Sunday, September 29, 2013

Statins and Mitochondrial Damage Part 5 - Graveline

Please be sure to read all of the articles in this series. Links to all are at the end of this article.


By Duane Graveline MD, MPH

Statins and Mitochondrial Damage Part 5 of 11

Updated September 2013

Why is it that at the time statin drugs first were marketed, doctors had such rudimentary knowledge of the true role of cholesterol in the human body?  Just as I draft this sentence on 5 October 2009, Prof. Ernest Arenas of the Karolinska Institute(10) announces, "Cholesterol vital for brain development." 

After some 40 years of brainwashing about the evils of cholesterol and the necessity to avoid such cholesterol-rich foods as butter, whole milk and eggs, doctors were convinced that cholesterol was the cause of heart attacks and strokes and should be reduced at all costs.

Of course, this was passed on to patients, with the result that today you can use the word cholesterol to frighten small children.  In 1999, some 10 years after the marketing of statins began, the first serious adverse reports started to arrive at Medwatch, FDA's post-marketing surveillance system.

A peculiar form of amnesia appeared wherein the victim abruptly lost the ability to formulate new memory, along with reports of other evidence of cognitive dysfunction, such as confusion, disorientation, forgetfulness and a dementia resembling that of Alzheimer's disease.

Then came Prieger's landmark publication in 2001 of the vital role of cholesterol in the formation and function of memory synapses, followed by one research report after another documenting the importance of cholesterol and the wide ranging demand for cholesterol in so many of our vital bodily functions, including nerve, muscle and even personality. 

Many of these problems seemed to be permanent, persisting for years after the offending statin was stopped, and resistant to all traditional treatment.  Increased rate of mitochondrial mutations began to be reported and more recently we have found that our dependence for cholesterol begins even at the molecular level where cholesterol is necessary for such fundamental electrochemical reactions as mitochondrial sodium, potassium and proton exchange in our ATP synthesis.

It seems that everywhere we look, we find a critical role for cholesterol. How then can such a ubiquitous and vital biochemical be harmful? The reality is that cholesterol, in its natural form, cannot be harmful. Cholesterol is irrelevant to atherosclerosis. Far from being harmful, cholesterol is perhaps the most important biochemical in our bodies. 40 years of anti-cholesterol brainwashing has been nothing but a massive "con" job. With immense profit to the drug, food and health care industry and the promise of extra years of life in return for lowered cholesterol, it was a win/win situation that spread like wildfire.
Cholesterol is not only the most common organic molecule in our brains, it is also distributed intimately throughout the entire body.  Additionally, cholesterol is the precursor for a whole class of hormones known as the steroid hormones that are absolutely critical for life as we know it. Such hormones include estrogen, progesterone, testosterone, aldosterone, cortisol and calcitrol (vitamin D).
These hormones determine our sexuality, control the reproductive process, and regulate blood sugar levels and mineral metabolism.  Beyond this, there is yet another class of cholesterol's steroid offspring without which our metabolic well-being might be in serious jeopardy:  the production of bile acids.  Bile makes it possible for us to emulsify fats and other nutrients.  Without bile, we could not digest and absorb the fats in our diet and must slowly starve.

Additionally, cholesterol is an essential constituent of the membrane surrounding every cell.  The presence of cholesterol in this fatty double layer of the cell wall adjusts the fluidity and rigidity of this membrane to the proper value for both cell stability and function.

Only in the past decade have we learned that cholesterol contributes much more than stability to bipolar layer function.  Biochemists such as Thomas Haines (11), while diligently studying this fatty double-layered membrane, have revealed some astounding new information bearing on the role of the lipids involved as gate-keepers in the basic process of transfer of sodium and proton ions though the tiny pores in our double layered membranes.

Dolichols and coenzyme Q10 have long been known to be principle players in this control function.  Only recently has it been discovered that cholesterol also is critical to this gatekeeper role.
The subject of cholesterol depletion now provokes major concerns (12) with a summary on Wikipedia: wikipedia.org/wiki/Cholesterol_Depletion

10. Arenas J. Karolinski Institute, October 2009
11. Haines T. sci.ccny.cuny.edu/chemistry/faculty/haines_proglip.pdf   
12. Wainwright G and others. Arch Med Sci 5. 2009

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

11. Statins and Mitochondrial Damage - Conclusion

Read the complete article here.

Thursday, September 26, 2013

Statin drug found to impair learning and memory in animals

One of my blogs last week focused on the potential impact statins have on the development or symptoms of dementia. Interest in this area is an example of the growing recognition that statins have the ability to affect brain functioning. As I briefly mentioned last week, even the Food and Drugs Administration in the US has recognised the potential for statins to induce symptoms such as memory loss, forgetfulness, and confusion.

There is no doubt that statins have the potential for toxicity. However, any direct affects on the brain has generally been believed to be related to the ability of statins to cross what is known as the ‘blood-brain-barrier’. An agent’s ability to breach the blood brain barrier is traditionally thought to be related to several factors, including its affinity to fat or water. Substances that have a high affinity for fat are described as ‘lipophilic’ and have traditionally been believe to cross the blood brain barrier relatively easily. On other hands, conventional wisdom tells us that substances with a high affinity for water (‘hydrophilic’ compounds) do not cross the blood brain barrier readily.

It is known that some statin drugs such as atorvastatin (Lipitor) are lipophilic, white others such as pravastatin (Pravachol) are hydrophilic. In theory, atorvastatin would be expected to be more likely to have adverse effects on the brain compared to pravastatin.

This week saw the publication of a study in which rats were treated for 18 days with one of two statins: pravastatin (Pravachol) or atorvastatin (Lipotor) [1]. Before during and after treatment, the rats were subjected to a learning test. This was adversely affected by pravastatin but not atorvastatin. The animals were also subjected to a memory task, which was also adversely affected by pravastatin but not atorvastatin. The adverse effects induced by pravastatin were ‘reversible’ (resolved on discontinuation of the drug).

These results are the perhaps the opposite of what one might expect from the theory of the propensity of different statins to gain access to the brain. However, the authors of the study point out that pravastatin tends to distribute itself more widely in the body than atorvastatin, and this may ultimately increase pravastatin’s ability to gain entry to the brain.

As to how statins may impair brain function, the researchers suggest one potential mechanism directly relates to lowered cholesterol levels. Cholesterol is required, among other things, for the formation of the fatty sheathes (myelin sheathes) that surround nerves, and any disruption in this may impair neurological functioning. Cholesterol also contributes to the functioning of ‘synapses’ – the tiny gaps between cells via which nerves communicate with each other.

I suspect we have much to learn about the potential for statins to disrupt brain function, and this recent animal study is only a small piece in the puzzle. However, it does support the idea that different statins can pose different risks here, and suggests that the conventional wisdom on lipophilic statins being more hazardous than hydrophilic ones may not actually hold true.

1. Stuart SA, et al. Chronic Pravastatin but Not Atorvastatin Treatment Impairs Cognitive Function in Two Rodent Models of Learning and Memory. PLoS ONE 8(9): e75467

Thursday, September 19, 2013

Another large study is linking statin use to the development of cataracts - Wood

Statins linked to cataracts in large, retrospective study

September 19, 2013
San Antonio, TX - Another large study is linking statin use to the development of cataracts [1]. The latest, following on a Canadian analysis last year, is a propensity score-matched analysis of over 45 000 subjects in a military healthcare system, published this week in JAMA Ophthalmology.
As Dr Jessica Leuschen (Wilford Hall Ambulatory Surgery Center, San Antonio, TX) and colleagues point out, observational studies of statins have been conflicting, with some suggesting an increased risk of cataracts with statin use while others appear to show a beneficial effect of statins on cataract risk. At the recent European Society of Cardiology (ESC) 2013 Congress, Dr John B Kostis (Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ) presented the results of a random-effects meta-analysis, showing a 20% lower rate of cataracts with statin use compared with no statin use, with a more pronounced benefit seen when statins were started in younger patients. 
The meta-analysis published today, however, found the opposite. It matched 6972 statin users with nonusers within the San Antonio Military Multi-Market Area health system using propensity scores based on variables that increased the likelihood of receiving statins and increased the risk of developing cataracts. Statin users had to have been on the drugs for more than 90 days; simvastatin was prescribed in almost three-quarters of the patients.
They found that statin users in the propensity-matched analysis had a 9% increase in cataracts. In secondary analyses that looked at all patients with no comorbidities (based on the Charlson index) at baseline, the risk of developing cataracts was 29% higher in the statin users. Results were consistent regardless of whether patients had been taking statins for two, four, or six years, authors note.
The study is the first to use propensity matching to try to eliminate baseline confounding—making it a key contribution to the relatively recent research into this potential interaction. To heartwire, senior author Dr Ishak Mansi (VA North Texas Health Care System, Dallas) noted that there are a number of ways in which statins could be a marker for important confounders, including accessible healthcare and health insurance, as well as underlying risk factors such as smoking, diabetes, and older age—all of which are also risk factors for cataract.
That kind of confounding may have been a factor in the Kostis et al meta-analysis at ESC, Mansi commented, when asked about the divergent findings, adding that since the paper is not yet published, he hasn't had a chance to review its methodology.
"Without knowing the specifics of the paper . . . I can generally say the following: During the mid-1990s and early 2000s, there were many papers that associated statin use with improved outcomes of many diseases such as cataract, fracture, infection, dementia, etc; however, recently, it was realized that statin use was associated with 'healthy-user bias.' That is to say, individuals who are health-conscious are more likely to take statins, and better outcomes may be secondary for their health consciousness and not due to the statin itself. . . . Therefore, if this meta-analysis included large-volume studies that date back to this period of time, their results may be affected by these biases of these studies."
Cardiologists have had plenty of experience with seemingly contradictory studies, he added. "Historically, we have been through these controversies on several topics, such as the use of hormonal-replacement therapy, treatment of chronic systolic heart failures with antiarrhythmic drugs, etc. We will have to study and search for our best capabilities until we reach an answer."
"Statins are very effective medications; therefore, side effects are expected. Healthcare providers should make sure that there is justifiable indication to prescribe statins according to guidelines and that the potential benefits outweigh the potential risks of side effects for individual patients. These medications should not be prescribed lightly."
For the public, however, the message is slightly different. "For some patients, these medications have been a main tool in treatment of heart disease and should not be stopped because of a small higher risk of association with other diseases," Mansi said. All effective medications can be expected to have side effects, he continued. "It is much better to do your best to lower your own risk of cardiovascular disease (if feasible) by stopping smoking and keeping physically active than to take a pill to lower your risk of heart disease."
  1. Leuschen J, Mortensen EM, Frel CR, et al. JAMA Ophthalmol 2013; DOI:10.1001/.jamainternmed.2013.4575. Available at: http://archopht.jamanetwork.com/journal.aspx.
Read the complete article here.http://www.theheart.org/article/1584825.do

Wednesday, September 18, 2013

Thyroid Pills & Heart Disease - Dach

Thyroid Pills Prevent Heart Attacks by Jeffrey Dach MD

bottle,pills,thyroid,westhroid,capsulesThyroid Pills Prevent Heart Attacks by Jeffrey Dach MD

The Low Thyroid Condition and Heart Disease

In 1976 Broda Barnes was the first to connect low thyroid function with heart attacks and heart disease.  His book is called, Hypothyroidism The Unsuspected Illness by Broda Barnes, Click Here to read my Book Review..

Above Left Image: Photo of WP Thyroid Pills Bottle courtesy of RLC labs Natural thyroid pills

Discovering the Connection
How did Broda Barnes discover the connection between low thyroid and heart disease?  Barnes took summer vacations in Graz Austria every year to study the autopsy files.  Graz had a high prevalence of thyroid disorders, and anyone in Graz who died over the past 100 years required an autopsy to determine cause of death, as mandated by the authorities.  This rather large amount of autopsy data showed that low thyroid patients survived the usual childhood infectious diseases thanks to the invention of antibiotics, and years later develop heart disease.  Barnes also found that thyroid treatment was protective in preventing heart attacks, based on his own clinical experience.  Likewise for diabetes, Dr. Barnes found that adding thyroid medication was beneficial at preventing the onset of vascular disease in diabetics.  Again, blood tests are usually normal.
New research like the Hunt Study confirms that Broda Barnes was right all along, creating a paradigm shift in thyroid treatment, and constituting a frontal assault on the Institution of Medicine’s thyroid dogma.

The Hunt Study - Thyroid Function and  Heart Disease
TSH is short for thyroid stimulating hormone, made by the pituitary gland.  TSH actually stimulates the thyroid gland to make more thyroid hormone, and can therefore be used as a barometer of thyroid function.  If thyroid function is low, the pituitary sends out more TSH to stimulate the thyroid to make more thyroid hormone.  
Mainstream Medicine regards the TSH as the single most important test for determining thyroid function. High TSH means low thyroid function, and a Low TSH means normal or high thyroid function.

What Did The Hunt Study Find?
Thyroid GlandThe Hunt Study from the April 2008 Archives of Internal Medicine examined mortality from coronary heart disease (CHD) and TSH level.  The authors conclude,
“The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD.”
Above Image: Thyroid Gland makes thyroid hormone.

The Hunt Study measured thyroid function with the TSH test in 17,000 women and 8,000 men with no known thyroid disease or heart disease. All patients had “normal TSH” levels meaning the TSH values were in the lab reference range of 0.5 to 3.5.   The women were stratified into three groups, lower TSH, intermediate and upper TSH levels, and mortality from heart disease was recorded over an 8 year observation period.

 (see chart below).
70% Increase in Heart Disease Mortality for TSH in Upper Normal Range
Heart Attack with Occluded Artery The Hunt study found that group with the higher TSH had a 70% increased mortality from heart disease compared to the lower TSH group.  Remember all these TSH vales were in the normal lab range. See chart below for results of the Hunt Study:

Left Image: Heart with Occluded Coronary Artery and Infarction at the apex, courtesy of wikimedia commons.

Results of the Hunt Study:

   TSH   Death from Heart Disease
 Group 1 0.50-1.4 baseline risk
 Group 21.5-2.440% higher than baseline
 Group 32.5-3.570% higher than baseline

This Finding is Earthshaking !!

This means that merely by taking natural thyroid pills to reduce TSH to the low end of “normal” (0.5), one can reduce death from cardiovascular disease by 70 percent.  This mortality benefit is mind boggling and far exceeds any drug intervention available.

Thyroid Hormone Also Improves LDL Lipo-Proteins
Another report from the Hunt Study published in 2007 showed that LDL cholesterol was linearly associated with TSH level. (see chart below).
Below Chart showing LDL cholesterol (non-HDL) goes up as TSH goes up.  Note that TSH always remains within in the lab “normal range” (0.5-3.5).
Above chart shows linear increase in LDL cholesterol as TSH increases.
Image Courtesy of Hunt Study European Journal of Endocrinology, Vol 156, Issue 2, 181-186, 2007
The Conclusion is Clear:
The best way to normalize lipoprotein profile and reduce mortality from heart disease is to reduce TSH to the lower end of the normal range with thyroid medication.  A TSH in the upper end of the normal range is associated with increased cardiovascular mortality and elevations in LDL lipo-protein measurements.  A TSH at the lower end of the normal range is associated with protection from heart disease.

Statin Drugs or Thyroid to Prevent Heart Disease in Women?
My previous article discussed the issue of statin drugs for women.  Decades of published statin drug studies show that statin drugs simply don’t work for women, and don’t reduce mortality from heart disease in women.  But on the other hand, the HUNT study shows that TSH levels in the lower normal range provide a 70% reduction in heart disease mortality for women.  This can be accomplished safely with inexpensive thyroid medication under a physician’s supervision.  So for women concerned about preventing heart disease, this is good news, pointing out a natural alternative to statin drugs that works much better.

Natural Thyroid is Better
Thyroid HormoneRather than Synthroid, we prefer to use natural thyroid which is a dessicated porcine thyroid gland from RLC Labs.  The reason for this is that we have seen better clinical results with the natural thyroid preparations compared to synthroid.
Above image: thyroid hormone Courtesy Wikimedia .
Natural Thyroid is Safer, but can Cause Adverse Effects of Palpitations
Although natural thyroid is safe, there is always the possibility of adverse effects from thyroid excess, defined as too much thyroid medication.  The first sign of thyroid excess is usually a rapid heart rate at rest or perhaps palpitations (at rest).  We spend about five minutes at the office going over this adverse effect before starting patients on thyroid medication.  Usually patients will notice the heart rate going up or the heart beat sounding louder than usual as the first sign that can be easily recognized.  Once recognized, the patient is instructed to stop the thyroid medication, and symptoms usually resolve within 6 hours (for natural thyroid).  It is perfectly safe to stop the thyroid medication at any time, as there will be no acute changes, merely a gradual reversion to the original state that existed before starting the thyroid pills.

Some patients are very sensitive to thyroid medication and will have thyroid excess symptoms such as rapid heart rate and palpitations from small amounts of thyroid medication.  These are usually the elderly with underlying heart disease and/or magnesium deficiency, and we usually avoid giving thyroid medication to these patients.  We also liberally supplement everyone with magnesium if their RBC magnesium levels are low.

About 5 per cent of our patients initially started on thyroid will notice symptoms of thyroid excess with a rapid heart rate, and they will stop the medication for a day or two and restart at a lower dosage with no problem.  This is more common in Hashimoto’s patients whose own production of thyroid hormones may fluctuate from month to month.  Patients with magnesium deficiency or adrenal fatigue with low cortisol output on salivary testing will also tend to be more sensitive to small amounts of thyroid medication, so caution is advised in these groups as well.

Thyroid Excess Can Rarely Cause Atrial Fibrillation
Upper Image: EKG strip with Red Arrow shows atrial fibrillation, no recognizable P-wave.  Lower Image: EKG strip with normal rhythm with recognizable P wave (blue arrow). Courtesy of Wikimedia Commons.
So far, we have not had a patient go into atrial fibrillation from thyroid medication, probably because we spend so much time with each patient discussing the symptoms of thyroid excess, and the importance of stopping the thyroid medication if these symptoms are noted.

Mainstream Docs Don’t Have Time To Discuss Adverse Effects
Doctor thinking about thyroid dosageOne of the reasons the mainstream conventional docs will give only a minuscule amount of synthroid to the low thyroid patient is that they simply don’t have the time to discuss thyroid excess and can’t afford an adverse event which is more likely if the patient doesn’t have a clue about what to watch out for.  In addition, mainstream medical docs don’t recognize the syndrome of adrenal fatigue or magnesium deficiency , so they can run into problems with thyroid excess without understanding why, and this also makes them very cautious, tending to under treat.
Left Image: Doctor thinking about thyroid dosage.
In patients with underlying heart disease who are prone to cardiac arrhythmias, thyroid excess can cause atrial fibrillation with characteristic EKG appearance.  Atrial fibrillation can be a problem, because if it becomes chronic and doesn’t go away on its own, the cardiologist will try a maneuver called cardioversion, the application of an electrical shock to restart a normal cardiac rhythm.  Or, if that doesn’t work, prescribe blood thinners, all of which is not without risk.  So it is better to avoid atrial fibrillation altogether by simply stopping the thyroid pills whenever symptoms of rapid heart rate or palpitations are noted while at rest.  Exercise induced rapid heart rate, of course, doesn’t count since that is normal cardiovascular response to exercise.

How To Design A Better Hunt Study
How would I design an even better Hunt Study? That’s easy. Include another group of patients with TSH levels above and below the study group, namely, below 0.5, and above 3.5.  I would also include data on annual CAT coronary calcium scores.  I would predict that the lower TSH group (below 0.5) would have even less heart disease than the higher TSH group, and that coronary calcium score, indicating plaque burden, would go up as TSH went up.

Read More About the Hunt Study from William Davis MD and Jacob Teitelbaum MD:
Is normal TSH too high?   by William Davis MD
Low Thyroid (Even if Tests are Normal) is a Major Cause of Heart Attacks by Jacob Teitelbaum, MD.

Credit and Thanks is given to William Davis MD and Jacob Teitelbaum MD for bringing the Hunt Study to my attention.

For more information on thyroid and heart disease, read my previous articles:
Saving Time Russert and George Carlin
Healthy Men Should Not Take Statin Drugs
Heart Disease Vitamin C and Linus Pauling
Getting Off Statin Drug Stories
How to Reverse Heart Disease with the Coronary Calcium Score (part one)
Reversing Heart Disease Part Three
Cholesterol Lowering Drugs for the Elderly, Bad Idea
Cholesterol Lowering Statin Drugs for Women Just Say No

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie Florida 33314
(c) 20013 Jeffrey Dach MD All Rights Reserved, This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given.
Link to this article:http://wp.me/P3gFbV-LU
Links and References:
Arch Intern Med. 2008;168(8):855-860. Thyrotropin Levels and Risk of Fatal Coronary Heart Disease,
The HUNT Study

Arch Intern Med. 2008;168(8):855-860. Background  Recent studies suggest that relatively low thyroid function within the clinical reference range is positively associated with risk factors for coronary heart disease (CHD), but the association with CHD mortality is not resolved.
Methods  In a Norwegian population-based cohort study, we prospectively studied the association between thyrotropin levels and fatal CHD in 17 311 women and 8002 men without known thyroid or cardiovascular disease or diabetes mellitus at baseline.
Results  During median follow-up of 8.3 years, 228 women and 182 men died of CHD. Of these, 192 women and 164 men had thyrotropin levels within the clinical reference range of 0.50 to 3.5 mIU/L. Overall, thyrotropin levels within the reference range were positively associated with CHD mortality (P for trend = .01); the trend was statistically significant in women (P for trend = .005) but not in men. Compared with women in the lower part of the reference range (thyrotropin level, 0.50-1.4 mIU/L), the hazard ratios for coronary death were 1.41 (95% confidence interval [CI], 1.02-1.96) and 1.69 (95% CI, 1.14-2.52) for women in the intermediate (thyrotropin level, 1.5-2.4 mIU/L) and higher (thyrotropin level, 2.5-3.5 mIU/L) categories, respectively.
Conclusions  Thyrotropin levels within the reference range were positively and linearly associated with CHD mortality in women. The results indicate that relatively low but clinically normal thyroid function may increase the risk of fatal CHD.
Author Affiliations: Department of Public Health, Faculty of Medicine (Drs Åsvold and Vatten), and Human Movement Science Programme (Dr Nilsen), Norwegian University of Science and Technology, Trondheim, Norway; St Olavs Hospital, Trondheim University Hospital, Trondheim (Dr Åsvold); Department of Medical Biochemistry, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (Dr Bjøro); and Department of Social Medicine, University of Bristol, Bristol, England (Dr Gunnell).
European Journal of Endocrinology, Vol 156, Issue 2, 181-186, 2007  CLINICAL STUDY  The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study
Bjørn O Åsvold1,2, Lars J Vatten1, Tom I L Nilsen1 and Trine Bjøro3  1 Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway, 2 St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway and 3 Department of Medical Biochemistry, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway (Correspondence should be addressed to L J Vatten
Jacob Teitelbaum MD
Jacob Teitelbaum, MD. Low Thyroid (Even if Tests are Normal) is a Major Cause of Heart Attacks,
William Davis MD
William Davis MD, begin quote:”Is normal TSH too high? There’s no doubt that low thyroid function results in fatigue, weight gain, hair loss, along with rises in LDL cholesterol and other fractions of lipids. It can also result in increasing Lp(a), diabetes, and accelerated heart disease, even heart failure.  But how do we distinguish “normal” thryoid function from “low” thyroid function? This has proven a surprisingly knotty question that has generated a great deal of controversy.  Thyroid stimulating hormone, or TSH, is now the most commonly used index of the adequacy of thyroid gland function, having replaced a number of older measures. TSH is a pituitary gland hormone that goes up when the pituitary senses insufficient thyroid hormone, and a compensatory increase of thyroid hormone is triggered; if the pituitary senses adequate or excessive thyroid hormone, it is triggered to decrease release of TSH. Thus, TSH participates in a so-called “negative feedback loop:” If the thyroid is active, pituitary TSH is suppressed; if thyroid activity is low, pituitary TSH increases.  An active source of debate over the past 10 years has been what a normal TSH level is. In clinical practice, a TSH in the range of 0.4-5.0 mIU/L is considered normal. (Lower TSH is hyperthyroidism, or overactive thyroid; high TSH is hypothyroidism, or underactive thyroid.)  The data from a very fascinating and substantial observation called the HUNT Study, however, is likely to change these commonly-held thyroid “rules.” endquote WIlliam Davis MD
International Hormone Societyhttp://www.intlhormonesociety.org/ref_cons/

International Hormone Society, references, clinically hypothyroid , lab euthyrroid
Other Blogs:
Thyroid Blog by Dr. Richard B. Guttler M.D., F.A.C.E.
Location: Santa Monica, California, United States

Stop the Thyroid Madness Blog – a patient tries in vain to convince soctors to switch from Synthroid to Armour
MAry Shomon thyroid blog
Disclaimer click here: http://www.drdach.com/wst_page20.html
The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship.  Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.  Finally, the material produced by myself may be reproduced for personal use, provided that appropriate credit is given
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(c) 2007-2013 Jeffrey Dach MD All Rights reserved. This article may be copied or reproduced on the internet provided a link and credit is given.

Sunday, September 15, 2013

Statin Therapy: Risks vs Benefit - Medscape

Statin Therapy: Risks vs Benefit: An Expert Interview With Eliot A. Brinton, MD

Editor's Note: Dr. Brinton is Director of the Metabolism Section of Cardiovascular Genetics, and Associate Professor at the University of Utah School of Medicine, Salt Lake City, Utah. He is board certified in internal medicine and endocrinology.
Dr. Brinton's areas of clinical interest include the management of dyslipidemia and prevention of atherosclerosis and the treatment of diabetes mellitus and metabolic syndrome. He also has research interests in lipoprotein metabolism and HDL-cholesterol metabolism in vivo and in vitro, including the effects of estrogen and other agents.
The author of numerous original scientific studies, Dr. Brinton has received many peer-reviewed research grants, and has held numerous leadership and advisory positions in scientific and governmental organizations, and in the pharmaceutical industry. He is a founding board member of the National Lipid Association. Dr. Brinton was interviewed for Medscape by Linda Brookes, MSc.
Medscape: Why is the safety of statins such a widely discussed issue at the moment?
Dr. Brinton: The safety of statins is of great interest to the public, as well as to clinicians and policy makers, in part because of the problems with the safety of cerivastatin (Baycol, Bayer), which ultimately led to its withdrawal from the market. With the recent advent of a new statin, rosuvastatin (Crestor, AstraZeneca), these concerns have resurfaced. Medication safety is always an issue, but especially so with the statins, for several reasons. First, and perhaps most importantly, they are prescribed frequently. Statins are the single most prescribed category of agents, in dollar value, in the United States today. Second, they are prescribed for long periods of time. Over the many years that a typical patient takes a statin, there are many chances for adverse events, including unforeseen changes in the patient's health status. A third and very important factor is that statins are most commonly used in middle-aged or elderly patients, who tend to be taking many other medications for other problems. This heightens safety concerns, both because the polypharmacy typical of these age groups greatly increases the overall risk of drug-drug interactions and because many of the diseases common in older patients contribute to drug safety concerns, and finally, because advanced age itself, even with excellent health, probably increases the risk of drug toxicity.

Medscape: There has been much discussion about myopathy in relation to statins. What is the difference between myopathy, myalgia, and rhabdomyolysis?
Dr. Brinton: There are 4 interrelated terms for muscle problems that can occur with statins. Unfortunately, they are often confused even by healthcare professionals.

Myopathy is a general term for disease of the muscles, and it is usually characterized by weakness. In the setting of statin treatment, myopathy is used to describe any muscle problem, whether or not it is actually related to the statin use.

Myalgia refers specifically to pain in the muscles. Muscle pain is often seen with statin-based myopathy; however, painless myopathy from statin therapy is also quite common and may be rather dangerous because it is often ignored. If the healthcare provider has not instructed the patient to look for this, the patient may not report it or, if the patient reports weakness without pain, the healthcare provider may not recognize it as constituting a true myopathy.

Myositis is inflammation of the muscle confirmed by histologic findings of muscle biopsy. We rarely know whether the patient has myositis because we rarely perform muscle biopsies. These are very accurate and, in many ways, they are the gold standard for diagnosing a statin-induced myopathy; however, the pain, inconvenience, and cost of biopsies make them impractical for most clinical and research settings. Since the word myositis is probably best reserved for biopsy-proven myopathy, it is not of much use. A recent study[1] showed that patients without an elevation of their serum creatine phosphokinase (CPK) level can nevertheless have myositis on biopsy. Thus, we need to have a fairly high index of suspicion for myopathy, realizing that it may be more common than we think, especially if we are looking only for myalgia or only for an elevated CPK.

Finally, rhabdomyolysis is the extreme type of myopathy, in which the muscle tissue is so inflamed that it breaks down in large quantities. It brings large amounts of myoglobin, the predominant muscle protein, to the circulation from which it then has to be removed by the kidney. Since the kidney is not well equipped to handle large amounts of myoglobin, it can become overwhelmed and damaged. Although the kidney usually recovers over time, rhabdomyolysis may be fatal due to acute renal failure and sequelae to other organs. Thankfully, most cases of rhabdomyolysis do not result in death, although they usually require hospitalization. Due to its seriousness, rhabdomyolysis is better prevented than treated, so we must do our best to see that myopathy does not progress to rhabdomyolysis.

Medscape: How often does myopathy occur?
Dr. Brinton: In most clinical trials involving statins, less than 1% of subjects are reported to develop myopathy. In clinical practice, however, far more than 1% of patients will experience at least 1 symptom of myopathy. The much lower rate reported in clinical trials may be because eligibility criteria usually exclude patients with significant potential for drug-drug interactions or concurrent health problems, whereas healthcare providers cannot usually exclude those patients in clinical practice. Some studies have suggested that a quarter or even upwards of a third of patients who take statins will sooner or later develop a clinically significant myopathy.

Medscape: What are the risk factors for myopathy?
Dr. Brinton: The main risk factors for myopathy are: female gender, advanced age (> 60 years) dehydration, underlying renal or liver disease, and concomitant medications. There is a fairly long list of medications that increase the risk of myopathy. Some of these are relatively specific for one statin vs another, but most of them appear to apply to all statins.

Medscape: How do you monitor patients for myopathy?
Dr. Brinton: The first and best step is to ask about symptoms, but we have to be careful to ask about the right ones. We must ask not only about muscle pain, but about weakness and stiffness. Sometimes there can be stiffness without identifiable weakness or pain. When I start patients on a statin, I mention that they may experience any 1 or a combination of these 3 symptoms. I always make it a point to ask my patients about those 3 symptoms as I follow them in the clinic.

I measure CPK prior to starting statin treatment, and then, rather than measuring follow-up CPK levels routinely, I do so only when a patient presents with symptoms suggestive of myopathy. The reason for this is that CPK levels vary tremendously from day to day, and one may see a spurious elevation of CPK that has nothing to do with statin-based myopathy. If a patient has convincing myopathic symptoms but a normal CPK, I will defer to the patient and treat it as a true case of myopathy. If, in contrast, the CPK is clearly elevated but the muscle symptoms are somewhat equivocal, then the CPK elevation can be helpful to determine whether or not the patient has a true myopathy. Also, the degree of CPK elevation can be useful in estimating the severity of a myopathy.
Some physicians and lipidologists do not measure CPK at all, because the correlation is fairly poor between CPK levels and symptoms, but I find it useful for the above reasons. In any case, however, one should not rely on the CPK level to diagnose myopathy, because even a relatively severe case of myopathy may have normal or minimally elevated CPK.

Medscape: Can CPK be used to exclude patients from starting a statin?
Dr. Brinton: A patient with a very high CPK elevation initially should not be started on a statin. This is another reason to measure CPK at baseline. The upper threshold for a clinically significant CPK is quite high, 10 times the upper limit of normal, because CPK levels are so variable. If a patient develops a CPK over 10 times the upper limit of normal on statin use, you should stop statin therapy, at least temporarily, and consider either lowering the dose or switching to a different statin. In rare cases, for example, in a patient with a history of rhabdomyolysis, one may need to abandon the statin class altogether, even perhaps without trying other available statins.

Medscape: Are there other signs that would exclude a patient from treatment with a statin?
Dr. Brinton: Individuals with chronic active hepatitis are not good candidates for statin therapy. But one subset of patients with hepatitis -- those with nonalcoholic steatohepatitis (NASH), where the hepatitis is due to fatty infiltration of the liver -- may actually improve with a statin or other lipid-lowering agent.

Medscape: If CPK levels become elevated once a patient has started on a statin, do you always stop the drug?
Dr. Brinton: There are several different levels of action one can take if one suspects myopathy. If the myopathy appears to be mild or equivocal, the best action may simply be to continue the statin and monitor the patient without reducing the dose.

A second option, for slightly more severe but still relatively mild cases, is to stop the statin temporarily and allow the symptoms to resolve. This also will allow a CPK elevation, if present, to normalize. Later one can rechallenge the patient at the same dose of the same drug. This approach can be useful in cases where the statin may not have been responsible for the myopathy.

In a third scenario, where the symptoms are more severe and the case is more troubling biochemically and/or clinically, one may conclude that the particular dose of that particular statin is no longer tenable. If this occurs at a high statin dose, one can consider giving a lower dose of the same statin or switching to a different statin. There are few published data about switching statins in this way, and most of our experience is anecdotal, but I can say that switching to a different statin often resolves the symptoms.

Finally, as I mentioned earlier, there are cases of myopathy so severe that one does not dare go back to any dose of any statin.

Medscape: How often are the symptoms of myopathy simply due to negative expectations on the part of the patient?
Dr. Brinton: One very interesting aspect of statin therapy is that physicians are pretty much required to create an adverse expectation, or negative placebo effect, when initiating statin therapy. This is true primarily for myopathy but can occur with other safety questions as well. Most of our patients know already that statin safety is an issue, but whether they do or not, as we start a patient on a statin for the first time, we are obligated to point out its possible adverse symptoms and effects. We must describe the symptoms of myopathy and ask patients to watch out for them. We also need to inform the patient of the possibility of liver dysfunction and perhaps other potential adverse events. Such warnings give patients the expectation that they are going to have a problem, and probably make it more likely that they will have adverse symptoms.

Patients' heightened awareness of the risks of statin therapy is good in the sense that if something truly bad happens, they are more likely to notice it early and contact us promptly. But it also means that when a patient reports muscle symptoms, we do not always know if myopathy is really present. Everyone has aches and pains; and so their association with drug treatment is often open to question. So we are setting up our patients to find something that may not truly exist. The good news, however, is that we can turn the effects of our suggestions to our advantage when and if a patient reports symptoms of myopathy. We do this by explaining that the myopathy often resolves with whatever course of action we have chosen from the several options I mentioned earlier. Whether we have the patient continue, temporarily stop, reduce the dose, change drugs, or stop statins altogether, we suggest that his/her symptoms will improve soon. We thus create a positive placebo situation. When the patient hears from his trusted healthcare provider that his symptoms are likely to get better, it becomes much more likely to occur.

Obviously we will not ignore a true myopathy, but it is reasonable to try to reverse any negative anticipation on the part of the patient, which may worsen any symptoms otherwise present.

Medscape: How do the statins compare in their propensity for inducing myopathy?
Dr. Brinton: First, we have to acknowledge that despite the clinical importance of statin-induced myopathy, we understand very little about its causes, which makes it hard to develop good treatments or preventive strategies.

Statin-induced myopathy is strongly dose related, so low doses of a given statin are usually much less likely to cause myopathy than high doses. For this reason, and perhaps because muscle benefits from statin-free periods of recovery, every-other-day dosing of a statin can be helpful in reducing muscle symptoms. This dosing regimen may be especially attractive for a statin with a longer half-life, or for a sustained-release formulation, where the longer dosing interval may still provide relatively continuous suppression of hepatic cholesterol synthesis, and hence still provide effective cholesterol lowering.

There are differences among the statins in terms of their propensity to cause myopathy. The statins that carry a higher than average overall risk are among the more potent: lovastatin (Mevacor, Merck; Altocor, Andrx; and generic) and simvastatin (Zocor, Merck). Myopathy risk is not, however, simply directly proportional to cholesterol-lowering efficacy, since it appears to be relatively low with atorvastatin (Lipitor, Pfizer), and may not be elevated with rosuvastatin (Crestor, AstraZeneca), which are the most effective for LDL cholesterol lowering. By contrast, the 2 statins that appear to have lower-than-average risk of myopathy are fluvastatin (Lescol, Reliant) and pravastatin (Pravachol, Bristol-Myers Squibb). These can be especially useful in patients with symptoms or risk of myopathy.

Pravastatin has been considered by many as the only safe statin with regard to myopathy. Evidence in the scientific literature, however, is actually stronger for fluvastatin as having the lowest myopathy risk. There are few comparative data between fluvastatin and pravastatin, but in the Assessment of Lescol in Renal Transplantation (ALERT)[2] study, fluvastatin passed perhaps the most severe test of myopathy risk. That trial included more than 2000 patients who had undergone renal transplantation and were taking cyclosporine. Half of these, or about 1000 patients, also took fluvastatin.
Surprisingly, over several years of follow-up, the patients receiving both cyclosporine and fluvastatin were at no higher risk for myopathy than those on placebo. This is impressive evidence for a low myopathy risk with fluvastatin. We are often looking to use statins in such high-risk patients, and so the ALERT data are very encouraging with regard to the use of full-dose fluvastatin for atheroprevention when the risk of drug-drug interaction is high.

Medscape: What about other drug interactions?
Dr. Brinton: Fluvastatin and pravastatin each appears to have fewer drug-drug interactions than other statins. Although some clinicians have felt that the safety of pravastatin was primarily due to its water solubility, the other water-soluble statin, rosuvastatin, has yet to be fully proven as safe. Moreover, fluvastatin, which is not water soluble, has excellent safety data, few potential adverse drug-drug interactions, and appears to be as safe as, or even safer in many contexts than pravastatin.
Mention has been made in the scientific literature about the risk of myopathy when the dosage of a statin is increased in patients concurrently receiving niacin. Interestingly, however, there is a Food and Drug Administration (FDA)-approved tablet (Advicor, Kos) that combines extended-release niacin (Niaspan, Kos) and generic lovastatin, and appears to carry no excess myopathy risk. Use of any combination therapy for lipid disorders should not be done in a cavalier manner, but the added risk of myopathy with niacin plus a statin appears to be at least as low as it is for fenofibrate.
Gemfibrozil is a very commonly used fibrate that is inexpensive and well proven to reduce coronary heart disease (CHD) events. However, it increases circulating statin levels and possibly CPK levels and muscle symptoms when administered with all the statins except fluvastatin. So fluvastatin is particularly useful in this situation. By contrast, the other fibrate available in the United States, fenofibrate, appears to be safe in combination with all statins. Unfortunately, it is more expensive and less widely available on managed care formularies. Also, its ability to reduce CHD events is not as well proven.

I should also mention that the bile acid sequestrants have a likely adverse interaction with statins in that if they are taken at the same time as the statin, they may reduce its absorption. This is also true of many other medications. Otherwise, however, there are no safety or toxicity issues surrounding the concurrent use of bile-acid sequestrants and statins. The intestinal cholesterol absorption inhibitor ezetimibe (Zetia, Merck/Schering Plough) has no adverse interaction with statins. Specifically, the likelihood of statin myopathy is not increased by concurrent ezetimibe use and any effects on liver dysfunction are very small. If anything, ezetimibe may reduce myopathy risk by allowing a reduction in the statin dose needed for a given patient.

Medscape: How do you follow transaminases in patients on statins?
Dr. Brinton: We measure transaminases at baseline, either alanine aminotransferase or aspartate aminotransferase or both. If one reading is > 3 times the upper limit of normal, a statin should not be started except to treat NASH. Follow-up usually consists of another transaminase at the next visit, usually after 2 or 3 months. If a transaminase elevation occurs, it usually happens early in the course of the statin use, so a single measurement after starting the statin is usually sufficient. The one exception to this rule is a patient with underlying liver disease or a high risk of it, such as a binge drinker. In lower-risk patients, transaminases need be measured in follow-up primarily only if the statin dose is increased, if the patient is switched to another statin, or if another medication like niacin, a fibrate, or ezetimibe is added.

Medscape: Which patients are more likely to have elevations of transaminases while on statins?
Dr. Brinton: Risk factors for transaminase elevation are advanced age, female gender, alcohol use, and prior history of hepatitis.

Medscape: What do you do in a case of transaminase level elevation?
Dr. Brinton: The approach is much the same as it is for myopathy. One has several options. If the elevation is minor, one can continue the statin and check the transaminase levels again. If the elevation is more significant, one can stop the drug and then consider rechallenging the patient at the same dose. If it is more severe, one can lower the dose of the same statin since transaminase elevations are usually dose-related. Finally, one can switch to a different statin. Of course, one can always try to reduce or eliminate the adverse effects of other hepatically adverse factors, such as other hepatotoxic drugs. There does not appear to be any large difference among statins in terms of risk of transaminase elevations.

Medscape: What are the properties of statins that affect their safety profile?
Dr. Brinton: The statins that are metabolized through the cytochrome P450 3A4 systems are more prone to drug-drug interactions because so many medications use the same pathway. Other cytochrome P450 pathways are much less problematic. Two statins are available in extended-release formulation: fluvastatin (Lescol XL, Reliant) and lovastatin (Altocor, Andrx). Both probably reduce the tendency for systemic complications of the drug, such as myopathy and possibly other drug-drug interactions. This is especially important when choosing a statin for a patient who may be at elevated risk of 1 or more drug-drug interactions, due to polypharmacy, frailty, or advanced age.
Both fluvastatin and rosuvastatin are metabolized primarily by the cytochrome P450 2C9 pathway, yet they appear to have different safety profiles. We do not know why this might be. We have much safety evidence for fluvastatin, but little so far for rosuvastatin. Recent concerns about an apparent excess of myopathy induced by high-dose rosuvastatin have prompted the European Union (EU) to make its label for rosuvastatin more conservative regarding the recommended starting doses. Although this only brings the EU label closer to the existing US label for this agent, the FDA has felt the need to alert healthcare practitioners to carefully follow US label instructions to reduce myopathy risk.

Medscape: Are there other safety concerns with the statins?
Dr. Brinton: Just about any drug can cause headache, skin rash, fatigue, and malaise, but statins do not cause these any more than placebo. One or two earlier studies suggested that statins increase the risk of cancer, but more recent reviews show no increase in any cancer with any statin.[3]
Medscape: What is the rationale for combination therapy in treating dyslipidemia?
Dr. Brinton: Combination therapy is, I believe, the wave of the future for the management of dyslipidemia. First, we are learning more and more about the benefits of LDL-cholesterol lowering. We have long known that LDL-cholesterol levels strongly predict CHD risk, but we are continually seeing new data suggesting that the lower the level of LDL-cholesterol, the better. Which is not to say that we should treat every patient to lower his or her LDL-cholesterol to, say, 40 or 50 mg/dL, but in patients at unacceptably high risk, more aggressive LDL-cholesterol lowering can be useful.
Even with more effective statins, cost, safety, and logistical concerns often make it impossible to attain the desired level of LDL cholesterol with statin monotherapy. The problem is that doubling the dose of any statin gives only about an additional 6% LDL-cholesterol-lowering effect, while that same doubling may bring a significant increase in cost, and a geometric rise in potential toxicity. An exception to these rules about uptitration is fluvastatin in the extended-release formulation (Lescol XL) at the 80-mg dose, which is the dose and formulation of this agent most often used. In this one case, you actually pay less to uptitrate a statin. Second, there is no increase in safety concerns with this dose and formulation compared to lower doses of fluvastatin or other statins. It may, in fact, be the safest statin of all. Third, as an extended-release formulation, it has more LDL-cholesterol-lowering efficacy than the immediate-release form.

Medscape: Are there benefits of statin combination therapy beyond greater LDL-cholesterol lowering?
Dr. Brinton: There are other, independent benefits of combination therapy in terms of atheroprevention. For example, we know that niacin lowers lipoprotein (a) and that statins do not. So adding niacin to a statin will give that added dimension that you cannot get from a statin. In addition, niacin would be much more effective in raising HDL cholesterol than any statin. For triglyceride lowering, a fibrate is more effective than a statin. Even though niacin is comparable with statins in terms of its triglyceride lowering, adding niacin to a statin will give more triglyceride lowering than a statin alone. Ezetimibe, which is a not a very potent HDL-cholesterol-raising or triglyceride-lowering drug, will add to the HDL-cholesterol-raising effect and the triglyceride-lowering effect of statins, just as it adds to the LDL-cholesterol lowering.

Another advantage for combination treatment is in atheroprevention. Most statins reduce cardiovascular events by 20% to 35%. Studies of combination therapy have generally shown an event reduction of 70% to 90%, and even though we cannot extrapolate directly from this, clinical data strongly suggest that combination therapy is much more efficacious in reducing cardiovascular events, which is not surprising given that the lipid-lowering effect is much greater. Thus, almost without exception, adding an agent to a statin will give at least additive lipid benefit, and in some cases an additional benefit that a statin cannot give. As we learn more and more about atheroprevention and have more targets for therapy and more aggressive goals with those targets, combination therapy will become more and more appealing, not only in terms of efficacy with regard to lipids and atheroprevention, but also from a safety standpoint.

Combination therapy has not been widely used in the past, but it is increasing and I anticipate that it will continue to increase. Only 1 combination tablet is currently available in the United States, lovastatin plus extended-release niacin (Advicor, Kos), which produces more LDL-cholesterol lowering and a greater increase in HDL-cholesterol than either agent alone. There is indirect evidence that it may be effective in terms of event reduction. Another combination tablet that will be available soon in the United States, simvastatin plus ezetimibe (Vytorin, Merck/Schering Plough), is very promising.

Not every patient who needs to be treated for dyslipidemia should get 2 or more drugs, but in general we are undertreating our patients. Combination therapy is often a much better way to increase treatment benefit than uptitration of statin monotherapy.

Medscape: With safety in mind, what is your opinion about the possibility of statins being made available over the counter (OTC)?
Dr. Brinton: The FDA is currently considering whether statins should be made available without a prescription in the United States. OTC status would make statins more widely accessible and more widely used, which would address one of the biggest single problems with statins in this country, which is that they tend to be underutilized.

Despite that major advantage, however, there are a number of serious objections to making them available over the counter, the first of which is the safety issue. Although statins are quite safe, the safety issues are best addressed by a physician or other licensed healthcare provider. Even though I am confident that the vast majority of patients would have no safety problems with OTC statins, I believe that many significant and even severe safety problems would arise that could not be handled by laypersons. Another disadvantage is that statin use is always based on baseline lipid levels and the availability of OTC lipid testing is somewhat limited and problematic. I am certain that cholesterol testing performed by regular laboratories in a controlled setting with proper standards and controls is far superior to the type of testing that a patient could do at home.

Other issues that would arise with OTC status are related to coordination of treatment of dyslipidemia with other atheropreventive measures. I believe that there is much benefit in having healthcare professionals involved in issues such as diet and exercise, smoking cessation, treatment of obesity, insulin resistance, diabetes, and hypertension, and in the screening for progression of disease. Other serious concerns would be that statins might be used inappropriately, such as by someone who does not need them, or there could be overtreatment or inappropriate choice of a statin. This currently happens only rarely.

And so there are many reasons why the movement to make statins available over the counter is a bad idea. I am very much in favor of patient empowerment and involvement, but I believe that because of the complexities of atheroprevention in general and lipid treatment in particular, we are ill-advised to make these very powerful medications available to the general public without proper supervision by a physician.


As a class, the statins are remarkably safe and their use in patients who need LDL lowering for atheroprevention has a very high benefit/risk ratio. But because they are most commonly used in older patients with complicated health histories, and because of heightened public concerns, we must always remember to address several safety issues when prescribing statins. Although there is increasing impetus toward more and more aggressive lipid-lowering therapy, we need to keep the following always in mind:
  1. Safety, cost, and efficacy considerations often point to:
    1. Use of lower doses of a given statin and/or
    2. Use of safer statins such as fluvastatin and pravastatin; and
    3. Use of other agents (ezetimibe, niacin, fibrates, and/or sequestrants) in combination with statins for greater LDL-lowering and/or other lipid benefits
  2. When starting statins, patients must always be informed of potential safety risks, and any symptoms or signs of adverse effects must be taken seriously and handled properly.
Read the complete article here.

Saturday, September 14, 2013

Large meta-analyses of statins

The following was posted on the Track Your Plaque forum on 9/14/2013

  Here are some highlights from here: http://chriskresser.com/the-diet-heart-myth-statins-dont-save-lives-in-people-without-heart-disease backed up by studies. 

An analysis by Dr. David Newman in 2010 which drew on large meta-analyses of statins found that among those with pre-existing heart disease that took statins for 5 years (1):

96% saw no benefit at all

1.2% (1 in 83) had their lifespan extended (were saved from a fatal heart attack)

2.6% (1 in 39) were helped by preventing a repeat heart attack

0.8% (1 in 125) were helped by preventing a stroke

0.6% (1 in 167) were harmed by developing diabetes

10% (1 in 10) were harmed by muscle damage  A heart attack or stroke can have a significant negative impact on quality of life, so any intervention that can decrease the risk of such an event should be given serious consideration. But even in the population for which statins are most effective—those with pre-existing heart disease—83 people have to be treated to extend one life, and 39 people have to be treated to prevent a repeat heart attack.

Primary prevention (those without pre-existing heart disease)Statins do reduce the risk of cardiovascular events in people without pre-existing heart disease. However, this effect is more modest than most people assume. Dr. Newman also analyzed the effect of statins given to people with no known heart disease for 5 years (5):

98% saw no benefit at all

1.6% (1 in 60) were helped by preventing a heart attack

0.4% (1 in 268) were helped by preventing a stroke

1.5% (1 in 67) were harmed by developing diabetes

10% (1 in 10) were harmed by muscle damageThese statistics present a more sobering view on the efficacy of statins in people without pre-existing heart disease. They suggest that you’d need to treat 60 people for 5 years to prevent a single heart attack, or 268 people for 5 years to prevent a single stroke. These somewhat unimpressive benefits must also be weighed against the downsides of therapy, such as side effects and cost. During that hypothetical 5 year period, 1 in 67 patients would have developed diabetes and 1 in 10 patients would have developed muscle damage (which can be permanent in some cases, as we’ll see later in this section).

To summarize:

The only population that statins extend life in are men under 80 years of age with pre-existing heart disease.

In men under 80 without pre-existing heart disease, men over 80 with or without heart disease, and women of any age with or without heart disease, statins have not been shown to extend lifespan.

Statins do reduce the risk of cardiovascular events in all populations. A heart attack or stroke can have a significant, negative impact on quality of life—particularly in the elderly—so this benefit should not be discounted.

However, the reductions in cardiovascular events are often more modest than most assume; 60 people with high cholesterol but no heart disease would need to be treated for 5 years to prevent a single heart attack, and 268 people would need to be treated for 5 years to prevent a single stroke.

Statins have been shown to cause a number of side effects, such as muscle pain and cognitive problems, and they are probably more common than currently estimated due to under-reporting.

My intention here is not to suggest that statins have no place in the treatment of heart disease, but rather to give you the objective information you need to decide (along with your doctor) whether they are appropriate for you. The decision whether to take them should be based on whether you have pre-existing heart disease, what your overall risk of a heart attack is, how healthy your diet and lifestyle is, what other treatments you’ve already tried, and your own risk tolerance and worldview. It’s clear that statins reduce heart disease as well as the risk of death in those that have already had a heart attack, so if you’re in this group and you’ve already tried diet and lifestyle interventions without much impact on your lipid or inflammatory markers, you are more likely to benefit.
Read the whole thing here if you are a member.

Wednesday, September 11, 2013

Lancet retracts Jikei Heart Study - Steve Stiles

  1. The Lancet editors. Retraction—Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): A randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 2013; DOI:10.1016/S0140-6736(13)61847-4. Available here.
  2. Retraction of: Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: KYOTO HEART Study. Eur Heart J 2013; 34:1023.
  3. Mochizuki S, Dahlof B, Shimizu M, et al. Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): A randomised, open-label, blinded endpoint morbidity-mortality study. Lancet 2007; 369: 1431-1439.
  4. Sawada T, Yamada H, Dahlof B, Matsubara H. Effects of valsartan on morbidity and mortality in uncontrolled hypertensive patients with high cardiovascular risks: Kyoto Heart Study. Eur Heart J 2009; 30: 2461-2469.
  5. Retraction Watch. Lancet retracts Jikei Heart Study of valsartan following investigation. Available here.