Sunday, April 13, 2014

Preventing and Reversing Heart Disease - DACH

Preventing and Reversing Heart Disease, Part Three

Coronary Angiogram Real Time Cath Lab
Preventing and Reversing Heart Disease
Part Threeby Jeffrey Dach MD
This Article is Part Three.
For Part One Click Here,
and for  Part Two Click Here.

A Man with Progressive Coronary Artery Disease Unresponsive to Statins
62 year old Jim came just had his third cardiac stent.  A year ago, Jim noticed a “tight feeling” in his chest radiating to his throat, was rushed to the ER, and doctors found he was having a heart attack. A coronary angiogram showed extensive coronary artery disease with irregular plaque formation.

Progressive Coronary Artery Plaque in Spite of Low Cholesterol
For 12 years now, Jim’s cholesterol level had been driven down into the 140 area by the “top cardiologist in the area”, who prescribed a hefty dose of a statin anti-cholesterol drug.  In spite of the lowest cholesterol level on the planet,  Jim’s heart disease progressed relentlessly with worsening calcium scores, worsening angiograms, and worsening symptoms of chest pain.   His disease progression was obviously not caused by an elevated cholesterol level.  For a discussion of how elevated cholesterol is NOT the Cause of Heart Disease, see my article on patients with familial hypercholesterolemia who have very high cholesterol, yet have no heart disease, proving the hypothesis that cholesterol levels are not necessarily a risk factor for heart disease, and reducing cholesterol levels with drugs may be a fruitless endeavor.

Doctors advise Jim to Stop Testosterone
Jim had been taking topical testosterone for the past 5 years, and recently stopped it because of advice from his cardiologist who pointed a finger and said, “You should stop the testosterone….The testosterone is bad for your heart and probably caused your heart attack“.  Jim came to see me for a second opinion.

Jim’s Doctor is Right About That
Jim’s doctor is right in that a number of recent studies have shown a small increase in heart attack rate in men starting testosterone.   This is caused by increased hematocrit (red blood cell count) and increased iron stores which thicken the blood and make it more susceptible to blood clot formation, all risk factors for heart attack.  See  my article on this.  The simple solution is to monitor blood count and iron levels, and donate blood at the blood bank every 4 to 6 weeks to reduce iron and red cells.

Our Approach to Preventing Heart Disease
I must preface these remarks with our approach to prevention and reversal of heart disease which is outlined in Part One  and Part Two  of this series.  We credit and rely heavily on the  “Track Your Plaque Program ” by William Davis MD.  We also use the Linus Pauling Protocol.

Bioidentical Hormones For Prevention and Reversal of Heart Disease
In this article we will revisit the role of the testosterone and estradiol in prevention and reversal of heart disease, looking at the latest research.  Firstly, let’s try to answer the question:
” Is low testosterone a risk factor for heart diease, and is normal testosterone level protective of heart disease?” 
Here we assume red cell count and iron levels are kept under control with monthly trips to the blood bank, so there is no short term increase in heart attack rate from hypercoagulability, as noted in a few recent studies of men started on testosterone.

Low Testosterone is Predictive for Increased Mortality from Heart Disease
If testosterone was causative of heart disease,  one would expect men with high testosterone to have more heart disease, and men with low testosterone to have less heart disease.  This is exactly opposite of four major studies showing men with low testosterone have both increased all-cause mortality and increased heart disease mortality.(1-4)

Testosterone Levels in Men With Heart Disease
A recent study by Malkin looked at Testosterone levels in men with known underlying heart disease.  He showed that low Testosterone is common in men with underlying heart disease, and this is associated with almost double the mortality rate.(5)  Again these findings suggest that higher Testosterone is protective and prevents progression of heart disease.  The assumption that Testosterone causes progression of atherosclerosis plaque has been shown false.(6-9).
arterial plaqueAbove image: Cross section of arteries (left to right) showing development of fatty streak which enlarges into the atherosclerotic plaque.
Animal Studies on Mechanism of Protection
A number of elegant animal studies have been done to elucidate the mechanism by which testosterone is protective of heart disease.  A 1999 study by Alex Andersen in rabbits showed that testosterone reduced aortic atheroscleosis.(10)  Castrated rabbits had low testosterone levels and doubled the  aortic atherosclerosis plaque formation, suggesting that testosterone has a strong preventive effect on male atherosclerosis. In the groups receiving testosterone or DHEA they found marked inhibition of atherosclerosis compared with placebo. The mechanism was not clearly defined.  They speculated on a non-lipid mediated mechanism, possibly related to aromatase conversion of testosterone to estrogen.(10 )

Mouse Model- It’s Really the Estrogen That’s Protective
In an elegant 2001 study published in PNAS, Nathan et al used a mouse model of accelerated atherosclerosis to show that testosterone inhibits atherosclerosis by its conversion to estradiol by the aromatase enzyme.  Similar protection from atherosclerosis was obtained by administering estradiol.  In addition, blocking conversion of testosterone to estradiol with the aromatase inhibitor, anastrazole, eliminated the protective effect, and these animals had progressive atherosclerosis.(11)  Dr Nathan says:
“Testosterone attenuates early atherogenesis most likely by being converted to estrogens by the enzyme aromatase expressed in the vessel wall”.(11)
This information suggests that men with heart disease should NOT take arimidex (anastrazole) along with their testosterone replacement therapy.

Genetically Altered Mouse Model Provides Answers
These findings were confirmed  by Nettleship  in a 2007 study published in Circulation using the Tfm genetically modifired mouse.  This is a mouse genetically altered to have a defective androgen receptor.  In these mice,  testosterone cannot work through its normal pathway, since there is no receptor.  In spite of the lack of androgen receptor, Nettleship found that testosterone replacement in these mice attenuated atherosclerotic changes (fatty streak formation), suggesting the protective effect of testosterone was independent of the testosterone receptor.  The authors concluded that the protective benefits of testosterone were through aromatase conversion to estradiol, and then via the estrogen receptor pathways.(12)

Dr Nettleship’s findings were confirmed by Bourghardt  in a Nov 2010 study published in Endocrinology which using ”ARKO” mice, genetically modified to “knock out” the Androgen Receptor, modified to be Apo-E deficient (to accelerate atherosclerosis).  The authors showed that testosterone therapy administered to the ARKO mice inhibited atherosclerosis.  However inhibition of atherosclerosis was more profound in the wild type mice that still had intact androgen receptors.  The authors concluded the mechanism of protection of testosterone was due to both mechanisms, through the Androgen Receptor as well as through aromatase conversion to estradiol.(13 )

These genetically modified mouse studies suggest that testosterone’s cardio-protective benefits are due to conversion to estrogen, and that estrogen is the cardioprotective agent.  Both estrogen and testosterone are bioidentical hormones.   Clearly the message here is Testosterone Replacement Therapy should be an important part of any heart disease prevention program,  in those patients who have low Testosterone levels.

Why Do Men Have More Heart Disease Than Women ?
Men and women are quite different when it comes to heart disease.  Men have more than twice the risk of dying from coronary disease than women. (14)  In women, coronary artery disease (CAD) develops on average 10 years later than in men.(15)  Could higher levels of estrogen (estradiol) in women explain the protection enjoyed by women?

Estrogen is Protective
Dr Xing from the University of Alabama would say, yes of course.  In a 2009 article, Dr Xing names a number of mechanisms by which estradiol protects both men and women from heart disease. He says:
“Estrogens have antiinflammatory and vasoprotective effects.  Natural endogenous estrogen 17β-estradiol (bioidentical) has been shown to cause rapid endothelium-independent dilation of coronary arteries of men and women, to augment endothelium-dependent relaxation of human coronary arteries, and improve endothelial function…Observational studies have shown substantial benefit (50% reduction in heart disease) of hormone therapy in women who choose to use menopausal hormones.”(15 )
Estrogen is Protective of Heart Disease
A 2010 study in European Heart by Kitamura et al  compared males to female heart attack rates. They found 61% fewer heart attacks in women of reproductive age with high estrogen levels compared to males of the same age.  The authors conclude that estrogen confers cardioprotective benefits.(16)
A review of the Nurse Health Study published in the 2000 Annals  showed 40% reduction in heart disease in hormone replacement users and that “postmenopausal hormone use decreases risk for major coronary events.” (17-18)

See my article on how estrogen protects women from heart disease: Bioidentical Hormones Prevent Heart Disease.

Coronary bypass surgeryComparing Three Treatment Modalities
There are three mainstream treatment modalities for coronary artery disease.
1) Surgery with coronary artery bypass.
2) Balloon angioplasty with stenting.
3) Medical Therapy with drugs such as calcium channel blockers and beta blockers.
Which one of these treatment modalities confers the most benefit? The answer is:  None of Them.
Medical Management with Drugs Provides the Same Benefit as Cardiac Angioplasty, Stenting or Bypass
Eleven randomized studies reviewed 3,000 patients with stable coronary artery disease.  Treatment with  angioplasty and stenting showed the same mortality and heart attack rate as drug treatment (also known as medical management).  They both offer the same benefit.(19)(20)
The MASS II study  published in the 2007 Circulation showed medical managment with drugs to have similar outcome to stent or bypass. (21)    A troubling fact remains that after all these studies have been completed,  there is no conclusive evidence that intervention with CABG (coronary artery bypass graft) or coronary stent  is superior to medical therapy (drugs) for treating multivessel coronary artery disease with stable angina and preserved ventricular function.(21 )  Sorano attempts to sort out the fine points of selecting between treatment modalities in her 2009 report. (22)

How Can Drugs Provide the Same Outcome as Surgery or Stenting?
The EPC, the Endothelial Progentor Cell.
Now we have an important question to ask.  How is it possible that the humble country doctor with a few drugs can provide similar outcomes when compared to the high and mighty cardiac surgeon and the interventional cardiologist?  How can drug treatment do as well or better than the cardiac stent or surgical bypass procedure?

I suggest the answer resides in the phenomenon known as “collateral vessel formation”.  The heart has the ability to grow new blood vessels which provide blood flow around the blocked artery.  Medical treatment gives the heart time to grow new collateral vessels. The key to understanding this new vessel formation is the endothelial progenitor cell, also known as the EPC. The EPC is a special type of stem cell found in the bone marrow that circulates to injured myocardium where they promote local angiogenesis, making new blood vessels. (23)

Turning On The Endothelial Progenitor Cell – How to Do It?
A previous article on telomeres and anti-aging discussed the role of estrogen as an activator of telomerase which serves as an anti-aging therapy.  Recent research shows that estrogen  activates the telomeres on endothelial progenitor cells and improves the EPC functional capacity. (24)  Another study showed reduced numbers of EPC cells in the peripheral blood of men with low testosterone levels. (25)

Estradiol Enhances Recovery After Myocardial Infarction – Collateral Vessels
An elegant mouse study was published by Isakura in 2006 Circulation .  They used a mouse model in which myocardial infarction (heart attack) was induced by ligation of the left coronary artery.  The estradiol treated mice showed increased circulating EPC’s and greater capillary density in the recovering myocardium.  This indicates enhanced recovery in the estradiol treated mice by regrowth of collateral vessels. (26)(27)(28)

A study from Bolego in Italy showed that the cardio protective benefits of estrogen could be duplicated with an estrogen receptor drug called PPT. They found that:
“myocardial ischemia-reperfusion injury was exacerbated by ovariectomy (which reduced estrogen levels).   This injury returned to baseline following treatment with estrogen-like drug PPT.”
The protective effects were linked to increased levels of endothelial progenitor cells (EPCs).(29)

Recent research shows the cardioprotective benefits of the bioidentical hormones, testosterone and estrogen.  Testosterone benefit appears mediated by conversion to estradiol via the aromatase enzyme.  Estradiol’s benefits appear related to activation of Endothelial Progenitor Cells which invoke new collateral circulation in areas of injury.

Another treatment modality called EECP also creates new collateral vessels.  Read my article on EECP here.
Read the complete article here.

Monday, March 31, 2014

Patients Managed to Target LDL Particle Number Experience Fewer Cardiovascular Events

Patients Managed to Target LDL Particle Number Experience Fewer Cardiovascular Events Than Patients Managed to Target LDL Cholesterol, According to Study

Data demonstrates that the NMR LipoProfile® test provides clinically reliable information to help reduce cardiovascular events, especially in patients with diabetes and those on statin therapy

WASHINGTON, March 31, 2014 /PRNewswire/ -- LipoScience, Inc. (NASDAQ: LPDX), a diagnostic company pioneering a new field of personalized nuclear magnetic resonance (NMR) diagnostics to advance the quality of patient care in cardiovascular, metabolic and other diseases, today announced data showing that patients managed to a target LDL particle (LDL-P) number, as measured by LipoScience's NMR LipoProfile test, achieved a 22 to 25 percent greater reduction in the risk of cardiovascular (CV) events over a three-year period compared to patients who attained LDL cholesterol (LDL-C) targets.
These data, presented in a poster session at the 63rd American College of Cardiology (ACC) Scientific Sessions in Washington, D.C., are derived from a real-world sample of commercially insured patients who were at a high risk of CV events, including patients with Coronary Heart Disease and Diabetes Mellitus. The investigators found that patients who achieved target LDL-P levels (<1000 aggressive="" concentrations="" dl="" ldl-c="" lipid-lowering="" mg="" more="" nmol="" p="" reaching="" received="" target="" than="" those="" treatment="">
Those treatment differences were associated with better outcomes (as measured by the reduction in CV event rates) over one to three years of follow-up. The study was sponsored by LipoScience and jointly designed by LipoScience and HealthCore, with clinical input from Terry A. Jacobson, MD, Professor of Medicine at Emory University, Atlanta, and Peter P. Toth, MD, PhD, Director of Preventive Cardiology at CGH Medical Center in Sterling, Ill.
"These new data add to the growing body of evidence suggesting that NMR measurement of LDL particle number, when used in conjunction with other lipid measurements, is a valuable cardiovascular risk management tool," commented Dr. Jacobson, the lead author of the study. "Due to the wide variance in the cholesterol content of LDL particles among individuals, measurements of LDL cholesterol and LDL particle number frequently disagree, especially in patients with insulin resistance and those treated with lipid-lowering therapies. When a disagreement between LDL-P and LDL-C is present, quantification of LDL particle number is a more clinically reliable measure of LDL and of treatment outcomes than measurement of LDL cholesterol."
Dr. Jacobson and colleagues analyzed data from more than 4,000  high-risk patients (over 2,000 with LDL-P < 1000 nmol/L and over 2,000 with LDL-C < 100 mg/dL) selected from the HealthCore Integrated Research DatabaseSM who were followed for as long as three years. Those who achieved LDL-P target <1000 100="" 22="" 25="" a="" above="" achieved="" as="" at="" baseline="" below="" but="" compared="" concentrations="" cv="" dl.="" event="" follow-up.="" group="" higher-potency="" in="" ldl-c="" ldl-p="" levels="" likely="" lower="" measured="" medications="" mg="" more="" nmol="" not="" noted="" of="" one="" over="" p="" patients="" percent="" receive="" risk="" statin="" target="" than="" the="" three="" to="" was="" were="" who="" whose="" years="">
Dr. Jacobson's poster, "Comparison of cardiovascular events between patients achieving low-density lipoprotein particle targets and patients achieving low-density lipoprotein cholesterol targets," will be presented Monday, March 31 from 9:30 a.m. to 12:30 p.m. in Hall C of the Washington Convention Center. The poster number is 150.
"The HealthCore data add an important, real-world, analysis to the ongoing discussion of how best to optimize individual patient management. These findings are consistent with the recommendations of various expert panels and organizations such as the National Lipid Association, the American Association for Clinical Chemistry, and the American Association of Clinical Endocrinologists, each of which advocates the use of LDL-P as a target of therapy in managing at-risk patients," stated William C. Cromwell, MD, Chief Medical Officer of LipoScience.  "We hope the findings encourage greater adoption by clinicians to manage their patients to an LDL-P target to reduce CVD events."
The ACC Scientific Session also includes the following poster presentations that support the clinical utility of NMR-based lipoprotein particle measurement:
  • Poster #143: May HT, et al. Utility of high-density lipoprotein cholesterol, particle concentration, and size in predicting future major adverse cardiovascular events among patients undergoing angiography: The Intermountain Heart Collaborative Study.
    • Saturday, March 29, 9:30am to 12:30pm, Hall C
  • Poster #146: Muhlestein JB, et al. GlycA and GlycB, novel NMR biomarkers of inflammation, strongly predict future cardiovascular events, but not the presence of coronary artery disease (CAD), among patients undergoing coronary angiography: The Intermountain Heart Collaborative Study.
    • Sunday, March 30, 9:30am to 12:30pm, Hall C
  • Poster #128: Koren MJ, et al. Effects of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9, on lipoprotein particle concentrations determined by nuclear magnetic resonance: Substudy of a randomized double-blind phase II clinical trial.
    • Sunday, March 30, 9:30am to 12:30pm, Hall C
  • Poster #134: Xu R, et al. Effects of evolocumab on lipoprotein particles and subclasses in hypercholesterolemic and heterozygous familial hypercholesterolemia subjects on statin therapy
    • Sunday, March 30, 9:30am to 12:30pm, Hall C
  • Poster #141 Alexander V, An antisense inhibitor of apolipoprotein C-III significantly decreases apolipoprotein C-III, triglycerides, Very-Low-Density Lipoprotein cholesterol and particle number, and increases High-Density Lipoprotein cholesterol and particle number in hypertriglyceridemic patients on a fibrate.
    • Monday, March 31, 9:30am to 12:30pm, Hall C
Read the complete article here.

Thursday, March 20, 2014

Ezetimibe Prescribing Fails to Keep Up With Evidence - JAMA

Ezetimibe Prescribing Fails to Keep Up With Evidence     
Mike Mitka, MSJ 
JAMA. Published online March 19, 2014. doi:10.1001/jama.2014.2896
Although physicians like to think they practice evidence-based medicine, that appears to not be the case with prescribing the cardiovascular drug ezetimibe. And some critics say that use of surrogate markers to guide practice rather than clinical outcomes such as occurrence of myocardial infarction, stroke, or death has likely played a role.
Ezetimibe is an intestinal cholesterol absorption inhibitor found to reduce low-density lipoprotein cholesterol (LDL-C) levels by about 20% when given alone. It also further reduces LDL-C levels when added to statin therapy, which blocks cholesterol synthesis in the liver by inhibiting HMG-CoA reductase.
The Food and Drug Administration approved ezetimibe in 2002 for use in the United States primarily because it lowered LDL-C levels, a surrogate marker for prevention of cardiovascular disease. Whether ezetimibe improved clinically meaningful outcomes remained a question.
That question was somewhat answered in January 2008, with the announcement that the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) trial, sponsored and conducted by industry, found that the addition of ezetimibe failed to reduce atherosclerosis progression compared with simvastatin alone, despite lowering LDL-C levels. Atherosclerosis progression was determined by a change in the intima-media thickness of the walls of the carotid and femoral arteries—yet another surrogate end point (Kastelein JJP et al. N Engl J Med. 2008;358[14]:1431-1443).
Place holder to copy figure label and caption
US and Canadian physicians continue to prescribe ezetimibe even after a study found giving the drug with a statin failed to reduce atherosclerosis progression compared with the statin alone.
The ENHANCE result prompted some leaders in the cardiology community to question ezetimibe’s place in cardiovascular disease treatment. Harlan Krumholz, MD, professor of medicine and epidemiology and public health at Yale University in New Haven, Connecticut, said the study should change practice. “Although not definitive, [ENHANCE] increases our uncertainty about the clinical value of this novel drug. Without some evidence of improved outcomes associated with its use, ezetimibe should be relegated to a last option for patients who need medication for hypercholesterolemia, and even in these cases, it is reasonable for clinicians and their patients to wait for further information before considering it,” he wrote in NEJM Journal Watch (http://tinyurl.com/pk9xr29).
So did the ENHANCE results change practice? In the United States, the answer is “somewhat,” while in Canada, the answer appears to be “no.”
In a study published in the American Heart Journal, researchers looked at ezetimibe prescription trends before and after ENHANCE, using data collected from CompuScript in Canada and IMS Health in the United States from January 1, 2002, to December 31, 2009. The researchers found the monthly number of ezetimibe prescriptions per 100 000 population rose from 6 to 1082 in the United States from November 2002 to January 2008 and then declined to 572 per 100 000 population by December 2009, a decrease of 47.1%. In Canada, however, use continuously increased from 2 to 495 per 100 000 from June 2003 (when the drug was approved in Canada) to December 2009 (Lu L et al. Am Heart J. doi:10.1016/j.ahj.2014.01.014 [published online February 27, 2014]).
Coauthor Cynthia A. Jackevicius, PharmD, MSc, a professor of pharmacy practice and administration at Western University of Health Sciences in Pomona, California, and an adjunct scientist, Institute for Clinical Evaluative Sciences, in Toronto, said her team was initially surprised by the Canadian results.
“Previous findings showed ezetimibe use in Canada experienced a more conservative uptake, so we expected to see a decrease in use in response to the ENHANCE study,” Jackevicius said. “So we looked for different factors, and one is the Canadian lipid guidelines, which specifically said ezetimibe could be added to statins, and that didn’t change after ENHANCE came out.”
A study of ezetimibe use in Saskatchewan, the only Canadian province that lists the drug for open formulary access, even though guidelines say it’s a second-line agent for lowering cholesterol, reflects Jackevicius’s team’s findings. Using data from provincial health administrative databases, the Saskatchewan researchers found that ezetimibe prescriptions were 2.5% of cholesterol-lowering dispensations in 2004 and 8.8% of such dispensations in 2011 (Alsabbagh WM et al. Can J Cardiol. 2014;30[2]:237-243). The authors concluded that allowing unrestricted use of ezetimibe in Saskatchewan may have led to a large number of inappropriate prescriptions, at odds with Canadian clinical guidelines.
And although ezetimibe use declined in the United States, its use per 100 000 population is still greater than Canada’s, generating US expenditures of more than $2.2 billion in 2009.
Krumholz, one of the coauthors on the study with Jackevicius, remains perplexed as to the continuing popularity of ezetimibe. “The drug continues to defy gravity, and that’s probably a result of really strong marketing and the singular focus on cholesterol numbers,” he said.
Krumholz said heart health campaigns urging patients to “know your numbers” and treatment goals based on cholesterol measurements, such as getting asymptomatic individuals’ LDL-C levels below 130 mg/dL, have worked in ezetimibe’s favor at the expense of evidence-based medicine. “Is this the drug that lowers your LDL-C and helps you? We don’t know that,” he said. “The comfort of hitting a target offers little benefit if you don’t know that it is really protecting you.”
Although ENHANCE has not derailed ezetimibe prescribing, the newest cholesterol management guidelines just might. The guidelines, issued late last year by the American College of Cardiology and the American Heart Association, abandon the idea of reaching a target level for LDL-C, instead recommending the use of statins to reduce LDL-C levels only for certain types of patients.
Will this change in the guidelines affect ezetimibe prescribing? “It will be interesting to see what the guidelines will do,” Krumholz said.
Read the complete article here.

Friday, March 14, 2014

Researchers pronouncing ‘statins are safe’ are undermined by their own observations - Briffa

Researchers pronouncing ‘statins are safe’ are undermined by their own observations

Listen to most ‘key opinion leaders’ talk about statinsand you will hear soothing reassurances about their safety. Yet, my experience as a doctor suggests that adverse effects such as fatigue and muscle pain occur more commonly than ‘official statistics’ suggest. However, a study published this week claims to provide evidence that, for the most part, statin side effects are ‘imagined’ [1].

In this research, the adverse effect rates from statins was compared with those seen in individuals taking placebo (dummy) pills in a total of 29 studies. The conclusion was that apart from increasing the risk of diabetes, statins don’t generally have any more adverse effects than placebo. The actual words the authors use in their conclusion are: “Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo.”

This is confident, seemingly ‘evidence-based’ stuff, indeed. However, these findings do appear to me to be at odds with what I and many other doctors observe in real life: that a significant number of people who take statins have side-effects that resolve (sometimes slowly) on discontinuation of their medication. Of course, as the authors of this most recent study allude to, these side-effects may be nothing more than a negative placebo response – sometimes referred to a ‘nocebo’ response.
However, is there anything about the way statin trials may be designed and conducted that could jeopardise our ability to get accurate data on the adverse effects of these drugs?

Several explanations are possible. First, commercial sponsors of clinical trials may not be motivated to search exhaustively for potential side effects. One pointer towards this is that, although evidence of liver damage is documented in the majority of trials, diabetes diagnoses were only documented in three of the 29 trials assessed in the recent study.

Second, many trials do not state clearly how and how often adverse effects were assessed. Because of this, it far from certain that all adverse events were ‘caught’ and logged appropriately.

Third, some trials’ exclude patients with severe diabetes, kidney failure or high blood pressure. In reality, though, these individuals may come to be prescribed and take statins.

Fourth, trial volunteers tend to be enthusiastic, and may therefore be less likely to report side effects than patients in routine clinical practice.

Fifth, many trials have a ‘run-in’ period where individuals are given a placebo to help ensure adequate compliance with medication. This can cause studies to be ‘enriched’ with highly motivated individuals who, again, may be less likely to complain of side-effects.

Finally, many trials excluded patients on medication sharing the same liver metabolic pathway as statins (e.g. fibrates and macrolide antibiotics). Patients on such drugs, in the real world, might well suffer higher rates of pharmacologically mediated effects.

I make no secret of the fact that I think the benefits of statins are over-hyped and that the adverse effects are generally downplayed. As a result, a cynical observer might read my reservations here and think ‘well, he would say that’.

But, here the kicker: those six issues I detail above were plucked from the very same study that trumpets the safety of statin [1]. Much of what is written in this section of the post was actually lifted verbatim from the study.

So, by the authors’ own admission, there are many reasons why the adverse effect rates seen in statin studies may not accurately reflect the rates seen in the real world. But then how can the authors conclude that: “Only a small minority of symptoms reported on statins are genuinely due to the statins: almost all would occur just as frequently on placebo.”

The reality is the deficiencies of the studies do not allow the authors (or anyone) to conclude that at all. The authors’ pronouncement on safety is utterly undermined by their own admissions about the incompleteness and untrustworthiness of the study data.

The opening line of the study is this: “Patients and doctors need clear reliable information
about benefits and risks to make informed decisions.” The only clear thing about the risks of statins, to my mind, is that there isn’t much clarity. Making bold pronouncements on the safety of statins without us having the facts is potentially misleading, and may cause many to come to considerable harm, needlessly.

1. Finegold JA, et al. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. European Journal of Preventive Cardiology March 12, 2014

Thursday, March 6, 2014

Early atherogenesis and visceral fat in obese adolescents


Early atherogenesis and visceral fat in obese adolescents

A H Slyper, H Rosenberg, A Kabra, M J Weiss, B Blech, S Gensler and M Matsumura
Little information is available as to the cause of increased thickening of the intima-media of the carotid artery (cIMT) in the pediatric population. Therefore, cIMT was compared in obese adolescents and normal-weight controls, and associations between cIMT and lipid and non-lipid cardiovascular risk factors were assessed.

Subjects included 61 obese non-diabetic male and female volunteers aged 12–18 years inclusive with a body mass index (BMI) >95th percentile for age and 2-h blood glucose <200 class="mb" span="">
mgdl−1 matched to 25 normal-weight control volunteers with normal glucose levels. Each subject underwent a 2-h glucose tolerance test and measurement of hemoglobin A1c, ultrasensitive C-reactive protein, fasting insulin, blood lipids, visceral, subcutaneous abdominal and hepatic fat, and cIMT.
Maximum cIMT was 0.647±0.075mm in the obese subjects versus 0.579±0.027mm in normal-weight controls (P<0 .001="" 2-h="" and="" assessment="" between="" bmi="" cholesterol="" cimt="" correlations="" difference="" fasting="" female="" glucose="" hdl="" high-density="" homeostasis="" in="" insulin="" ldl="" lipoprotein="" low-density="" male="" maximum="" model="" no="" significant="" sub="" subjects.="" there="" total="" very="" was="" were="" z-score="">2
cholesterol, HDL3 cholesterol, triglycerides, remnant lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, lipoprotein(a), apoprotein B100, abdominal subcutaneous fat volume, visceral fat volume and hepatic phase difference. On multiple regression analysis, visceral fat was the most significant predictor of maximum cIMT. Two-hour blood glucose, HOMA and systolic blood pressure were also significant predictors of maximum cIMT.
cIMT was increased in the obese adolescents compared with the normal-weight-matched controls. Visceral fat was a key predictor of arterial wall thickening in these subjects. The results suggest that the focus of cardiovascular disease prevention in the adolescent obese should be visceral obesity, and not blood lipids or lipid subclasses.

Tuesday, February 18, 2014

Low Cholesterol’s Cancer Link Illustrates Innate Intelligence - Campos

Low Cholesterol’s Cancer Link Illustrates Innate Intelligence

Dr. Nick Campos

Oh boy, here we go…so you know that I’m not shy about discussing my health. I’ve got nothing to hide, and I approach my health from a very proactive position. I also have a belief system that is integral to how I care for my health—I know that one day I am going to die, could be tomorrow, but for me to experience my life to the fullest today, I am quite certain that it requires me to care for my body as one of my most valuable assets. So I don’t obsess about “never getting sick,” I just treat my body like I love it, and I trust that it knows—through its innate intelligence–how to run my body, provided I treat it in the right ways. Simple.

So long-time readers of this blog will recall that I have high cholesterol. Have I ever been worried about it? No, never. Not even a little. In fact, I just had my annual physical in February. Once again, stellar health, thank you, thank you…athlete’s numbers…’cept I have high cholesterol.

If you’ve been following my story, you’ll recall that my doc (love him, bless his heart…and I mean that sincerely; he is the greatest) has, of course, recommended I go on statins. Now I’ve got my inner theories about it, regarding liability and stuff like that, but whatever…he knows I’m not going to take them. It’s simple: my HDL levels (“good” cholesterol) are above and beyond excellent. My total cholesterol to HDL ratio is at the “optimum” level. Ha ha ha…I’m in the absolute lowest risk category for heart disease: I’m not taking statins!

And my doctor knows this. I saw the perplexed look on his face when I pointed out those values to him (I guess that’s not the typical presentation of his high cholesterol patients). Shrugging it off, he still recommended the statins (and has every year for the last four). Sigh

Okay, here’s the point of this piece: A recent study has shown that low levels of LDL (“bad”) cholesterol, in the absence of cholesterol lowering medications, has a strong link to cancer. What?! That’s right, and although we’ve known of this link for a long time (30+ years), this study was the first ever look at the low LDL-cancer link over an extended period of time (~19 years), and only in patients with no history of taking cholesterol-lowering drugs.

The results showed a couple things. One, the link cannot be due to taking statins since all subjects were statin-free throughout the study, and two, low cholesterol cannot be a byproduct of the cancer itself, since low LDL levels were observed well before any preclinical signs of cancer were present. In other words, statins don’t cause cancer, and cancer doesn’t cause low cholesterol. That we know.

What we don’t know is what the connection is. Hmmm…. Well let me give it a try: I believe that the body has an internal wisdom, an Innate Intelligence, that directs its operation. I believe this system is flawless. The body knows what to do at all times, and provided with the right fuel (whole, natural foods), necessary movement, proper bodywork and tension relief, adequate rest, adequate hydration, full, deep abdominal breath and minimal toxins, it will continue to operate flawlessly until it expires (which it will also do flawlessly).

However, too many people do not observe the natural laws of health—they eat poorly, fail to exercise regularly, ignore bodywork until they are in so much pain they can’t stand it, get little rest, drink too many sodas and not enough water, breathe shallowly from their chest, and take multiple drugs and other toxins, and so, yeah…their Innate Intelligence get severely challenged and fatigued; or it can only do the minimum with the resources it is given and becomes overloaded.

Further, we have a medical science that believes its own limited observations are the whole to the puzzle, and it make erroneous conclusions based on this small, piece-wise information, and yet it still believes it knows how to run the body better than Mother Nature does. And then we find out later that there is, in fact, more to the puzzle. You don’t say…?

But taking all the above points into consideration: Somehow when LDL cholesterol is disrupted from one of its many functions—that is, when it’s in too low of concentration—leads to cell overgrowth or cancer. Thus, not that statins, by lowering cholesterol, will cause cancer, but instead, perhaps this medical campaign to reduce cholesterol at all costs is an erroneous one. Perhaps the body produces what it needs (cholesterol can be both endogenous [created within] and exogenous [recieved from without]), and putting everybody on statins, particularly those with stellar numbers in all other health measurements, is just plain foolish.

No medical doctor or pharmaceutical researcher will ever know human physiology better than the human body does. Why the arrogant medical scientific (?) machine believes that it understands what cholesterol levels should be better than the body does is completely perplexing to me. If we were simply talking about a few hundred thousand people on statins because they have super-dangerously high levels that puts them at severe risk of heart disease, then…okay, I would understand. But to have tens of millions of Americans on these useless and dangerous cholesterol lowering drugs is purely idiotic.

So once again I have to believe it all comes down to three things–money (pharmaceuticals), liability (doctors protecting their asses) and job protection (medical professionals making sure they do not become obsolete). That’s the reality behind the cholesterol-statin push in the western world. I’m sure that’s why my doctor recommends statins to me despite my excellent health, I’m sure it’s why statins are called “the best selling drugs of all time,” and I’m sure it will continue until the next blockbuster drug addressing normal physiology comes along to take it’s place. Shouldn’t be too far off—stay tuned.
Read the complete article here.

Effect of wheat on irritable bowel syndrome- FreeTheAnimal

Looks Like Dr. William Davis Was Right in Wheat Belly

February 18th, 2014     

Well what do you know?

I've been following Dr. Davis for a long time and have really applauded a lot of the work he was doing over the years getting really good results for people, primarily by getting them off wheat and getting their vitamin D levels up. The results often showed up in significant reductions in heart scan calcification scores. Davis in a cardiologist. Since I was pretty hardcore Paleo at the time, it made a lot of sense, but I attributed that success mostly to the removal of grains period.

Then comes his book—Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back To Health

The above is a quote from here.

Below is a copy of the abstract from  a double-blinded randomised dietary intervention trial. The original can be found here.

Effect of Triticum turgidum subsp. turanicum wheat on irritable bowel syndrome: a double-blinded randomised dietary intervention trial.


The aim of the present study was to examine the effect of a replacement diet with organic, semi-whole-grain products derived from Triticum turgidum subsp. turanicum (ancient) wheat on irritable bowel syndrome (IBS) symptoms and inflammatory/biochemical parameters. A double-blinded randomised cross-over trial was performed using twenty participants (thirteen females and seven males, aged 18-59 years) classified as having moderate IBS. Participants received products (bread, pasta, biscuits and crackers) made either from ancient or modern wheat for 6 weeks in a random order. Symptoms due to IBS were evaluated using two questionnaires, which were compiled both at baseline and on a weekly basis during the intervention period. Blood analyses were carried out at the beginning and end of each respective intervention period. During the intervention period with ancient wheat products, patients experienced a significant decrease in the severity of IBS symptoms, such as abdominal pain (P< 0·0001), bloating (P= 0·004), satisfaction with stool consistency (P< 0·001) and tiredness (P< 0·0001). No significant difference was observed after the intervention period with modern wheat products. Similarly, patients reported significant amelioration in the severity of gastrointestinal symptoms only after the ancient wheat intervention period, as measured by the intensity of pain (P= 0·001), the frequency of pain (P< 0·0001), bloating (P< 0·0001), abdominal distension (P< 0·001) and the quality of life (P< 0·0001). Interestingly, the inflammatory profile showed a significant reduction in the circulating levels of pro-inflammatory cytokines, including IL-6, IL-17, interferon-γ, monocyte chemotactic protein-1 and vascular endothelial growth factor after the intervention period with ancient wheat products, but not after the control period. In conclusion, significant improvements in both IBS symptoms and the inflammatory profile were reported after the ingestion of ancient wheat products.
PMID: 24521561 [PubMed - as supplied by publisher]
Read the complete articles here and here.

Friday, February 14, 2014

Cholesterol is absolutely vital for our existence - Attia

the essential nature of cholesterol


“Cholesterol is absolutely vital for our existence.       
  Peter Attia, MD
Let’s note right off the bat, there’s no such thing as ‘good and bad’ cholesterol. As shown below, cholesterol is a single natural substance – the grandmother steroid – featuring a four-ring structure of carbon atoms.

All steroid hormones (such as Vitamin D) are made from cholesterol, but, as we shall learn, cholesterol is much more than a hormone.

Cholesterol is made in a complex 27-step process from the 2-carbon substance called acetyl-CoA. The 4-ring structure is the chemical signature of a steroid. On the bottom left, there’s a hydrocarbon tail (HO), where cholesterol esterifies (or attaches) to other molecules and a hydroxyl group- top right.
Classified as a fat-soluble lipid, cholesterol is not a fat, it has no calories, and it’s not a source of energy. Cholesterol is a sterol – a high molecular weight alcohol. Animals, plants, and microorganisms require different sterols.
Cholesterol is the animal sterol – found in every cell in animal bodies. It is true that, as a minor component, cholesterol can be found in plant membranes, but the sterols  sitosterol and stigmasterol predominate in plants.
According to UK lipid biochemist Michael Gurr:   “Only cholesterol will allow animal cells to function as required. Without cholesterol, our bodies would not function properly and we would die.”
Cholesterol waterproofs our trillions of membranes, making it possible for our cells to regulate their internal environments – policing and maintaining “cellular security.” Cholesterol also plays a key role in intra and inter-cellular communications and signaling.
Cholesterol ensures that the cell’s lipid bi-layer (two layers of fat in phospholipid form) is neither too rigid nor too flexible. If that’s not enough, cholesterol is the goddess-like precursor to all adrenal, steroid and sex hormones such as estrogen and testosterone. Without cholesterol, we could not stand, move, think, respond to stress – or reproduce!
Cholesterol is also a major component of bile, an emulsifier required for dietary fats to be broken down and utilized. As a constituent of bile – on its singular route out of the body – cholesterol coats our slowly transiting feces. Only the liver can order cholesterol out of the body – and much of it is recycled.  Sorry Cheerios!
The liver is the main site of cholesterol synthesis, but every cell can make cholesterol (except nervous tissue).  Our bodies contain up to 100 grams of cholesterol – 90 percent in cell membranes and the rest dissolved in adipose and other tissues. The highest concentration (25 percent) is in the nerve cell connections and in the myelin that protects brain and nervous tissue.
In particular, infants need a large amount of cholesterol for proper brain development – and very large amounts of cholesterol are supplied in human milk – not in formula. Cholesterol is needed to properly form the part of the brain that allows the eyes to develop normally. In young and old alike, cholesterol is a primary raw material for many healing processes.

As an example, when an injury occurs on the Teflon-like, slick endothelial layer in an artery – say from high blood sugar – the body’s first responders are cholesterol, blood platelets, specialized white blood cells, and other materials that patch up the injury – similar to a scab forming over a break in the skin.

In the Optimal Diet, eggs are a “free food.”
“Cholesterol is absolutely essential for life,” writes Peter Attia, MD, President and co-Founder of the Nutrition Science Initiative:

“The animal body must have cholesterol to function properly and  to manufacture vital hormones and chemicals.”

And, for people whose bodies may not properly synthesize cholesterol, cholesterol in food may be a conditionally essential nutrient.

As you may note, the medical profession has utterly failed to properly describe the essential nature of cholesterol. Future editions of Diet Heart News will continue to expound on the importance of cholesterol and saturated fat in the American diet.
Read the complete article here.

Wednesday, February 12, 2014

Should Everyone Be Taking Cholesterol-Lowering Drugs? - Eenfeldt

Should Everyone Be Taking Cholesterol-Lowering Drugs?

Andreas Eenfeldt, MD.
A new review of previous research shows that even people with no history of heart disease may slightly lower their risk for heart disease with preventative statin medication*.

Independent.co.uk: ‘Millions’ more to be prescribed statins to beat high cholesterol
There are three reasons to be skeptical of mass medication of the healthy population:


All studies included in the review were sponsored by pharmaceutical companies, that sell the drugs involved. It’s not controversial that this leads to positive effects being exaggerated and negative side effects being silenced.

When big money like this is at stake, pharmaceutical companies will use every trick in the book. One of the more obvious examples was when the gigantic JUPITER trial was prematurely terminated by AstraZeneca, just when the figures for their drug happened to look good.


These are not harmless vitamin pills we’re talking about. Statins come with relatively frequent side effects, such as muscle pain, muscle weakness, fatigue, a slightly reduced cognitive functioning (on average) and an increased risk of diabetes.


The reduction in risk of heart disease in previously heart healthy individuals is hardly great. According to this review the chance of preventing a heart attack, or a similar event, by taking a drug for five years is 1.8 percent! Thus, there is a 98.2 percent likelihood that taking the drug for five years doesn’t protect against such health problems. The risk of troublesome side effects? Significantly greater than the chance of any benefit.

Note that a 1.8 precent chance of benefitting from five years of medication only applies if we blindly trust the pharmaceutical companies’ own studies. Most likely the results are exaggerated, so the chance of a benefit would likely be significantly less than 1.8 percent.


Most people probably wouldn’t accept the risk of side effects and long-term medication if told about the 98 percent (at least) risk of having done so in vain.

Would you?
Read the complete article here.

Statins for the primary prevention of cardiovascular disease - BMJ

Statins for the primary prevention of cardiovascular disease

"The reason why statin treatment may result in cancer is probably not an effect of the drug, but that low cholesterol predisposes to cancer. Thus, nine cohort studies including more than 140 000 individuals found that cancer was inversely associated with cholesterol measured 10–30 years earlier, and the association persisted after exclusion of cancer cases appearing during the first 4 year."

Read the complete article here.