All posts by Dr. AnthonyP

Cardiologist, blogger, musician

Why Does The TV Tell Me Xarelto is a BAD DRUG?

One of my patients called the office today concerned about a medication she was taking because she was “seeing about 4-5 commercials a day about how bad Xarelto is”.

She is the latest of many of my patients who have been inundated with ads like these which state in very strident tones that a drug is bad and that if “you or a loved one has had a serious bleeding problem” contact 1-800-BAD DRUG and see if you are eligible for compensation.

These drugs are not bad and the only reason these advertisements are being played is that tort lawyers sense an opportunity to make money.

To understand why they are flooding the TV market now I will have to give you some background on atrial fibrillation , stroke and the drugs available to reduce stroke risk.

Preventing Stroke Associated With Atrial Fibrillation

Patients with atrial fibrillation are at increased risk of stroke and since the 1950s the only drug available for doctors to reduce clot formation in the heart and susbsequent strokes was warfarin (brand name Coumadin). Warfarin is only effective and safe within a narrow window and its effects are strongly influenced by Vitamin K in the diet and most medications. Thus, frequent blood testing is needed, and close monitoring of diet and changes in medications. Even with this close monitoring, serious and sometimes fatal bleeding occurs frequently with warfarin.

Novel Anticoagulants

In recent years, three new drugs for reducing strokes in patients with atrial fibrillation which are much less influenced by diet and medications have gained approval from the FDA. These are generally referred to as “novel anticoagulants” reflecting their newness, different effects from warfarin or aspirin, and their blood thinning properties.  The first  (brand name Pradaxa) was released to much excitement and fanfare in October, 2010.  The press release for this approval read as follows:

PRADAXA, an oral direct thrombin inhibitor2 that was discovered and developed by Boehringer Ingelheim, is the first new oral anticoagulant approved in the U.S. in more than 50 years. As demonstrated in the RE-LY® trial, PRADAXA 150mg taken twice daily has been shown to significantly reduce stroke and systemic embolism by 35 percent beyond the reduction achieved with warfarin, the current standard of care for patients with non-valvular atrial fibrillation. PRADAXA 150mg taken twice daily significantly reduced both ischemic and hemorrhagic strokes compared to warfarin

Differences Between Warfarin and the Novel Anticoagulants

What was very clear from the study with Pradaxa  and stated very clearly in all publications and patient and doctor  information sources was that just like warfarin, patients could have severe bleeding complications, sometimes fatal. Overall serious bleeding complications were about the same (the rate of major bleeding in patients Pradaxa  in the RE-LY trial was 3.1% versus 3.4% in the warfarin group) but Pradaxa had about 50% more bleeding from the gastrointestinal tract and warfarin about 50% more bleeding into the brain.

Another big difference between the novel anticoagulants and warfarin is that we have antidotes (Vitamin K, fresh frozen plasma) that can reverse the anticoagulation state rapidly for warfarin but none for the newer drugs. This information also was made very clear to all doctors prescribing the medications in the package insert and educational talks. Despite this, in the major trials comparing these newer agents to warfarin, the newer agents were as safe or safer than warfarin.

The Pradaxa Bad Drug Ads

Beginning about a  year after Pradaxa was released advertisements paid for by law firms seeking “victims” of Pradaxa  identical to the ones we are now seeing for Xarelto began to appear.

The Pradaxa ads went away in mid 2014 when these lawsuits were settled and almost immediately the lawyers began paying for Xarelto ads. Xarelto was the second “novel anticoagulant) to be approved by the FDA and, similar to Pradaxa, was proven to as effective as warfarin in preventing strokes with a similar rate of serious bleeding complications.

As the Wall Street Journal noted (with the catchy title “The Clot Thickens” and opening line “Is a blood thinner causing lawyers to smell blood?”)

“Spending (on Xarelto ads)  jumped to $1.2 million in July from just $8,000 in June, according to The Silverstein Group Mass Tort Ad Watch, which noted the number of ads that ran in July exceeded 1,800. …

The spending increased shortly after Boehringer Ingelheim, which sells a rival blood thinner called Pradaxa, last May agreed to pay $650 million to settle about 4,000 lawsuits over claims the drug caused serious bleeding episodes. The settlement likely emboldened attorneys to turn their sights toward Xarelto which, like Pradaxa, is one of a relatively new batch of blood thinners.”

The third drug to be approved for preventing strokes in atrial fibrillation was Eliquis. Data from the large, randomized study comparing it to warfarin suggest that it is more effective at preventing stroke than warfarin and significantly less likely to have bleeding complications. However, I predict that within the year (especially if the Xarelto lawsuits also are settled by its manufacturer) we will start to see lots of TV ads telling us that Eliquis is a BAD DRUG.

It’s important to remember that all drugs have benefits and side effects. Seemingly harmless antibiotics can increase your risk of dying suddenly (see here), rupturing your achilles tendon or developing a life-threatening colitis.

Xarelto is not a BAD DRUG. When prescribed to appropriate patients with atrial fibrillation with  appropriate precautions it prevents strokes which are potentially life-threatening or disabling. All blood thinners are two-edged swords: they stop good clots and bad clots.

Ignore The Ads

Patients are better off ignoring both positive, direct to consumer, advertisements, promoting these newer anticoagulants and negative, greedy-lawyer sponsored advertisements, soliciting “victims”.

Hopefully when your doctor discusses the choices of blood thinners with you he will present to you a balanced discussion of the pros and cons both of whether or not to take  a blood thinner and whether to take the old standby warfarin or one of the newer agents. An interactive discussion should follow in which your particular issues and concerns factor into the final decision.

 

Shoddy Cardiovascular Screenings Are More Likely to Cause Harm Than Good

I was recently made aware, by one of my patients, of a brochure from one of the large hospital chains in the St. Louis area  that advertised “healthy heart screenings.” The website for this enterprise says the following:

Healthy Heart Screenings

In partnership with Health Fair, SSM Health Care will utilize a mobile clinic that will travel around the St. Louis area approximately 16 times per month. Screenings range from basic biometrics to cardiovascular.

Basic test package ($179) includes:
Echocardiogram Ultrasound
Stroke / Carotid Artery Ultrasound
Abdominal Aortic Aneurysm Ultrasound
Electrocardiogram (EKG)
Peripheral Arterial Disease (PAD) Test
Hardening of the Arteries Test (ASI)

Steven Nissen has discussed the dangers of these types of screenings in an article for Cardiosource.org (the online voice of the American College of Cardiology)  entitled “Screenings and Executive Physicals: Hazardous to Your Health.”

Being proactive about cardiovascular health is generally considered to be a good thing, however, these types of screenings have the potential for doing more harm than good.

First off, individuals should recognize that this service is being offered by hospital systems solely for the purpose of getting more patients into their system for further testing and procedures.

Secondly, the service is being performed by a “mobile clinic.” These types of mobile clinics typically exist to make as much money as they can. Quality control is not one of their goals. They seek high volume , rapid throughput and minimal expenses. The mobile clinic is most likely utilizing the cheapest equipment, technicians  and interpreters of these studies that they can get.

Cheap equipment and inexperienced or poorly trained technicians are more likely to yield studies which are difficult to interpret or introduce errors and artifacts. Artifacts in an imaging study are images which appear to be abnormalities but are not. The more artifacts in a study, the more inappropriate subsequent testing will most likely be performed.

One of the tests offered in this package is an ultrasound of the heart or echocardiogram. The echocardiogram is a brilliant technological development that allows us to image the structure and function of the heart. Abnormalities ranging from weakness in the pump function of the heart to leakage from the valves can very accurately be diagnosed with echocardiography when it is done right.  I have devoted a large part of my career to studying, writing about and insuring quality control in echocardiography and I have seen first hand many misdiagnoses made in the hands of the inexperienced, shoddy, greedy or unscrupulous.

Let’s consider the many ways a poorly done or interpreted echocardiogram can lead to more harm than good.

Overcalling valve problems

In addition to imaging the structure or anatomy of the heart, during an echocardiogram a technique called Doppler allows us to measure the direction, velocity and location of blood flow within the heart. Doppler, developed in the 1980s, allows us, among other things, to see if the heart valves are doing their job of allowing blood to move forward while preventing back flow. In many normal individuals, a small or trivial  amount of back flow (called regurgitation or insufficiency) can be noted. The honest, experienced cardiologist will recognize this as normal. However, if the study is performed ineptly and misread, a normal individual could be mislabeled as having a significant heart valve problem leading to unnecessary stress and anxiety and the potential for additional inappropriate and potentially dangerous testing.

This might seem like just a theoretical concern, but in the 2000s as part of a settlement with the drug company Wyeth, the maker of Fen-Phen, hundreds of thousands of patients who had taken Fen-Phen for weight loss were screened by echocardiography to look for valve problems.  Thousands of individuals with normal hearts were diagnosed with significant valvular problems after undergoing echocardiography examinations set up by the lawyers engaged in the suit. These exams were often done in hotel suites and some cardiologists made millions reading thousands of these in a short period of time. Forbes has a good summary of the scandal entitled the $22 Billion Gold Rush  here. To quote:

“Material misrepresentations” amounting to “pervasive fraud” drove 70% of the serious claims that were found payable by the Wyeth trust fund, says Joseph Kisslo, a court-appointed cardiologist who reviewed a sample of 1,000 echocardiograms in late 2004. “Thousands of people have been defrauded into believing that they have valvular heart disease when in fact they do not,” Kisslo said in a report he wrote for the trust.

I saw a number of patients who had been identified by these shoddy echocardiograms as having significant valve problems and were convinced they had serious heart problems. After I obtained and reviewed the echocardiograms I was able to reassure the patients that their hearts were normal.

Misdiagnosing the function of the heart

The echocardiogram is our premier tool for looking at how the main pumping chamber or left ventricle (LV) is working. A left ventricle that is not functioning properly leads to heart failure. The LV fills with oxygen-rich blood from the lungs when it is relaxed (diastole) and then contracts (systole) and pumps the blood out into the aorta and to the rest of the body. Precise and well-made recordings and measurements of the blood flow during diastole allow the knowledgeable cardiologist to interpret how well the heart is functioning during diastole. Similarly, recordings of the LV allow interpretation of function during systole.

Misinterpretation of both the systolic and diastolic function of the heart are common in echocardiograms that are done by inexperienced sonographers and/or cardiologists.

Misinterpretation of artifacts

Due to various technical factors (outlined in detail here), a normal heart imaged by echocardiography may appear to have an abnormality. These artifacts are more likely due to poor quality equipment and inexperienced or incompetent sonographers. The more experienced the cardiologist reading the study, the less likely that these will be interpreted as pathology.

I have encountered numerous examples of what are normal variations of the heart anatomy or artifacts read on echocardiograms as possible tumors or clots or masses within the heart. Patients invariably end up getting unnecessary testing or surgery when such misdiagnoses are made; they also experience unnecessary stress and worry.

Making Sure You Get a Good Echocardiogram

If you are undergoing an echocardiogram, whether it be for screening which I (and the American Heart Association and the American College of Cardiology) do not recommend or for an appropriate indication (see here for appropriate indications), then it is in your best interest for you to make sure that the test is done and interpreted optimally.

Ideally, your test is being done by a sonographer who has undergone a recognized training program and is credentialed as a Registered Diagnostic Cardiac Sonographer (RDCS by the American Registry of Diagnostic Sonographers) or a Registered Cardiac Sonographer (RCS by the Cardiovascular Credentialing International).

Your echocardiogram should be done in a facility which has been certified by the Intersociety Accreditation Committee for Echocardiography (ICAEL). This will insure that the equipment, personnel , reports and interpretations are meeting minimal standards and that there is in place an ongoing program of quality assessment.

Your echocardiogram should be interpreted by a cardiologist who has undergone appropriate training in echocardiography and is staying up to date with the latest technology and information in the area. ICAEL certification of the lab will verify this to some extent. Even better, is a cardiologist who is Board Certified in Echocardiography.

In summary, don’t pay for an echocardiogram done by a mobile lab as part of a cardiovascular screening program no matter where it is performed or who is promoting it.  Although you may think you are being proactive about your health, chances are you will be more harmed than helped by the outcome.

 

Happy Thanksgiving: UpToDate Says Don’t Worry About Saturated Fat Consumption

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UpToDate now says high fat dairy OK!

Despite mounting evidence to the contrary, mainstream nutritional guidelines have, for the last 30 years, instructed Americans to reduce fat and, more specifically, saturated fat in their diets.

As I have written here and here, that advice is not supported by the bulk of evidence and is being challenged. Despite this, the USDA guidelines and the American Heart Association guidelines continue to recommend reducing fat intake.

On October 26, 2014 a highly respected online resource called UpToDate changed its recommendations in this area. I became aware of this when I found an outstanding blog post by Dr. Axel Sigurdsson. Dr. Sigurdsson is a cardiologist and the former president of the Icelandic Cardiac Society who writes a blog called Doc’s Opinion; his recent post is titled: “About Heart Disease, Nutrition, Healthy Lifestyle and Prevention of Disease.”

His post, entitled “We no longer recommend avoiding saturated fats per se” provides an outstanding summary of the importance of the change and I highly recommend reading it.

UpToDate is by far the most commonly utilized online clinical decision resource in the world. A recent paper surveyed physicians and found that

the 4 most frequently used resources were online journals (46%), PubMed/MEDLINE (42%), UpToDate(40%), and online books (30%). The overall rating for UpToDate was high due to the large proportion of residents who reported using this resource (77%).

My hospital pays for a subscription to UpToDate and the medical staff and residents (doctors in training) use it very frequently to access the latest information on preventing, diagnosing and treating diseases.  Hopefully, since the residents represent the future of medicine, these changed dietary recommendations will become more widespread and become the dominant nutritional message to the public.

The UpToDate authors wrote:

“Although it is known that there is a continuous graded relationship between serum cholesterol concentration and coronary heart disease (CHD), and that dietary intake of saturated fats raises total serum cholesterol, a 2014 meta-analysis of prospective observational studies found no association between intake of saturated fat and risk for CHD.

The meta-analysis also found no relationship between monounsaturated fat intake and CHD, but suggested a reduction in CHD with higher intake of omega-3 polyunsaturated fats; a benefit with omega-6 polyunsaturated fats remains uncertain.

Given these results, we no longer suggest avoiding saturated fats per se, although many foods high in saturated fats are less healthy than foods containing lower levels.

In particular, we no longer feel there is substantial evidence for choosing dairy products based on low-fat content (such as choosing skim milk in preference to higher fat milk). We continue to advise reducing intake of trans fatty acids.”

I’m particularly happy to see this change with respect to dairy products because I think the switch to non or low fat diary has been deleterious to Americans’ health and is not supported by data.

As Dr. Sigurdsson observes:

Today, blaming the rising incidence of coronary heart disease 40-50 years ago on the intake of red meat, whole-fat milk, cheese, cream, butter and eggs appears naive at best.

To condemn one macronutrient and suggest it be replaced with another, without having any scientific evidence that such and intervention is helpful, would today be considered careless and irresponsible.

Sticking with the same conclusion for 40 years, despite abundant contradictory evidence is shocking and hard to understand. Hopefully, UpToDate’s recent reconsideration of the issue is a sign that the tide is turning.

Of course, there’s no reason to promote high consumption of saturated fats and surely there will often be healthier options. However, it’s time we stop telling people that avoiding saturated fats may protect them from heart disease. Why should we say such a thing if it’s not supported by evidence?

It will be interesting to see how public authorities such as the American Heart Association will react to recent scientific evidence on the proposed link between saturated fats and coronary artery disease. Will we see a change in the forthcoming 2015 version of The Dietary Guidelines for Americans?

Will their approach be evidence-based or not? Will they accept that red meat, whole-fat milk, cheese, cream, butter and eggs can be a part of a healthy diet? Will they reconsider their recommendations as UpToDate has now officially done? Only time will tell.

Ezetimibe (Zetia) Shown to Reduce Heart Attack and Stroke After Thirty Billion Dollars in Sales

Important findings from the IMPROVE-IT trial were presented at the American Heart Association meeting yesterday. They demonstrate for the first time that the cholesterol lowering drug ezetimibe (brand name Zetia) lowers the risk of heart attack and stroke when added to a statin drug in high risk patients (those who have sustained a heart attack or had unstable angina) over a statin drug plus placebo.

That study showed

 The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was significantly lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99; p = 0.016).

Prior to this study, Zetia had been prescribed to millions of patients since 2002 garnering Merck, its maker, profits of 30 billion dollars despite there being no evidence that it reduced heart attack or stroke.

Dr. Melissa Walton-Shirley wrote an excellent article on the status of Zetia at the beginning of 2014, summarizing thusly:

Perhaps the lesson to be learned is that starting in 2014, let’s not put compounds on the market for human ingestion without knowing if they help or hurt. Let’s make it unacceptable for a company to make tens of billion dollars from the sale of a compound without knowing if it lowers mortality or improves quality of life

I have previously bashed Zetia on this site and I only prescribe it in very rare cases. These new data may change my approach.

Before embracing Zetia, though, I want to see the full paper in published form and examine the data in detail. Many questions need to be answered. For example, the addition of the drug to simvastatin lowered heart attack and stroke compared to simvastatin alone but there was no difference in overall death rates or cardiovascular death rates. That raises a red flag.

In addition, this study does not support the use of Zetia in patients who have not had heart attacks or near heart attacks (primary prevention).

Science moves slowly but inexorably toward the truth if done properly. It’s important that public policy and drug prescribing not get in front of the science as it did with this drug.

 

Greek Yogurt: Extensively Processed and Marketed To Appear Natural and Healthier

IMG_2902Greek Yogurt sales have skyrocketed  in the last five years by 2500%, driven by a perception that it is a “natural” food, healthier than regular yogurt. Plastic bins of Oikos, Fage  or Chobani Greek Yogurt are dominating supermarket dairy section shelves.

The doctor’s lounge refrigerator still has excluisvely Yoplait non fat yogurt which I have written about here and compared to a Snickers bar here.

Greek Yogurt typically costs twice as much as regular yogurt but affluent women are choosing it because when the natural dairy fat is removed from the milk  it is high in protein, very low in fat, convenient and (apparently) tastes good.

What makes a yogurt Greek?

Traditionally Greek yogurt is made by straining regular yogurt through a t-shirt or cheese cloth for a few hours thus separating out the liquid whey component. The whey contains the milk sugar, lactose, and the  whey protein and is acidic. The resulting yogurt is thicker, has less lactose and a higher protein content.

There are no regulations requiring that yogurt labeled Greek yogurt be created in this way and some yogurt makers have utilized the wonders of food processing and technology to add certain thickeners (powdered protein or starch) to regular yogurt , mimicking Greek yogurt and labeling it as such.

You can make Greek yogurt yourself by straining it in a refrigerator for a few hours. You’ll find the liquid whey in the bowl below the strainer. The large manufacturers of Greek Yogurt, Fage and Chobani  in their large factories in upstate New York are creating so much Greek yogurt they have a problem disposing of the  acidic whey . Ultimately, Chobani has begun paying farmers to take the whey and it is fed to livestock.

Chobani Greek Yogurt: How Matters.

Chobani has become the #1 American Greek yogurt by convincing Americans it is the most natural and healthiest. Chobani’s marketing campaign for its 100 calorie products featured messages on the bottom of the aluminum tops one of which stated “Nature got us to 100 calories, not scientists. #howmatters.” When Piper Klemm, a food scientist read this and tweeted a picture of the lid there was a backlash from scientists which ultimately resulted in Chobani apologizing.

One science writer pointed out in detail the contributions of science to all of the ingredients in the Chobani Cherry product including chicory root fiber which is “largely inulin, a polysaccharide that is only partially digested in the human body. It behaves as a soluble fiber and allows the “5 g of fiber” claim on the label”. Other components which owe their origin to science more than nature are “natural flavors” (various compounds extracted from a plant and blended by a flavorist to resemble cherry flavor), and locust bean gum, a “polysaccharide thickener extracted from the seeds of the carob tree”.

It turns out there is a lot of food processing and technology going into Chobani all natural Greek yogurt. In fact, Chobani’s plant in New York was chosen as Food Engineering’s 2013 Plant of the Year. One of the components of that plant is a “separator” manufactured by Westfalia which uses a centrifuge to separate the whey from the yogurt, thus the process of creating Chobani greek yogurt does not involve “straining” the whey from the yogurt in the traditional manner.

Chobani is also disingenuous in its labeling, attempting to hide added sugar by calling it evaporated cane juice. The New York Post reported in June that two separate class action lawsuits were filed against Chobani and Fage for “Defendants purposefully misrepresented and continue to misrepresent to consumers that their products contain ‘evaporated cane juice’ even though ‘evaporated cane juice’ is not ‘juice’ at all – it is nothing more than sugar dressed up to sound like a healthier sweetener,”

Whole Foods Market, Inc. earlier this year said it will stop selling Chobani Inc. yogurt by early next year to make more room for smaller, exclusive brands, especially those that are organic, or don’t contain genetically modified ingredients.

Greek Yogurt: Extensively Processed To Appear Healthy and Natural

If you can find a Greek Yogurt on your supermarket shelves that hasn’t gone through extensive engineering manipulation to remove the healthy dairy fat and has not had a lot of sugar added back then it should make a fine addition to your diet.

Unfortunately the vast majority of Greek Yogurt sold in the U.S. is non or low fat and is made palatable by adding lots of sugar.

I agree with Chobani that how matters when it comes to yogurt. The less processing, the better when it comes to how food is produced and I choose yogurt made very simply from organic,  grass-fed cow  milk plus  live cultures like  that from Trader’s Point Creamery (which is, by the way, on the shelves of Whole Foods in both St. Louis and Atlanta)!

 

 

 

 

Dealing With The (Cardiovascular) Cards You’ve Been Dealt

The skeptical cardiologist was in Atlanta recently  visiting  his Life Coach (LCOSC). Oddly enough, the wife of the LCOSC (who I’ll call Lisa) had just undergone a coronary calcium scan  and it came back with a high score.  Most women her age (58 years old) have a zero score but hers came back at 208 .

What is the significance of a calcium score of 208 in this case?

The CT scan for calcium (discussed by me in more detail here) focuses entirely on quantifying the intense and very specific kind of x-ray absorption from calcium. The three-dimensional resolution of the scan is such that the coronary arteries which supply blood to the heart can be accurately located and the amount of calcium in them very accurately and reproducibly added up. Calcium is not in the arteries normally and only accumulates as atherosclerotic plaque builds up over time. The build up of fatty plaque (atherosclerosis) is the major cause of coronary artery disease (CAD, sometimes termed coronary heart disease (CHD)) which is what causes most heart attacks and most death in both men and women in the U.S.

We can enter Lisa’s numbers into the online MESA calculator to see how she compares to other white 59 year old women. The calculator tells us that 72% of her peers have a zero calcium score and a score of 208  is higher than 95% of her peers. Although the 95th percentile is a good place to be for SAT scores it is not for atherosclerosis. This means substantial amount of fatty atherosclerotic plaque has built up in the arteries and puts the individual at significantly greater risk for heart attack and stroke. A calcium score of 100-300 confers a 7.7 times increased risk compared to an individual with similar risk factors with a zero calcium score.

Most of the risk factors that we can measure to assess one’s risk of heart attack (blood pressure, diabetes, smoking) were absent in Lisa. Her cholesterol levels had risen in the last 10 years but when I entered her numbers (total cholesterol 221, HDL 68) into the ASCVD risk estimator her 10 year risk came back at 2.5%. This is considered low and no treatment of cholesterol would be advised by the new guidelines.

The only clue that her cardiologist would have that Lisa has advanced premature atherosclerosis is that her mother had coronary heart disease at an early age, something we call premature CAD. Her mom at the age of 62 suffered a heart attack and had a stent placed in one of her coronary arteries. The occurrence of significant premature CAD in a parent or sibling  substantially increases the chances that a patient will have premature CAD and the earlier it occurred in the parent or sibling the higher the risk.

Some of this excess risk is transmitted by measurable risk factors such as hypertension and hyperlipidemia and some through lifestyle factors but the majority of it is through genetic factors that we haven’t fully identified.

How much of an individual’s risk for heart attack  is determined by genetics versus lifestyle?

A large Swedish study found that adopted men and women with at least one biological parent with CHD were 1.5 times more likely to have CHD than adoptees without. In contrast, men and women with one adoptive parent were not at increased risk.

Since 2007 an intense project to identify genetic factors responsible for CAD has been underway at multiple academic centers. Thus far 50 genetic risk variants have been identified. According to Dr. Robert Roberts

” All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis”

 How well do the standard risk factors capture the individuals risk for heart attack?

The standard approach to estimating risk fails in about 25% of individuals as it does not accurately convey the high risk of the patient with family history and it overestimates risk in many elderly individuals who have an excellent family history.

It is in these patients that testing for the actual presence of atherosclerosis, either by vascular screening or coronary calcium is helpful.

Reducing The Excess Risk of Premature CAD

For many individuals there are clear-cut lifestyle changes that can be implemented once advanced CAD is identified: cigarette smoking cessation, weight loss through combinations of diet and exercise with resulting control of diabetes, However, many patients like Lisa, are non-smokers, living a good lifestyle, eating an excellent diet with plenty of fresh fruit, vegetables, fish and healthy oils and  without obesity or diabetes. There is no evidence that modifying lifestyle in this group is going to slow down an already advanced progression of atherosclerosis.

Patients like Lisa have inherited predisposition to CAD, it is not due to their lifestyle.

Lisa’s cardiologist  suggested she get a copy of Dr. Esselstyn’s book “Prevent and Reverse Heart Disease”. This book, based on the author’s experience in treating 18 patients with advanced CAD espouses an ultra low fat diet. The author declares that “you may not eat anything with a face or a mother (meat/poultry/fish)” and bans  full fat dairy products and all oil (“not even a drop”)

Such “plant-based diets” (codeword for vegan or vegetarianism) lack good scientific  studies supporting efficacy and are extremely hard to maintain long term. There is nothing to suggest that Lisa’s long term risk of heart attack and stroke would be modified by following such a Spartan dietary regimen.

Her cardiologist did recommend two things proven to be beneficial in patients with documented advanced CAD: statins and aspirin.

Taking a statin drug will arrest the atherosclerotic process and reduce risk of heart attack and stroke by around 30% as I’ve discussed here and here.

An aspirin is now indicated since significant atherosclerosis has now been documented to be present as I’ve discussed here.

We can blame a lot of heart disease on lifestyle: poor diets and lack of exercise are huge factors leading to obesity, diabetes, hypertension and hyperlipidemia, but in many patients I see who develop heart disease at an early age, lifestyle is not the issue, it is the genetic cards that they have been dealt.

Until we develop reliable genetic methods for identifying those at high risk it makes sense to utilize methods such as vascular screening or coronary calcium to look for atherosclerosis in individuals with a family history of premature CAD.

Once advanced atherosclerosis is identified, we have extremely safe and effective medications that can help  individuals like Lisa deal with the cardiovascular cards they have been dealt.

 

 

Examining the Heart of Franklin Delano Roosevelt

The skeptical cardiologist has been watching the Ken Burns documentary on the Roosevelts with the SOSC. I find TR fascinating and have always identified with him (bad eyesight, asthma, bullied as a child) but after he dies in the documentary, my interest flagged. The SOSC soldiered on, continuing to watch the series as FDR guided America through the Depression and into WW2.

My ears perked up and I began watching again when I heard that FDR was diagnosed with severe heart disease and that this was kept secret from the public even after his death until 1970.

In early 1944, he developed symptoms that his personal physician, Vice Admiral Ross McIntire, the Surgeon General of the US (an ENT doctor) thought were lingering aftereffects of  the flu. Ultimately, a second opinion was sought and he was examined at the Bethesda Naval Hospital by a young Naval medical officer, Dr. Howard Bruenn. Dr. Bruenn, unusual for the time, specialized in diseases of the heart. The upstart cardiologist  found the President had a markedly elevated blood pressure and  an enlarged heart and diagnosed him as having heart failure. Mcintire refused to accept this diagnosis initially but was overruled by a panel of “honorary consultants” who agreed with Bruenn after listening to the facts.

What fascinated me about this case was the very limited diagnostic and therapeutic modalities available to the cardiologist at that time, even for the most important person in the world. I tend to think of 1945 as in the modern era. After all, this is when the atomic bomb was developed and we had remarkably sophisticated ways of killing other humans. But in medical and cardiology advances, it was still the equivalent of the dark ages.

Cardiac Diagnostic Tools circa 1945

The diagnostic tools available to Dr. Bruenn were as follows:

1. Physical exam. He was able to listen to the lungs and hear “sibilant and sonorous rales” which suggested fluid accumulation. He palpated the point of maximal impulse of the heart (the apex) and felt that it had shifted more laterally, thus suggesting enlargement. He heard a “blowing systolic murmur at the apex.”   A murmur is basically a sound that corresponds to blood flowing across the cardiac valves, and when heard, often corresponds to a valve leakage (regurgitation) or narrowing (stenosis).

The physical exam remains an important tool for cardiologists. It is free of radiation, cost and (usually) discomfort. It does take time and an experienced examiner to do properly. The findings are often not accurate enough to be sure about a diagnosis. For example, the crackling sounds or rales heard in FDR’s lungs could be due to fluid seeping into the small air sacs of the lungs from high pressures in the heart or they could be related to a lung problem (possibly related to his long time cigarette smoking).

The murmur that was heard during systole (the time that the heart muscle is contracting or squeezing) could be due to leakage from the mitral or tricuspid valve, narrowing across the aortic valve or a hole between the left and right ventricles.

2. Vitals signs. Blood pressure and pulse with techniques essentially unchanged from today.

BP was 186/108. Very high and in the range where one could anticipate damage to “end-organs” such as the heart, the kidneys and the brain. His resting pulse was 72 beats per minute.

3. Chest radiograph of x-ray. This test suggested congestion in the lungs and enlargement of the cardiac silhouette. Prior to the advent of more advanced cardiac testing, the only information on heart chamber sizes came from chest x-rays. We still utilize chest x-rays in heart failure patients to look at the lungs for fluid and congestion but their accuracy is limited.

4. EKG. The electrocardiogram had been utilized clinically to record the electrical activity of the heart  since the early 1900s. FDR’s initial ECG is depicted below. He was in the normal rhythm but showed evidence for enlargement of the left ventricle and perhaps a problem with ischemia, our term for lack of blood flow to the heart.ekgfdr1

 

 

 

We still use these diagnostic tools to the present day, but recognize that a significant amount of heart failure patients will be misdiagnosed without more sophisticated testing and that the precise cause of the heart failure will remain obscure.

Modern Cardiac Diagnostic Tools

By 1984, when I began my training in cardiology, cardiologists had developed the cardiac catheterization and the two-dimensional echocardiogram which precisely tell us about the complete anatomy and physiology of the heart.  These tools, if present in 1945 would have allowed determination of the pumping function of FDR’s heart, the level of pressure within each chamber of his heart, the function of the valves (and cause of his murmur) and the presence of any blocked arteries supplying blood to the heart. Without them, his cardiologist could only speculate and without an autopsy (forbidden by Mrs. Roosevelt despite the urgent request of the Russian authorities who thought he might have met foul play) we will never know what was causing his symptoms with certainty.

Once the diagnosis was made, FDR’s doctors had very limited treatment modalities available.

Hypertension Treatment Entirely Unsatisfactory

Mark Silverman, has summarized the entirely unsatisfactory approach to hypertension in 1950:

In many cases, no treatment was given on the belief that the symptomatic patient would live for many years without complications. Furthermore, physicians did not want to frighten patients by creating alarm, often informing them of a “tendency” to high blood pressure. Patients were strongly advised to achieve mental and physical tranquility by living at a lower tempo, resting and sleeping long hours and avoiding the strains of work, heavy meals and emotional upset. A mental component was strongly suspected and sedatives such as phenobarbital, chloral hydrate and bromides were used and psychotherapy might be recommended. Alcohol in moderation was permitted and thought to be helpful as a sedative and vasodilator. Salt was stringently restricted,… Drug treatment was limited to thiocyanate and veratrum alkaloids, both highly toxic drugs that were poorly tolerated.

Dr. Bruenn recommended bed rest to which Dr. McIntire replied: “You can’t do that. He’s the President of the United States.”

Despite the recognition that FDR’s BP was dangerously high and the likely cause of his heart failure, there were no medications available to lower his blood pressure.

Over the next year, FDR’s BP remained dramatically high as you can see in this chart taken from Dr. Bruenn’s 1970 paper:

BPS of FDR
After FDR suffered his fatal cerebral hemorrhage his BP was recorded as “well over 300 mm Hg systolic” and 190 mm Hg diastolic, numbers higher than any I have ever encountered in my practice.

 

 

 

 

 

Bruenn felt that FDR definitely had coronary artery disease, based on one episode of very typical chest pain during a speech.

“He never complained of any chest pain except, if you remember, on one occasion when he gave a speech at Bremerton, WA, on the fantail of a destroyer. 2 He kept on with the speech and came below and said, “I had a helluva pain!” We stripped him down in the cabin of the ship, took a cardiogram, some blood and so forth, and fortunately it was a transient episode, a so-called angina, not a myocardial infarction. But that was really a very disturbing situation. That was the first time under my observation that he had something like this. He had denied any pain before. But this was proof positive that he had coronary disease, no question about it.”

In 1946, one year  after FDR’s death, Dr. McIntire wrote  that FDR’s blood pressure and heart signs had been normal. Dr. McIntire has been accused by historians of destroying FDR’s medical records (they disappeared mysteriously) to hide his misdiagnosis and mismanagement of the President’s case.

It wasn’t until the publication in 1970 by Dr. Bruenn of “Clinical Notes on the Illness and Death of President Franklin D. Roosevelt” in the Annals of Internal Medicine that the record was set straight. I obtained the EKG and BP graph of FDR above from that paper.

Fortunately, in the years since FDR suffered from many of the consequences of untreated hypertension multiple effective and safe antihypertensive drugs have been  developed. It is the rare patient now that we  cannot get the blood pressure down to the current guideline level of 140/90mm Hg (150/90 for >60 years). With this success in BP reduction has come substantial drops in stroke, heart failure and heart attack rates.

 

Sugar in the Morning, Evening and Supper Time

IMG_2885Added sugar is everywhere you turn in America. The skeptical cardiologist visited Home Depot recently to buy a rake and was confronted by row upon row of candy and processed  treats at the check-out counter.

I’m pretty sure I could have raked leaves for an hour and not burned off the useless calories from one of those Kit Kat bars.

Whole Foods, self-proclaimed “America’s healthiest grocery store”  always has vast rows of useless “function drinks” full of added sugar (and useless chemicals) prominently displayed at strategic spots throughout their stores.

The easy target in the battle against obesity and cardiovascular disease would seem to be added sugar. Sugar-sweetened beverages, which have no nutritional value and just contribute empty calories, are easiest target of all.

How can we convince our patients to reduce added sugar consumption? One approach that has been suggested is to tax added sugar in some way.

Voters in San Francisco and Berkeley today are deciding whether their communities will impose a tax on sugary beverages.

In San Francisco this would be a 2 cent tax per ounce on  any beverage that contains added sugar and 25 or more calories per 12 oz.  Prop. E would levy tax on some juices, coffees and flavored waters and  would raise more than $31 million a year. The money would go to children’s nutrition and physical education programs.

The soda industry has spent 7.7 million dollars in San Francisco fighting this with a heavy marketing campaign. The feeling is that if such a measure passes in one city, it could spread across America.

Readers of this blog know that I consider sugar not fat as the major toxin in our diet, contributing to obesity, diabetes and ultimately heart attack and stroke. I’ve also pointed out that huge amounts of added sugar that are hidden in smoothies, coffee drinks, and non fat yogurt.

I’m a huge advocate of not consuming these types of beverages but I’m not convinced  that this tax is the right approach.

We certainly have a precedence for taxing products which individuals consume that science and society agrees are harmful such as alcohol and tobacco. Added sugar is different in that there are so many different vehicles for its delivery.  Will taxing soda result in more candy and donut consumption?

I’d like to see one or both of these measures pass and hopefully we can monitor closely the results in these northern California cities, gathering data on overall sugar consumption as well as sugar-sweetened beverage consumption. Hopefully, measures like these will lead to greater consumer awareness of the problem of added sugar and reduction in its consumption.

Two Spades or Two Diamonds, Two Ladies and Two Studies

I saw two delightful eighty-something ladies recently whose cases highlight some important points about atrial fibrillation, stroke and long term heart monitors.

Ms. M was playing bridge and found that she had 7 spades solid (solid, Mrs M informed me, means you have 7 of the suit with all of the honors (ace, king, queen, jack). Instead of bidding 2 spades which she meant to do, she bid 2 diamonds, and her partner responded by bidding 5 diamonds. This miscommunication resulted in a disastrous hand for the pair.

Ms. K  told me she had had an episode of “mass confusion” two weeks earlier during which for 15 seconds her “thinking process was not working properly.”

These cases illustrate the subtlety and brevity with which transient ischemic attacks (TIAs) or mini strokes can manifest. In contrast to the normal forgetfulness that is associated with aging, these women recognized  a sudden, transient and disturbing major alteration in their baseline mental processing.

TIAs are basically strokes that resolve quickly, generally within 24 hours, and leave no residual symptoms. They are often a warning that larger, more permanent strokes will follow.

In both of these cases, when I first saw the patients, they were in normal or sinus rhythm but subsequent monitoring revealed atrial fibrillation (AF).

Cryptogenic Strokes

A quarter of the 500,000 strokes occurring annually in America are unexplained (the medical literature tends to use the exotic and Halloween-appropriate term, cryptogenic for unexplained strokes). This means that imaging of the brain and arteries to the brain finds no abnormalities that would cause a stroke and that the patient has no history of AF. Since there is such a strong association between atrial fibrillation, clot formation in the heart, and stroke, (see my post on AF here) doctors assume that an otherwise unexplained stroke in a patient with AF is due to a clot leaving the heart and landing in an artery to the brain. These patients benefit from medications which reduce the risk of clot formation (either warfarin or one of the newer anticoagulants everyone has been hearing about either from negative TV ads from lawyers or positive direct-to-patient drug company ads).

New evidence suggests that if we monitor the heart rhythm for 30 days of patients who have had unexplained strokes a significant percentage will manifest atrial fibrillation.

A Canadian study of 572 men over the age of 55 who had had a cryptogenic stroke or TIA found that atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in those who underwent 30 day monitoring, as compared with 9 of 277 (3.2%) in those who were only monitored for 24 hours.

Another study evaluated 441 patients following cryptogenic stroke with half randomized to receiving an insertable cardiac monitor (we call these implantable loop recorders (ILR) in the US). The ILR is a small device that can be inserted under the skin in the left chest region and allows continuous monitoring of the heart rhythm. After 6 months, atrial fibrillation had been detected in 8.9% of patients in the ILR group, versus 1.4% of patients in the control group. At 12 months it was 12.4% versus 2%.

Neither of my two ladies felt palpitations (a sense of the heart beating irregularly) that would have suggested a problem with the heart. About half of my patients with AF will feel their heart fluttering or “flip-flopping” or racing when the heart goes out of rhythm but the rest of my patients feel nothing. Thus, AF can be silent and I have many patients whose first symptom was a TIA or stroke.

These two ladies and two studies have taught (or reinforced for) me the following:

TIAs can be very subtle. Patients need to be aware of transient episodes of significant confusion or speech difficulties and report them to their doctors. We doctors need to pay close attention when patients report such episodes.

The patient who has had a cryptogenic stroke or TIA should undergo long term cardiac rhythm monitoring looking for AF. My take on the literature at this point is that we don’t need to do the more expensive and invasive ILR. I think a 30 day monitoring device that is capable of automatically identifying AF is sufficient.

Trends in Fat and Yogurt Consumption: We Eat Less Fat yet Get Fatter

A recent paper in JAMA and a Seinfeld episode shed some light on the change in diet and fat consumption in Americans initiated by national nutritional recommendations beginning in the 1970s.

Based on weak to nonexistent scientific evidence Americans were told to consume less total fat and cut saturated fat consumption to less than 10% of calories.

The paper shows that women in the St. Paul-Minneapolis area  followed this advice and cut fat consumption as a % of total calories from 38.4% in 1980-1982 to 30.6% in 1995-1997. Saturated fatty acids dropped from 13.5 to 10.5%. (Since then, total fat % and SFA % has drifted slightly upward and calories downward )(for the full table see fat consumption table (PDF))

Media summaries and reports on this paper have emphasized that Americans have failed to cut their saturated fat consumption to meet recommendations of the USDA (<10%) and the American Heart Association (<6%) with a call for more promotion of these (mis)guidelines.

The skeptical cardiologist has a different take.

Interestingly total calories during these time intervals went up from 1645 to 1851. Thus, in replacement of the fat calories, the women were consuming the carbohydrates and sugars the food industry had obligingly added to food to make it more palatable,  “heart healthy” and comply with guidelines.

The authors discuss the fact that during these time intervals, despite slashing fat consumption,  overall rates of obesity substantially rose. Their explanation was that the women were “underreporting” fat consumption.

A simpler and more compelling explanation is that replacement of fat with carbohydrates along with overall increase in calorie consumption was the culprit.

The Non-Fat Yogurt Scam and Seinfeld

One ongoing contributor to the phenemon of replacing healthy real food fats with engineered, highly processed and highly sugared foods is the yogurt industry.

I wrote about the non fat yogurt scam about a year ago in this post.

I happened to see the fantastic Seinfeld episode “The Non-Fat Yogurt” last night . In this episode Jerry, Elaine and George eat at a non-fat frozen yogurt shop. Everyone concurs that the yogurt is surprisingly delicious given that it is “non-fat” and begin eating it regularly.  Jerry and Elaine gain weight  and begin suspecting that the yogurt is not truly “non-fat”.

This episode aired in 1993 during the height of the shift toward unhealthy low fat, processed substitutes.  An analysis of the yogurt revealed that it was not non-fat and this is why they were gaining weight. In reality,  people get fat on truly non-fat yogurt (even Greek Yogurt) and non-fat cookies and non-fat smoothies and  anything with added sugar.

Fat consumption doesn’t make you fat.

Enjoy this snippet from the episode (and please excuse the bad language)