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Tuesday, June 6, 2017

The High-Cholesterol Paradox - Wainwright




"Being told you have ‘high cholesterol’ is commonly taken as a sign of an unhealthy destiny. Research suggests that for many elderly people the news that they have ‘high cholesterol’ is more often associated with good health and longevity . For over 50 years this has been a paradox, the ‘High-Cholesterol Paradox’. What is really going on? "


Our review found that cholesterol lowering therapies were implicated in:


  • Damage to muscles (including the heart) and exercise intolerance
  • Increased risk of Dementias (Impaired Synaptogenesis and Neurotransmission)
  • Failure of Myelin Maintenance (Multiple Sclerosis Risks)
  • Neuro-muscular problems, aches and pains (Amyotrophic Lateral Sclerosis)
  • Diabetes (Insulin release inhibited)
  • Poor Maintenance of Bones and Joints
  • Suppression of protective skin secretions (Apo-B) and increased MRSA infection


We have found compelling evidence that cholesterol-sulphate is vital to good vascular health so the question is..... Why would anyone want to lower cholesterol? What is needed is a lowering of damage to lipids - caused by sugar.


Read the complete article here.

Friday, May 26, 2017

The Elderly on Primary-Prevention Statins: No Survival Gains in ALLHAT - Medscape

The Elderly on Primary-Prevention Statins: No Survival Gains in ALLHAT

CHICAGO, IL — Statins for primary prevention do not lower the risk of death, whether cardiovascular or from any cause, when given to people aged 65 years or older with CV risk factors, suggests a secondary analysis of a major trial that caused a stir 15 years ago[1].
The ALLHAT-LLT trial had randomized >10,000 people aged >55 with dyslipidemia and hypertension but no clinical heart disease to receive open-label pravastatin 40 mg/day or usual care. In its 2002 publication[2], the trial famously saw no significant mortality reduction for the statin after 6 years, nor an improvement in fatal or nonfatal coronary heart disease events.

The results were similar in the new post hoc analysis of the trial focusing on the 2867 participants aged 65 years and older, as a whole and by the two age groups 65 to 74 years and >75 years, according to a report published May 22, 2017 in JAMA Internal Medicine with lead author Dr Benjamin H Han (New York University Langone School of Medicine, NY).
Although no significant outcomes differences were seen between the two randomized groups in any of the age categories, there was a trend (P=0.07) for increased all-cause mortality on the statin in the oldest age group.

As Han pointed out for heartwire from Medscape, the overall trial had well-recognized limitations. For example, the statin was given on an open-label basis. Also, it has been long noted that the ALLHAT-LLT usual-care group could receive statins at the physicians' discretion, which could potentially blur any differences in treatment outcomes.

Calls for Caution

"I would be very cautious in drawing any real conclusions from this study, as the study was not specifically designed to study statins in older adults, so all of the analyses are underpowered. None of their major conclusions were statistically significant," according to Dr Ann Marie Navar (Duke Clinical Research Institute, Durham, NC), who isn't connected with the ALLHAT-LLT report.
"Most statin trials have shown no difference in mortality, but [they showed] that statins do reduce the risk of coronary heart disease, a trend also seen in this secondary analysis," Navar told heartwire by email.


"The trend toward increasing mortality is certainly provocative but really needs to be explored in a trial specifically designed to test this issue."
The post hoc analysis included 1467 participants who had been randomized to pravastatin; their mean age was 71.3, and 48% were women. Their mean LDL-C level was 147.7 mg/dL at baseline and 109.1 mg/dL after 6 years.
The 1400 participants in the usual-care group had a mean age of 71.2 years, and 51% were female. Their mean LDL-C level was 147.6 mg/dL at baseline and 128.8 mg/dL after 6 years.
For all patients over the age of 65 who took pravastatin, the hazard ratio for all-cause mortality was 1.18 (95% CI 0.97–1.42, P=0.09) compared with the usual-care group. It was 1.08 (95% CI 0.85–1.37, P=0.55) for the 65–74 group and 1.34 (95% CI 0.98-1.84 P=0.07) for those aged 75 and older. Nor were there significant HRs for the secondary CHD end points.

In multivariate analysis, the corresponding HRs were 1.15 (95% CI 0.94–1.39) for 65 and older, 1.05 (95% CI 0.82–1.33) for those 65 to 74, and 1.36 (95% CI, 0.98-1.89) for 75 and older. The prospectively defined covariates included age, sex, race/ethnicity, primary-prevention aspirin use, smoking history, type 2 diabetes, body mass index, and systolic and diastolic blood pressures.

The Issues
"We are seeing a lot more older adults being put on statins for primary prevention, but the problem is, the evidence for doing so is limited," Han said.

"As geriatricians, we emphasize that treatment recommendations really need to be individualized with patients and need to also take into account not just what their cardiovascular risk is, but what their life expectancy is, what other competing risks they may have, and what their functional status and everyday activities are," Han observed.
Moreover, "for older adults, taking another medicine every day for the rest of your life isn't a small thing, especially if you have other chronic conditions, and right now we don't have any evidence that there's any benefit to doing so if you do not have any history of cardiovascular disease."

An editor's note accompanying the ALLHAT-LLC report points out the potential risks of extending statins to groups that may be unlikely to benefit clinically[3]. For example, statin therapy may be associated with myopathy, myalgias, muscle weakness, and arthropathies, notes Dr Gregory Curfman (Harvard Medical School, Boston, MA).

"These disorders may be particularly problematic in older people and may contribute to physical deconditioning and frailty. Statins have also been associated with cognitive dysfunction, which may further contribute to reduced functional status, risk of falls, and disability," he writes.
"The combination of these multiple risks and the ALLHAT-LLT data showing that statin therapy in older adults may be associated with an increased mortality rate should be considered before prescribing or continuing statins for patients in this age category."

Is There a "Point of No Return"?

"It takes decades for the plaque to build up in the arteries that eventually causes strokes and heart attacks. Data from thousands of adults studied in clinical trials show us that statins, when started early, can interrupt or slow down that process," according to Navar.

But, "we don't know if there is a 'point of no return' where it's too late to start a statin, and ALLHAT was not designed to answer that question. We need a large randomized trial to really know how effective statins are when started in older adults without cardiovascular disease," she said.
"There is a lot of negative press about statins, and I really worry about the effect of studies like these on the public's perception. This study was a secondary analysis of a trial that was not designed to study the effect of statins in older adults," Navar observed.

"Data from thousands of adults in multiple randomized trials have shown that statins prevent heart disease and do not kill people. I hope that the media, in the never-ending search for clickbait, doesn't overemphasize the statistically nonsignificant mortality trend and lead people who are known to benefit to discontinue their statins."

The study was funded by the National Heart Lung & Blood Institute. Study medications were contributed by Pfizer, AstraZeneca, and Bristol-Myers Squibb, and financial support was provided by Pfizer. The study authors and Curfman report no relevant financial relationships. Navar reported research support from the National Institutes of Health, Amgen, and Sanofi & Regeneron Pharmaceuticals and serving as a consultant for Amgen and Sanofi.

Read the full article here.

Thursday, May 18, 2017

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease - Gibson

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease


C. Michael Gibson MD           
Proud to be co-author of this New England Journal Med article showing lowering LDL does not always improve outcomes

Background

The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.

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.

 (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998.)


Read the complete article here.

Monday, May 8, 2017

It’s official, statins do not have any side effects - Kendrick

It’s official, statins do not have any side effects


"The reality is, that unless you have had a previous heart attack, statins have no effect on overall mortality. To put that another way, they don’t save lives. They don’t even prevent heart attacks or strokes in women with no previous history of heart disease.

The statistic you really want to know about statins is the following. If you have had a heart attack, or stroke, and take a statin for five years, you will increase your life expectancy by 4.2 days. Balance that against a twenty per cent chance of having side effects, some of which are very unpleasant and long-lasting, and you can see why I am not a fan of statins."
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"A number of things were found. The most important of which, is just how many people stopped taking their statins after one year. A pretty staggering 75%. Why did they stop?
‘More than six in ten respondents (62%) said they discontinued their statin due to side effects, with the secondary factor (17%) being medication cost. Only 12% of respondents cited lack of efficacy in cholesterol management as a reason for stopping their medication. On average, respondents who experienced side effects due to their statin stopped after trying two different statins.
Three out of ten respondents experienced side effects of muscle pain and/or weakness, and 34% stopped taking their statin because of these side effects without consulting with their doctor.'
Read the complete article by Dr Kendrick here.

Wednesday, April 12, 2017

How much longer will you live if you take a statin?


"Looking at the Heart Protection Study (HPS) done in the UK, we used a technique for analysing survival time called RMST (restricted mean survival time). I won’t go into the details. The HPS study lasted for five years, and we calculated that the average increase in survival time was 15.6 days. This was at the end of five years of treatment (with a confidence interval of 5 days either side). For 4S, the figure was 17 days."

"Framing this slightly differently, what this meant was that taking a statin for one year, in the highest risk group possible, would increase your life expectancy by around three days."

"However, more recently the BMJ did decided to publish another paper entitled: ‘The effect of statins on average survival in randomised trials, an analysis of end point postponement.

Results: 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively."

Conclusions: Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered
Overall their findings were far less impressive, even, than ours. They calculated, approximately, a single day of increase in life expectancy for each year of taking a statin. Slightly more in secondary prevention, slightly less in primary (people who have not previously had a heart attack or a stroke).
The main take away message I believe, is the following. Statins do not prevent fatal heart attacks and strokes. They can only delay them. They delay them by about one or two days per year of treatment. For those who have read my books you will know that I have regularly suggested we get rid of the concept of ‘preventative medicine’. We need to replace it with the concept of ‘delayative medicine’.


Read Dr. Kendrick's complete article here.
The effect of statins on average survival in randomised trials, an analysis of end point postponement
  1. Malene Lopez Kristensen
  2. Palle Mark Christensen
  3. Jesper Hallas
  4. Objective To estimate the average postponement of death in statin trials.
  5. Primary outcome measures The average postponement of death as represented by the area between the survival curves.
    Results 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.
  6. Conclusions Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered.

Strengths and limitations of this study

  • This is the first study ever to systematically evaluate statin trials using average postponement of death as the primary outcome.
  • We have only estimated the survival gain achieved within the trials’ running time, whereas in real life, treatment is often continued much longer.
  • We have only focused on all-cause mortality. Other outcomes may also be relevant, for example, non-fatal cardiovascular end points.
Read the complete article here.

Wednesday, March 29, 2017

Cholesterol Paradox: A Correlate Does Not a Surrogate Make


Abstract

The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.


Read the complete article here.

Friday, February 3, 2017

The Functional Medicine Approach to High Cholesterol

"The message that “cholesterol is bad and if you have high cholesterol you should take a statin to lower it” is out of date and not in sync with the most recent scientific evidence. Unfortunately, the latest findings have not trickled down to the average primary care doctor—or even the average cardiologist. Today I discuss the six underlying causes of high cholesterol and how addressing those issues can often alleviate the need to take statins."

The Functional Medicine Approach to High Cholesterol

Tuesday, January 10, 2017

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.

Thursday, March 10, 2016

Thursday, 10 March 2016

Congenital abnormalities in baby born to mother using lovastatin

This study was published in the Lancet 1992 Jun 6;339(8806):1416-7

Study title and authors:
Congenital abnormalities (VATER) in baby born to mother using lovastatin.
Ghidini A, Sicherer S, Willner J.

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/1350826

This paper reports the case of an infant born with many malformations after the mother used a statin during pregnancy.

(i) A woman was treated for five weeks with lovastatin, starting approximately six weeks from her last menstrual period.
(ii) The statin was discontinued when her pregnancy was diagnosed at 11 weeks' gestation.
(iii) A female infant was delivered by cesarean section at 39 weeks' gestation. The infant had a constellation of malformations termed the VATER association (vertebral anomalies, anus not developed properly, an abnormal connection between the oesophagus and the trachea with part of the oesophagus missing, and kidney, forearm and wrist abnormalities).
(iv) Her anomalies included a deformed chest, spinal deformity, absent left thumb, foreshortened left forearm, shortened left elbow, fusion of the ribs on the left, anomalies in the spine, deformed left forearm, and a narrow lower oesophagus.