Pistachios: Are Their Shells A Portal to Contamination, The Key To Weight Loss, or A Manicure Destruction Device?

The results of the “Fourth Nut” poll are in and the winner is a nut first cultivated in Bronze Age Central Asia,

Almost 60% of readers who took the time to vote selected the pistachio nut.

Coming in a distant second was the macadamia nut. One reader prized it because it only contained saturated fat and monounsaturated fats. Another bemoaned their candy-like quality which makes over-consumption an issue.

A couple of readers were strong proponents of Brazil nuts. This prompted me to enter a selenium rabbit hole from which I have yet to emerge. If I can escape with my selenoproteins intact I’ll let you know.

Pistachios are a fine choice from a health standpoint and seem to be embraced by all nutritional cults, with the exception of  the very nutty Caldwell “NO OIL” Esselstyn’s acolytes.

The Pistachio Principle PR Institute

I’m in the process of sorting through the nutritional studies on pistachios, and the hardest part is determining which data are sponsored by the pistachio industry.

For example, poorly researched online articles about pistachios will typically state that “research suggests” that “pistachios could help to reduce hypertension and promote development of beneficial gut microbes. They’re even gaining credibility as a tool for weight loss”

The first reference is an open access review article which clearly just wants to extoll any and all positive pistachio data and was paid for by the American Pistachio Growers. The second article comes directly from “The Pistachio Health Institute,” a PR voice for the pistachio industry.

To Shell or Not to Shell

My major dilemma was deciding if the pistachios should be shelled or left in-shell. (This has led me down the pistachio production rabbit hole).

I was concerned that the outsides of the pistachio shells could be contaminated in some way and the idea of mixing them in with unshelled nuts seemed a little strange.

If you Google images of mixed nuts pistachio you only see mixtures with unshelled pistachios.

Why, then, are most pistachios sold and consumed in-shell?

According to How Stuff Works Louise Ferguson, author of the Pistachio Production Manual believes:

Between 70 and 90 percent of pistachios develop a natural split in their shells during the growing process, After those pistachios are shaken off the trees by harvesting machines, they can be salted and roasted while still inside the shells as that natural crack allows heat and salt access to the nut, eliminating a step in the industrial process and saving processors some money.

The pistachio PR machine would also have us believe that eating pistachios in-shell can lead to weight loss:

Why choose any other nut?

This pistachios principle is based on 2 studies in the journal Appetite (seems to be a legitimate journal) by JE Painter of the department of “Family and Consumer Sciences” Eastern Illinois University in Charleston, Illinois.

I’m awaiting a full copy of the paper, but the abstract notes that students offered in-shell pistachios consumed only 125 calories, whereas those offered shelled pistachios consumed 211 calories yet “fullness and satisfaction” were similar.

My skeptical sensors were exploding when I read about this study. I doubt that it will ever be reproduced.

If we look at cost, an unofficial analysis revealed:

The pre-shelled pistachios were priced at $5.99 for 6.3 oz of nuts.

The 8 oz bag of pistachios were priced at $4.49.  After shelling he was left with 4.3 oz of nuts.

Un-shelled pistachios = $1.04 per oz.

Shelled pistachios = $0.95 per oz.

If you go the lazy route, you save $.09 per oz!

Most likely, the fourth nut will be a shelled pistachio unless readers convince me otherwise or the blather from the pistachio PR machine  annoys me too much.

The eternal fiance’e has just weighed in and tells me that women who care about their well-groomed  nails will not consume  in-shell pistachio nuts for fear of damaging their manicures.

That, my friends, is the  nail in the coffin for shelled pistachios as the fourth nut.

Pistachoprincipaly Yours,

-ACP

Does Eating Saturated Fat Lower Your Risk of Stroke and Dying?: Humility and Conscience in Nutritional Guidelines

A study presented at the European Society of Cardiology  meetings in Barcelona and simultaneously published in The Lancet earlier this month caught the attention of many of my readers. Media headlines trumpeted  “Huge New Study Casts Doubt On Conventional Wisdom About Fat And Carbs” and “Pure Shakes Up Nutritional Field: Finds High Fat Intake Beneficial.”

Since I’ve been casting as much doubt as possible on the  conventional nutritional wisdom  to cut saturated fat, they reasoned, I should be overjoyed to see such results.

What Did the PURE Study Find?

The Prospective Urban Rural Epidemiology (PURE) study, involved more than 200 investigators who collected data on more than 135000 individuals from 18 countries across five continents for over 7 years.

There were three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe)

This was the largest prospective observational study to assess the association of nutrients (estimated by food frequency questionnaires) with cardiovascular disease and mortality in low-income and middle-income populations,

The PURE team reported that:

Higher carbohydrate intake was associated with an increased risk of total mortality but not with CV disease or CV disease mortality.

This finding meshes well with one of my oft-repeated themes here, that added sugar is the major toxin in our diet (see here and here.)

Higher fat intake was associated with lower risk of total mortality.

Each type of fat (saturated, unsaturated, mono unsaturated ) was associated with about the same lower risk of total mortality. 

 

These findings are consistent with my observations that it is becoming increasingly clear that cutting back on  fat and saturated fat as the AHA and the Dietary Guidelines for Americans have been telling you to do for 30 years is not universally helpful (see here and  here ).

When you process the fat out of dairy and eliminate meat from your diet although your LDL (“bad”) cholesterol drops a little your overall cholesterol (atherogenic lipid) profile doesn’t improve (see here).

Another paper from the PURE study shows this nicely and concluded:

Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.

Further findings from PURE:

-Higher saturated fat intake was associated with a lower risk of stroke

-There was no association between total fat or saturated fat or unsaturated fat with risk of heart attack or dying from heart disease.

Given that most people still believe that saturated fat causes heart disease and are instructed by most national dietary guidelines to cut out animal and dairy fat this does indeed suggest that

Global dietary guidelines should be reconsidered …”

Amen!

Because the focus of dietary guidelines on reducing total and saturated fatty acid intake “is largely based on selective emphasis on some observation and clinical data despite the existence of several randomizesed trials and observational studies that do not support these conclusions.”

Pesky Confounding Factors

We cannot infer causality from PURE because like all obervational studies, the investigators do not have control over all the factors influencing outcomes. These confounding factors are legion in a study that is casting such a broad net across different countries with markedly different lifestyles and socioeconomic status.

The investigators did the best job they could taking into account household wealth and income, education, urban versus rural location and the effects of study centre on the outcomes.

In an accompanying editorial, Christopher E Ramsden and Anthony F Domenichiello, prominent NIH researchers,  ask:

“Is PURE less confounded by conscientiousness than observational studies done in Europe and North American countries?

 

“Conscientiousness is among the best predictors of longevity. For example, in a Japanese population, highly and moderately conscientious individuals had 54% and 50% lower mortality, respectively, compared with the least conscientious tertile.”

“Conscientious individuals exhibit numerous health-related behaviours ranging from adherence to physicians’ recommendations and medication regimens, to better sleep habits, to less alcohol and substance misuse. Importantly, conscientious individuals tend to eat more recommended foods and fewer restricted foods.Since individuals in European and North American populations have, for many decades, received in influential diet recommendations, protective associations attributed to nutrients in studies of these populations are likely confounded by numerous other healthy behaviours. Because many of the populations included in PURE are less exposed to in influential diet recommendations, the present findings are perhaps less likely to be confounded by conscientiousness.”

It is this pesky conscientiousness factor (and other unmeasured confounding variables) which limit the confidence in any conclusions we can make from observational studies.

I agree wholeheartedly with the editorial’s conclusions:

Initial PURE findings challenge conventional diet–disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well designed randomised controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility.

 

Ah, if only the field of nutrition had been injected with a healthy dose of humility and a nagging conscience thirty years ago when its experts declared confidently that high dietary fat and cholesterol consumption was the cause of heart disease.!

Current nutritional experts and the guidelines they write will  benefit from a keen awareness of the unintended consequences of recommendations which they make based on weak and insufficient evidence  because such recommendations influence the food choices  (and thereby the quality of life and the mechanisms of death) of hundreds of millions of people.

PUREly Yours,

ACP

The Fourth Nut

The skeptical cardiologist has given out the entire first batch of Dr. P’s Heart Nuts to his patients.

This precisely constructed mixture of hazelnuts, almonds and walnuts designed to maximize heart healthiness has been warmly received and hopefully enthusiastically consumed.

To some extent I feel like I may be preaching to the choir as many of the Heart Nuts recipients told me they were already avid nut fans and consumers.

However, I plan to press on with my mission to increase the amount of nut snacking in the world.

To this end, I have reorganized my blog and created a page devoted to Nuts and Drupes. You can find it here and I’ll reproduce it below.

Furthermore, I have decided to add a fourth nut to the mixture. At this time, I am intensely researching pistachio nuts and macadamia nuts to be the honored nut.

Please feel free to suggest other candidates to be  the Fourth Nut (along with appropriate justification) in the comments below and vote in the poll.

Macadamiamaniacaly Yours,

-ACP

From The Nuts Page

Nuts, despite containing a lot of fat, are a fantastic heart-healthy snack.

I’ve started handing out my special Dr. P’s Heart Nuts to patients along with the following:

Congratulations!

You have received a packet of cardiovascular disease-busting Dr. P’s Heart Nuts!
One packet 15 grams of almonds, 15 grams of hazelnuts and 30 grams of walnuts.

There is very good scientific evidence that consuming 1/2 packet of these per day will reduce your risk of dying from heart attacks, strokes, and cancer.

The exact components are based on the landmark randomized trial of the Mediterranean diet, enhanced by either extra-virgin olive oil or nuts (PREDIMED, in which participants in the two Mediterranean-diet groups received either extra-virgin olive oil (approximately 1 liter per week) or 30g of mixed nuts per day

In other observational studies it has been found that for every 28 grams/ day increase in nut intake, risk was reduced by:

29% for coronary heart disease 7% for stroke
21% for cardiovascular disease 15% for cancer

22% for all-cause mortality
Surprisingly, death from diseases, other than heart disease or cancer, were also significantly reduced:
52% for respiratory disease
35% for neurodenerative disease
75% for infectious disease
74% for kidney disease

So when you are considering snacking, snack on nuts not processed food! Dr. Pearson

Posts About Nuts

Posts relevant to nuts and prevention of heart disease on my blog are

Nuts, Drupes, Legumes and Mortality

Kind Bars versus Nuts: Choose Just Plain Nuts

Although Nutella contains some hazelnuts it is full of sugar and other processed ingredients: why not eat hazelnuts instead?

Nutty Due Diligence

I spent a lot of time sourcing the nuts for my Dr. P’s Heart Nuts and discovered some disturbing things about almonds.

First, almost all almonds sold in the US have been gassed with proplyene oxide.

Second, roasting almonds can lead to an increase in toxic chemicals.

After finding out the first two facts about almonds I ended up getting raw, organic almonds from Spain. Unfortunately, about 1 in 10 of these were extremely bitter. It turns out these bitter almonds have significant amounts of cyanide.  So I wrote “Beware The Bitter Almond.”

I switched my raw, organic almond source to Nuts.com and with their almonds I very rarely encounter the bitter almond.

The other nuts in the mixture are raw and organic and obtained from Nuts.com.

 

Ignore The New York Times and The American Heart Association and Feel Free to Skip Breakfast

A friend recently sent the skeptical cardiologist  a link to a very disappointing NY Times article  entitled “The Case For A Breakfast Feast”

The writer, Roni Rabin (who has a degree in journalism from Columbia University)  struggles to support her sense that there is a “growing body of research” suggesting we should all modify our current dietary habits in order to eat a  breakfast and make breakfast the largest meal of the day.

Many of us grab coffee and a quick bite in the morning and eat more as the day goes on, with a medium-size lunch and the largest meal of the day in the evening. But a growing body of research on weight and health suggests we may be doing it all backward.

Rabin’s first  discussion is of an observational study of Seventh Day Adventists published in July which adds nothing to the evidence in this area because (as she points out):

The conclusions were limited, since the study was observational and involved members of a religious group who are unusually healthy, do not smoke, tend to abstain from alcohol and eat less meat than the general population (half in the study were vegetarian)

She then discusses experiments on mice from 2012 with a Dr. Panda, a short term feeding trial in women from 2013 and studies on feeding and circadian rhythm in a transgenic rat model from 2001.

There is nothing of significance in the NY Times piece that changes my previous analysis  that it is perfectly safe to skip breakfast and that it will neither make you obese nor give you heart disease.


In what follows I’ll repost my initial post on breakfast (Breakfast is Not The Most important Meal of the Day: Feel Free to Skip it) followed by a follow up post (Feel Free To Skip Breakfast Again) I wrote in 2015.

Finally, I’ll take a close look at a statment from the American Heart Association  from earlier this year which Rabin quotes and which many news outlets somehow interpreted as supporting the necessity of eating breakfast for heart health when, in fact, it confirmed the lack of science behind the recommendation.


Feel Free To Skip Breakfast

It always irritates me when a friend tells me that I should eat breakfast because it is “the most important meal of the day”. Many in the nutritional mainstream have propagated this concept along with the idea that skipping breakfast contributes to obesity. The mechanism proposed seems to be that when you skip breakfast you end up over eating later in the day because you are hungrier.

The skeptical cardiologist is puzzled.

Why would i eat breakfast if I am not hungry in order to lose weight?

What constitutes breakfast?

Is it the first meal you eat after sleeping? If so, wouldn’t any meal eaten after sleeping qualify even it is eaten in the afternoon?

Is eating a donut first thing in the morning really healthier than eating nothing?

Why would your first meal be more important than the last?

Isn’t it the content of what we eat that is important more than the timing?

The 2010 dietary guidelines state

eat a nutrient-dense breakfast. Not eating breakfast has been associated with excess body weight, especially among children and adolescents. Consuming breakfast also has been associated with weight loss and weight loss maintenance, as well as improved nutrient intake

The US Surgeon General website advises that we encourage kids to eat only when they are hungry but also states

Eating a healthy breakfast is a good way to start the day and may be important in achieving and maintaining a healthy weight

Biased  and Weak Studies on the Proposed Effect of Breakfast on Obesity (PEBO)

A recent study anayzes the data in support of the “proposed effect of breakfast on obesity” (PEBO) and found them lacking.
This is a fascinating paper that analyzes how scientific studies which are inconclusive can be subsequently distorted or spun by biased researchers to support their positions. It has relevance to how we should view all observational studies.

Observational studies abound in the world of nutritional research. The early studies by Ancel Keys establishing a relationship between fat consumption and heart disease are a classic example. These studies cannot establish causality. For example, we know that countries that consume large amounts of chocolate per capita have large numbers of Nobel Prize winners per capitaChocolate Consumption and Nobel Laureates

Common sense tells us that it is not the chocolate consumption causing the Nobel prizes or vice versa but likely some other factor or factors that is not measured.

Most of the studies on PEBO are observational studies and the few, small prospective randomized studies don’t clearly support the hypothesis.

Could the emphasis on eating breakfast come from the “breakfast food industry”?

I’m sure General Mills and Kellogg’s would sell a lot less of their highly-processed, sugar-laden breakfast cereals if people didn’t think that breakfast was the most important meal of the day.

My advice to overweight or obese patients:

-Eat when you’re hungry. Skip breakfast if you want.
-If you want to eat breakfast, feel free to eat eggs or full-fat dairy (including butter)
-These foods are nutrient-dense and do not increase your risk of heart disease, even if you have high cholesterol.
-You will be less hungry and can eat less throughout the day than if you were eating sugar-laden, highly processed food-like substances.


Breakfast Cereal

The “must eat breakfast” dogma reminds me of a quote  from Melanie Warner’s excellent analysis of the food industry, “Pandora’s Lunchbox.”

“Walk down a cereal aisle today or go onto a brand’s Web site, and you will quickly learn that breakfast cereal is one of the healthiest ways to start the day, chock full of nutrients and containing minimal fat. “Made with wholesome grains,” says Kellogg’s on its Web site. “Kellogg’s cereals help your family start the morning with energy by delivering a number of vital, take-on-the-day nutrients—nutrients that many of us, especially children, otherwise might miss.” It sounds fantastic. But what you don’t often hear is that most of these “take-on-the-day” nutrients are synthetic versions added to the product, often sprayed on after processing. It’s nearly impossible to find a box of cereal in the supermarket that doesn’t have an alphabet soup of manufactured vitamins and minerals, unless you’re in the natural section, where about half the boxes are fortified.”

The Kellogg’s and General Mills of the world strongly promoted the concept that you shouldn’t skip breakfast because they had developed products that stayed fresh on shelves for incredibly long periods of time. They could be mixed with easily accessible (low-fat, no doubt) milk to create inexpensive,  very quickly and easily made, ostensibly healthy breakfasts.

Unfortunately, the processing required to make these cereals last forever involved removing the healthy components.

As Warner writes about W.K. Kellogg:

“In 1905, he changed the Corn Flakes recipe in a critical way, eliminating the problematic corn germ, as well as the bran. He used only the starchy center, what he referred to as “the sweetheart of the corn,” personified on boxes by a farm girl clutching a freshly picked sheaf. This served to lengthen significantly the amount of time Corn Flakes could sit in warehouses or on grocers’ shelves but compromised the vitamins housed in the germ and the fiber residing in the bran”

This is a very familiar story in the world of food processing;  Warner covers, nicely, the same processes occurring with cheese and with milk, among other things.


The AHA (Always Horribly Awry) Weighs In

I pick on the American heart Association (AHA) a lot in this blog but the AHA scientific statement on “Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention” published earlier this year in Circulation is for the most part a balanced summary of research in the field.

Unfortunately, the media grossly distorted the statement and we ended up with assertive headlines such as this one from Reuters:

Eating Breakfast and Eating Mindfully May Help The Heart

Reuters went on to say (red added by me for emphasis):

“Planning meals and snacks in advance and eating breakfast every day may help lower the risk of cardiovascular disease, new guidelines from U.S. doctors say.”

however, the AHA statement says nothing close to that.

This is the summary that was actually in the AHA paper:

“In summary, the limited evidence of breakfast consumption as an important factor in combined weight and cardiometabolic risk management is suggestive of a minimal impact. There is increasing evidence that advice related to breakfast consumption does not improve weight loss, likely because of compensatory behaviors during the day. …… Additional, longer-term studies are needed in this field because most metabolic studies have been either single-day studies or of very short duration”

The lead author of the paper, Marie-Pierre St-Onge, (Ph.D., associate professor, nutritional medicine, Columbia University, New York City) apparently very clearly told Reuters in an email:

“We know from population studies that eating breakfast is related to lower weight and healthier diet, along with lower risk of cardiovascular disease,” .

“However, interventions to increase breakfast consumption in those who typically skip breakfast do not support a strong causal role of this meal for weight management, in particular,” St-Onge cautioned. “Adding breakfast, for some, leads to an additional meal and weight gain.”

“The evidence, St-Onge said, is just not clear enough to make specific recommendations on breakfast.”

Health New Review published a  nice summary of news reports on the AHA statement with a discussion on the overall problem of making broad public policy dietary recommendations from very weak evidence.

New York Times Gets It Right

The New York Times does have writers who can put together good articles on health. One of them, Aaron Carroll wrote a piece in 2016 entitled “Sorry, There’s Nothing Magical About Breakfast” which does a great job of sorting through weak evidence in the field.

Carroll is a professor of pediatrics at Indiana University School of Medicine and writes excellent articles on The New Health Care blog for the Times.

His conclusions are identical to mine from 2013:

“The bottom line is that the evidence of breakfast is something of a mess. If you’re hungry, eat it. But don’t feel bad if you’d rather skip, and don’t listen to those who lecture you. Breakfast has no mystical powers.”

Mindful and Intentional Eating

If you read the AHA statement completely you come across a lot of mumbo-jumbo on intermittent fasting, meal frequency and “mindful” eating.  The abstract’s last sentence is

Intentional eating with mindful attention to the timing and frequency of eating occasions could lead to healthier lifestyle and cardiometabolic risk factor management.

and they reference this table:

 Yikes! I have no idea what they are talking about.
For those of us who need to get to work early in the morning, breakfast is likely to be the worst time for “mindful” eating.
I have a cup of coffee first thing upon arising and only eat much later in the day when I feel very hungry.
Dinner, on the other hand we can plan for, prepare with loved ones and consume  in  a very mindful and leisurely fashion with a glass of heart healthy wine or beer while enjoying good conversation.
So, ignore what apparently authoritative sources like the New York Times, Reuters, and  the AHA tell you about eating breakfast like a king, lunch like a prince, and dinner like a pauper, mindfully or otherwise.
After all, in the Middle Ages, kings likely didn’t eat breakfast as the Catholic church frowned on it. Per Wikipedia:
Breakfast was under Catholic theological criticism. The influential 13th-century Dominican priest Thomas Aquinas wrote in his Summa Theologica (1265–1274) that breakfast committed “praepropere,” or the sin of eating too soon, which was associated with gluttony.[2]Overindulgences and gluttony were frowned upon and were considered boorish by the Catholic Church, as they presumed that if one ate breakfast, it was because one had other lusty appetites as well, such as ale or wine.
Gluttonously Yours,
-ACP
 Image of king and pauper eating from the New York Times article created by Natalya Balnova.

 

Do Statins Cause Memory Loss? The Science, The Media, The Statin-Denialist Cult, and The Nocebo Effect

The Skeptical Cardiologist was recently contacted by a television reporter  working on a segment about statins. and looking for a cardiologist to interview who “is concerned about the cognitive side effects of these drugs.”

Since I regularly prescribe statin drugs to my patients to reduce their risk of heart attack and stroke,  I am very concerned about any possible side effects from them, cognitive or otherwise. However, in treating hundreds of patients with statins, I have not observed a consistent significant effect on brain function.

When the U.S. Food and Drug Administration (FDA) issued a statement in 2012 regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use it came as quite a surprise to most cardiologists.

The FDA made a change in the patient information on all statin drugs which stated:

Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken

This FDA statement was surprising because prior observational and randomized controlled trials had suggested that patients who took statins were less likely to have cognitive dysfunction than those who didn’t.

Early studies implied that statins might actually protect against Alzheimer’s disease.

In fact these signals triggered two studies testing if statins could slow cognitive decline in patients with established Alzheimer’s disease  One study used 80 mg atorvastatin versus placebo and a second 40 mg simvastatin versus placebo and both showed no effect on the decline of cognitive function over 18 months.

More recently, multiple reviews and meta-analyses have examined the data and concluded that there is no significant effect of statins on cognitive function. Importantly, these have been written by reputable physician-scientists with no financial ties to the pharmaceutical industry.

 

Data Show No Evidence of Causality Despite Case Reports

The FDA added the warning to statin patient information based on case reports  Occasional reports of patients developing memory loss on a statin do not prove that statins are a significant cause of cognitive dysfunction.

Case reports have to  be viewed in the context of all the other scientific studies indicating no consistent evidence of negative effects of the statins. Case reports are suspect for several reasons:

First, patients receiving statins are at increased risk for memory loss because of associated risk factors for atherosclerosis and advancing age. A certain percentage of such patients are going to notice memory loss independent of any medications.

Second. The nocebo effect: If a patient taking a statin is told that the drug will cause a particular side effect,that patient will be more likely to notice and report that particular side effect.

A recent study in The Lancet looked at reported side effects in patients taking atorvastatin versus placebo and found substantial evidence for the nocebo effect.

Analysis of the trial data revealed that when patients were unaware whether they were taking a statin or a placebo, the number of side effects reported was similar in those taking the statin and those taking placebo. However, if patients knew they were taking statins, reports of muscle-related side effects in particular increased dramatically, by up to 41 per cent.

Third, a review of the FDA post-marketing surveillance data showed the rate of memory loss with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 per million prescriptions for statins , 1.6 per million prescriptions for losartan) and clopidogrel (1.9 per million prescriptions for clopidogrel.)

What Most Media Prefer: Controversy And Victims

I thought my experience and perspective on statins and cognitive function might be useful for a wider audience of patients to hear so I agreed to be interviewed. After I expressed interest the  reporter responded:

I would like to interview you and also a person who has experienced memory and/or thinking problems that they attribute to statin use.  
 I responded with “let me see what I can find,”  although I was concerned that  this reporter was searching for a cardiologist to support attention-grabbing claims of  severe side effects of statins rather than seeking a balanced, unbiased perspective from a knowledgeable and experienced cardiologist.
If I produced a “victim” of statin-related memory loss this would boost ratings.
I then began racking my brain to come up with a patient who had clearly had statin-related memory loss or thinking problems. I asked my wonderful MA Jenny (who remembers details about patients that I don’t) if she could recall any cases. Ultimately, we both came up without any patients for the interview. (Any patient of mine reading this with definite statin memory loss please let me know and I will amend my post. However, I won’t be posting anecdotes outside of my practice.)
I have had a few patients relate to me that they feel like their memory is not as good as it was and wonder if it could be from a medication they are on.  Invariably, the patient has been influenced by one of the  statin fear-mongering sites on the internet (or a friend/relative who has been influenced by such a site.)
I wrote about one such site in response to a patient question a while back:
The link appears to be a promotional piece for a book by Michael Cutler, MD. Cutler’s website appears to engage in fear-mongering with respect to statins for the purpose of selling his books and promoting his “integrative” practice. I would refer you to my post entitled “functional medicine is fake medicine”. Integrative medicine is another code word for pseudoscientific medicine and practitioners should be assiduously avoided.
The piece starts with describing the case of Duane Graveline, a vey troubled man who spent the latter part of his life attempting to scare patients from taking statins. Here is his NY Times obituary.
You can judge for yourself if you want to base decisions on his recommendations.
There is no scientific evidence to suggest statins cause dementia.
An Internet-Driven Cult With Deadly Consequences
Steve Nissen recently wrote an eloquent article which accuses statin deniers of  being  an “internet–driven cult with deadly consequences.”  Nissen has done extremely important research helping us better understand atherosclerosis  and is known for being a patient advocate: calling out drug companies when they are promoting unsafe drugs.
I have immense respect for his honesty, lack of bias, and his courage to be outspoken .  He writes:

“Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search en- gine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled “The Grave Dangers of Statin Drugs—and the Surprising Benefits of Cholesterol”. We are losing the battle for the hearts and minds of our patients to Web sites de- veloped by people with little or no scientific expertise, who often pedal “natural” or “drug-free” remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity— or even worse, dementia.”

He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.

The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:

“The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administra-tion. The bill’s principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies.”

Dealing With Statin Side Effects In My Practice

When a patient tells me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I’ve concluded that in any individual patient, it is possible for any drug to cause  side effects.  And, chances are that if we don’t address the side effects the patient won’t take the medication.

If the side effect is significant I will generally tell the patient to stop the statin and report to me how they feel after two to four weeks.

If there is no improvement I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.

If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn’t prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.

At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or livalo.)  If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.

For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long term therapy.

Today a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I’m sure there is a forum somewhere on the internet where patients have reported this). Fortunately he accepted my expert opinion and will continue taking the drug.

If the symptoms persist and the patient continue to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.

Since statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold  for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denials cult thus minimizing the nocebo effect

Antinocebonically Yours

-ACP

N.B. It turns out the reporter had an open mind about the issue of statin-related memory loss. We had a good discussion  and at some point you may see the skeptical cardiologist on TV being interviewed on the topic.

I could bring to the interview one of  my many patients who since starting to take statins have  not had a heart attack or stroke and who have taken statins for decades without side effects.

Now that would make for some compelling and exciting TV!

For a nice discussion of Nissen’s article see Larry Husten’s excellent piece at Cardiobrief.org here (/nissen-calls-statin-denialism-a-deadly-internet-driven-cult/)

 

AliveCor (Kardia) Has A Premature Beat Problem: How PVCs and PACs Confuse The Mobile ECG Device

The skeptical cardiologist has many patients who are successfully using their AliveCor/Kardia devices to monitor for episodes of atrial fibrillation (afib).

However, a significant number of patients who have had atrial fibrillation also have premature beats. Sometimes patients feel these premature beats as a skipping or irregularity of the heart beat. Such palpitations  can mimic the feeling patients get when they go into atrial fibrillation.

The ideal personal ECG monitor, therefore,  would be able to reliably differentiate afib from premature beats for such patients.

Premature Beats: PVCs and PACs

I’ve discussed premature ventricular contractions (PVCs) here and here.  Premature beats can also originate from the upper chambers of the heart or atria.

Such  premature atrial contractions (PACs) have generally been considered benign in the past but a recent study showed that frequent (>30 s per hour) PACs  or runs of >20 PACs in a row were associated with a doubling of stroke risk.

For patients who experience either PVCs or  PACs the AliveCor device is frequently inaccurate.

PACs Misdiagnosed As Atrial Fibrillation

Here is a panel of recordings made by a patient of mine who has had documented episodes of atrial flutter in the past and who monitors his heart rhythm with Alivecor regularly:

Of the ten recordings , four were identified as “possible atrial fibrillation.”

Unfortunately only one of the four “possible atrial fibrillation” recordings has any atrial fibrillation: this one has 7 beats of afib initially then changes to normal sinus rhythm (NSR).

The other 3 recordings identified by AliveCor as afib are actually normal sinus rhythm with premature beats.

The first 3 beats are NSR. Fourth beat is a premature beat

In addition, frequently for this patient AliveCor yields an “Unclassified” reading for NSR with PACs as in this ECG:

PVCs Misread As Atrial Fibrillation

I wrote about the first patient I identified in my office who had frequent PVCs which were misdiagnosed by AliveCor as afib here.

Since then, I’ve come across a handful of similar misdiagnoses.

One of my patients began experiences period palpitations 5 years after an ablation for atrial fibrillation. He obtained an AliveCor device to rec  ord his rhythm during episodes.

For this patient,, the AliveCor frequently diagnoses “possible atrial fibrillation” but  all of his episodes turn out not to be afib. In some cases he is having isolated PVCs:

The first 3 beats in the lower strip are NSR. The fourth beat (purpose circle) is a PVC. AliveCor interpreted this as afib

At other times he has periods of atrial bigeminy  which are also called afib by AliveCor. In this tracing he has atrial bigeminy and a PVC.

 

 

PVCs Read As Normal

Premature beats sometimes are interpreted by AliveCor as normal. A reader sent me a series of  recordings he had made when feeling his typical palpitations. all of which were called normal. Indeed, all of them but one showed NSR. However on the one below the cause of his palpitations can be seen: PVCs.

The NSR beats (blue arrows) followed at times by PVCs (red arrows))

I obtained the “Normal”  tracing below from a patient in my office with a biventricular pacemaker and frequent PVCs who had no symptoms.

Paced beats (blue arrows) PVCs (red arrows)

PVCs Read As Unclassified 

A woman who had undergone an ablation procedure to eliminate her very frequent PVCS began utilizing AliveCor to try to determine if she was having recurrent symptomatic PVCs. She became quite frustrated because AliveCor kept reading her heart rate at 42 BPM and giving her an unclassified reading.

AliveCor is always going to call rhythms (other than afib) unclassified when it counts a  heart rate less than 50 BPM or greater than 100 BPM.

In this patient’s case, every other beat was a PVC (red circles). Her PVCs are sufficiently early and with low voltage so the AliveCor algorithm cannot differentiate them from T Waves and only counts the normal sinus beats toward heart rate.

Accurate AliveCor Readings

I should point out that many of my patients get a very reliable assessment from their devices. These tracings from a woman with paroxysmal atrial fibrillation  are typical: all the Normal readings are truly normal and all the atrial fibrillation readings are truly atrial fibrillation with heart rates  above 100.

AliveCor’s Official Position on Premature Beats

The AliveCor manual states

The Normal Detector in the AliveECG app notifies you when a recording is “normal”.  This means that the heart rate is between 50 and 100 beats per minute, there are no or very few abnormal beats, and the shape, timing and duration of each beat is considered normal.

What qualifies as “very few” abnormal beats is not clear. The manual goes on to state that the AliveCor normal detector has been designed to be conservative with what it detects as normal.

What is clear is that premature beats  significantly confuse the AliveCor algorithm. Both PVCs and PACs can create a false positive diagnosis of atrial fibrillation when it is not present.

Consequently, if you have afib and premature beats you cannot be entirely confident that a reading of afib is truly afib. Strongly consider having the tracing reviewed by a cardiologist before concluding that you had afib.

On the other hand if you are experiencing palpitations and make a recording with Alivecor that comes back as normal do not assume that your heart rhythm was totally normal. While highly unlikely to be afib, your palpitations could still be due to PACs or PVCs.

If a patient of mine has an abnormal or questionable AliveCor recording it is currently a very simple process for me to review the recording online  through my AliveCor doctor dashboard. The recordings can also be emailed to me.

However, Kardia appears to be trying to move new AliveCor purchasers to a subscription or Premium service. In addition, Kardia keep giving me messages that “the doctor dashboard is going away.”

Coralively Yours,

-ACP

Quackery Promotion By Mainstream Media: Part I, Reader’s Digest and Naturopathy

As the skeptical cardiologist surveys the heart health information available to his patients and the lay public, he sees two broad categories of misinformation.

First we have the quacks and snake oil salesman. These are primarily characterized by a goal of selling more of their useless stuff online.

I’ve described this as the #1 red flag of quackery. Usually I’m inspired to investigate these charlatans because a patient asks me about one of their useless supplements.

The second category is more insidious: the magazine or internet news site seems to have as its legitimate goal, promoting the health of its readers. There is no clear connection to a product.

Web MD, which I wrote about here, is an example of this second type.  Hard copy versions of these types of media frequently make it into doctor’s waiting rooms: not because doctor’s have read and approved what is in them. These companies send their useless and misleading magazines for free to doctor’s offices, and the staff believe it to be legitimate.

How does glaringly inaccurate and often dangerous information get into media that ostensibly has as its goal promoting its readers health? Most likely, it is a result of media’s need  to constantly produce new and interesting ways for readers to improve their health.

Clearly, readers will not continue subscribing, clicking and reading such sources of information if there isn’t something new and exciting that might prolong their lives: gimmicks, miracles cures, and “natural” remedies are more alluring than the well-known advice to exercise more, watch your weight, stop smoking and get a good night’s sleep.

Reader’s Digest and Stealth Quackery

A patient recently brought in a printout of Reader’s Digest’s “40 things cardiologists do to protect their heart” which is typical of the second category.

Reader’s Digest was a staple of my childhood. My parents subscribed to it consistently and I would read parts of it. It was small and enticing. Allegedly its articles were crafted so that they could be read in their entirety during a session in the bathroom.

To this day it has a wide circulation. Per Wikipedia”

The magazine was founded in 1920, by DeWitt Wallace and Lila Bell Wallace. For many years, Reader’s Digest was the best-selling consumer magazine in the United States; it lost the distinction in 2009 to Better Homes and Gardens. According to Mediamark Research (2006), Reader’s Digest reaches more readers with household incomes of $100,000+ than Fortune, The Wall Street Journal, Business Week, and Inc. combined.[2]

Global editions of Reader’s Digest reach an additional 40 million people in more than 70 countries, via 49 editions in 21 languages. The periodical has a global circulation of 10.5 million, making it the largest paid circulation magazine in the world.

Reader’s Digest used to run a recurring educational feature on the various body parts and organs of Joe and Jane which intrigued me.

Here’s the first paragraph of “I am Joe’s heart:”

I am certainly no beauty. I weigh 340 grams, am red-brown in color and have an unimpressive shape. I am the dedicated slave of Joe. I am Joe’s heart.

The health information in this series was generally accurate but the presentation lacks the kind of sizzle that apparently attracts today’s readers.

The article my patient brought to my attention is typical of the mix of good and bad information and fluff that mainstream media can produce to attract followers:

Not So Bad But Not Clearly True Medical Advice

#1. I keep a gratitude journal. An internist “at NYU” is quoted as saying: “Studies have recently shown that expressing gratitude may have a significant positive impact on heart health.”

Fact Check: following the links provided provides no evidence to support this claim.

#2  I get 8 hours of sleep a night, every night.  This cardiologist seems to have been misquoted, because her comment is actually “getting a good night sleep is essential. I make a point of getting seven to eight hours of sleep every night…Poor sleep is linked to higher blood pressure.”

Fact Check. One review noted that:

Too little or too much sleep are associated with adverse health outcomes, including total mortality, type 2 diabetes, hypertensionand respiratory disorders, obesity in both children and adults, and poor self-rated health.

Another broke down mortality according to number of hours of sleep.

A J-shaped association between sleep duration and all-cause mortality was present: compared with 7 h of sleep (reference for 24-h sleep duration), both shortened and prolonged sleep durations were associated with increased risk of all-cause mortality (4 h: relative risk [RR] = 1.05; 95% confidence interval [CI] = 1.02–1.07; 5 h: RR = 1.06; 95% CI = 1.03–1.09; 6 h: RR = 1.04; 95% CI = 1.03–1.06; 8 h: RR = 1.03; 95% CI = 1.02–1.05; 9 h: RR = 1.13; 95% CI = 1.10–1.16; 10 h: RR = 1.25; 95% CI = 1.22–1.28; 11 h: RR = 1.38; 95% CI = 1.33–1.44; n = 29; P < 0.01 for non-linear test)

Thus, in comparison to those who sleep 7 hours, those who sleep 5 hours have a 5% increase in mortality and those who sleep 11 hours have a 38% increase in mortality.

These data are based entirely on observational studies so it is impossible to know if the shortened sleep is responsible for the increased mortality or if some other (confounding) factor is causing both.

My advice: Some people do fine with 6 hours and 45 minutes of sleep. Some require 8 hours 15 minutes for optimal function. Rather than obsessing about getting a specific amount of sleep time, it makes more sense to find our through your own careful observations what sleep time works best for you and adjust your schedule and night time patterns accordingly.

#3. I do CrossFit.

Fact Check. There is nothing to support CrossFit as more heart healthy than regular aerobic exercise (which the vast majority of cardiologists recommend and perform).

#4. I meditate. “Negative thoughts and feelings of sadness can be detrimental to the heart. Stress can cause catecholamine release that can lead to heart failure and heart attacks.”

Fact Check. There is a general consensus that stress has adverse consequences for the cardiovascular system. Evidence of meditation improving cardiovascular outcomes is very weak.

A recent review

Participation in meditation practices has been shown to reduce depression, anxiety, and negative mood and thus may have an indirect positive effect on CV health and well-being. This possibility has led the American Heart Association to classify TM as a class IIb, level of evidence B alternative approach to lowering BP.32

Non randomized, non blinded studies with small numbers of participants have suggested a reduction in CV death in those performing regular TM.

However, we need better and larger studies before concluding there is a definite benefit compared to optimal medical therapy.

Thus far, the recommendations have been pretty mundane: exercise, stress reduction and a good night’s sleep is good advice for all, thus boring.

Seriously Bad Advice From Quacks Mixed In With Reasonable Advice

In order to keep reader’s interest (and reach 45 things) Reader’s Digest is going to need to add seriously bad advice.

My patient had circled #34. “I mix magnesium powder into my water. If sufficient magnesium is present in the body, cholesterol will not be produced in excess.”

This bizarre and totally unsubstantiated practice was recommended by Carolyn Dean MD, ND.

What do we know about Dr. Dean?

-She was declared unfit to practice medicine and her registration revoked by the College of Physicians and Surgeons of Ontario in 1995. From quackwatch.org :

  • After being notified in 1993 that a disciplinary hearing would be held, Dean relocated to New York and did not contest the charges against her.
  • Dean had used unscientific methods of testing such as hair analysis, Vega and Interro testing, iridology and reflexology as well as treatment not medically indicated and of unproven value, such as homeopathy, colonic irrigations, coffee enemas, and rotation diets.

-The initials after her name (ND, doctor of naturopathy) should be considered the second red flag of quackery. See quackwatch.org (here) and rational wiki (here) and the confessions of a former naturopath  (here ) for discussions of naturopathy. As noted at science-based medicine:

Naturopathy is a cornucopia of almost every quackery you can think of. Be it homeopathy, traditional Chinese medicine, Ayurvedic medicine, applied kinesiology, anthroposophical medicine, reflexology, craniosacral therapy, Bowen Technique, and pretty much any other form of unscientific or prescientific medicine that you can imagine, it’s hard to think of a single form of pseudoscientific medicine and quackery that naturopathy doesn’t embrace or at least tolerate.

-She has a website (Dr. Carolyn Dean, MD,ND, The Doctor of The Future) where she incessantly promotes magnesium as the cure for all ills.

-She has written a book called “The Magnesium Miracle” (hmm. wonder what that’s about).

-She sells her own (really special!) type of magnesium (see red flag #1 of quackery).

-She writes for the Huffington Post (I’m considering making this a red flag of quackery).

-She is on the medical advisory board of the Nutritional Magnesium Association (an organization devoted to hyping magnesium as the cure for all ills and featuring all manner of magnesium quacks).

Prevention Magazine 

Reader’s Digest is not alone in allowing the advice of pseudoscience practitioners to stand side by side with legitimate sources.

For example, Prevention Magazine in its August 2017 issue highlights “35 All-Time Favorite Natural Remedies” with the subheading

“Go ahead, try them at home: Experts swear by these nondrug cures for back pain, nausea, hot flashes, and other common ailments.”

Who are these “experts”? Let the reader beware because the first quote comes from “Amy Rothenberg, past president of the Massachusetts Society of Naturopathic Doctors.”

Finding The Truth

It’s getting harder and harder for the lay public to sort out real from fake health stories and advice.

When seemingly legitimate news media and widely followed sources like Reader’s Digest and Prevention Magazine  either consciously or inadvertently promote quackery, the truth becomes even more illusive.

Readers should avoid any source of information which

  1. Profits from selling vitamins and supplements.
  2. Utilizes or promotes  naturopaths or other obvious quacks as experts in health advice.

IamJoesfootingly Yours,

-ACP

Dupixen Has Miraculously Cured My Eczema

Although this post is most unskeptical and decidedly noncardiac, the skeptical cardiologist feels compelled to share this information with readers who have or know friends or family with eczema or atopic determatitis, a chronic skin condition that results in itchy, scaly, dry and red skin.

For most of my life I have dealt with periodic flare-ups of eczema along with continuously itchy skin . Control of flare-ups was by meticulous attention to keeping my skin clean and moisturized along with frequent applications of topical corticosteroids.

Things worsened a few years ago and I began to think I might have Red Skin Syndrome, which some dermatologist believe is due to withdrawal from topical corticosteroids.

Two months ago, however, my spirits brightened when I heard that the FDA had approved a new biologic injectable called Dupixent (dupilumab), to treat adults with moderate-to-severe eczema (atopic dermatitis), whose eczema is not controlled adequately by topical steroids.

My fantastic dermatologist, Dr. Amy Ney, agreed this was appropriate therapy for me, and within a week I received a refrigerated package containing the initial dosage: two syringes filled with the drug.

The pre-loaded syringe filled with Dupixent. The syringes come with very detailed instructions to guide you through the process of injecting the liquid into either the abdominal region or the thighs.

 

Within a week of injecting the contents of the syringes into my abdomen, my itching ceased and I had no more eczematous rashes. For me this was a minor miracle.

Since then I’ve injected one 300 mg syringe every two weeks and I continue to be free of my life-long signs and symptoms of eczema.

Atopic Dermatitis and Dupixent

The cause of atopic dermatitis is a combination of genetic, immune and environmental factors. In atopic dermatitis, the skin develops red, scaly and crusted bumps, which are extremely itchy. Scratching leads to swelling, cracking, “weeping” clear fluid, and finally, coarsening and thickening of the skin.

Dupixent’s active ingredient is an antibody (dupilumab) that binds to a protein [interleukin-4 (IL-4) receptor alpha subunit (IL-4Ra)], that causes inflammation. By binding to this protein, Dupixent is able to inhibit the inflammatory response that plays a role in the development of atopic dermatitis.

Dupixent acts by inhibiting two cytokines that are responsible for the hyperimmune response in skin. They are called IL-4 and IL-13. IL is an abbreviation for interleukins, proteins that are produced by leukocytes (3) and play a part in regulation of the immune system. Steroids, such as prednisone, also suppress the immune system, but taking them for an extended period of time will get you into trouble. (See: Prednisone: Satan’s Little Helper) Unlike prednisone, Dupixent inhibits specific targets. It works more like a scalpel than a bomb.

More Stories of Miraculous Relief

I am not alone in experiencing miraculous relief from this new drug. I first heard of it from a  New York Times article in 2016 which details the dramatic responses of several patients who were involved in the clinical trials that proved the drug’s efficacy:

One participant in the trial, Lisa Tannebaum, a 53-year-old harpist in Stamford, Conn., was so thrilled that she wrote a letter to Regeneron suggesting they use her before and after photographs in advertisements. She developed a severe form of the disease 14 years ago and tried everything imaginable in conventional and alternative medicine without relief — specialized diets, immunosuppressive drugs, special clothing, bleach baths. She even had the gold fillings removed from her teeth on the theory that they may be causing an allergic response, but to no avail.

“It was like every day I had poison ivy and fire ants on myself,” she said. “You don’t sleep at all. You can’t go out, you have staph infections all the time,” because the skin’s protective barrier is broken by the rash. “I couldn’t drive my kids to school because the itching was so bad I couldn’t put my hands on the steering wheel.”

Now, she is performing again and will be playing her harp at Carnegie Hall on Oct. 30.

Randomized Controlled Trials Proving Efficacy

Of course we can’t rely on anecdotes to prove the safety and efficacy of drugs: we need randomized, controlled, double-blind studies.

Dupixent has three such clinical trials with a total of 2,119 adult participants, and the results were remarkable. (for details see here). Overall, participants who received Dupixent achieved greater response, defined as clear or almost clear skin, and experienced a reduction in itch after 16 weeks of treatment.

Panel A shows the proportions of patients with the primary end point (both a score of 0 or 1 [clear or almost clear] on the Investigator’s Global Assessment [IGA; scores range from 0 to 4, with higher scores indicating more severe disease] and a reduction from baseline of 2 points or more on the IGA at week 16) among patients who received dupilumab every week, dupilumab every other week, or placebo in SOLO 1 and SOLO 2. Panel B shows the proportions of patients with the key secondary end point (which was considered to be a coprimary end point by regulators in the European Union and Japan) of an improvement from baseline of at least 75% on the Eczema Area and Severity Index (EASI-75) at week 16 in the two trials. P<0.001 for all comparisons between dupilumab and placebo. For binary end points, patients who received rescue medications or withdrew from the study were categorized as having had no response, as were those with all other missing values.
The only side effect which was more common with Dupixent than placebo was conjunctivitis, an inflammation of the eye.

Cost of Dupixent

When I first read of this drug I assumed it would be horribly expensive. In cardiology we have two injectable biologics (Repatha and Praluent, PCSK9 inhibitors) for lowering cholesterol, which typically have been costing my patients with insurance coverage over 1000$ per month.

Fortunately Sanofi/Regeneron have learned from prior experience and priced the drug at $37,000, a number that insurance companies have apparently warmly welcomed. This article suggests that the drug is priced significantly lower than newer biologics now available for psoriasis and rheumatoid arthritis.

With my  insurance (United Health Care) coverage I was asked to pay 150$ for 2 injections per month.

I then discovered that Sanofi has a co-pay card that covers that 150$ so that for now I am paying zero dollars out of the 37,000$.

I’m paying nothing for a brand new biologic injectable that has cured my eczema. Now that is miraculous!

Unskeptically Yours,

-ACP

N.B. Featured Image before and after hand is from National Eczema organization and is not of my hand.

Why Are The Dutch So Heart Healthy and Happy (And Tall)? Part I: Is It Their Diet?

The Skeptical Cardiologist and his  eternal fiancee’ recently spent 5 days in the Netherlands trying to understand why the Dutch are so happy and heart healthy.

We were driven by Geo (former statin fence-sitter) from Bruges to Haarlem, a city of 150,000, which lies about 15 km west of Amsterdam and about 5 km east of the North Sea.

 

Haarlem is one of the most delightful towns I’ve ever stayed in.

 

 

I was struck by  the beauty of its architecture, its canals and the happiness, height and friendliness of its inhabitants.

I was lucky enough to have a bike at my disposal. One day I set off randomly, and after 20 minutes of riding on delightfully demarcated bike lanes, I scrambled up a sand dune and looked out at the North Sea.

Just down the road was the  beach resort of Zandvoort, where one can enjoy sunbathing, surfing or a fine meal while gazing at a glorious sunset.

 

 

 

 

Like Amsterdam, which is a 15 minute train ride away, bikes and biking abound in Haarlem, but unlike Amsterdamers, the Haarlemers were universally engaging, polite and friendly. Everything and everyone seemed clean, well-organized, relaxed and pretty…and, well, …happy.

The Dutch High Happiness Rating

The World Happiness Report 2017, which ranks 155 countries by their happiness levels, was released in March of this year at the United Nations at an event celebrating The International Day of Happiness.

The report notes that:

Increasingly, happiness is considered to be the proper measure of social progress and the goal of public policy

Norway was at the top of the happiness list but

All of the other countries in the top ten also have high values in all six of the key variables used to explain happiness differences among countries and through time – income, healthy life expectancy, having someone to count on in times of trouble, generosity, freedom and trust, with the latter measured by the absence of corruption in business and government.

The top 4 were closely bunched with Finland in 5th place, followed by the Netherlands, Canada, New Zealand, and Australia and Sweden all tied for the 9th position.

Despite the immense wealth of Americans, the report notes:

The USA is a story of reduced happiness. In 2007 the USA ranked 3rd among the OECD countries; in 2016 it came 19th. The reasons are declining social support and increased corruption  and it is these same factors that explain why the Nordic countries do so much better.

Dutch children seem to be especially happy.

A UNICEF report from 2013 found that Dutch children were the happiest of the world’s 29 richest industrialized countries.  America ranked 26th, barely beating out Lithuania and Latvia.

Cardiovascular Disease in The Netherlands

Ischemic heart disease (IHD) deaths are due to blockages in the coronary arteries. Typically, this comes from the build up of atherosclerotic plaques in the arterial system and in most countries heart attacks from this process are the major cause of death.

The Netherlands has the third lowest rate of IHD deaths in developed countries, only slightly higher than France and less than half the rate of the USA.Screen Shot 2017-07-26 at 10.53.26 AM

In all developed countries over the last thirty years we have seen a marked drop in deaths due to IHD. In The Netherlands it has dropped 70% and the rate in 2013 was nearly as low as France’s rate.

In addition, the Netherlands has a very low rate of deaths from  hypertensive heart disease. This table from 2008 shows that they are second only to Japan and their mortality rate is a third of that in the US.

A recent update noted

The current Dutch age-standardised mortality from circulatory disease is 147 per 100,000, and only Spain and France have lower cardiovascular mortality rates (143 and 126 per 100,000, respectively). In all other European countries, including for instance Switzerland and Greece, cardiovascular mortality is higher [26].

What factors could be causing all this happiness and heart healthiness?

The Seemingly Horrid Dutch Diet

We have been programmed to believe that heart attack rates are related to saturated fat in our diets.

The fact that the French consume lots of saturated fat and rank so low in IHD deaths has been called the French Paradox as it seems to contradict the expected association.

One thing is clear-the Dutch are not following a whole foods, plant-based diet. They are among the world leaders in consumption of both fat and sugar as the graph below indicates.

While in The Netherlands I sought out raw herring,  a dish which Rick Steves and others indicate is a Dutch obsession.

Since there is evidence that fish consumption, especially fatty ones like herring and mackerel, is associated with a lower risk of coronary heart disease, perhaps this was protecting the Dutch.

I didn’t see much herring consumption in Haarlem (a native Haarlemer informs me that the Dutch raw herring consumption might be confined to older generations or tourists).

It turns out that the Dutch aren’t meeting their own nutritional guidelines for healthy food .

The recommendation to eat fish at least twice a week, of which at least once fatty fish such as salmon, herring or mackerel, is followed by a mere 14 percent of the population. Less than 25% of them meet the recommended daily amount of fish, fruit, and vegetable consumption.

Screen Shot 2017-07-26 at 11.58.57 AM
purple bar=women yellow bar=men orange bar= total

They do catch and export a lot of fish and shellfish and are in the top 10 of seafood exporting countries (99% of all those mussels consumed in Belgium come from The Netherlands).

And, to my great surprise, they eat lots of French, or as I have started calling them, Flanders fries.

 

I personally witnessed  massive amounts of cheese and butter consumption.

In fact, the Dutch average 15% of calories from saturated fat, which is far above the 10% recommended by the Dietary Guidelines for Americans.

A recent analysis of Dutch fat consumption found:

The mean baseline intake of total saturated fatty acids (SFAs)  in the population was 15.0% of energy. More than 97% of the population exceeded the upper intake limit of 10% of energy/d as recommended by the Health Council of the Netherlands.

The Dutch weren’t eating so-called healthy fats as “The main food sources of SFAs were cheese (17.4%), milk and milk products (16.6%), meat (17.5%), hard and solid fats (8.6%), and butter (7.3%).”

Surprisingly, the more saturated fat the Dutch consumed, the LOWER their risk of death from IHD:

After multivariable adjustment for lifestyle and dietary factors (model 4), a higher intake of energy from SFAs was significantly associated with a 17% lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93)

The Dutch Paradox

Data shows that  the Dutch are eating lots of saturated fat from dairy and meat, but it appears to be lowering their risk for heart attacks

Yes, despite 40 years of high saturated fat consumption, the Dutch have seen a 70% drop in mortality from heart attacks. Their rate of dying from ischemic heart disease is lower than the US and only slightly higher than the French.

Thus, rather than talk about a French paradox, we should be talking about the Dutch paradox.

For the French paradox many theories, both fanciful and serious,  have been proposed

The one most laypeople remember (due to a 60 Minutes episode in 1991) is that the French are protected by their high red wine consumption. Although this theory proved a great boon to the red wine industry (sales rose 40% the year after Morley Safer made his presentation on 60 Minutes), it has never had any serious scientific credibility.  Current thinking is that all forms of alcohol in moderation are equally protective.

Others have proposed garlic or onion or faux gras consumption. My own theory for the French is that it is fine cheese and chocolate consumption that protects them.

In subsequent posts I’ll lay out the evidence for my startling new theory to explain the Dutch paradox.

 

 

What Pain Medications Are Safe For My Heart?

The skeptical cardiologist is frequently asked by patients if it is OK to take certain pain medications.

Yesterday, I got a variation on this  when a patient called and indicated that he had been prescribed meloxicam and tramadol by his orthopedic surgeon for arthritic leg joint pain. The orthopedic surgeon said to check with me to see if it was OK to take either of these medications. (Patients, if you want to skip to my answer skip down to the last two sections of the post and avoid the background information.)

What Is The Risk Of Pain Medications?

Cardiologists have been concerned about the increased risk of heart attack and heart failure with non steroidal anti-inflammatory drugs (NSAIDs) since Vioxx was withdrawn from the market in 2004.

NSAIDS have long been known to increase risk of gastrointestinal (GI) bleeding  by up to 4-5 fold, Scientists developed Vioxx, a COX-2 inhibitor, hoping to reduce that risk but Vioxx  turned out to  increase the risk of heart attack.

Since this revelation it has become clear that NSAIDS in general increase the risk of heart problems as well as GI problems

This includes the two over the counter (OTC) NSAIDS:

-ibuprofen (in the US marked most commonly as Motrin or Advil, internationally known as Nurofen). For extensive list of brand names see here.

-naproxen (most commonly sold as Aleve. Per wikipedia “marketed under various brand names, including: Aleve, Accord, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Maxidol, Midol Extended Relief, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Pronaxen, Proxen, Soproxen, Synflex, MotriMax, and Xenobid. It is also available bundled with esomeprazole magnesium in delayed release tablets under the brand name Vimovo.)

In 2015  the FDA mandated  warning labels on all prescription NSAIDs including

1) a “black box” warning highlighting the potential for increased risk for cardiovascular  (CV) events and serious life-threatening gastrointestinal  bleeding, ulceration, and perforation;

(2) statements indicating patients with, or at risk for, CV disease and the elderly may be at greater risk, and that these reactions may increase with duration of use;

(3) a contraindication for use after coronary artery bypass graft surgery on the basis of reports with valdecoxib/parecoxib;

(4) language that the lowest dose should be used for the shortest duration possible

5) wording in the warning section that there is no evidence that the concomitant use of aspirin with NSAIDs mitigates the CV risk, but that it does increase the GI risk

Since then, hardly a day goes by without me having a discussion with a patient about what drugs they can safely take for their arthritis.

A reasonable approach to using NSAIDS, balancing GI and CV risks, that I have used in the past comes from a 2014 review
This table and many authorities recommend naproxen as the NSAID of choice for patients with high CV risk.

Indeed prior to the publication of the PRECISION study in 2016 I believed that naproxen was the safest NSAID for my cardiac patients. I told them it was OK to use from a CV standpoint but to use the least amount possible for the shortest time in order to minimize side effects.

The PRECISION study compared a COX-2 NSAID (celecoxicib or Celebrex) to ibuprofen and naproxen in patients who required NSAIDS for relief of their joint pain.

The findings:

cardiovascular death (including hemorrhagic death), nonfatal MI, or nonfatal stroke, occurred in 2.3% of celecoxib-treated patients, 2.5% of the naproxen-treated patients, and 2.7% of the ibuprofen group.

There was no placebo in this trial so we can only look at relative CV risk  of the three NSAIDS and it did not significantly differ.

GI bleeding was less with celecoxib than the other two NSAIDS.

Although this study has flaws it throws into question the greater CV safety of naproxen and suggests that all NSAIDS raise CV risk.

My Current Patient Advice on Cardiac Safety of Pain Meds

Here is an infographic I came across from the Arthritis Foundation (complete PDF….here)

It’s a reasonable approach for these OTC drugs and I will start handing this out to my patients.

We should consider that all NSAIDS have the potential for increasing the risk of heart attack and heart failure, raising blood pressure, worsening renal function and causing GI bleeding.

Therefore, if at all possible avoid NSAIDS.

Acetaminophen (Tylenol) is totally safe from a heart standpoint and overall if you don’t have liver disease it is your safest drug for arthritis. However, it provides no anti-inflammatory effects and often is inadequate at pain relief.

Treating The Whole Patient

Meloxicam is an NSAID so my patient should , if at all possible, avoid it.

The other drug he was prescribed, tramadol, is an opiod. Opiods have their own set of problems including, most importantly,  addiction and abuse.

A recent review concluded

 reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date. Accumulating evidence supports the increased risk for serious harms associated with long-term opioid therapy, including overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction; for some harms, the risk seems to be dose-dependent.

As his cardiologist I am concerned about his heart, of course, but a good cardiologist doesn’t just focus on one organ, he looks at what his recommendations are doing to the whole person.

I certainly don’t want to have him become addicted to narcotics in order to avoid a slightly increased risk of a heart attack. On the other hand, the risks of the NSAIDS involve multiple organs, most of which don’t fall in the domain of the cardiologist.

My patient’s risk of taking either the meloxicam or the tramadol is best assessed by his primary care physician, who has the best understanding of his overall medical condition and the overall risk of dangerous side effects from these drugs.

Ultimately, I think the decision of which pain pill to take for chronic arthritis has to be made by an informed patient in discussion with his  informed (and informative) primary care physician. Only the patient can decide how much pain he is having and how much risk he/she wants to assume in relieving that pain.

Analgesically Yours,

-ACP

Unbiased, evidence-based discussion of the effects of diet, drugs, and procedures on heart disease

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