Category Archives: Statin Drugs

STATINS OF NO BENEFIT AGE 80 AND UP, even after a heart attack!

Finally IT HAS BEEN LOOKED AT AND TRUTHFULLY PUBLISHED, statin drugs for individuals 80 years of age and older  WITH DOCUMENTED HEART DISEASE SHOWS NO BENEFIT, EVEN AFTER A HEART ATTACK

Here is the abstract from the study

Statin Therapy and Mortality in Older Adults With CAD
Abstract
Objectives: To examine the effect of statins on long-term mortality in older adults hospitalized with coronary artery disease (CAD).
Design: Retrospective analysis.
Setting: University teaching hospital.
Participants: Individuals aged 80 and older (mean aged 85.2, 56% female) hospitalized from January 2006 to December 2010 with acute myocardial infarction (AMI), unstable angina pectoris, or chronic CAD and discharged alive (N = 1,262). Participants were divided into those who did (n = 913) and did not (n = 349) receive a discharge prescription for a statin.
Measurements: All-cause mortality over a median follow-up of 3.1 years.
Results: Participants treated with statins were more likely to be male, to have a primary diagnosis of AMI, to have traditional cardiovascular risk factors, and to receive other standard cardiovascular medications in addition to statins. In unadjusted analysis, statin therapy was associated with lower mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.71–0.96). After adjustment for baseline differences between groups and propensity for receiving statin therapy, the effect of statins on mortality was no longer significant (HR = 0.88, 95% CI = 0.74–1.05). The association between statins and mortality was similar in participants aged 80 to 84 and those aged 85 and older.
Conclusion: In this cohort of older adults hospitalized with CAD, statin therapy had no significant effect on long-term survival after adjustment for between-group differences. These findings, although preliminary, call into question the benefit of statin therapy for secondary prevention in a real-world population of adults aged 80 and older and underscore the need for shared decision-making when prescribing statins in this age group.

In layman’s terms. This study compared patients aged 80 and older who were hospitalized with documented coronary artery disease and compared those sent home on statins and those sent home without a prescription for statins. There was no difference in death rates between the two groups. The use of statins in this situation (known heart disease) is referred to as secondary prophylaxis. Secondary prophylaxis would be expected to have greater risk reduction when compared to primary prophylaxis (no know heart disease).

I have advocated against the use of statins in primary prophylaxis. Statin Guidelines, one step forward, two steps backwards | Practical Evolutionary Health

The data in this study shows no protection from statins when used for secondary prophylaxis (higher risk group) for age 80 and above.

For more discussions on statins, atherosclerosis, coronary artery disease, go here. Statin Drugs | Practical Evolutionary Health

Live clean, eat clean, sleep well.

Bob Hansen MD

Why do our tax dollars continue to subsidize death, disability and disease?

Yesterday I posted a comment on Medscape after reading an article Longtime Dietary Fat Advice Unsupported by Data: Analysis . Medscape is a website with articles and news written for physicians and other health professionals. Anyone can access this information by creating a user name and password, there is no fee.

Here is my comment. It is long and technical. I will provide an explanation in lay terms after quoting myself.

Sugar, especially HFCS (high fructose corn syrup), used in so many foods is more inflammatory than saturated fat. Grass fed meat from ruminants has a fatty acid mix that is exactly the same as wild game, which we evolved to eat, along with tubers, green leafy vegetables, and fruit in season. Excess refined fructose intake AND use of modern refined “vegetable oils” along with non-healthy grains combine to cause excess caloric intake, NAFLD (non-alcoholic fatty liver disease), obesity, metabolic syndrome and CAD (coronary artery disease). N6 PUFA (omega six polyunsaturated fatty acids) are easily oxidized. N3 PUFA (omega 3 fatty acids) despite greater number of double bonds are protected from oxidation in cell and Lipoprotein membranes by plasmalogens as opposed to linoleic acid which is not easily  incorporated into plasmalogens. The PUFA in vegetable oils (linoleic acid) is the FA (fatty acid) that is oxidized on LDL particles and remnant particles, stimulating monocytes to transform to macrophages and then foam cells. The USDA, ADA and AHA have had it upside down for decades and they still fail to admit folly. We evolved for > 1 million years without grains and they have contributed to disease. Per calorie fresh vegetables have five times the amount of fiber compared to whole grains. We do not need grains and would be better without them. They contain anti-nutrients and wheat, hybridized in the 1980s to a storm resistant dwarf plant, now has 50 times more gluten/gliadin than the old wheat. This has generated more gluten intolerance and celiac. Our greatest nutritional threats to public health include refined sugar, carbohydrates predominantly from grains and refined vegetable oils. Vegetable oils are not healthy, we did not evolve to eat them. N3 FAs are anti-inflammatory but have been competing in our diets with a sea of inflammatory N6 PUFA from unnatural refined and easily oxidized “vegetable oils”. Even though PUFA can reduce LDL-C they wreak havoc by creating ox-LDL particles which initiate the cascade of atherosclerosis. Substituting SFA (saturated fatty acids) with PUFA results in increased levels of Lp(a) and oxLDL in humans, not a good thing. Close the feed lots, stop government subsidy of corn, wheat, dairy and soy, eat meat from grass fed ruminants, wild seafood, fresh organic vegetables and fruits in season. Nibble on tree nuts. Stop creating carcinogens with high dry heat cooking methods and we will watch obesity, insulin resistance, metabolic syndrome and atherosclerosis melt away.

That was my comment. Here is some explanation.

I have previously discussed the pro-inflammatory nature of refined “vegetable oils”. “Vegetable oils” are actually not from vegetables, they are from grains, seeds and legumes. The two major sources of excess omega six polyunsaturated fats in the American diet are corn oil and soy oil marketed by various brand names such as Wesson. They are major components of margarine and other butter substitutes and are present in most salad dressings. Most salad dressings sold in our supermarkets contain high levels of easily oxidized unhealthy refined “vegetable oils” and HFCS. The use of these salad dressings converts a healthy salad into a vector for disease.

The major source of caloric sweeteners in our food and beverages is high fructose corn syrup. Both corn (oil and sugar) and soy predominate our processed food supply because they are cheap. They are cheap because our tax dollars subsidize their production. This subsidy started during the Nixon administration. Once a food subsidy is put in place it is very difficult to eliminate, Big Agriculture provides a deep pocket for lobby money and our elected officials from the mid-west bread-basket respond to $$.

Another major source of disease causing elements in the standard American diet is highly refined flour from wheat. Doctors Davis and Perlmutter discuss the problems associated with wheat-flour foods in their books Wheat Belly and Grain Brain respectively. The production of wheat has also been subsidized since the Nixon administration.

Wheat is not what it used to be. A new dwarf hybrid wheat has predominated the US market since the 1980s. Bread and pasta are not what they used to be when great grand-mother made her own bread and pasta in the kitchen from coarsely ground whole flour. But even if we all went back to making our own whole-grain bread and pasta from locally ground pre-1980s wheat, bread, pasta and pastry would still present a health risk because of issues related to intestinal permeability, auto-immune disease (now epidemic in the USA), and the presence of nasty lectins and phytates (discussed in my manifesto and previous posts).

The Medscape comment quoted above describes  adverse consequences caused by replacing saturated fat in the diet with “vegetable oils”. This is a complex subject and I will try to be brief for now but promise to expand on this in a future post.

Many factors contribute to atherosclerosis, heart attack and stroke. Sedentary lifestyle, stress, inadequate restorative sleep, smoking and poor dietary choices top the list. These factors also contribute to obesity, diabetes, metabolic syndrome, insulin resistance and many cancers.

DIETARY FACTORS:

The combination of sugared foods and beverages (predominantly sweetened with HFCS), refined flour foods, and excess consumption of the PUFA in “vegetable oils” TOGETHER  contribute to the formation of plaque in the walls of our arteries (atherosclerosis).

How does this happen?

LDL (low density lipoprotein) is a particle that transports cholesterol and triglycerides through our blood to our organs. This particle is comprised of a core and a surrounding membrane.  Here is a picture.

LDL 2

The core contains cholesterol in a storage form (esters) and triglycerides. The outer membrane includes a large protein called apoprotein B-100, “free” cholesterol molecules and phospholipids. The phospholipids contain fatty acids, including PUFA.

LDL has been demonized as “the bad cholesterol” and that demonization has mislead the public.

hdl_ldl good guy bad guy

LDL is the major lipoprotein in our blood but there are others that have different names.

Cholesterol is cholesterol, whether it is carried in LDL or HDL. When carried in the core of a lipoprotein it is carried as a cholesterol ester. 80% of the cholesterol in an LDL particle is carried as an ester in the core. 20% is carried as “free” cholesterol on the outer surface or membrane.

LDLand cholesterol molecule

HDL (high density lipoprotein) is smaller and denser. HDL has been called “the good cholesterol”, another misnomer.

HDL particles, when they are functioning correctly can protect us from atherosclerosis but in patients with diabetes, obesity, and insulin resistance, HDL particles do not function well and in fact probably contribute to disease. (More about that in a future post)

But back to LDL.

Although the risk of cardiovascular disease is correlated with the amount of cholesterol carried by LDL in our blood (referred to as LDL-C), the total amount of cholesterol shuttled by LDL particles is much less relevant than one would be led to believe given the great use of statin drugs to lower LDL-C.

The short version is as follows.

Compared to LDL-C, a much better predictor of cardiovascular disease is the amount of “modified” LDL particles circulating in the blood. Oxidized LDL particles are one form of “modified LDL”. LDL can also  be modified by excess blood sugar levels (especially from HFCS). This modification is referred to as glycosylated or glycated LDL. In this latter form of modification, the major protein on the outer membrane of the LDL particle (apo B 100 in the picture above) becomes attached to a sugar and the result is an LDL particle that is not easily cleared by normal processes. The modified LDL is not “recognized” by the LDL receptors that act as entry points into our cells for proper processing. The result is that the glycated LDL particles circulate longer and are more likely to use up their anti-oxidants (Vitamin E and  Co-enzyme Q 10).

As a result glycated LDL are more likely to become oxidized. That is not good because oxidized LDL sets up a cascade of unhealthy events.

The portion of the LDL particle that becomes oxidized is the fat (fatty acid) from “vegetable oil”, specifically the fatty acid called linoleic acid. This fatty acid has two double bonds making it more likely to be oxidized than for example oleic acid, the major fatty acid in extra virgin olive oil which has only one double bond.

The double bonds between the carbons in the fatty acids are unstable and easily oxidized. The single bonds in saturated fat do not get oxidized.

All other things being equal (and you will see that they are not), the more double bonds in a fatty acid the greater chance for oxidation.

Here is a picture showing the linoleic acid, also called linoleate, on the outer membrane of the LDL particle.

LDL with linoleate

And here is a picture that shows the phospholipids that contain the linoleic acid.

LDL 3

Let’s say it again. The fatty acid found in “vegetable” oil, linoleic acid, is easily oxidized because it has two double bonds.

Saturated fats are not oxidized because they contain no double bonds.

The part of the LDL particle that becomes oxidized is the fatty acid that comes from “vegetable oils”.

A particular kind of immune cell (white blood cells called monocytes) have  special receptors for oxidized LDL particles. When ox-LDL are “seen” by these monocytes, the monocytes become transformed into macrophages. Macrophages are designed to destroy bacteria that invade our bodies. The oxidized LDL particles resemble the structures of invading bacteria. The macrophages, with very specialized receptors for oxidized LDL, “swallow” the LDL particles and release toxic chemicals to destroy “the invader”.  The macrophages then become “foam cells” in the walls of our arteries, initiating the creation of plaque. Here is a picture.

ldl_mechanisms oxidation in vessel wall

This picture depicts the oxidation occurring in the wall of the artery after LDL particles have penetrated the wall. However LDL particles can and do become oxidized while still circulating in the blood and these oxidized particles can stimulate monocytes to transform into macrophages and gobble up the oxidized or modified LDL while these particles are still circulating in the blood.

How and whether unmodified LDL particles cross the wall of arteries into the “sub-endothelial” area remains an unsolved complex issue. The picture above implies that LDL particles simply move across the endothelial cells that line the wall of the artery but that is a presumption.

Clearly, macrophages that have “swallowed” modified LDL particles have mechanisms to work their way between the junctions formed by adjacent endothelial cells.

This is an important distinction because many cardiologists believe that what drives atherosclerosis is a mass effect. The greater the number of LDL particles, the more likely they are to cross the endothelial barrier, get oxidized and retained and start the process of plaque formation. However the process is much more complex and not clearly understood.

We do not yet know or understand completely the factors that influence the permeability of the endothelium to Lipoprotein particles. We do know that modified (oxidized and glycated LDL) disrupt the protective surface of endothelial cells which is called the glyocalyx. Other factors that disrupt the glyocalyx include high blood sugars, dramatic fluctuations in blood pressure (too high or too low), oxidative stress, infections, and circulating endotoxin (which is governed by intestinal permeability).

It is clear from several studies that modified (oxidized) LDL as a single variable predicts cardiovascular disease and heart attacks with much greater accuracy than LDL-C (total cholesterol content of LDL particles). It is also clear that monocyte receptors are specific for modified LDL and that the  process that initiates the cascade of events that leads to plaque formation involves the interaction between modified lipoprotein particles and the immune system (monocytes).

Now here is another twist.

Omega 3 fatty acids in fish oil are considered “heart healthy”. They help prevent heart attacks and strokes. They also decrease inflammation throughout the body thereby producing many health benefits.

BUT OMEGA 3 FAT HAS MORE DOUBLE BONDS THAN OMEGA 6 FAT (LINOLEIC ACID) YET THEY HELP PROTECT THE HEART. HOW CAN THAT BE?

How do they avoid contributing to atherosclerosis? Are they not even more readily oxidized than linoleic acid?

The simple answer is no.

The major reason is that the omega three fatty acids are protected by “plasmalogens” which are important components of our LDL particle outer membranes. Plasmalogens are found in the membranes of lipoprotein particles and in the membranes of human cells. Because of their chemical structures, omega three fats are easily incorporated into plasmalogens which protect the double bonds of omega three fats from oxidation. Linoleic acid, the predominant component of “vegetable oils” is not easily incorporated into the protective arms of plasmalogens.

This selective protection is well described on pages 141-142 of  “The Fats of Life”, written by Dr. Glen Lawrence and published in paperback in 2013. (link below)

I asked Dr. Lawrence about this issue in an email and here was his response.

“The omega-3 fatty acids are preferentially incorporated into plasmalogens, which act as antioxidants due to the double bond adjacent to the ether linkage of these phospholipids. This structure would tend to scavenge free radicals or reactive oxygen species near the surface of the membrane, rather than allowing them to penetrate deeper in the membrane where the double bonds of PUFA are located. This makes any polyunsaturated fatty acids attached to the plasmalogens more resistant to oxidation than they would be in a regular phospholipid. See pp 141-142 of The Fats of Life. The shorter chain and less unsaturated linoleic acid does not tend to be incorporated into plasmalogens.”

In summary:

  1. “Vegetable oil” is actually not oil from vegetables but rather a highly processed and refined oil. This oil contains primarily the easily oxidized omega 6 PUFA (polyunsaturated fatty acid) linoleic acid. Oxidation can occur during manufacture,  before consumption while sitting in the bottle, but especially during high heat cooking (fried foods). Oxidation can also in your body as this fat circulates in your blood on the membrane of lipoprotein particles.
  2.  LDL particles are the major lipoprotein particles that shuttle cholesterol and fatty acids (in in the form of triglycerides) through our bodies in our bloodstream.
  3. Modified LDL particles (glycated and/or oxidized LDL) stimulate monocytes (immune cells) to transform into macrophages and gobble up the modified LDL. In addition, glycated LDL particles are more easily oxidized because they circulate longer in our blood.
  4. Macrophages become filled with modified LDL. These are called foam cells. Foam cells  initiate a cascade of events that lead to the formation of plaque in the walls of our arteries.
  5. The part of the LDL particle membrane that becomes oxidized is the phospholipid that contains linoleic acid which comes from “vegetable oils”
  6. High amounts of sugar, especially HFCS, and highly refined flour foods in our diets cause larger blood sugar fluctuations than whole foods and therefore contribute to the glycation of LDL particles. This glycation leads to more oxidation of LDL. In this manner HFCS and refined flour foods contribute to the process of atherosclerosis.
  7. High amounts of sugar, HFCS and refined flour foods also contribute to obesity, insulin resistance and diabetes which then increase the risk of heart attack and stroke.
  8. Several factors contribute to the disruption of the glycocalyx which is the protective surface of the endothelial cells that line our arteries. These include but are not limited to modified LDL, inflammation, high blood sugars, abnormal fluctuations in blood pressure, circulating endotoxin (associated with increased intestinal permeability), infections. Disruption of the glycocalyx contributes to the formation of plaque (atherosclerosis).
  9. Modified LDL particles might also migrate through the junctions that connect adjacent endothelial cells either inside macrophages or on their own. Many factors, known and unknown likely determine the susceptibility or permeability of these junctions to this migration.

These are the major points, but there is allot more to discuss. Substituting “vegetable oils” for saturated fat in our diets not only increases the amount of oxidized LDL but also increases a dangerous lipoprotein called Lp(a). On third of Americans have an amount of Lp(a) that is considered “high risk” for heart attack and stroke. More about that in a future post.

Then there is the process of an actual heart attack or stroke which involves disruption of plaque and the creation of a blood clot that ultimately disrupts the flow of blood and the death of heart or brain tissue. The susceptibility of plaque to disruption is a huge topic that involves high blood pressure, diabetes, insulin resistance, oxidative stress, inadequate sleep, and stress to name a few. So much more to discuss.

But getting back to the title of this post, why don’t you ask your elected representatives why our tax dollars continue to subsidize nutritional root causes of death, disability and disease?

Here are some links to papers and books that support the discussion above.

Circulating Oxidized LDL Is a Useful Marker for Identifying Patients With Coronary Artery Disease

Cholesterol deposition in macrophages: foam cell formation mediated by cholesterol-enriched oxidized low density lipoprotein.

Erythrocyte fatty acid profiles can predict acute non-fatal myocard… – PubMed – NCBI

Changes in Dietary Fat Intake Alter Plasma Levels of Oxidized Low-Density Lipoprotein and Lipoprotein(a)

Low-density lipoprotein subclass patterns and risk of myocardial in… – PubMed – NCBI

Subendothelial Lipoprotein Retention as the Initiating Process in Atherosclerosis

Oxidative susceptibility of low density lipoprotein subfractions is… – PubMed – NCBI

Effects of linoleate-enriched and oleate-enriched diets in combinat… – PubMed – NCBI

Enhanced oxidative susceptibility and reduced antioxidant content o… – PubMed – NCBI

Susceptibility of small, dense, low-density lipoproteins to oxidati… – PubMed – NCBI

Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions

Oxidized Lipoproteins Degrade the Endothelial Surface Layer

S1P Control of Endothelial Integrity

Mechanical control of the endothelial barrier. – PubMed – NCBI

Therole of actin-binding proteins in the control of endothelial bar… – PubMed – NCBI

The Fats of Life, Dr. Glen Lawrence

Functions of plasmalogen lipids in health and disease

Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar–Your Brain’s Silent Killers: David Perlmutter, Kristin Loberg: 9780316234801: Amazon.com: Books

Finally a quote from the Dali Lama (thanks to my cousin Diane for bringing this to my attention).

“Man. Because he sacrifices his health in order to make money. Then he sacrifices money to recuperate his health. And then he is so anxious about the future that he does not enjoy the present, the result being that he does not live in the present or the future, he lives as if he is never going to die, and dies having never really lived.”

Eat clean, live clean, sleep well, exercise wisely, rest often, enjoy the company of loved ones, spend time outdoors and live in the present.

BOB

Weight Gain, Another Reason to Avoid Statins

Published on line two days ago in advance of print publication, a new study demonstrates an association between statin use and increased caloric intake resulting in weight gain. (1)

A brief editorial (Written by Dr. Rita Redberg, on faculty at UCSF and editor of JAMA: INTERNAL MEDICINE). is worth quoting in entirety as it succinctly reviews many criticisms of statin overuse that I have discussed in previous posts here and here.

“There remains much controversy over the risks and benefits of statins for primary prevention. Besides the risks of muscle aches, diabetes, and cognitive dysfunction, I have observed over the years that for many patients, statins provide a false reassurance, as people seem to believe that statins can compensate for poor dietary choices and a sedentary life. In an elegantly performed analysis of NHANES data from 1999 to 2010, Sugiyama and colleagues have documented exactly such behavior. They found that compared with statin nonusers, statin users significantly increased their fat intake and calorie consumption, along with their BMI, in the last decade. This article raises concerns of a potential moral hazard of statin use, in addition to the already known adverse effects. Focusing on cholesterol levels can be distracting from the more beneficial focus on healthy lifestyle to reduce heart disease risk.” (2)

Of course association does not imply causation, but the editorial above suggests a plausible explanation for the relationship.

I have previously discussed how a carbohydrate restricted whole foods diet (here and here) results in superior weight loss, improved glucose control, reduced blood pressure, reduced triglycerides and improved HDL when compared to a low fat American Heart Association type diet. The former results in spontaneous reduction of caloric intake (improved satiety-no calorie counting required), the latter requires calorie counting in order to reduce caloric intake. The carbohydrate restricted approach does NOT result in increased net fat intake but because carbohydrates are reduced, fat as a % of total calories is increased. On average most studies in adults report a spontaneous reduction of about 400-600 calories per day when carbohydrates are significantly restricted.

A paleolithic diet that eliminates all processed foods, refined vegetable oils, grains, legumes and dairy but includes pastured grass-fed meat, wild seafood, free range poultry and eggs, organic fresh vegetables, fruit and nuts is typically low carbohydrate compared to the standard American diet (SAD). A paleolithic nutritional approach produces similar metabolic improvement within a few weeks. (3)

(1) Sugiyama T, Tsugawa Y, Tseng C-H, Kobayashi Y, Shapiro MF. Different time trends of caloric and fat intake between statin users and nonusers among US adults: gluttony in the time of statins? [published online April 24, 2014]. JAMA Intern Med. doi:10.1001/jamainternmed.2014.1927. PubMed

(2) Statins and Weight Gain: Redberg RF. JAMA Intern Med. 2014 Apr 24. doi: 10.1001/jamainternmed.2014.1994. [Epub ahead of print]  PubMed

(3) Metabolic and physiologic improvements from consuming a paleolithic, hunter-gatherer type diet L A Frassetto1, M Schloetter, M Mietus-Synder, R C Morris Jr1 and A Sebastian European Journal of Clinical Nutrition (2009) 63, 947–955; doi:10.1038/ejcn.2009.4; published online 11 February 2009 PubMed

Go in peace

Bob Hansen MD

Statin Guidelines, one step forward, two steps backwards

The new statin guidelines published jointly by the AHA (American Heart Association) and ACC (American College of Cardiology) present some good news but also allot of bad news.

The good news (one step forward) is that the guidelines acknowledge the following:

1. None of the cholesterol lowering drugs (except for statins) have ever demonstrated the ability to save lives by lowering cholesterol.

2. The ability of statin drugs to save lives (after a heart attack) is independent of whether and by how much the cholesterol is lowered.

This acknowledgement is very important because it sheds light on the fact that statins work primarily by effects independent of how much cholesterol is circulating in the blood. This is a fact that is not well understood by many physicians or patients. This fact will create some confusion because the American public has been misinformed for many years by physicians, the media and professional organizations all using terms like “good cholesterol” and “bad cholesterol”. These terms are meaningless, confusing, and counter-productive.

The new guidelines are two steps backwards for a few reasons:

1. They expand the number of patients under the guidelines in the US by tens of millions of people who will not benefit from their use and implementation of the guidelines will likely harm many.

2. The guidelines continue to assume and quote unrealistically low and inaccurate complication rates.

3. The risk assessment tool that accompanies the guidelines over-estimates risk for heart attack and stroke by 75-150%. This calculation of the over-estimate is based upon application of the guidelines to a huge database of real patients. This analysis has been published in a Peer Reviewed Journal and this analysis has already been discussed by the lay-press to the embarrassment of the AHA and ACC. This particular concern was communicated to the guideline committee one year ago by a prominent research cardiologist and statistician on the faculty of Harvard Medical School, but ignored by the guideline committee.

4. The guidelines have lowered the recommended 10 year  risk threshold for use of statins from the previous 10-20% level to a 7.5% level (thereby tremendously increasing the number of people who would be placed on statins). And since the risk calculator, as discussed in #3 above, greatly inflates the risk it essentially would apply the statin guidelines in reality to individuals with only a 3.75 to 4% risk of a cardiovascular event in the next 10 years. This shifts the risk/benefit ratio to a much higher level than the already high risk/benefit ratio of the previous guidelines.

Gratefully the excessive use of statins as well as the folly of the previous and new guidelines have  been brought to the public arena and the debate has finally drawn attention. Perhaps some reasonable discussion will ensue and perhaps the medical community at large will finally think about the bias represented in policy statements and guidelines as well as the bias presented in the many review articles that have been published on this topic.

Here are links to some reading of recent articles in the lay press.

Cholesterol Guidelines Under Attack – NYTimes.com

New Cholesterol Advice Startles Even Some Doctors – NYTimes.com

Risk Calculator for Cholesterol Appears Flawed – NYTimes.com

“After the guidelines were published, two Harvard Medical School professors identified flaws in the risk calculator that apparently had been discovered a year ago but were never fixed, as Gina Kolata reported in The Times on Monday.

In a commentary to be published Tuesday in The Lancet, a leading medical journal, the professors estimate that as many as half of the 33 million do not actually have risk thresholds exceeding the 7.5 percent level. Other experts who have tested the calculator found absurd results; even patients with healthy characteristics would be deemed candidates for statins.”

Be careful out there.

Peace,

Bob Hansen MD

Don’t Give More Patients Statins

On November 14, the following editorial was published in the New York Times.

Don’t Give More Patients Statins

By JOHN D. ABRAMSON and RITA F. REDBERG

New guidelines published on Tuesday of last week widely expand the category of who should take statins.

Two physicians authored the article providing an excellent analysis and warning against implementation of the new guidelines which are unfortunately and again, not based on sound evidence or reasonable analysis.

” based on the same data the new guidelines rely on, 140 people in this risk group would need to be treated with statins in order to prevent a single heart attack or stroke, without any overall reduction in death or serious illness.”

“At the same time, 18 percent or more of this group would experience side effects, including muscle pain or weakness, decreased cognitive function, increased risk of diabetes  (especially for women),  cataracts or sexual dysfunction.”

“We believe that the new guidelines are not adequately supported by objective data, and that statins should not be recommended for this vastly expanded class of healthy Americans. Instead of converting millions of people into statin customers, we should be focusing on the real factors that undeniably reduce the risk of heart disease: healthy diets, exercise and avoiding smoking. Patients should be skeptical about the guidelines, and have a meaningful dialogue with their doctors about statins, including what the evidence does and does not show, before deciding what is best for them.”

History repeats itself, soon the AHA and ACA will want statins in the water. The 18% estimate of serious side effects in my opinion is understated. Every week in the pain clinic I diagnose statin myopathy and/or cognitive impairment on at least one patient. Here are some stories about patients that appeared in the comments section of the oped on-line.

Noreen stated:

I am a victim of statin “therapy.” At the age of 72, with just a moderately high LDL, Simvastatin was prescribed. I took it for approximately 2 weeks, and severe pain developed in my whole body, but, primarily in my lower legs. I read the side effects on line and stopped taking it.
The pain went away, but my legs were weak. After much investigation by neurologists at University of California, SFMC, I was diagnosed with statin-induced neuropathy. The calf muscle in both legs has totally gone — nothing left but sinew. My life has been severely damaged by an inability to walk properly. I cannot raise on my toes. It has been three years since I took this medication, and there is no further hope of recovery. Prior to taking Simvastatin I was an athlete all my life. At the time of this pharmaceutical invasion I was still, hiking, exercising regularly and downhill skiing. Shame of this hired committee of “experts.”

Here is how a physician/patient described his experience.

I agree with Abramson and Redburg that treating a numbers instead of the patient is wrong. I am in a high risk group and I would hope to prevent another heart attack (I had one in 2009), yet I cannot take statins as I repeatedly developed muscle pain and then progressive weakness and loss of balance with all the statins I tried. My cardiologists (including Mayo physicians) and internists continued to push trying different statins and other cholesterol lowering medications even though I complained of side effects. Although some of my loss of power is due to aging and not statins, I used to be able to hike 10 to 20 miles with up to 5 to 6,000 feet elevation gain in a day before my statin era and now I can barely manage 4-5 miles at a slow pace. I’ve seen this in others taking statins. Even though the percentage who develop weakness may be low compared to the majority, it is a real debilitating effect for some. Doctors are brain washed (and the lay public too by TV and other ad bombardment), by the pharmaceutical industry to treat numbers rather than individuals. The result is the standard of care is now to treat the lab test instead of the person. Statins are dangerous medications and should not be prescribed lightly. SD Markowitz, MD

George from CA describes his experience as follows.

I had been on statins for over 15 years. Slowly, I began experiencing cognitive dysfunction, balance issues, muscle weakness, etc. even though I exercised both my body and brain. I quit several months ago and have been feeling better all around every day with improvement in every area. I’d rather die feeling good in 10 or 20 years than be miserable for however long this terrible medicine might extend my life.

JR Hoffman MD from Los Angeles provided further insight.

Congratulations to Drs Abramson and Redberg for their outstanding editorial, and to the NYT for having the courage to print it. As the authors note, this new guideline’s major beneficiary will be the pharmaceutical industry, while the American people will likely be its primary victim.

The British Medical Journal has recently printed a series of papers (disclosure — I co-authored one of those papers) addressing the biases and distortions that enter far too many published clinical guidelines, because a large majority of panel members and panel chairs have a financial conflict of interest, and because panels are stacked to support viewpoints reflecting those conflicts, independent of the evidence. This is particularly true of guidelines from prominent medical specialty societies … societies which themselves receive major financial support from industry. 

How many people targeted by the new guidelines would take one of these medicines if they were told that far more than 9 out of 10 (in fact probably more than 99%) would get no possible benefit whatever? And essentially none would get an overall reduction in major morbidity or mortality? And that this would come at a substantial cost in the side effects that a good many would suffer (not even considering the cost in dollars)?

If your physician tells you that you “need” a statin, please ask her for the details of how likely you as an individual are to benefit, and at what chance of harm.

Statin drugs interfere with the human production of many important substances. One of these is Coenzyme Q 10 also called uibiquinone. Co Q 10 functions as an important anti-oxidant and as an essential component of the apparatus inside every cell that produces ATP, the fundamental unit of energy that provides energy for every cellular function. Without ATP the cells in every organ shut down and cannot do any work.

Statin side effects can include not only muscle pain and weakness but also nerve damage, dementia, amnesia.  Shortness of breath can be the only symptoms when the muscles of respiration are affected.  Diabetes can be caused by any of the statin drugs and this can be permanent.  Rarely, statins can cause death . This happens when a massive amount of muscle damage causes a flood of debris that overwhelms the body’s ability to clear the debris. Damage to muscles and nerves can be permanent without any recovery after  the statin is stopped. A former astronaut and flight surgeon suffered transient global amnesia which fortunately cleared after stopping the statin drug. He has since published a few books about the dangers and inappropriate use of statins. Kidney failure requiring dialysis or kidney transplant is also a rare but potential result of statin medication.

Cardiologists and primary care physicians often ignore complaints about muscle pain, fatigue, weakness and forgetfulness in older patients and attribute it to old age. But even when these complaints are recognized as a side effect, rarely does a physician report it  to the FDA. As a result, post marketing surveillance data underestimates tremendously the frequency of side effects.

Be careful out there. Read my first post about statin medications. it provides risk-benefit data. Remember, we do not know with certainty the frequency of side effects and permanent damage, but you can be sure it happens more often than the drug company states. It happens more often than most physicians realize.

Peace

Bob Hansen MD

Number Needed to Treat (NNT) website and Statin Drugs

My 85 year old mother-in-law was placed on a statin drug two years ago by her primary care physician. She had no risk factors for coronary disease other than age, she had a prior completely normal cardiac catheterization (coronary angiogram) and was totally without symptoms before being placed on the statin. Within weeks she developed muscle pain and weakness, suffered fatigue and overall felt poorly. I convinced her to stop the statin and within a few weeks she felt great. I see similar scenarios frequently in the pain clinic. I personally suffered severe statin induced myopathy pain from two different statins (in the days before enlightenment) and gratefully recovered when I stopped the drug each time. I have since learned more about coronary artery disease, cholesterol metabolism, statins, and related topics.

There is a great website that analyzes data from multiple studies to estimate the number of patients needed to treat in order to help and/or harm a patient. Two such analyses on this website are the NNT with statin drugs for five years to achieve certain results. They analyze data  in patients without known coronary artery disease (primary prophylaxis) and in patients with known coronary artery disease (secondary prophylaxis).

Here is the website:

TheNNT

Here is the page for primary prophylaxis:

Statins for Heart Disease Prevention (Without Prior Heart Disease) | TheNNT

Here is the link to the page on secondary prophylaxis:

Statins for Heart Disease Prevention (With Known Heart Disease) | TheNNT

Here are the results for primary prophylaxis.

“In Summary, for those who took the statin for 5 years:

  • 98% saw no benefit
  • 0% were helped by being saved from death
  • 1.6% were helped by preventing a heart attack
  • 0.4% were helped by preventing a stroke
  • 1.5% were harmed by developing diabetes*
  • 10% were harmed by muscle damage

In Other Words:

  • None were helped (life saved)
  • 1 in 60 were helped (preventing heart attack)
  • 1 in 268 were helped (preventing stroke)
  • 1 in 67 were harmed (develop diabetes*)
  • 1 in 10 were harmed (muscle damage)”

Here are the results for secondary prophylaxis.

“In Summary, for those who took the statin for 5 years:

  • 96% saw no benefit
  • 1.2% were helped by being saved from death
  • 2.6% were helped by preventing a repeat heart attack
  • 0.8% were helped by preventing a stroke
  • 0.6% were harmed by developing diabetes*

In Other Words:

  • 1 in 83 were helped (life saved)
  • 1 in 39 were helped (preventing non-fatal heart attack)
  • 1 in 125 were helped (preventing stroke)
  • 1 in 167 were harmed (develop diabetes*)”

If anything, the side effects (harm) are understated and the authors acknowledge this because many of the studies do not adequately report side effects and complications. (The studies were funded in part or in totality by the pharmaceutical company that makes the drug and that is a problem as discussed below)

Association of funding and conclusions in randomized dr… [JAMA. 2003] – PubMed – NCBI

It is rare that this sort of analysis would be presented to a patient in the physician’s office to help a patient decide whether the risks and benefits are acceptable. (I provide patients with this data on a multi-page handout with significant narrative and explanation when I diagnose statin myopathy.)

The obsession that American physicians have with cholesterol (another topic to be addressed in future posts) creates a knee-jerk reaction to a lab value that results too often in muscle damage and pain and sometimes cognitive impairment.

My experience in the pain clinic has been that the % of elderly with statin induced muscle damage and/or muscle pain is much higher. When I suggest that the patient stop the statin drug because they are suffering disabling pain and possibly permanent muscle damage they often return at the next visit to tell me they were started on a different statin drug. Most patients who suffer this complication will have a repeat of the same complication when placed on a different statin drug. This complication can cause permanent damage.

In the medical literature, many studies presented as “primary prophylaxis” are not truly primary prophylaxis because there are some patients included that have known diagnosed coronary disease. This tainted data is then presented as if it were a true primary prophylaxis study.

A more recent study purported to demonstrate once and for all that statins in primary prophylaxis can save lives. Unfortunately, there were problems with this study as well. Here is an excerpt from a commentary in the publishing journal:

“There are reasons to be cautious about the findings of the meta-analysis by Taylor and colleagues. As the authors note, all but 1 of the trials were partly or fully funded by pharmaceutical companies. Trials funded by for-profit organizations are more likely to recommend the experimental drug than are trials funded by nonprofit organizations (4). Further, adverse event reporting in the original trials was poor, with few details about type or severity, and quality of life was rarely assessed. Some adverse events, such as cognitive impairment, are rarer and not assessed.”

Disappointingly, the commentary failed to point out that the study data again included some patients with diagnosed coronary artery disease. (up to 10%).

Here are the authors own words.

“We included randomized controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD.”

Once again we have a “primary prophylaxis” meta-analysis that is not really a primary prophylaxis study. It never seems to end.

When drug companies fund studies the conclusions often overstate the benefit and understate the risks. If you do not look for a side effect or complication, you will not find one. Here is an excerpt from a large study that look at the issue of bias in drug company sponsored research.

“CONTEXT:

Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions.

OBJECTIVE:

To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events.

CONCLUSIONS:

Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results. Readers should carefully evaluate whether conclusions in randomized trials are supported by data.”

Association of funding and conclusions in randomized dr… [JAMA. 2003] – PubMed – NCBI

There are many ways that authors can present data to give the appearance of success. A more recent study published in Lancet alleged to demonstrate benefit (death prevention) for statins in primary prophylaxis.

Here it is.

The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials : The Lancet

But when you drill down into the data you  discover a mechanism of deception. The benefits reported in the paper applied only to patients whose cholesterol dropped significantly. Looking at all patients in the study who took the statin did not result in decreased death rates. Selecting those whose cholesterol dropped 40 points did show death prevention benefit. They presented risk reduction per unit of cholesterol reduction. From a scientific point of view this is less than honest. The authors simply demonstrated that patients who responded to the drug benefited.

DUH***All previous studies that simply compared patients on statins vs. those not on statins (primary prophylaxis) showed no prevention of death. This is an important distinction, The cost implications of putting low risk individuals on statins are enormous. Statins also rarely can cause death (from rhabdomyalysis) and frequently caused harm.  One comment about this studies’ conclusions was titled “Statins for all by the age of 50 years?” That frightens me.

The mechanism of statin drug benefits are likely related to many known potentially beneficial physiologic effects, not from a reduction of cholesterol. As you will learn in future posts, cholesterol reduction in and of itself is almost meaningless. The amount of circulating cholesterol in your blood is not the problem. The problem is much more complex and relates in part to the oxidation of LDL particles, which has little to do with the amount of cholesterol carried in those particles. Other important factors include systemic inflammation and the response of the innate immune system to factors such as circulating LPS which in turn reflects intestinal permeability. I apologize for the sudden onslaught of abbreviations and medical terms but stay tuned and you will learn what they all mean.

Finally, in the secondary prophylaxis group, the benefits of statin drug use are equivalent to the benefits achieved with exercise-based cardiac rehabilitation following a heart attack. Cardiac rehab offers many benefits in addition to saving lives, produces no significant negative side effects, and improves quality of life and sense of well-being. Many patients on statins feel lousy.

Efficacy of exercise-based cardiac rehabilitation… [Am Heart J. 2011] – PubMed – NCBI

In my next post I will discuss saturated fat  and coronary artery disease. This issue represents the crux of controversy in the heart-healthy diet debate which most physicians and the AHA consider clarified (eat less saturated fat). You already know generally what I have to say about that if you have read my Manifesto page. The next post will expand on the saturated fat section in the Manifesto. Subsequent posts will discuss cholesterol, LDL cholesterol, LDL particle number, oxidized LDL and glycated LDL (the last two are referred to as modified LDL)

Bob Hansen MD