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Showing posts with label mortality. Show all posts
Showing posts with label mortality. Show all posts

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.

Wednesday, November 6, 2013

The controversial study that started the War on Cholesterol - Watson

The controversial study that started the War on Cholesterol…

      
| June 14, 2012   
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Revisiting the Coronary Primary Prevention Trial (CPPT) – 1973 to 1984

Using "relative risk statistics" and changing the study's design, the CPPT researchers declared success and the War on Cholesterol began in earnest
 
Launched in 1973 by the National Institutes of Health, the Coronary Primary Prevention Trial (CPPT) set out to prove that lowering blood cholesterol with a drug and a low cholesterol, low saturated fat diet would reduce the risk of coronary heart disease and extend the lives of the study participants.

(As part of the study, twelve new Lipid Research Clinics were set up by the Heart Institute at large universities throughout the country including Baylor, Stanford, Johns Hopkins and the University of Washington in Seattle.)

The researchers were looking for middle-aged men with total cholesterol levels exceeding those of 95 percent of Americans. (Only men with the highest 0.8 percent total cholesterol qualified.) The CPPT researchers screened 480,000 applicants in order to select 3,806 high risk men between the ages of 35 and 59.

This meant that many of the participants had familial hypercholesterolemia, a rare genetic defect in cholesterol metabolism present in about 1 percent of the population. The trials chance of success was therefore greatly increased by focusing on this particular group of presumably vulnerable men.
In their preliminary report, CPPT researchers announced that they would study two separate outcomes:  (1) Nonfatal heart attacks and (2) fatal heart attacks or deaths from coronary heart disease. The CPPT directors emphasized that they would be satisfied with nothing less than the strongest statistical proof of their findings; they had to be “99 percent certain that the results were not due to chance.”

The researchers also announced their goal of reducing blood cholesterol in the treatment group by 25 percent and reducing the risk of heart disease in the treatment group by at least 50 percent.
Approximately half of the 3,806 men were provided low cholesterol, low saturated fat dietary advice and were treated with cholestyramine, a cholesterol-lowering bile acid resin (Questran).

(Cholestyramine lowers cholesterol by interfering with digestion. Statins such as Lipitor, Mevacor and Zocor were not available yet.)

The control group was provided the same dietary advice and an unpleasant tasting placebo – an indigestible mixture of sand, sugar and food coloring. Both trial groups suffered with moderate to severe gastrointestinal distress. There were eight gastrointestinal cancer deaths in the treatment group (out of 21 cases) and one in the placebo group (out of 11 cases).

(There were more deaths from cancer, intestinal disease, stroke, violence and suicide in the group taking the cholesterol-lowering drug, and overall mortality was essentially the same for both groups.)

Disappointing Results

In 1984, the disappointing results were tabulated. Cholesterol levels in the treatment group had decreased by no more than 7 percent. Cholestyramine and the low cholesterol, low saturated fat diet had failed to lower cholesterol enough to prove that lowering cholesterol would reduce the risk of heart disease and extend the lives in the treatment group.

The difference in nonfatal heart attacks was not statistically significant. In the treatment group, 130 participants (6.8 percent) had a heart attack versus 158 in the placebo group (8.3 percent). After 7 years, the fraction of the treatment group that had benefited was less than 2 percent.

                                       Nonfatal heart attacks               Fatal heart attacks/coronary deaths
1,900 Control Group:         158 or 8.3 percent                               38 or 2.0 percent
1,906 Treatment Group:     130 or 6.8 percent                              30 or 1.6 percent

The difference in fatal heart attacks was not significant either. In the treatment group, 30 participants (1.6 percent) suffered a fatal heart attack compared to 38 in the placebo group (2.0 percent) Again – after 7 years of taking an unpleasant drug (and following a low fat diet), the fraction of the treatment group that benefited was less than 1 percent.

However, by applying relative risk statistics (a percentage of a percentage), the CPPT researchers improved their results. They took the number of people who presumably didn’t have a heart attack because of taking the drug (28) and looked at it as a percentage of the people who did have heart attacks (158) but didn’t take the drug:

The less than 2 percent absolute difference in nonfatal heart attacks rose to a reported 19 percent reduction in risk of a heart attack!
 
In similar statistical fashion, the researchers announced a 24 percent reduction in the risk of dying from a heart attack. The 8 men or 1.6 percent out of 1,900 who presumably did not have a fatal heart attack because they took the drug became the same 24 percent who reduced their risk of mortality compared to those in the control group who did die (38) but did not take the drug.

Additional study design changes

To prop up their victory, the CPPT researchers decided to exclude  “uncertain” nonfatal heart attacks from the treatment group while including  “uncertain” fatal heart attacks in the placebo group. Also, using the original 99 percent standard, the small favorable trend in either group could only be explained by chance (as defined by the researchers themselves at the start of the trial.)
By applying the less stringent 95 percent standard and by combining the two groups into one (nonfatal and fatal heart attacks), the CPPT researchers improved their results – declared victory – while the press responded with unbridled enthusiasm.

In 1984, the press and medical journals portrayed CPPT as the long sought proof that animal fats were the cause of heart disease. It was widely reported that for the first time:

“It had been proven that lowering cholesterol would reduce the mortality from heart disease and lower the risk of having a heart attack.”
 
Much of what we hear today about diet and heart disease can be traced back to this notorious failed study. When other scientists voiced their objections to the trial’s design changes, the CPPT directors simply denied that they had ever embraced the original more stringent standards.

In January 1984, the Journal of the American Medical Association (JAMA) dutifully reported:

“The trial’s implications…could and should be extended to other age groups and women, and to others with more modest elevations of cholesterol levels. The benefits that could be expected from cholestyramine treatment are considerable.”
 
George Mann, M.D., professor in medicine and biochemistry at Vanderbilt University, severely criticized the CPPT directors and the trial’s unsupportable results:

“The managers at the National Institutes of Health have used Madison Avenue hype to sell this failed trial in the way the media people sell an underarm deodorant…”
 
 Giving cholestyramine for over seven years to 1,906 middle age men – many with a genetic predisposition to atherosclerosis – had only saved the lives of eight but the Heart Institute was now recommending that cholesterol-lowering drug treatment be extended to patient groups that had not been part of the trial.

Even without the solid evidence they sought, the medical elite in the American Heart Association and the National Institute of Health decided to push ahead with cholesterol-lowering drugs and the still unproven low cholesterol, low saturated fat diet:

 “Now we have proved that it is worthwhile to lower blood cholesterol; no more trials are necessary. Now is the time for treatment.”
 
 The long War on Cholesterol had begun
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Read the complete article here.

Thursday, August 29, 2013

Statins Do Not Save Lives - Smith

New Study Confirms Statins Do Not Save Lives
A 'new' study of statin medications has just been published in the Journal of the American College of Cardiology. I say new, but actually its a new manipulation of old data.

The researchers looked at eight previously conducted clinical trials done on statins. The population studied was elderly people without existing cardiovascular disease. After doing their calculations, it was concluded that statins did slightly reduce the risk of heart attack and stroke, but the use of statins did not reduce the risk of death from cardiovascular disease. There was also no reduction in the risk of death from all causes.

The bottom line is that it has once again been established that statins do not extend life expectancy for people without cardiovascular disease.

This is one of the key points that STATIN NATION exposes.  The video excerpt below provides a summary of this issue:



A Bit More Detail
Around 75% of all the people who take a statin, are taking it for  primary prevention. This means they do not have a heart problem but are taking the medication in the hope of preventing a heart problem in the future.  When it comes to primary prevention none of the largest clinical trials have been able to conclusively show any net benefit.

The AFCAPS (1), ASCOT (2), CARDS (3), PROSPER (4) and WOSCOPS (5) clinical trials all failed to show a statistically significant reduction in all cause mortality (deaths from all causes, not just heart disease related deaths).

All cause mortality data, of course, is the only true measure one can use to determine if a statin is going to extend life expectancy or not. Whilst some clinical trials of statins have shown a very slight reduction in heart disease, in primary prevention, this has always been countered by deaths from other causes. The net result is that people do not live any longer after taking a statin.

In 2010, a meta-analysis of 11statin trials was published in the Archives of Internal Medicine. Professor Kausik Ray and colleagues concluded that statins provided no benefit in terms of deaths from all causes, when used for primary prevention (6). This analysis had the “cleanest” dataset of any analysis completed to date - the researchers were able to exclude patients with existing heart disease (known as secondary prevention) and only include data associated with primary prevention.
When we look at the use of statins for people who already have a diagnosed heart problem (the 25% of people, in secondary prevention) the picture becomes less clear cut. Some trials have found significant increases in life expectancy for these people, however, the trials have always been too short for us to assess the long-term impact of being on a statin.

Even if statins do provide a short-term benefit for those with a heart problem, it is debatable that this has anything to do with the cholesterol-lowering effect of statins. Quite simply, the amount of benefit does not match up with the degree of cholesterol-lowering. The potential beneficial affects of statins for people with heart disease is now widely recognised to be associated with a reduction in inflammation. And recent evidence suggests that this is mediated through an improvement in iron metabolism (7).

“Benefits Outweigh Risks” 
Any decision to take a medication should of course involve a clear understanding of the benefits balanced against the risks. Many authorities have repeatedly stated that the benefits of statins far outweigh the risks. Clearly, this is not correct.

First of all, as we have seen above, there is no net benefit for the 75% of people who take a statin in primary prevention. So, for these people, the choice should be abundantly clear, since they will only expose themselves to the significant adverse effects associated with statins.

Statins have been linked with more than 300 different adverse effects. The most common adverse effects include: depression, suicide, sleep disturbances, memory loss, sexual dysfunction, lung disease, muscle-related problems, cognitive loss, neuropathy, pancreatic dysfunction and liver dysfunction. More recent studies have also shown that statins cause type 2 diabetes and acute kidney injury.

In addition, many doctors are concerned about statins and a potential increase in the risk for cancer and heart failure. A recent study found that the long term use of statins doubles the risk of breast cancer in women.

The best estimates suggest that at around 20% of the people who take a statin will experience significant adverse effects. This needs to be considered when thinking about both primary and secondary prevention, since this 20% is a much greater number than the number of people who might benefit, even in secondary prevention.

References: 
1. Downs JR, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279:1615-22.
2. Sever PS, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361:1149-1158.
3. Clhoun HM, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atovastatin Diabetes Study (CARDS). Lancet 2004; 364:685-696.
4. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360:1623-1630.
5. Shepherd J, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia (WOSCOPS). N Engl J Med 1995; 333:1301-1307.
6. Ray KK, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010; 170:1024-31.
7. Zacharski, LR et al. The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention. American Journal of Public Health. Published online ahead of print February 14, 2013.
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Read the complete article here.

Tuesday, May 28, 2013

Is salt really so bad for you? - Fenster

Is salt really so bad for you?

Decades of science show NO conclusive evidence that cutting back on dietary sodium reduces cardiovascular morbidity

                     
                        
(Credit: This piece originally appeared on Pacific Standard.
 
Pacific Standard No salt, low salt, salt free, heart-healthy salt substitution–any added salt will hurt your constitution. It reads like some bizarre, Seussian tale. Excepting that we’ve heard it not from the good Dr. Geisel but from the medical community and public health advocates everywhere. We watch as celebrity chefs take the salt elimination cooking challenge to prepare an “improved healthy” cuisine. Self-anointed “experts” cadge, coax, and cajole us to decrease our salt, or, more specifically, sodium intake. If that doesn’t work then the specter of heart attacks and strokes is unleashed upon us, along with a dash of fire and brimstone for good measure. It is, after all, clearly in our best personal and the greater public interest.
The hypothesis is sound and the supporting data is impeccable, right?

The theory goes as follows: Salt acts to make us retain fluid. When we retain more fluid it increases our blood pressure (albeit temporarily). Increased blood pressure is hypertension. Hypertension is a risk factor for cardiovascular disease like heart attacks and stroke. Heart attacks and strokes are bad. Therefore, hypertension is bad. Thus, sodium must be bad; A causes B which causes C, therefore A causes C. Get rid of A and you get rid of C—simple basic arithmetic, no? Reduce sodium intake and you will reduce blood pressure and thus reduce the incidence of stroke and heart attack. Reducing sodium intake is good—simple, effective, and undeniably the prevailing conventional wisdom these days.

Except… one thing is missing.

The conclusive data—or any data-that definitively shows that cutting back on dietary sodium reduces mortality or significantly reduces cardiovascular morbidity. For over half a century, starting in the 1960s, there has been a vehement and salty exchange just out of public earshot involving respected scientists on both sides of this line. But with the advent of an aggressive public policy to reduce dietary sodium intake for presumed public health benefit and studies emerging suggesting negative consequences of a low-sodium diet, the clamor of dissension is heating up.
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JAMA on salt HERE.
Read the complete article here.

Here is an article from The Kennebec Journal on the division regarding the salt controversy. Here are a couple of quotes:

"Four months after an Institute of Medicine report said reducing salt to the lowest recommended level doesn't improve health and may harm it, the U.S. Centers for Disease Control and Prevention said they disagree. In an article published Monday in the American Journal of Hypertension, the CDC and New York City health officials said getting Americans to eat less salt remains a key objective with the potential to save thousands of lives."

and

"Lowering sodium to the extent required to lower blood pressure has a variety of other effects," including some that boost heart attacks, strokes and death, he said. "It's just not that simple. The message from the evidence is we don't know."

Here is another article from Food Politics by Marion Nestle.
Another article on salt here.

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/
 

Sunday, April 7, 2013

Low Salt Diet Found to Increase Mortality - Dach

Low Salt Diet Found to Increase Mortality
Part 1
by Jeffrey Dach MD

Low Salt Diet Found to Increase Mortality The Low Salt Diet Revisited

A recent Lancet study on the effect of a low salt diet made headlines, finding that a low salt diet increases mortality for patients with congestive heart failure.(1-6) The study concluded there was not enough evidence to advise a low-salt diet for the rest of us. They doubted a low salt diet would benefit the population.(6) In this article we will re-examine the low salt diet, clear away the confusion, and make recommendations about salt intake, hypertension, and health.


Health Benefits of Salt

We know from many years of published studies that increasing salt intake increases blood volume and also blood pressure. Salt is essential for maintaining blood volume, blood pressure, and overall health. The salt content of blood is similar to ocean water. Both have sodium chloride, also known as salt.

Importance of Salt

One example of the importance of salt is the common practice of starting an intravenous solution of salt and water as the first line treatment for the trauma patient upon arrival to the hospital Emergency Room.

Low Salt Diet to Reduce Blood Pressure

One of the central dogmas of mainstream medicine is the “low salt diet” as a treatment for reducing blood pressure in the hypertensive patient. Indeed, popular wisdom says that the “low salt diet” is also healthy for the rest of us “normal” people who don’t have hypertension.(25) Along with the rest of my medical school class, I was indoctrinated to believe this. Is this really true? Many studies have looked at this question. They show the “low salt diet” will in fact reduce blood pressure slightly. However, this effect is minimal, and is counteracted by compensatory mechanisms that release harmful substances into the bloodstream, hormones and chemical mediators that counteract the “low salt diet”. The released chemical mediators include insulin, epinephrine, norepinephrine, renin, aldosterone, etc. These are harmful and damaging to the vascular system. (7-11)

Low Salt Diet Increases Cardiovascular Mortality

In addition, a number of studies have found that a “low salt diet” increases cardiovascular mortality. (5) A study published in the 1995 Hypertension found 4.3 times greater mortality in hypertensive men on a low salt diet.(12) They also found higher plasma renin in these men, a hormone produced by the body which causes salt and water retention by the kidney to compensate for the low salt diet.(12-15)

A 2011 JAMA provides the reasons for this increased mortality and says … (16)
The underlying mechanisms explaining the inverse association between cardiovascular mortality and 24-hour urinary sodium excretion might be that a salt intake low enough to decrease blood pressure also increases sympathetic nerve activity, decreases insulin sensitivity, activates the renin-angiotensin system, and stimulates aldosterone secretion. (16)
A 1998 JAMA report found that a low salt diet increased plasma renin 3.6-fold and aldosterone by 3.2-fold, increases that were proportional to the degree of sodium restriction. (17) The authors also reported the “low salt diet” increased other harmful substances such as noradrenaline, cholesterol, and low-density lipoprotein cholesterol (LDL). (17) A 1999 report in American Journal of Hypertension found that “moderate salt restriction aggravates both systemic and vascular insulin resistance.” (18)
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Read the complete article here.


Low Salt Diet Part Two

In Part One, we discussed the low salt diet, and studies which show an increased mortality from a salt restricted diet. You may have been wondering about this if you saw a recent article in the New York Times by Jane Brody extolling the virtues of a low salt diet.(1) Jan Brody quotes a computer simulation model that predicted 500,000 lives saved by eliminating dietary salt in a program similar to Finland which was described in a New England Journal article.(2,3)

Gary Schwitzer does a good job on their blogs explaining where the Jane Brody article goes wrong.(4,5).

Research by Jan A. Staessen, MD, PhD, of the University of Leuven in Belgium and colleagues, raises questions regarding whether population-wide sodium restriction will actually lower cardiovascular risks. (5,6) In actually clinical studies where 24 hr sodium excretion is measured in 3681 participants and followed over 8 years, this is what they found:

In this population-based cohort, systolic blood pressure, but not diastolic pressure, changes over time aligned with change in sodium excretion, but this association did not translate into a higher risk of hypertension or CVD complications. Lower sodium excretion was associated with higher CVD mortality.(5,6)
 
This type of data seems to suggest that salt restriction has been over-hyped as an intervention, and although will help to slightly reduce blood pressure, does not reduce mortality or complications of cardiovascular disease.

I would agree with Jane Brody that hypertension, heart disease and other health problems are a direct result of diets containing large amounts of processed salt (NaCl), Trans Fats, Sugars, MSG, Aspartame, GMO corn and GMO Soy, and added wheat fillers. To focus attention on the salt content alone, while ignoring the other harmful additives may be not be a valid exercise.

The “low salt diet” for reducing blood pressure in the hypertensive patient is a central dogma of mainstream medicine. Indeed, popular wisdom says that the “low salt diet” is also healthy for the rest of us “normal” people who don’t have hypertension. Along with the rest of my medical school class, I was indoctrinated to believe this. Is this really true? Many studies have looked at this question. They show the “low salt diet” will in fact reduce blood pressure slightly. However, this effect is minimal, and is counteracted by compensatory mechanisms that release harmful substances into the bloodstream, that counteract the “low salt diet”. The released chemical mediators include insulin, epinephrine, norepinephrine, renin, aldosterone, etc. These are harmful and damaging to the vascular system.

In addition, a number of studies have found that a “low salt diet” increases cardiovascular mortality. A study published in the 1995 Hypertension found 4 times greater mortality in hypertensive men on a low salt diet.
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Read the complete article here.

This new link added April 30, 2013: WebMD offers dangerous junk science-based dietary salt advice… This article states that "… even though one of its cited “experts” tacitly admits there is no established cause-and-effect relationship between typical/normal/current salt intake and adverse health effects."

Another article from Food Politics by Marion Nestle found here and

here: http://news.nationalpost.com/2013/09/22/little-evidence-sharp-reductions-in-salt-consumption-will-improve-health-heart-researcher-says/

More data in the Salt Wars - Aug 14, 2014; http://www.medpagetoday.com/Cardiology/Hypertension/47203

An article by Marion Nestle - http://www.foodpolitics.com/2014/08/its-salt-arguments-again-new-research-arguments-over-public-health-recommendations-and-issues-of-conflicts-of-interest/

Sunday, June 10, 2012

The truth about statin drugs - Kresser


pills and bills Statins have been almost universally hailed as “wonder drugs” by medical authorities around the world. The market for statins was $26 billion in 2005, and sales for Lipitor alone reached $14 billion in 2006. Merck and Bristol Myers-Squib are actively seeking “over-the-counter” (OTC) status for their statin drugs. Statins are prescribed to men and women, children and the elderly, people with heart disease and people without heart disease.

In fact, these drugs have a reputation for being so safe and effective that one UK physician, John Reckless (I’m not kidding – that’s actually his name!) has suggested that we put statins in the water supply.

That’s a bold suggestion, of course, and it begs the question: are statins really as safe and cost effective as mainstream medical authorities claim? The unequivocal answer is no.

Statins don’t increase survival in healthy people

Statins have never been shown to be effective in reducing the risk of death in people with no history of heart disease. No study of statins on this “primary prevention population” has ever shown reduced mortality in healthy men and women with only an elevated serum cholesterol level and no known coronary heart disease. (CMAJ. 2005 Nov 8;173(10):1207; author reply 1210.) In fact, an analysis of large, controlled trials prior to 2000 found that long-term use of statins for primary prevention of CHD produced a 1% greater risk of death over 10 years compared to placebo.

Statins don’t increase survival in women

Despite the fact that around half of the millions of statin prescriptions written each year are handed to female patients, these drugs show no overall mortality benefit regardless of whether they are used for primary prevention (women with no history of heart disease) or secondary prevention (women with pre-existing heart disease). In women without coronary heart disease (CHD), statins fail to lower both CHD and overall mortality, while in women with CHD, statins do lower CHD mortality but increase the risk of death from other causes, leaving overall mortality unchanged. (JAMA study)

Statins don’t increase survival in the elderly

The only statin study dealing exclusively with seniors, the PROSPER trial, found that pravastatin did reduce the incidence of coronary mortality (death from heart disease). However, this decrease was almost entirely negated by a corresponding increase in cancer deaths. As a result, overall mortality between the pravastatin and placebo groups after 3.2 years was nearly identical.

This is a highly significant finding since the rate of heart disease in 65-year old men is ten times higher than it is in 45-year old men. The vast majority of people who die from heart disease are over 65, and there is no evidence that statins are effective in this population.

Do statins work for anyone?

Among people with CHD or considered to be at high risk for CHD, the effect of statins on the incidence of CHD mortality ranges from virtually none (in the ALLHAT trial) to forty-six percent (the LIPS trial). The reduction in total mortality from all causes ranges from none (the ALLHAT trial) to twenty-nine percent (the 4S trial).

However, the use of statins in this population is not without considerable risk. Statins frequently produce muscle weakness, lethargy, liver dysfunction and cognitive disturbances ranging from confusion to transient amnesia. They have produced severe rhabdomyolysis that can lead to life-threatening kidney failure.

Aspirin just as effective as statins (and 20x cheaper!)

Perhaps the final nail in the coffin for statins is that a recent study in the British Medical Journal showed that aspirin is just as effective as statins for treating heart disease in secondary prevention populations – and 20 times more cost effective! Aspirin is also far safer than statins are, with fewer adverse effects, risks and complications.

The bottom line

  1. Statin drugs do not reduce the risk of death in 95% of the population, including healthy men with no pre-existing heart disease, women of any age, and the elderly.
  2. Statin drugs do reduce mortality for young and middle-aged men with pre-existing heart disease, but the benefit is small and not without significant adverse effects, risks and costs.
  3. Aspirin works just as well as statins do for preventing heart disease, and is 20 times more cost effective.
So what if you are at risk for heart disease and you’d prefer not to take a statin? Other than aspirin, there are many clinically proven ways to prevent heart disease involving simple adjustments to diet and lifestyle. In fact, the recent INTERHEART study which looked at the incidence of heart disease in 52 countries revealed that over 90% of heart disease is preventable by diet and lifestyle modifications.

I’ll discuss these natural methods of preventing heart disease in my next post. Stay tuned!

Recommended links

Sunday, April 29, 2012

Why Asians Should Ignore the Cholesterol Sham, and Why Healthy People Should Not Take Statins- Colpo

Why Asians Should Ignore the Cholesterol Sham, and Why Healthy People Should Not Take Statins

  Saturday, April 28th, 2012

Folks, before I get rolling, I would just like to dedicate this first instalment of many more cholesterol updates to come to my good buddies Pee Pee and Don Matesz and all those other dopey buggers who make a pastime of accusing me of being a cherry-picker. Today, I’m going to share with you studies you’ve probably never heard of, because they just happen to flatly contradict the mainstream assertion that low cholesterol is healthy and hence are quietly shoved aside by purveyors of this belief due to their embarrassing nature. As we know, one of the favourite strategies humans have for dealing with evidence that contradicts their cherished dogmas is to simply ignore it.

In the twisted worldview of Don, Pee Pee and their ilk, by presenting the studies that you likely never would have heard of due to their embarrassing nature, it is people like me – not them – that are cherry-picking.

Yeah, no worries.

Come and Get ‘Em!
Folks, who wants some cherries? I’ve got a basket full here, and you’re all welcome to grab a handful. They might not be highly-hyped, front page, AHA- or Big Pharma-press-release cherries, but they are definitely sweet, tasty, and certified peer-reviewed delicacies. Enjoy!

Low Cholesterol is Accompanied by Increased Mortality from Stroke, Heart Disease, and Cancer: The Jichi Study
The Asians we are told, are shining examples of the cholesterol theory. They eat a low-fat diet, which gives them wonderfully low cholesterol levels, which in turn not only protects them from heart disease but endows them with the longest average life expectancy on Earth.
Sounds great, doesn’t it?

Too bad it’s complete nonsense.

Being the cherry-picker I am, I discussed the evidence, so often ignored by others, in The Great Cholesterol Con that low cholesterol is strongly associated with increased mortality in Japan.
Yeah, shame on me for pointing out to our Japanese brethren that this whole cholesterol-lowering thing is just another overhyped Western wank, one with the potential to harm instead of hurt their health.

Funnily enough, I don’t feel any shame at all. Au contraire, I believe reporting the facts is a noble thing to do, even if it upsets every last dogmatic sod who can’t get his head around the fact he has fallen hook, line and sinker for a load of unscientific rot.

Which is why, dear readers, I bring you the results from The Jichi Medical School Cohort Study, which involved 12,334 healthy Japanese adults aged 40 to 69 years who underwent a mass screening examination (1992-2005), including total cholesterol measurement. Information regarding cause of death was obtained from death certificates, and the average follow-up period was 11.9 years. In total, 635 men and 423 women died during the study period.

The subjects were divided into 4 groups according to total cholesterol level (<4.14mmol/L; 4.14mmol/L to <5.17 mmol/L; 5.17 mmol/L to <6.20 mmol/L, and; >6.21 mmol/L).
Before I report the results, it should be pointed out that the lowest quartile of cholesterol (<4.14mmol/L) , in both male and female participants, was marked by a higher number of current cigarette smokers.

So did multivariate analyses, which many misguided Western researchers seem to think grants epidemiology the same accuracy as RCT data, and which in this instance included adjustment for smoking, age, systolic blood pressure, HDL, drinking, and body mass index confirm the wonderful life-saving benefits of having low cholesterol?

Nope.

The safest cholesterol range in the study was 4.14–6.20 mmol/L in men, and 4.14mmol/L – >6.21 mmol/L in women. As the researchers stated:

“We noted a clear relationship between low cholesterol and increased mortality. Okamura et al reported that occult liver diseases are associated with mortality; however, in the present study, the relationship between low cholesterol and increased mortality was unchanged in analyses that excluded deaths due to liver disease. Our results suggest that hemorrhagic stroke and heart failure excluding myocardial infarction,contribute to the relationship between low cholesterol and high mortality.”

You can check out the full text of the study here:

Nago N, et al. Low Cholesterol is Associated With Mortality From Stroke, Heart Disease, and Cancer: The Jichi Medical School Cohort Study. Journal of Epidemiology, 2011; 21 (1): 67-74.
Yeah, I know, shame on me for allowing you to view the paper yourself…I need to do what folks like Don and Pee Pee do and make sweeping claims and libelous accusations, then refuse to back them up with even a single paper!

Must be the cherry-picker in me…

Low Cholesterol is Associated with Increased Mortality from CVD in Korean adults.
Maybe the Koreans can save the cholesterol cartel’s Asian thesis, no?
No.

A total of 12,740 Korean adults aged 40 to 69 who underwent a mass screening examination were followed up from 1993 to 2008. Groups with the lowest cholesterol (< 160 mg/dL) as well as the highest (>= 240 mg/dL) were associated with higher CVD mortality in analysis adjusting for age, sex, smoking and drinking status, body mass index, level of blood pressure, triglyceride and HDL.

The researchers noted:

“Based on the results of this study, caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk in Korean adults.”

Aw c’mon guys, the nice folks from Big Pharma won’t like that, will they? Don’t you know that the Asian market, especially China, represents a huge and largely untapped reservoir of profit, but by showing the kind of independent and critical thinking sadly lacking in most of your Western colleagues you’re ruining the party?

Tsk tsk.

Again, dear readers, if you’d like to read the paper yourself, feel free to do so here:

Bae JM, et al. Low cholesterol is associated with mortality from cardiovascular diseases: a dynamic cohort study in Korean adults. J Korean Med Sci. 2012 Jan; 27 (1): 58-63.

Statins are Largely a Waste of Time
As for statins, they’re not just a wank for Asians, they’re a load of cobblers for Westerners too.
The Journal of the American Medical Association recently published a “for” and “against” installment posing the following hypothetical question:

“Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature CHD be treated with a statin?”

To answer this question, JAMA enlisted Blaha, Nasir and Blumenthal from The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease for the “yes” case, and Redberg and Katz from the Division of Cardiology, Department of Medicine, University of California, San Francisco (Dr Redberg) and Department of Health Services, County of Los Angeles (Dr Katz) for the “no” case (Drs Redberg and Katz are also Editor and Deputy Editor, respectively, over at the Archives of Internal Medicine).

To support their “yes” case, the Hopkins crew begin by citing a bunch of cholesterol guidelines that were formulated by panel members sponsored by manufacturers of statins. Yep, I’m sure we can rely on those for accurate, unbiased guidance when tooling around with someone’s health!

They then cite the WOSCOPS and AFCAPS/TexCAPS trials and report the former lowered heart attack and CHD mortality by 31%, while the latter reduced heart attacks by 40%.
Um, fellas … isn’t there something you’re forgetting to tell us about those studies?

Like the fact that the 27% reduction in CHD mortality in AFCAPS/TexCAPS did not reach statistical significance? And that there was no reduction whatsoever in overall mortality?

And the fact that the 27% reduction in CHD mortality in WOSCOPS also did not reach statistical significance?

Instead of reporting these facts about actual death rates, the researchers only reported (read: cherry-picked) outcomes that managed to reach statistical significance and ignored those that didn’t.
Recommending a toxic drug to healthy individuals free of CHD using such dubious interpretation of these largely unsuccessful studies is, to my way of thinking, BoLLOCKS.

The Hopkins team then trot out the absolute farce that was JUPITER, this time including a total mortality reduction of 20% reported in that trial. For me to outline all the discrepancies in this trial – that was conveniently cut short as the mortality trajectories of the treatment and control groups began to menacingly converge – would be a whole other article. Luckily, someone else has already saved me the time and posted a pearler of a critique right here:

http://junkfoodscience.blogspot.com.au/2008/11/when-news-sounds-too-good-statins-new.html

After reading that, I’m sure most everyone apart from Pee Pee, Matesz and the JUPITER researchers themselves will agree that citing JUPITER in support of anything other than the all-too-frequent shadiness of Big Pharma-sponsored research is POPPYCoCK and HogWASH.

The Hopkins team then go onto cite some more theoretical figures, then argue that statins are safe, claiming only 5% of patients experience muscle pains.

Incorrect. The reality is that such complaints are dramatically underreported, thanks to doctors’ refusal to believe the ‘wonder drug’ statin they prescribed could ever do anything negative to their patient. And in those who do acknowledge the cause of the muscle pain, filing an official complaint is a time-consuming affair for which they receive no compensation and may even be subject to interrogation about the circumstances that led to the filing of the report.

But what happens when, instead of brushing people off and telling them their symptoms are just due to “getting old”, researchers carefully inspect patient data and make further enquiries? A study published in the October-November-December 2009 issue of Primary Care Cardiovascular Journal, indicates that statin-induced myopathy is far more common than previously claimed by drug companies and health officials. Researchers analyzed the patient records of one 8,000 patient practice and found only one recorded case of muscle symptoms in a patient taking statins. But after questioning 96 randomly selected statin-using patients from the practice, they identified 19 cases of potential muscle damage:

Sciberras D, et al. Is general practice the optimal setting for the recognition of statin-induced myotoxicity? Primary Care cardiovascular Journal, Oct-Nov-Dec, 2009; 2: 195-200.

As for the question of whether statins should be prescribed to women, Blaha et al cite a review by Kostis et al that claims statins also work in women – but ignore two other reviews that concluded statins do not:
  1. Walsh JM, Pignone M. Drug Treatment of Hyperlipidemia in Women. JAMA. 2004; 291 (18): 2243-2252.
  2. Petretta M, et al. Impact of gender in primary prevention of coronary heart disease with statin therapy: A meta-analysis. International Journal of Cardiology, 2010; 138 (1): 25-31.
So what do Redberg and Katz, who argue the “No” case, have to say in response to the selectively cited arguments of Blaha and co?

Instead of citing a small handful of incompletely reported trials, they report that:

“Data from a meta-analysis of 11 trials including 65 229 persons with 244 000 person years of follow-up in healthy but high-risk men and women showed no reduction in mortality associated with treatment with statins. A 2011 Cochrane review of treatment with statins among persons without documented coronary disease came to similar conclusions. The Cochrane review also observed that all but one of the clinical trials providing evidence on this issue were sponsored by the pharmaceutical industry. It is well established that industry-sponsored trials are more likely than non–industry-sponsored trials to report favorable results for drug treatment because of biased reporting, biased interpretation, or both of trial results.”

As for the commonly claimed low rate of side effects in statin users, they note:

“This underestimation of adverse events occurs because the trials excluded up to 30% of patients with many common comorbidities, such as those with a history of muscular pains, as well as renal or hepatic insufficiency. Many randomized trials also excluded patients who had adverse effects of treatment during an open label run-in period. For example, in the Treat to New Targets trial, after initial exclusions based on comorbidities, an additional 35% of eligible patients, or 16% of patients, were excluded during an 8-week, open-label, run-in phase because of adverse events, ischemic events, or participants’ lipid levels while taking the drug not meeting entry criteria. Additionally, the results of randomized trials of statin treatment likely underestimate common symptoms such as myalgia, fatigue, and other minor muscle complaints because these studies often only collect data on more quantifiable adverse effects such as rhabdomyolysis.

Numerous anecdotal reports as well as a small trial have suggested that statin therapy causes cognitive impairment, but this adverse outcome would not have been captured in randomized trials. The true extent of cognitive impairment associated with statins remains understudied. It is disappointing that more data are not available on important adverse events associated with statin treatment, despite millions of prescriptions and many years of use. This information could be easily collected in observational studies and from registries. One population-based cohort study in Great Britain of more than 2 million statin users found that statin use was associated with increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. The risk of diabetes with statin use has been seen in randomized clinical trials such as JUPITER, which found a 3% risk of developing diabetes in the rosuvastatin group, significantly higher than in the placebo group. In observational data from the Women’s Health Initiative, there was an unadjusted 71% increased risk and 48% adjusted increased risk of diabetes in healthy women taking statins.”

Their conclusion?

“Based on all current evidence, a healthy man with elevated cholesterol will not live any longer if he takes statins. For every 100 patients with elevated cholesterol levels who take statins for 5 years, a myocardial infarction will be prevented in 1 or 2 patients. Preventing a heart attack is a meaningful outcome. However, by taking statins, 1 or more patients will develop diabetes and 20% or more will experience disabling symptoms, including muscle weakness, fatigue, and memory loss.”

Statins. They still suck.
==============================================================
Read the complete article here.

Wednesday, March 21, 2012


Looks like the same U-shaped curves of mortality vs total cholesterol applies to half a million Korean men, too. Look at how cancer goes up at the lower TC levels, and how low CHD is compared to all the other causes of death. A full-text pdf file is available.

=================================================================================

Which Cholesterol Level Is Related to the Lowest Mortality in Population with Low Mean Cholesterol Level: A 6.4-Year Follow-up Study of 482,472 Korean Men

Yun-Mi Song1, Joohon Sung2 and Joung Soon Kim3

1 Department of Family Medicine, SungKyunKwan University School of Medicine Suwon, Korea
2 Department of Preventive Medicine, College of Medicine, Seoul National University Seoul Korea
3 Department of Epidemiology, Graduate School of Public Health, Seoul National University Seoul, Korea

Received June 1, 1998.
Accepted December 16, 1998.

Abstract

To evaluate the relation between low cholesterol level and mortality, the authors followed 482,472 Korean men aged 30–65 years from 1990 to 1996 after a baseline health examination. The mean cholesterol level of the men was 189.1 mg/100 ml at the baseline measurement. There were 7,894 deaths during the follow-up period. A low cholesterol level (>165 mg/100 ml) was associated with increased risk of total mortality, even after eliminating deaths that occurred in the first 5 years of follow-up. The risk of death from coronary heart disease increased significantly in men with the highest cholesterol level (≥252 mg/100 ml). There were various relations between cholesterol level and cancer mortality by site. Mortality from liver and colon cancer was significantly associated with a very low cholesterol level (>135 mg/100 ml) without any evidence of a preclinical cholesterol-lowering effect. With lengthening follow-up, the significant relation between a very low cholesterol level (>135 mg/100 ml) and mortality from stomach and esophageal cancer disappeared. The cholesterol level related with the lowest mortality ranged from 211 to 251 mg/100 ml, which was higher than the mean cholesterol level of study subjects. Am J Epidemiol 2000; 151:739–47.
emphasis added by bd
====================================================================

Read the full article here.


the Norwegian HUNT 2 study



Abstract
Rationale, aims and objectives
Many clinical guidelines for cardiovascular disease

(CVD) prevention contain risk estimation charts/calculators. These have shown a tendency

to overestimate risk, which indicates that there might be theoretical flaws in the algorithms.

Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate

that the predictive properties of cholesterol might not be as straightforward as widely

assumed. Our aim was to document the strength and validity of total cholesterol as a risk

factor for mortality in a well-defined, general Norwegian population without known CVD

at baseline.

Conclusion
Our study provides an updated epidemiological indication of possible errors

in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable,

clinical and public health recommendations regarding the ‘dangers’ of cholesterol should

be revised. This is especially true for women, for whom moderately elevated cholesterol

(by current standards) may prove to be not only harmless but even beneficial.
We assessed the association of



=============================================================================================
Read the complete article here.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2753.2011.01767.x/pdf

Saturday, March 17, 2012

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid?


J Eval Clin Pract. 2012 Feb;18(1):159-68. doi: 10.1111/j.1365-2753.2011.01767.x. Epub 2011 Sep 25.

Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study.

Source

Research Unit of General Practice, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. halfdanpe@gmail.com

Abstract

RATIONALE, AIMS AND OBJECTIVES:

Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline.

METHODS:

We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trøndelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total).

RESULTS:

Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality <5.0 and ≥7.0 mmol L(-1) . Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern.

CONCLUSION:

Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.
© 2011 Blackwell Publishing Ltd.
PMID:
21951982
[PubMed - in process]
PMCID:
PMC3303886
==========================================================
Read the article here.

Wednesday, June 30, 2010

News regarding statins.

Clare McHarris posted the following on the Stopped Out Statins Yahoo group which I pasted in its entirety here. Thank You Clare!

===========================
News regarding statins. The latest studies in the Archives of Internal Medicine are not supportive of statins. This was released today. Please read the two abstracts below.


Statins and All-Cause Mortality in High-Risk Primary Prevention
A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants (click here)


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]).

________________

Cholesterol Lowering, Cardiovascular Diseases, and the Rosuvastatin-JUPITER Controversy
A Critical Reappraisal
(click here)

Michel de Lorgeril, MD; Patricia Salen, BSc; John Abramson, MD; Sylvie Dodin, MD; Tomohito Hamazaki, PhD; Willy Kostucki, MD; Harumi Okuyama, PhD; Bruno Pavy, MD; Mikael Rabaeus, MD


Arch Intern Med. 2010;170(12):1032-1036.

Background Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels.

Methods Careful review of both results and methods used in the trial and comparison with expected data.

Results The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality—between 5% and 18%—whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study.

Conclusion The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.

Sunday, November 8, 2009

Horrible Hiney(H1n1) - Mortality in perspective

I just spent a week in Calgary where it was much cooler than my body is accustom to but the H1N1 panic was heated up to a fever pitch which was hard to explain in my mind.


My son emailed me a link to Michael Paukner's flickr site that has a chart that helps put the magnitude of the threat in perspective.

Go to this link to see it with better detail.


Note the H1N1 entry in red near the middle of the chart. Kind of dwarfs other health risks such as cardiovascular disease and cancer - right? I wonder where deaths due to water born diseases would lie on the chart. That's one we could actually do something significant on and reduce mortality especially among the young and most vulnerable. I'm convinced that H1N1 is a scare of the affluent.