosis and provide a crucial insight into a novel mechanism of action of anti-atherosclerosis drugs such as simvastatin and fenofibrate.

Also, it is good to take note that one in five people, at least, whose LDL levels are well controlled by their medications, still experience heart attacks or strokes.
Ezetimibe is another class of drugs, which lower cholesterol by another pathway and adding it to a Statin was recommended and yet another billion dollar drug was born.
A study with the dubious acronym of ENHANCE published its results in 2008, only to show that there were no additional benefits by adding Ezetimibe to a Statin medication. Yet the combination of the medications was able to drop the LDL cholesterol (the baddie) by 51mg/dl.
Of course all the research papers and their paid peons talk as if these people exist in vacuum and that the society in which they live have very little to contribute to moderate the individual results. The inflammation arrives in the body, from external sources, such as adulterated food or internal sources such as the felt stress and its subsequent metabolic alterations.
The Quality of food has taken a hit. Those of us who have lived or spent long times in Australia, UK or USA can attest to this. (Easily available food). It may not come as a surprise that these are the three fattest countries in the developed world as well..
Not eating processed meat can reduce your cholesterol up to 12 % ( i.e.  30 mg/dl in a patient with cholesterol value of 250), Moderate exercise increases HDL (the good cholesterol) by about 10-15 %. Much more than the current medications available and the newer drugs to raise HDL cholesterol have very serious side effects.
To support my contention that the society is responsible rather than the individual for this calamitous use of STATINS (13 million prescriptions per month in the USA alone), I was happy to read this cutting edge science from China (let us get used to it, folks, they will be making more than cheap tchotchkes!).

Food We Eat Might Control Our Genes

Scientists find rice microRNA inside human cells

The results, published in the journal Cell Research, showed that the subjects’ bloodstream contained approximately 30 different microRNAs from commonly eaten plants. It appears that they can also alter cell function: a specific rice microRNA was shown to bind to and inhibit the activity of receptors controlling the removal of LDL—“bad” cholesterol—from the bloodstream. Like vitamins and minerals, microRNA may represent a previously unrecognized type of functional molecule obtained from food.

Our bodies are highly integrated ecosystems, with influences from not just individual items of interest of the day (41 different food stuffs have been individually shown to be bad for your heart but some like Coffee and Chocolate later gone to achieve Benefactor status), also our culture, our philosophy about our lives, our relationships within the society we live in, also influence our bodies, not just food and exercise…

Many of the doctors, from Family Practitioners/GP to specialists have chosen to treat the paper and the numbers on them rather than the patient and what he or she represents in the society the patient lives in. One reason the symbolic healing among the American Indians is successful is that the basic belief system of the patient and the healer are similar and they tend to share the same society and its values and its merits and pitfalls.
Changing a biochemical marker is not the same as improving the outcome for patients, said the chief of Cardiology at the Cleveland Clinic.

Coming back to Dr. Eric Reiss, it is better to take care of that poor lady, and find out how she and what she is eating rather than prescribing a 100 dollars/month drug, just one statin can cost that, she in most probability cannot get.  Dr. Reiss, an eminent Endocrinologist of his time, was way ahead of others. Take care of the patient and not the numbers on the paper…

Sherlock Holmes was a fictional character created by a Physician, Sir Arthur Conan Doyle.
Sir Arthur said that the character of Sherlock Holmes was inspired by Dr Joseph Bell, for whom Doyle had worked as a clerk(medical assistant) at the Edinburgh Royal Infirmary. Like Holmes, Bell was noted for drawing large conclusions from the smallest observation. 

PS.  Dr Joseph Bell DID not describe Bell’s Phenomenon nor Bell’s palsy, credit for them goes to a fellow Scot, Sir Charles Bell

PPS  Dr Reiss who died in 1988 was married to Dr Louise Reiss, also a physician, who was instrumental in showing that atmospheric atomic tests increased the Sr90 levels in the teeth of children in St Louis. The Baby Tooth Study was influential in the banning of atmospheric nuclear testing.