LDL Cholesterol Particle Size and Number What Gives ?

Posted on February 27, 2018

LDL Particle Size and Particle Number, What Gives?

Ron is a 72 year old retired engineer, and has a total cholesterol of 174 which hasn’t changed over the seven years we have been following him. This is quite low. Yet, Ron is concerned because his LDL particle number and LDL particle size are “outside of the lab range”.  He is very worried about this and is concerned about his risk for future heart attack.  I explained to Ron the lab range doesn’t apply to him.  Ron’s Calcium Score is low, and his total cholesterol is 174, and he does not have metabolic syndrome or diabetes, so he doesn’t need to worry about the LDL particle size or particle number.

What does the mainstream cardiology say about the value of LDL particle size and number?

The Quebec Study – Small Dense LDL Associated with Increased Mortality from Coronary Artery Disease

You might say “wait just a minute here”, the Quebec study followed 2072 males over 13 years and found that small dense LDL was associated with increased mortality from cardiovascular disease above chart).(6)  The above chart is very convincing, and the three lines for small dense LDL are nicely separated. (6) However, as pretty as the above chart looks, Correlation is not necessarily causation.  If increased small dense LDL particle number causes coronary artery disease, then an intervention that reduces small dense LDL particles should be preventive.  However we know that it is not. Above image courtesy of Medscape.

Houston, We Have a Problem,  New Drug Reduces Small LDL,

However, No Benefit in Preventing Heart Disease

Treatment with the new cholesterol lowering drug, Evacetrapib, resulted in significant decreases in “total LDL particle number (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations”.(5) Yet, according to Dr Lincoff in NEJM 2017,

“treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.”(4)

As a matter of fact, Eli Lilly abandoned drug development after this failed study.(4)  So we see that reducing total LDL particle number, or increasing LDL particle size had no benefit for preventing death from heart disease.  The benefit was same as a placebo.

Dr Allaire  agrees that LDL particle size is not very useful.  Dr Allaire writes in 2017 Current Opinion in Lipidology:(1)

“LDL particle size….has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.”(1)

In other words, according to Dr Allaire,  the LDL particle size is not a good predictor of cardiovascular risk.(1)

Predicting Risk: LDL Subfraction Vs. Calcium Score

The next question you might ask: “If LDL cholesterol is not helpful, then what other test is useful for predicting risk of cardiovascular disease?” 

The answer is the Calcium Score which is an inexpensive test which uses a CAT scan to measure the amount of calcium in the coronary arteries.  Studies show that the higher the number the greater the risk, the lower the number the smaller the risk.  None of the cholesterol subfractions can provide this type of information, and in my opinion should be relegated to the medial museum, as a relic from the past.

Conclusion: When it comes down to a contest between LDL Cholesterol Subfractions and Calcium Score, there is no contest.  The Calcium Score wins every time.

Jeffrey Dach MD
7450 Griffin Road Suite 190
Davie Florida 33314
954 792-4663

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Links and References

Header Image LDL particle courtesy of Drs Wolfson

1) Curr Opin Lipidol. 2017 Jun;28(3):261-266. LDL particle number and size and cardiovascular risk: anything new under the sun? Allaire J1, Vors C, Couture P, Lamarche B.

LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.

We provide here an up-to-date perspective on the potential use of LDL particle number and size as complementary risk factors to predict and manage cardiovascular disease (CVD) risk in the clinical realm.
RECENT FINDINGS:  Studies show that a significant proportion of the population has discordant LDL particle number and cholesterol indices [non-HDL cholesterol (HDL-C)]. Data also show that risk prediction may be improved when using information on LDL particle number in patients with discordant particle number and cholesterol data. Yet, most of the current CVD guidelines conclude that LDL particle number is not superior to cholesterol indices, including non-HDL-C concentrations, in predicting CVD risk. LDL particle size, on the other hand, has not been independently associated with CVD risk after adjustment for other risk factors such as LDL cholesterol, triglycerides, and HDL-C and that routine use of information pertaining to particle size to determine and manage patients’ risk is not yet justified.
SUMMARY:  Additional studies are required to settle the debate on which of cholesterol indices and LDL particle number is the best predictor of CVD risk, and if such measures should be integrated in clinical practice.

Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes

2) Clin Chem. 2017 Apr;63(4):870-879. doi: 10.1373/clinchem.2016.264515. Epub 2017 Feb 7.  Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women.
Lawler PR1,2,3,4, Akinkuolie AO1,3, Ridker PM2,3, Sniderman AD5, Buring JE3,4, Glynn RJ3,4, Chasman DI3, Mora S6,2,3.
It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.
METHODS:Among 27533 initially healthy women in the Women’s Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.
RESULTS:Although all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.
CONCLUSIONS:Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment.

3)   Curr Opin Endocrinol Diabetes Obes. 2018 Jan 10. Discordance between lipoprotein particle number and cholesterol content: an update.
Cantey EP1, Wilkins JT2.
The cholesterol content within atherogenic apolipoprotein-B (apoB) containing lipid particles is the center of consensus guidelines and clinicians’ focus whenever evaluating a patient’s risk for atherosclerotic cardiovascular disease. The pathobiology of atherosclerosis requires the retention of lipoprotein particles within the vascular intima over time followed by maladaptive inflammation resulting in plaque formation and rupture in some. The cholesterol content is widely variable within each particle creating either cholesterol-deplete or cholesterol-enriched particles. This variance in particle cholesterol content varies within and between individuals. Discordance analysis exploits this difference in cholesterol content of particles to demonstrate the differential significance of LDL-cholesterol (LDL-C) and non-HDL-C from measures of lipoprotein particle number in terms of assessing atherosclerotic cardiovascular disease risks.
RECENT FINDINGS:Three studies have added to the growing body of literature of discordance analysis. Despite wide variability of discordance cutoffs, baseline risk of atherosclerotic disease, and populations sampled, the conclusion remains the same: risk of atherosclerotic disease follows apoB lipid particle concentration rather than cholesterol content of lipid particles.
SUMMARY:In addition to traditional lipid fractions, assessments of atherogenic particle number should be strongly considered whenever assessing CVD risk in nontreated and treated individuals. There is a need for clinical trials that focus not only on the reduction in LDL-C but apoB, as well.

4)  Lincoff, A. Michael, et al. “Evacetrapib and cardiovascular outcomes in high-risk vascular disease.” New England Journal of Medicine 376.20 (2017): 1933-1942.

Although treatment with evacetrapib has resulted in reductions of 60 to 70% in the levels of small dense LDL particles,29 effects on the total number of LDL particles and on apolipoprotein B levels (reductions of 22% and 20%, respectively) are considerably less pronounced.

CONCLUSIONS:Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease.

5)  Nicholls SJ, Ruotolo G, Brewer HB, et al. Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients. J Clin Lipidol 2016;10:519-527.e4

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.
OBJECTIVES:To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.
METHODS:VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).
RESULTS:Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.

CONCLUSIONS:Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

6) St-Pierre, Annie C., et al. “Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Quebec Cardiovascular Study.” Arteriosclerosis, thrombosis, and vascular biology 25.3 (2005): 553-559.Low density lipoprotein Risk of ischemic heart disease Quebec St Pierre Annie Arterio thrombo vasc bio 2005

The objective of the present study was to investigate the association between large and small low-density lipoprotein (LDL) and long-term ischemic heart disease (IHD) risk in men of the Quebec Cardiovascular Study.
METHODS AND RESULTS:Cholesterol levels in the large and small LDL subfractions (termed LDL-C> or =260A and LDL-C<255a 13="" 2072="" 262="" a="" all="" and="" angina="" at="" baseline="" cardiovascular="" cohort="" coronary="" death="" during="" electrophoresis="" estimated="" events="" examination="" first="" followed-up="" for="" free="" from="" gel="" gradient="" ihd="" in="" infarction="" men="" myocardial="" nbsp="" nonfatal="" of="" pectoris="" period="" plasma="" polyacrylamide="" population-based="" quebec="" recorded.="" respectively="" strong="" study.="" style="border: 0px; font-family: inherit; font-style: inherit; margin: 0px; outline: 0px; padding: 0px; vertical-align: baseline;" the="" unstable="" were="" which="" whole="" years="">Our study confirmed the strong and independent association between LDL-C<255a a="" and="" as="" dense="" ihd="" in="" ldl="" levels="" men="" of="" phenotype="" proxy="" risk="" small="" strong="" the="">, particularly over the first 7 years of follow-up. However, elevated LDL-C> or =260A levels (third versus first tertile) were not associated with an increased risk of IHD over the 13-year follow-up (RR=0.76; P=0.07).

CONCLUSIONS:These results indicated that estimated cholesterol levels in the large LDL subfraction were not associated with an increased risk of IHD in men and that the cardiovascular risk attributable to variations in the LDL size phenotype was largely related to markers of a preferential accumulation of small dense LDL particles.

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Study says there's no link between cholesterol and heart disease

Mon, 13 Jun 2016 12:33:00 EST

"Controversial report claims there's no link between 'bad cholesterol' and heart disease," the Daily Mail reports, while The Times states: "Bad cholesterol 'helps you live longer',".
The headlines are based on a new review which aimed to gather evidence from previous observational studies on whether LDL cholesterol (so-called "bad cholesterol") was linked with mortality in older adults aged over 60. The conventional view is that having high LDL cholesterol levels increases your risk of dying of cardiovascular diseases, such as heart disease.
Researchers chose 30 studies in total to analyse. 28 studies looked at the link with death from any cause. Twelve found no link between LDL and mortality, but 16 actually found that lower LDL was linked with higher mortality risk – the opposite to what was expected.
Only nine studies looked at cardiovascular mortality link specifically – seven found no link and two found the opposite link to what was expected.
However, there are many important limitations to this review. This includes the possibility that the search methods may have missed relevant studies, not looking at levels of other blood fats (e.g. total and HDL cholesterol), and the possibility that other health and lifestyle factors are influencing the link.
Most importantly, as the researchers acknowledge, these findings do not take account of statin use, which lowers cholesterol. People found to have high LDL cholesterol at the study's start may have subsequently been started on statins, which could have prevented deaths. 

Where did the story come from?

The study was carried out by researchers from the University of South Florida, the Japan Institute of Pharmacovigilance and various other international institutions in Japan, Sweden, UK, Ireland, US and Italy.
Funding was provided by the Western Vascular Institute. The study was published in the peer-reviewed BMJ Open and, as the journal name suggests, the article is open-access, so can be read for free.
Four of the study authors have previously written book(s) criticising "the cholesterol hypothesis". It should also be noted that nine of the authors are members of THINCS – The International Network of Cholesterol Skeptics. This is described as a group of scientists who "oppose…that animal fat and high cholesterol play a role [in heart disease]".
If you were playing Devil's Advocate, you could argue that this represents a preconceived view of the authors regarding the role of cholesterol, rather than the open, unbiased mind you would hope for in the spirit of scientific enquiry. That said, many important scientific breakthroughs happened due to the efforts of individuals who challenged a prevailing orthodoxy of thinking.
In general, the UK media provided fairly balanced reporting, presenting both sides of the argument – supporting the findings, but with critical views from other experts.

Read the complete article here.

Statins & Increase Diabetes Risk

Higher-Dose Statins Linked to Moderate Increase in Diabetes Risk
      By Kelly Young
          Edited by Susan Sadoughi, MD , and Jaye Elizabeth Hefner, MD

 Higher doses of statins are associated with greater risk for incident diabetes than lower doses, according to a BMJ study.

Using healthcare databases from Canada, the UK, and the US, researchers identified 137,000 patients who were prescribed statins after hospitalization for a major cardiovascular event. At 2 years, patients prescribed a higher-dose statin (rosuvastatin, 10 mg and up; atorvastatin, 20 mg and up; simvastatin, 40 mg and up) had a 15% higher rate of new diabetes diagnoses than lower-dose statin users. Incidence rates were highest in the first 4 months.

The authors conclude: "Clinicians should consider our study results when choosing between lower potency and higher potency statins in secondary prevention patients, perhaps bearing in mind that head-to-head randomized trials of higher potency versus lower potency statins have not shown a reduction in all-cause mortality or serious adverse events in secondary prevention patients with stable disease."


- See more at: http://www.jwatch.org/fw108892/2014/06/02/higher-dose-statins-linked-moderate-increase-diabetes#sthash.pAKrtJTt.dpuf


and

http://www.bmj.com/content/348/bmj.g3244

The burden of proof in science always lies with those who propose a theory - Curtis

Evidence Against Cholesterol Causing Atherosclerosis

by Ernest N. Curtis M.D. (Internal Medicine and Cardiology)

The burden of proof in science always lies with those who propose a theory. In this case the claim is that cholesterol is one of the chief causative agents for atherosclerosis.

Since the burden of proof is on those making the claim, we need only rebut their arguments. We don’t have to prove anything or advance an alternative theory.
The claim that cholesterol causes atherosclerosis can be rebutted on many levels. I don’t give much credence to epidemiologic evidence, but even that doesn’t pass scientific muster when it comes to cholesterol.

The correlations between cholesterol and heart attacks (the chief complication of atherosclerosis) cited in the medical literature are not even high enough to suggest an association between the two, much less a significant correlation. Even a high degree of correlation would not prove causation but the figures are nowhere near that level.

Another fly in the epidemiological soup is the fact that the incidence of heart attacks is fairly evenly distributed throughout the entire range of blood cholesterol levels. In fact more than half occur in those with cholesterol levels in the low normal range.

Many people with very high cholesterol levels live long healthy lives with no signs of complications from atherosclerosis. Conversely, many people with relatively low levels of cholesterol suffer from severe atherosclerosis and its complications. Add to that the fact that women have, on average, significantly higher cholesterol levels than men yet suffer far fewer heart attacks and I think we can conclude that the so-called evidence from epidemiology is nonexistent.

Many proponents of the cholesterol theory cite some of the statin drug trials as proof of the significance of cholesterol as an important factor by showing that reduction of its blood level provides a small degree of protection against heart attacks.

But these studies all showed a lack of normal response/exposure. There was a total disconnection between the small degree of outcome improvement and both the initial cholesterol level and the degree of cholesterol lowering attained. That is, the same small amount of benefit (which was so small as to be of no practical significance) was seen in subjects whose cholesterol declined only slightly and those in whom it declined a lot.

The benefit was also the same for those with low initial cholesterol levels and those with high initial levels. In scientific studies, this disconnection means that the factor being studied is not a cause of the outcome in question and that some other factor is at work. In this case it is possible that the anti-thrombotic action of the drug is the cause since the degree of protection against heart attack was almost identical to that seen in similar studies using aspirin or other anti-platelet drugs.

On the pathophysiologic level there are many reasons to doubt that cholesterol plays a causative role. Researchers have shown that some of the initial signs of atherosclerosis can be seen in the arteries of infants. These changes are seen in the same areas of the arteries where atherosclerotic lesions tend to occur later in life and consist of subintimal thickening with no sign of cholesterol infiltration or inflammatory reaction.

While the significance of these early changes can be debated, it is hard to deny the significance of the fact that atherosclerosis is a very focal disease process. It is found in the large and medium sized arteries and almost never in the smaller arterioles, capillaries, and veins.

Moreover, within the large and medium sized arteries there is a marked predilection for lesions to occur at branching points and along the lesser curvatures of arteries. These are areas of maximum shear stress on the arterial wall. Often one side of an arterial segment may be severely affected while the opposite wall shows no evidence of atherosclerosis whatsoever.

Atherosclerosis is often found in the arteries of the lower extremities but rarely in the arteries of the upper extremities. Atherosclerosis is never found in the veins of the body. However, veins that are subjected to arterial pressures when used as bypass grafts or arterovenous fistulas constructed for dialysis shunts often show rapid development of atherosclerosis.

These and other facts would seem to negate the possibility that atherosclerosis was caused by a chemical circulating in the blood since that should bring about a more generalized and/or random distribution of atherosclerotic lesions.

The blood flow through the larger arteries where atherosclerosis is typically found is much more rapid and laminar than it is in the smaller blood vessels. One would think that a slower flow would allow a noxious chemical to do more damage rather than less if it were a causative agent.
Einstein said that an elegant theory could be completely refuted by one inconvenient contradictory fact. In the case of cholesterol and atherosclerosis, there is a cornucopia of such facts.
Dr. Ernest N. Curtis, M.D
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Peripheral Neuropathy from Statin Use - Graveline

Peripheral Neuropathy from Statin Use
By Duane Graveline, MD, MPH







Neuropathy, short for peripheral neuropathy, simply means a malfunction of the peripheral nervous system that occurs without any inflammation of the nerves. There are many longstanding causes of neuropathy including diabetes, kidney problems and alcoholism.

Being placed on statin drugs is another more recent cause of peripheral neuropathy. Thousands of neuropathy cases have been reported to me over the past decade and in 2012, FDA's Medwatch finally warned about peripheral neuropathy as a major adverse reaction to all types of statins.

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Should Everyone Be Taking Cholesterol-Lowering Drugs? - Eenfeldt

Should Everyone Be Taking Cholesterol-Lowering Drugs?

Andreas Eenfeldt, MD.

 

Should everyone over 50 be treated with cholesterol-lowering drugs, regardless of whether they suffer from heart disease?

 

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:

1

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.

2

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.

3

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.

1+2+3+=

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?
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Not Everyone is Enthusiastic - Dach

New Statin Guidelines, Not Everyone is Enthusiastic

Posted on November 14, 2013 by Jeffrey Dach

New Statin Guidelines, Not Everyone is Enthusiastic

by Jeffrey Dach MD On Tuesday, The American Heart Association and the American College of Cardiology changed the guidelines giving even more people statin drugs.  The new Guidelines increases the number of healthy people to be placed on statins by 70%..(1)
OpEd in the New York TImes

Two highly respected MDs, John Abramson and Rita Redberg have been critical of statin drugs for years. Yesterday they published an Op Ed in the New York Times skeptical of the new Guidelines .  For one thing,  the doctors on the committee had conflicts of interest.  For a second thing, the New Guidelines are not based on objective data.



Conflict of Interest  in the Committee
Once again we have a committee of doctors creating guidelines to benefit their benefactors, the drug industry:  Here is a quote from Abramson and Redberg in the New York Times: 

“The group that wrote the recommendations was not sufficiently free of conflicts of interest; several of the experts on the panel have recent or current financial ties to drug makers. In addition, both the American Heart Association and the American College of Cardiology, while nonprofit entities, are heavily supported by drug companies.”(1)

 

Another Problem – Guidelines Are Not Supported by Adequate Data Drs Abramson and Redberg go on to say the new guidelines are not supported by objective data. This is a mind boggling statement,  and that patients should be skeptical of the new guidelines.
Here is the quote:

“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.”(1)

Jeffrey Dach MD 7450 Griffin Road, Suite 190 Davie, Fl 33314 954-792-4663
www.jeffreydach.com www.drdach.com
www.naturalmedicine101.com
www.bioidenticalhormones101.com
www.truemedmd.com

Articles with Related Content:
Australian Video Series on Statins and Cholesterol Mayanne DeMAsi
Getiing OFf Statin Drug Stories
Cholesterol Lowering Statin Drugs for Women Just Say No
How to Reverse Heart Disease with the Coronary Calcium Score (part one)
Reversing Heart Disease Part Three
Cholesterol Lowering Drugs for the Elderly, Bad Idea  
Healthy Men Should Not Take Statin Drugs

Jeffrey Dach MD

Links and References
(1) http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html?_r=0 Don’t Give More Patients Statins By JOHN D. ABRAMSON and RITA F. REDBERG Published: November 13, 2013
(2) http://content.onlinejacc.org/article.aspx?articleid=1770220 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines ONLINE FIRST David C. Goff, MD, PhD, FACP, FAHA; Donald M. Lloyd-Jones, MD, ScM, FACC, FAHA; Glen Bennett, MPH; Christopher J. O’Donnell, MD, MPH; Sean Coady, MS; Jennifer Robinson, MD, MPH, FAHA; Ralph B. D’Agostino, PhD, FAHA; J. Sanford Schwartz, MD; Raymond Gibbons, MD, FACC, FAHA; Susan T. Shero, MS, RN; Philip Greenland, MD, FACC, FAHA; Sidney C. Smith, MD, FACC, FAHA; Daniel T. Lackland, DrPH, FAHA; Paul Sorlie, PhD; Daniel Levy, MD; Neil J. Stone, MD, FACC, FAHA; Peter W.F. Wilson, MD, FAHA [+] Author Information J Am Coll Cardiol. 2013;():.
Jeffrey Dach MD 7450 Griffin Road, Suite 190 Davie, Fl 33314 954-792-4663 www.jeffreydach.com www.drdach.com www.naturalmedicine101.com www.bioidenticalhormones101.com www.truemedmd.com Click Here for: Dr Dach’s Online Store for Pure Encapsulations Supplements
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The reader is advised to discuss the comments on these pages with his/her personal physicians and to only act upon the advice of his/her personal physician. Also note that concerning an answer which appears as an electronically posted question, I am NOT creating a physician — patient relationship. Although identities will remain confidential as much as possible, as I can not control the media, I can not take responsibility for any breaches of confidentiality that may occur.
Link to this article:http://wp.me/p3gFbV-Ty Copyright (c) 2012-13 Jeffrey Dach MD All Rights Reserved. This article may be reproduced on the internet without permission, provided there is a link to this page and proper credit is given. FAIR USE NOTICE: This site contains copyrighted material the use of which has not always been specifically authorized by the copyright owner. We are making such material available in our efforts to advance understanding of issues of significance. We believe this constitutes a ‘fair use’ of any such copyrighted material as provided for in section 107 of the US Copyright Law. In accordance with Title 17 U.S.C. Section 107, the material on this site is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.
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Getting Off Statin Drug Stories - Dach

Getting Off Statin Drug Stories by Jeffrey Dach MD

Left Image: courtesy of Uffe Ravnskov, MD Fat and Cholesterol are Good for You.Book Cover

Just Ask Judith Walsh MD in JAMA

 

 

Getting Off Statin Drug Stories
by Jeffrey Dach MD
Case Number One, Martha
Martha is 55 years old, healthy and no history of heart disease.  Nonetheless, Martha has been taking a statin drug for “high cholesterol” under the care of “the top cardiologist” in South Florida for the past five years.  Martha has also been under my care taking a bioidentical hormone program for menopausal symptoms, and doing very well.  Every six months, we run a lab panel which always shows  low cholesterol of 170, courtesy of her statin anti-cholesterol drug.


 And, every time Martha comes into the office to review her lab results, I print out a 2004 JAMA article by Judith Walsh, MD who reviewed thirteen statin drug clinical trials from 1966 to 2003.(1)  Dr. Judth Walsh concludes that cholesterol lowering drugs provide no health benefit for women.  I give her this article and, at the same time, explain to her that no woman should be on a statin drug.  Lowering cholesterol with a statin drug has no health benefit for women, that’s a fact, and public information readily available.

Playing Games With Statins

Every six months I recommend to Martha stopping the statin drug, and every six month, her cardiologist puts her back on the statin drug.  This has been going on for three years now.

Finally Success At Convincing Martha to Stop the Statin Drug

Finally this last time, Martha seems more receptive to idea that the statin drug is harming her and not helping her.  She is sitting in my office recounting multiple health problems for which she sees numerous doctors: back pain, asthma, sinus infections, skin problems, and allergies.  I suggested to Martha the possibility that many of her health problems are  caused by the low cholesterol from the statin drug.  Martha finally sees the light, goes home and tosses the bottle of pills into the garbage can.

Feeling Better

About a week later, Martha called me and reported, “I feel so much better off that statin drug, thank you so much! “.  Apparently, the statin drug was causing adverse health effects, and Martha was now feeling much better.

Believing in the Propaganda
This case illustrates the difficulty in convincing patients to stop their statin drug.  It is difficult to counter the drug company propaganda, and convince these patients they are harming their health with the statin drugs. Many continue to believe in the myth that cholesterol causes heart disease, and they go on to become statin drug medical victims.  I see them every day.  When we have a success like Martha who finally gets off her statin drug, this is a cause for celebration.


Left Image: Ignore the Awkward.: How the Cholesterol Myths Are Kept Aliveby Uffe Ravnskov MD

Case Number Two – Roger
Roger is a seventy one year old retired executive, and an avid tennis player.  He has no history of coronary artery disease and has always been healthy. Two years ago, his cardiologist said his cholesterol of 210 was “too high”, and prescribed a statin anti-cholesterol drug.  A year later, Roger’s tennis game deteriorated, he found his timing and balance was off, and he lost every game to players who could never beat him before.

Adverse Effects of the Statin Drug

I suggested to Roger that the decline in his tennis game was most likely an adverse effect of the statin drug on his muscle and nerve function.  He was losing his balance and coordination. 

I recommended stopping the statin anti-cholesterol drug.  At first, Roger resisted and said his wife wanted him to take the statin drug because she thought it was ”good medical care”, and she (mistakenly) believed that a lower cholesterol was somehow preventive of heart disease.

How to Counter the Propaganda: A Book For You
In order to counter the drug company cholesterol propaganda, I gave Roger a copy of the book, Fat and Cholesterol are Good for You, by Uffe Ravnskov MD PhD. This book reviews the medical studies which supposedly show that cholesterol is the cause of heart disease, and reveals that they do no such thing. This is a medical myth.  Neither cholesterol consumption nor cholesterol blood levels cause heart disease.  Similarly, many medical studies demonstrate that anti-cholesterol drugs work very well to reduce blood cholesterol levels, however, this treatment does not prolong life and makes most people sick with adverse side effects.

Roger was amazed and his eyes practically popped out out of his head when he “saw the light”.  The statin drugs were turning him another medical victim.  Once Roger learned the truth about the ”cholesterol causes heart disease” myth,  he took his statin drug bottle and threw it into the garbage can.  Two weeks later, off the statin drug,  Roger was back to his old self, prancing about the tennis court like a gazelle, and winning every game with ease.


Left Image : The Cholesterol Myths: Exposing the Fallacy that Saturated Fat and Cholesterol Cause Heart Disease by Uffe Ravnskov MD
 Are You Still a Believer in Anti-Cholesterol Drugs?

If you are still a believer in Statin Drugs, take a look at this primary prevention study published July 2010 in the Archives of Internal Medicine by Dr. Ray.(3)  He reviewed 11 statin drug clinical trials with 65,229 participants followed for approximately 244,000 person-years.  The astounding results showed the statin drug group all-cause mortality was THE SAME as the placebo group ! (3)  There was no benefit from the statin drugs !!!  This article was published in the mainstream medical literature !!


If cholesterol was truly the cause of heart attacks, then one would expect heart attack victims to reveal the high cholesterol causing their heart attack.   They found the opposite.  Heart attack victims have low cholesterol.  A study  analyzed 137,000 heart attack patients from 541 US hospitals and found mean cholesterol was only 174.  This is low, not high. (4)

In addition, if high cholesterol was truely the cause of heart attacks, one would expect heart attack victims with the highest cholesterol to have the worst prognosis, and lowest cholesterol to have the best prognosis.  They don’t.  A study from Henry Ford Hospital in Detroit showed that three years after a heart attack, the patients with lowest cholesterol had the highest mortality (14% vs. 7 %) (5).

Conclusion:

The cholesterol theory of heart disease is a myth maintained by drug company propaganda to support massive profits from cholesterol lowering drugs.  These drugs provide no health benefit in terms of prolonging life, and at the same time produce harm from adverse side effects.  Avoid becoming a victim of the statin drug propaganda machine.

Articles with related interest:
Heart Disease Vitamin C and Linus Pauling
Getting Off Statin Drug Stories
How to Reverse Heart Disease with the Coronary Calcium Score
Cholesterol Lowering Drugs for the Elderly, Bad Idea
Cholesterol Lowering Statin Drugs for Women Just Say No
…………………………………………………………………………………………………….

Heart Disease Part Two – Atherosclerosis: How Does it Happen?Preventing and Reversing Heart Disease Part Three by Jeffrey Dach MDHeart Disease, Ascorbate, Lysine and Linus Pauling by Jeffrey Dach MDA Choirboy for Cholesterol Turns Disbeliever by Jeffrey Dach MD
Links and References
(1) http://jama.ama-assn.org/content/291/18/2243
JAMA. 2004;291(18):2243-2252. Drug Treatment of Hyperlipidemia in Women
Judith M. E. Walsh, MD, MPH; Michael Pignone, MD, MPH
(2) Fat and Cholesterol are Good for You, Uffe Ravnskov GB Publishing (January 26, 2009)
(3) http://archinte.ama-assn.org/cgi/content/abstract/170/12/1024
Statins and All-Cause Mortality in High-Risk Primary Prevention A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants. Kausik K. Ray, MD, MPhil, FACC, FESC; Sreenivasa Rao Kondapally Seshasai, MD, MPhil; Sebhat Erqou, MD, MPhil, PhD; Peter Sever, PhD, FRCP, FESC; J. Wouter Jukema, MD, PhD; Ian Ford, PhD; Naveed Sattar, FRCPath. Arch Intern Med. 2010;170(12):1024-1031.
Background  Statins have been shown to reduce the risk of all-cause mortality among individuals with clinical history of coronary heart disease. However, it remains uncertain whether statins have similar mortality benefit in a high-risk primary prevention setting. Notably, all systematic reviews to date included trials that in part incorporated participants with prior cardiovascular disease (CVD) at baseline. Our objective was to reliably determine if statin therapy reduces all-cause mortality among intermediate to high-risk individuals without a history of CVD.
Data Sources  Trials were identified through computerized literature searches of MEDLINE and Cochrane databases (January 1970-May 2009) using terms related to statins, clinical trials, and cardiovascular end points and through bibliographies of retrieved studies.
Study Selection  Prospective, randomized controlled trials of statin therapy performed in individuals free from CVD at baseline and that reported details, or could supply data, on all-cause mortality.
Data Extraction  Relevant data including the number of patients randomized, mean duration of follow-up, and the number of incident deaths were obtained from the principal publication or by correspondence with the investigators.
Data Synthesis  Data were combined from 11 studies and effect estimates were pooled using a random-effects model meta-analysis, with heterogeneity assessed with the I2 statistic. Data were available on 65 229 participants followed for approximately 244 000 person-years, during which 2793 deaths occurred.
The use of statins in this high-risk primary prevention setting was not associated with a statistically significant reduction (risk ratio, 0.91; 95% confidence interval, 0.83-1.01) in the risk of all-cause mortality. There was no statistical evidence of heterogeneity among studies (I2 = 23%; 95% confidence interval, 0%-61% [P = .23]).
Conclusion  This literature-based meta-analysis did not find evidence for the benefit of statin therapy on all-cause mortality in a high-risk primary prevention set-up.
(4) http://www.ahjonline.com/article/S0002-8703(08)00717-5/abstract
AHJ Volume 157, Issue 1, Pages 111-117.e2 (January 2009)
Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. Amit Sachdeva, MDa, Christopher P. Cannon, MDb, Prakash C. Deedwania, MDc, Kenneth A. LaBresh, MDd, Sidney C. Smith Jr, MDe, David Dai, MSf, Adrian Hernandez, MDf, Gregg C. Fonarow, MDa, on behalf of the GWTG Steering Committee and Hospitals
(5) http://www.ncbi.nlm.nih.gov/pubmed/19437396
Cardiol J. 2009;16(3):227-33. Low admission LDL-cholesterol is associated with increased 3-year all-cause mortality in patients with non ST segment elevation myocardial infarction. Al-Mallah MH, Hatahet H, Cavalcante JL, Khanal S.
Abstract
BACKGROUND: The relationship between admission low-density lipoprotein (LDL) levels and long-term outcomes has not been established in patients with acute coronary syndrome. We tested the hypothesis that patients who develop non-ST segment elevation myocardial infarction (NSTEMI) despite low LDL have a worse cardiovascular outcome in the long term.
METHODS: Patients admitted with NSTEMI between 1 January 1997 and 31 December 2000 and with fasting lipid profiles measured within 24 hours of admission were selected for analysis. Baseline characteristics and 3-year all-cause mortality were compared between the patients with LDL above and below the median. Multivariate analysis was used to determine the predictors of all-cause mortality, and adjusted survival was analyzed using the Cox proportional hazard model.
RESULTS: Of the total of 517 patients, 264 had LDL dL and 253 had LDL > 105 mg/dL. There was no difference in age, gender, severity of coronary artery disease, and left ventricular ejection fraction between the 2 groups. Thirty-six percent of patients with LDL 105 mg/dL were on lipid-lowering therapy on admission.
After 3 years, patients with admission LDL dL had higher all-cause mortality rate compared to patients with LDL > 105 mg/dL (14.8% vs. 7.1%, p = 0.005). The higher all-cause mortality persisted (OR 1.8, 95% CI 1.0-3.5, p = 0.05) even after adjustment for confounding variables.

CONCLUSIONS: In our cohort, lower LDL-cholesterol at admission was associated with decreased 3-year survival in patients with NSTEMI.

Jeffrey Dach MD
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BMJ exposes ways we have been misled over the ‘benefits’ of statins - Briffa

BMJ articles exposes the ways we have been misled over the ‘benefits’ of statins

By Dr John Briffa on 1 November 2013   

 

The ‘Cochrane Collaboration’ is an international collective of researchers whose self-proclaimed role is to provide accurate and robust assessments of health interventions. The group specialises in ‘meta-analyses’: the grouping together of several similar studies on interventions including drug therapies.
In 2011, Cochrane researchers assessed the evidence relating to statin use in individuals at low risk of cardiovascular disease (defined as a less than 20 per cent risk over 10 years), and concluded that there was limited evidence of overall benefit [1]. I appeared on Channel 4 news to discuss this publication and the issues surrounding it, and you can see the discussion here.

Earlier this year, the same Cochrane group updated their data and concluded that overall risk of death and cardiovascular events (e.g. heart attack or stroke) were reduced by statins in low risk individuals, without increasing the risk of adverse events (including muscle, liver and kidney damage) [2]. It seems the Cochrane reviewers had had quite some change of heart. A paper published in the BMJ on 22 October questions the evidence on which this U-turn appears to have been made [3].

The authors of the BMJ piece note that although the 2013 meta-analysis included four additional trials, these trials did not substantially change the findings. The change in advice was actually based on another meta-analysis, published in 2012, conducted by a group known as the Cholesterol Treatment Trialists’ (CTT) collaboration [4].

Among other things, the CTT authors concluded that, in low risk individuals, for each 1.0 mmol/l (39 mg/dl) reduction in LDL-cholesterol, statins reduce overall risk of death and heart attack by about 9 per cent and 20 per cent respectively. The conclusion was that statins have significant benefits in low risk individuals that greatly exceeded known risks of treatment.

However, the CTT authors took the odd step of calculating the benefits of statins according to a theoretical reduction in LDL-cholesterol levels. A much more realistic appraisal would be simply to calculate if, compared to placebo, statins actually reduce the risk of health outcomes.
The BMJ authors use the data from the CTT meta-analysis and found that risk of death was not reduced by statins at all. So, the CTT authors had used had extrapolated the data in a way that showed a benefit that actually does not exist in reality.

And what of the claim that statins reduce the risk of cardiovascular events such as heart attack or stroke? The data shows that about 150 low-risk individuals would need to be treated for five years to prevent one such event (i.e. only about one in 750 individuals will benefit per year).

They also draw our attention to the impact of statin treatment on ‘serious adverse events’. This outcome can be improved by statins as a result of, say, a reduced number of heart attacks, but worsened through side effects such as muscle or liver damage. The BMJ authors note that the CTT review did not consider serious adverse events (a major omission). Without knowing more about this, though, we simply cannot make a judgement regarding the overall effect of statins, and whether the net effect is beneficial or not. Interestingly, of three major trials that were included in the CTT review that assessed overall serious adverse effects, none found overall benefits from statin treatment.
So, while the CTT authors seem to have over-hyped the benefits of statins, they seem at the same time to have been quite keen to steer clear of talk of their very real risks and the absence of evidence foroverall benefit.

The BMJ authors draw our attention to the fact that every single trial included in the CTT was industry funded. Such trials are well known to report results more favourably and perhaps downplay risks than independently funded research. The BMJ authors cite specific ways in which the adverse effects of drugs seen in clinical trials can be ‘minimised’. These include:

• The exclusion of individuals from trials with known health issues likely to be exacerbated by statins or signal susceptibility to statin side effects (such as liver, kidney and muscle disease).
• The use of a ‘run-in’ period before the study starts which detects and then excludes individuals who do not tolerate statins.
• The possibility that individuals ‘drop out’ from the study because of side effects, meaning that the incidence of some side effects can be ‘lost’ from the data.
• Failure of the study investigators to assess and monitor adverse events such as muscle damage and changes in brain function.
• Failure to properly ascertain or report adverse events.

It is noted that the Cochrane authors admit the reporting of adverse effects in studies is generally poor, but also state that it’s unlikely statins have major life-threatening hazards. The authors of the BMJ piece are not convinced, though, writing: “[The] large discrepancies between the frequency of adverse events reported in commercially funded randomised controlled trials included in the CTT meta-analysesand non-commercially funded studies show that determination of harms cannot be left to industry alone.”

The BMJ piece is accompanied by an editorial from the journal’s editor, Fiona Godlee [5]. Her comment on this issue starts:

None of this does much to bolster confidence in the published literature.

Godlee goes on to write:

Nor am I reassured by discussions at two recent meetings co-hosted by the European Federation of Pharmaceutical Industry Associations (EFPIA). Drug company AbbVie is suing the European Medicines Agency to stop summary reports of its clinical trials becoming publicly available. AbbVie’s lawyer made clear that the company considers even the data on adverse events to be commercially confidential. Despite industry’s claims to be in favour of greater transparency, EFPIA and its American counterpart PhRMA are supporting Abbvie. The BMJ and BMA have joined forces to intervene on behalf of the EMA.

If I were to summarise, I’d say that, at best, there seems to be a degree of complacency regarding the veracity of statin data on the part of both the CTT and the Cochrane researchers. There is a sense that they are happy to present the ‘positive’ findings in the best possible light, and at the same time seem relaxed about the clear gaps we have in our knowledge about potential harms. The fact that statins appear to have no overall benefit in those at low risk of cardiovascular disease should not go unacknowledged, either.

Worse still, we have evidence that drug trials can be designed, conducted and reported in ways that obscure the truth. And sometimes, even when we have data that can help us make informed decisions about the appropriateness of a treatment, some drug companies will fight tooth and nail to prevent that data seeing the light of day.

This sort of subterfuge may be good for sales and share price, but it is almost certainly bad for our collective health. On this point, the BMJ authors state than instead of doctors following guidelines and prescribing statins for individuals at low risk of cardiovascular disease, they should explain the magnitude of benefits and uncertainties regarding harm. In addition, they might also discuss the fact that the vast majority of cardiovascular disease risk is linked with lifestyle factors such as smoking, diet and physical activity. Fiona Godlee backs this approach, but states that the benefits of lifestyle change are: “something that the dominance of industry sponsored clinical trials too often obscures.”
Personally, I am delighted that the misdeeds of drug companies and some researchers can now be exposed in this way, and in a high-profile medical journal at that. In the past, I think there was much more opportunity for the industry and its hired hands to mislead us. Greater transparency means that the industry as a whole is getting more of what I believe it deserves: our contempt.
References:
1. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2011;1:CD004816.
Medline
2. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev2013;1:CD004816.
3. Abramson JD, et al. Should people at low risk of cardiovascular disease take a statin?
BMJ 2013;347:f6123
4. Cholesterol Treatment Trialists’ (CTT) Collaborators. 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 2012;380(9841):581–90.
5. Godlee F. Statins for all over 50? No BMJ 2013;347:f6412.
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