Tag Archives: statin

Are You Taking A Statin Drug Inappropriately Like Eric Topol Because of the MyGeneRank App?

The skeptical cardiologist was listening to a podcast discussion between Sam Harris and Eric Topol recently and became  flabbergasted.

Topol, the “world-renowned cardiologist” who is seemingly everywhere in media these days was discussing what he considers the overuse of imaging technology during the podcast which Harris’s website describes as follows:

In this episode of the Making Sense podcast, Sam Harris speaks with Eric Topol about the way artificial intelligence can improve medicine. They talk about soaring medical costs and declining health outcomes in the U.S., the problems of too little and too much medicine, the culture of medicine, the travesty of electronic health records, the current status of AI in medicine, the promise of further breakthroughs, possible downsides of relying on AI in medicine, and other topics.

Personally, I have been amazed at the hype and promotion that artificial intelligence (AI) has been getting given the near total absence in cardiology of any tangible benefits from it and I wanted to hear what the man who wrote ” Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again ” had to say about it.

About 28 minutes into the podcast, Harris, who has lately been preoccupied with promoting meditation as a cure for all ills, begins describing a procedure he underwent:

I’ve had a few adventures in cardiology. CT scan, calcium score scan.

Harris, who in neuroscience and philosophy might speak precisely, here is very vague. Did he get a coronary calcium scan (CAC) or a coronary CT angiogram? There is a huge difference and he is conflating the two imaging procedures.

Apparently he is unhappy with having undergone it but:

I might be telling a different story if my life was saved by it.

And his doctor’s rationale  for getting the scan was lacking:

The way this was dispensed to me. We now have this new tool, let’s use it.

Let me just say at this point that if your doctor’s rationale for performing a test is that he has a machine that performs the test just say no. Or demand an explanation of how the results will change your management or prognosis.

Apparently the scan that Harris had didn’t turn out either horrifically worse than expected or remarkably better and didn’t change management:

In my case at the end it didn’t make sense.

Now, I can forgive Sam Harris for being somewhat naive and misguided when it comes to coronary artery scans or coronary CT angiograms but Eric Topol , the world’s leading talking cardiology head should fully understand the value of coronary artery calcium scans.

This is where I first become flabbergasted.

Topol says in response at this point that coronary artery calcium scans are “terribly overused” and that “I’ve never ordered one.”

Eric, you cannot be serious!

Are you telling me that you wouldn’t order one on your 60 year old airline pilot friend whose father dropped dead of a massive MI at age 50 but whose lipids look fine?

Why doesn’t Eric order CACs?

Because “There are so many patients who have been disabled by the results of their calcium score even though they have no symptoms.”

This is where the degree of my flabbergastment increased by an order of magnitude.

Our job as preventive cardiologists is to identify those at high risk and lead them to lifestyle choices and medicine that dramatically lowers that risk.  We educate them that the large build up of subclinical atherosclerosis we identified does not have to result in sudden death, crippling heart attacks or strokes. We reassure them that with the right tools we can help them live a long, productive and happy life.

Eric, what do you tell these people? The calcium score is irrelevant? You’re fine. You shouldn’t have gotten it. Surely not! This would be the preventive cardiology equivalent of sticking one’s head in the sand.

This is not the first time Topol has opined on the dangers of CAC. An excerpt from his book, ‘The Patient Will See You Now: The Future of Medicine Is in Your Hands” posted on Scientific American describes the ills created in a 58 year old man who had a CAC score of 710.

My patient was told that he had a score of 710—a high calcium score—and his physician had told him that he would need to undergo a coronary angiogram, a roadmap movie of the coronary anatomy, as soon as possible. He did that and was found to have several blockages in two of the three arteries serving his heart. His cardiologists in Florida immediately put in five stents (even though no stress-test or other symptoms had suggested they were necessary), and put him on a regimen of Lipitor, a beta-blocker, aspirin and Plavix.

This case is not an example of inappropriate usage of CAC it is an example of really bad doctoring and failure to utilize the CAC information properly.

One should never order a cardiac catheterization/coronary angiogram solely on the basis of a high CAC score. Even ordering a stress test in this situation is debatable as I discuss here.

And Topol’s patients symptoms were most likely related to a beta-blocker that he didn’t need (see here).

My Gene Rank

Later in the podcast I reached maximum flabbergast  levels when Topol announced that as a result of a high score for CAD risk he received using an iPhone app called MyGeneRank he had started taking a statin drug.

He enthusiastically promoted the app which his Scripps Translational Science Institute developed and urged listeners to utilize this approach to better refine the estimate of their risk of heart attack and stroke.

Per the Scripps website:

The MyGeneRank mobile app is built using Apple’s ResearchKit, an open source framework that enables researchers and programmers to build customized mobile apps for research purposes. With user permission, the app connects with the 23andMe application program interface and automatically calculates and returns a genetic risk score for coronary artery disease.

In addition, the app calculates a 10-year absolute risk estimate for an adverse coronary event, such as heart attack, using a combination of genetic and clinical factors. Users are able to adjust behavioral risk factors to see the influence of lifestyle habits on their overall risk.

Elsewhere, Topol, has stated

“We are excited to launch a unique study that combines an iOS app and genomics to help guide important health decisions,” says Eric Topol, MD, Founder and Director of the Scripps Translational Science Institute and Professor of Molecular Medicine at The Scripps Research Institute. “Not only does participating in the study arm individuals with their own data, but it also gives them the opportunity to participate in new type of research – one that is driven by and for patients.”

Curious, I downloaded the MyGeneRank app, answered some questions and gave it permission to access my 23 and Me data. After requiring me to complete a survey on my health it then  yielded  my coronary artery disease risk score.








Oh, no! My genetic risk score was at the 81st percentile! In the red zone.  According to Eric Topol I should take a statin like him. Based on these results I probably should be incredibly anxious and crippled by fears of cardiac death.

Fortunately, I have superior information to allay my fears. I’ve had CAC scans in the past which are well below average for men my age. Despite my dad’s history of early CAD, a recent coronary CT angiogram showed minimal plaque. I know exactly where I stand risk-wise.

How many cardiac cripples has Topol’s MyGeneRank inappropriately created?

Is the data that MyGeneRank utilizes superior to that from CAC scans?

For coronary artery calcium scanning there is a wealth of data supporting improved risk prediction and we are looking directly at the atherosclerotic process that eventually causes the diseases we want to prevent.

It’s interesting that a recent study looking at a polygenetic risk score’s ability to predict cardiac events was comparing the risk score’s ability to predict subclinital atherosclerosis:

Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque.

In the Scientific American article Topol quotes Mark Twain:, “To a man with a hammer, a lot of things looks like nails that need pounding.”

Topol’s hammer is artificial intelligence. We eagerly await the day he discovers a nail that he can bang on that  significantly advances medical care.

In the meantime I and the vast majority of progressive preventive cardiologists will be utilizing CAC scores intelligently to identify both those patients at high risk for cardiovascular events who need more aggressive treatment and those at low risk who can be reassured and have treatment de-escalated.

Polygenetic CAD risk scores do show promise to improve our predictive powers but more study is needed in this are before we make clinical treatment decisions based on the results.

Astoundingly Yours,


Ilene Has High Cholesterol With A “Wonderful Ratio” And A Branch Retinal Vein Occlusion: Should She Take A Statin?

Recently the skeptical cardiologist was asked by Ilene, a reader with an HDL almost as high as her LDL and a history of branch retinal vein occlusion (BRVO) whether she should take the statin her cardiologist had prescribed.

I enjoy reading your articles and would appreciate your opinion on my situation.  I recently took a lipid panel blood test: total cholesterol: 244 HDL:112 LDL:121 VLDL:11  CRP: 1.77 Triglycerides: 57.  Also my Cardiac Agatston  score is 21.
I had a Branch Retinol Vein Occlusion a year ago in my left eye  (it’s healing beautifully) and as a precaution  am now taking Amlodipine 5mg daily (my blood pressure was never too high to begin with) along with a daily baby aspirin.
I am otherwise a healthy 72 year old woman, exercise and eat healthy.
My regular doctor (Integrative MD) says my cholesterol ratio is wonderful….my cardiologist wants me to take a statin (Atorvastatin) in a low dose.  The ONLY med I take is Amlodipine and I am not one to be taking a plethora of meds for the rest of my life (unless “absolutely” necessary.  What is your suggestion…take a statin or not.
While I can’t provide medical advice to Ilene specifically it is worthwhile  to ponder  the general aspects of her case and how I would approach it as it likely applies to thousands of other patients including many of my own.
In my mind there are two questions here: 1) Should Ilene and patients like her take a statin to prevent future heart attacks and strokes and 2) Do statins  effect the Branch Retinal Vein Occlusion (BRVO)?
Although I’m not a fan of integrative or functional medicine Ilene’s integrative MD is correct in saying that her ratio of total cholesterol to HDL cholesterol is wonderful. Perhaps that high  HDL is protecting her from a build-up of atherosclerotic plaque.
On the other hand, Ilene tells me that  “My father did have a heart attack in his 60’s”.  Perhaps she inherited something from him that puts her in a higher than average risk category.
With the information from the CAC we don’t have to guess about the influence of the high HDL and the family history of CAD. Her score is at the 48th percentile, slightly below average for white women her age, thus it would appear she is not destined for her father’s fate.
Frequent readers of skepcard (especially my posts on statin fence sitters) will know I  plug all these numbers (preferably with the calcium score available) into the MESA coronary calcium risk calculator
In this case, the CAC score does not significantly alter our risk estimate as it is so close to the average for her age
Even if we count her as having hypertension because she is on the amlodipine her 10 year risk of heart attack and stroke is low at 3.2%.
Guidelines don’t recommend statin treatment unless risk is >7.5%.
Also, note that I answered yes to “Family history heart disease” but most studies generally only consider this a risk factor if father had heart attack prior to age 55 years. If we make that a no the risk drops to <3%.
Now that we’ve answered Ilene’s real question let’s see if the BRVO warrants statin therapy.
Branch Retinal Vein Occlusion
BRVO is the blockage of a vein from the retina and the second most
common cause of vision loss from retinal vascular disease, following diabetic retinopathy. It typically  results in the painless loss of vision in one portion of one eye due to hemorrhage and edema in the retina.
A reasonable summary of BRVO provided by the American Academy of Ophthalmology can be found here.
BRVO is not clearly related to atherosclerosis or hyperlipidemia and there is no evidence that taking a statin would prevent recurrence or help the condition.

The leading theory for what causes BRVO is that the more delicate and distensible retinal veins are squished or compressed at points where the stiffer and thicker retinal arteries cross them.  Up to Date notes:

Whereas branch retinal vein occlusion (BRVO) appears to be related to compression of the branch vein by retinal arterioles at the arteriovenous crossing points, central retinal vein occlusion (CRVO) is usually associated with primary thrombus formation.

Although BRVO is more common in patients with hypertension and atherosclerosis it is not clear that one causes the other or that treatment of hypertension or atherosclerosis diminishes the risk of BRVO.  So statins are not recommended.
More Questions
Every patient case for me leads to more questions,  more investigations and more knowledge. Here are some questions that occurred to me from ilene’s case.
-Why would someone with no symptoms and no heart problems be seeing a cardiologist?
(“I started seeing a cardiologist just to make sure all systems were “go” and stayed that way!… we take care of our cars so why not my body. )
I kind of like this answer and I definitely see lots of patients with that philosophy but if we extrapolate the car analogy: going to a cardiologist would be like taking your car to a mechanic who only works on engines or perhaps one specific part of the engine (help me out here people who know about cars.)
-Why was Ilene unwilling to take a statin? (I pretty much know the answer to this (see here) for most patients.
‘m just afraid of the horrible muscle related side effects of statin drugs…and that’s why I’m taking Berberine 500mg twice a day.
Yep. I feel a post abut Berberine may be in the works!
-Finally, should a 72 year old with a CAC score of 21 and BRVO be taking a baby aspirin?
I’ve generally advocated aspirin in primary prevention for scores >100  so wouldn’t advise it for prevention of cardiovascular events in this situation.
In addition, I have seen nothing in the literature that recommends aspirin for BRVO. These two BRVO experts do not recommend either aspirin or anticoagulants.
Proretinally Yours,
N.B. If you have a blockage of the the artery that supplies blood to the retina or a branch retinal artery occlusion ( BRAO)
you might benefit from a statin as this is often caused by a clot or plaque flying out of the heart or the carotid artery.

Prevention of Heart Attack and Stroke-Early Detection Of Risk Using Coronary Artery Calcium Scans In The Youngish

Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.

How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.

We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.

Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.

Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.

I’ve been utilizing CAC (also termed  heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for

adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain

Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.

To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.

Significant Of CAC Score

As the new ACC/AHA guidelines state:

If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.

A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.

Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years

Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400

Patients without a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.

On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.

Patients with CAC who were prescribed a statin had a significantly reduced risk of MACE (aSHR: 0.76; 95% CI: 0.60 to 0.95; p = 0.015), whereas patients without CAC had no associated MACE reduction (aSHR: 1.00; 95% CI: 0.79 to 1.27; p = 0.99). p = 0.097 for interaction between statin treatment and CAC presence. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s)

The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.

Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.

Benefit of statin therapy was significantly related to CAC group with benefit in patients with CAC score >100 but not in patients with CAC <100. aSHR = adjusted subhazard ratio; CAC = coronary artery calcium; CI = confidence interval; MACE = major adverse cardiovascular event(s).

But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).

Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)



Benefits of CAC Testing In The Young

So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.

But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.

The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events.  It was  a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.

The conclusions:

Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.

screen shot 2019-01-19 at 12.36.44 pmI read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.

The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them  10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.

Other Risk-Enhancing Factors To Consider In The Young

The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.

screen shot 2019-01-19 at 7.33.39 am

Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?

What about nontraditional lipid/biomarkers?  I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.

Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.

Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.

It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.

Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.

Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.

Skeptically Yours,


Don’t Stop Taking Your Statin Cholesterol Drug Based On The Latest News Headline

In a previous post the skeptical cardiologist discussed his approach to a typical sixty-something male, Geo,  who was “on the fence” about taking the statin drug his PCP had recommended (see here.)

After acquiring more information on his level of subclinical atherosclerosis (coronary calcium and vascular screening), and discussing the risks and benefits of statins for primary prevention, I wrote about his experience in using my recommended “compromise approach.”

This approach utilizes a low dose of rosuvastatin taken intermittently with the goal of minimizing any statin side effects, but obtaining some of the benefits of statin drugs on cardiovascular risk reduction.

It worked well for Geo; taking 5 mg rosuvastatin three times weekly lowered his LDL-C (bad cholesterol) by 50%, and he had absolutely no side effects when I reported on him 6 months after starting the drug.

However, when I stayed with Geo and his lovely wife, Wendy, over Thanksgiving in their Annapolis, Maryland house, Geo revealed that he had stopped taking his statin.

Like many patients, he was swayed by a news report suggesting an important “new study” that suggested there was no relationship between cholesterol and heart disease, and that statin drugs were dangerous and should be stopped.

At first I thought the story that he had read was the one I reported here which (appropriately) questions the benefit of statins for primary prevention in patients over the age of 75.

However, after a bit of searching, Geo told me the article that caused him to stop taking his statin was a UK Daily Mail one entitled:

‘No evidence’ having high levels of bad cholesterol causes heart disease, claim 17 physicians as they call on doctors to ‘abandon’ statins

The Daily Mail article says at one point

But the new study, based on data of around 1.3 million patients, suggests doling out statins as a main form of treatment for heart disease is of ‘doubtful benefit’.

Is this really a “new study” that contradicts the great body of evidence showing that statin treatment is safe and effective in preventing heart attacks and stroke in those at high risk for cardiovascular events?

In reality, this is an opinion piece published in a questionable journal* without any new research, and it is the opinion of a collection of well-known (approaching notorious) statin denialists, members of a cult-like organization called The International Network of Cholesterol Skeptics.(THINCS).

Larry Husten, who writes highly informed cardiac journalism at Cardiobrief, gives a good summary of their methods in this description of the authors of an editorial attacking the results of the JUPITER trial:

Nevertheless, the association of the authors with a group like THINCS raises some troublesome questions because, in fact, THINCS members don’t just object to one trial (JUPITER), or just one drug (rosuvastatin), or just the use of statins for primary prevention. They raise objections about ALL cholesterol-lowering trials, ALL cholesterol-lowering drugs, and the use of statins in ALL populations. They constantly harp on the dangerous side effects of  statins, and exploit any bit of evidence they can find to launch their attacks, always ignoring the considerable evidence that doesn’t support their views. So the Archives paper on JUPITER is not really part of the scientific process, since the authors have no interest in the give and take of medicine and science. Their only interest is to attack, at any point, and on any basis, anything related to mainstream science about cholesterol.

The lead and corresponding author, Uffe Ravnskov is the founder of THINCS and author of The Cholesterol Myths – Exposing the Fallacy that Saturated Fat and Cholesterol Cause Heart Disease (2000), which is considered the bible of cholesterol contrarianism.

Ravnskov’s book has been severely criticized in Bob Carroll’s The Skeptic’s Dictionary, which outlines the distortions and deceptive techniques found in the cholesterol skeptics’ arguments.

Harriet Hall wrote an excellent analysis of THINCS 10 years ago at Science-Based Medicine and her concluding sentences are still highly relevant:

“to reject the cholesterol connection and statins entirely is to throw the baby out with the bathwater. In my opinion, THINCS is spreading misinformation that could lead patients to refuse treatment that might prolong their life or at least prevent heart attacks and strokes.”

Indeed, if they were able to convince a highly intelligent patient like Geo, with a science background who also had easy access to the advice of a forward thinking cardiologist to stop taking his statins, who knows how many thousands have been convinced to stop their medications.

So my best advice for Geo and all of you taking statins is the following:

  1. Make sure you really need to be on the drug after engaging in shared-decision making with your physician and learning all you can about your personal risk of cardiovascular disease, the benefits of statins for you, and the potential side effects.
  2. Once you’ve made a decision based on good information and physician recommendation, try to ignore the latest headlines or internet stories that imply some new and striking information that impacts your health-most of these are unimportant.

The evidence for the benefit of statins is based on a deep body of scientific work, which will not be changed by any one new study. There is a very strong consensus amongst scientists who are actively working in the field of atherosclerosis, and amongst physicians who are actively caring for patients, that statins are very beneficial and safe. This consensus is similar to the consensus about the value of vaccines.

Science moves incrementally, and new studies inform those with open minds. The studies in this area that have been most significant in the last few years have actually strengthened the concept that drugs which lower LDL-C without causing other issues lower cardiovascular risk (see here on PCSK9 inhibitors and here on ezetimibe.)

Incrementally Yours,


N.B. *The Expert Review of Clinical Pharmacology”is an open access journal, many of which are predatory. Article are solicited and the authors pay to have their work published. For the article in question, the Western Vascular Institute payed the fee. It’s not clear that there is any peer-review process involved.

Some authors have suggested predatory journals are “the biggest threat to science since the inquisition”and I am very worried about the explosive growth in these very weak journals which exist solely to make money.

I realize that writing this piece will engender the wrath of many so before you leave comments impugning my integrity let me reiterate that I receive absolutely nothing from BIG PHARMA. In fact, by writing appropriate prescriptions for statin drugs I reduce my income as my compliant patients avoid hospital and office visits and all kinds of procedures for heart attacks and strokes!

Should You Take A Statin If You Are Over 75?: The Value of DeRisking in The Elderly

The NY Times published an article earlier this month with the provocative title “You’re Over 75, and You’re Healthy. Why Are You Taking a Statin?”

It’s actually a balanced presentation of this difficult question (although it includes the seemingly obligatory anecdote of a patient getting severe muscle aches and weakness on Lipitor) and I agree with the concept that patients should demand a good thoughtful explanation from their PCP if they are on a statin.  Shared  physician and patient decision-making should occur irrespective of age when a statin is prescribed.

Unfortunately, the NY Times piece was triggered by and contains references to a weak observational study that was recently published in the Journal of  the American Geriatric Society..

A much better article on this same topic was published earlier in January in what is arguably the most respected cardiology journal in the world (Journal of the American College of Cardiology).

It contains what I think is a very reasonable discussion of the problem: the elderly at are a substantially higher risk of adverse “statin-associated symptoms” but also at much higher risk of stroke, heart attack and cardiovascular-related death than the young.

Key Points To Consider For Use of Statins In Elderly

Some key points from that article to ponder for those over 75 years

  1. Major European and North Americans national guidelines differ markedly in this area as this graphic illustrates

“At one end of the spectrum, the 2016 ESC/EAS guidelines miss great opportunities for safe, cheap, and evidence-based prevention in elderly individuals 66 to 75 years of age. At the other end of the spectrum, the 2014 NICE guideline provides near-universal treatment recommendations well into the very elderly >75 years of age where RCT evidence is sparse and more uncertain.”

2. Data on from 2 large primary prevention trial (JUPITER and HOPE-3) show that rosuvastatin (Ridker, et al)

reduced the risk of a composite endpoint (nonfatal MI, nonfatal stroke, or cardiovascular death) substantially by 49% (RR: 0.51; 95% CI: 0.38 to 0.69), and the risk was reduced by 26% (RR: 0.74; 95% CI: 0.61 to 0.91) in those ≥70 years of age. The efficacy was similar in individuals ≥70 and <65 years of age, indicating little heterogeneity in treatment effect by age. Today, nearly all apparently healthy elderly individuals have RCT evidence supporting statin efficacy.

3. The elderly compared to the younger are much more likely to have a nonfatal event  which does not reduce their longevity but impacts their quality of life.

Thus, patient preferences are critical important for well-informed shared decision-making. If a patient only values longevity, there are little data to support primary prevention with statins in people >65 years of age. On the other hand, if preventing nonfatal and potentially disabling MI or stroke is of value to the patient, it might be reasonable to initiate statin therapy. From this perspective, it is noteworthy that the relative importance that people assign to avoiding death compared with avoiding nonfatal events appears to be highly age dependent. Although younger individuals <65 years of age weigh avoiding death highest, elderly individuals ≥65 years put a much higher weight on avoiding MI or stroke than death, These differences are compatible with elderly individuals having a greater focus on quality of life and avoiding disability than on extending life.

The Value of Derisking and Deprescribing

In my practice, I do a fair amount of deprescribing statins in the elderly. I have a very low threshold for initiating a trial  of temporary statin cessation if there is any question that a patient’s symptoms could be statin-related (see here.)

The older the patient, the higher the bar for initiating statins and I think in all patients a search for subclinical atherosclerosis (coronary calcium scan or vascular ultrasound) helps inform the decision.

Previously, I had no term for this higher bar but I like the  term  the  JACC paper introduces, derisking:

A promising approach to personalize treatment in elderly people is “derisking” by use of negative risk markers (i.e., absence of coronary artery calcification) to identify those at so low risk that statin therapy may safely be withheld . In the BioImage study of elderly individuals, for example, absence of coronary artery calcification was prevalent (≈1 of 3) and associated with exceptionally low ASCVD event rates

If you are >75 ponder all these factors and have an intense discussion with your doctor about taking a statin.

If you are still on the fence after this discussion consider a compromise approach that I have outlined here.

Deriskingly Yours,


Does Pravastatin Lower Your Risk of Diabetes?: The Joys of Continuing Education From Patients

One of the amazing perquisites of being a doctor is the opportunity to talk to a wide diversity of individuals with fascinating backgrounds and interests. I’ve always had some appreciation of this during my office interactions, but with age and ripening, I have come to relish and savor these conversations.

The skeptical cardiologist learns something from virtually every patient visit.  On a recent office day, I received patient pearls on topics ranging from Viking River cruises in Germany, to the method by which Express Scripts squeezes money from Walgreens and drug manufacturers, to certain novels of T. Coraghessan Boyle not centered on the maniacal vegetarian John Harvey Kellogg.

Not uncommonly, I’ll learn something about medicine or cardiology if I listen closely to my patients and keep an open mind.

I saw a 69 year old woman (we’ll call her Donna) the other day who had advanced plaque in her coronary arteries and with whom I had  initiated a discussion on the pros and cons of taking a statin drug to lower her risk of heart attack and stroke. This was not the first time we had talked about this topic; in previous visits she had shared with me her great fear of statin side effects and her desire to modify risk by dietary modification. On this visit, she came prepared with more research she had done on statins, and told me she was concerned about an increased  risk of diabetes with statin drugs.

I gave her my standard spiel:  statins, especially more potent ones like rosuvastatin and atorvastatin, appear to increase the risk of diabetes by 10-20%, however, this is offset by the benefits of statins, especially in someone with significant atherosclerosis, in reducing heart attack and stroke.

Donna then told me that she had read that pravastatin lowers the risk of diabetes. I hadn’t heard this (or more likely this slipped out of my ever-shrinking cerebral database) previously. Ten years ago, in the era before routine use of electronic health records (EHR), I would have had to just admit my ignorance and promise to look into that claim later (something that would not consistently happen due to time constraints and forgetfulness).  However, now I enter the patient exam room with my MacBook Air, primarily to access the patient’s EHR and look at old notes, cardiac tests etc.

Increasingly I also use the Mac to quickly look up information about a topic the patient has brought to my attention – either double checking what I believe to be true or researching claims I am unfamiliar with.

Often, the topic raised is the “snake oil du jour” (for example, is turmeric a cardiovascular panacea?), but in this case and many others, it is a relevant question about the nuances of disease or my proposed treatment.

A quick search (20 seconds) pulled up a 2009 meta-analysis of randomized trials of statins and the risk of diabetes. Sure enough, one of these trials (the West of Scotland Coronary Prevention Study) actually showed that patients treated with 40 mg of  pravastatin had a 30% lower risk of developing diabetes.  Four studies showed no effect of statins on risk of developing diabetes and only one, the JUPITER trial utilizing rosuvastatin (Crestor), showed a slight increase.

For some patients like Donna, a higher risk of diabetes may be a deal breaker for taking a life-saving medication. Although I can confidently tell her that the benefits outweigh the risks, if she has a specific fear of diabetes, perhaps related to a family member who had horrific complications of the disease, she could easily decline to take statins.

In Donna’s case, this new information about pravastatin, confirmed by the wonders of Google and a fast WiFi connection led to her giving statins (in the form of pravastatin) a chance.

I’ll remember this patient-triggered drop of wisdom for future discussions with patients whose  grave fear of diabetes makes them balk at taking statins.

Corasonically Yours,








west of scotland


Death Knell For Niacin For Lipids Sounded by FDA?

The skeptical cardiologist stopped writing new prescriptions for niacin extended release tablets in 2011. For any patient who was taking niacin, I recommended stopping it.

Because niacin had favorable effects on the cholesterol profile, physicians had been utilizing it for many years in high risk patients on statins who had low HDL  (good cholesterol) and/or high triglycerides.

The rationale was that, since high HDL was associated with lower risk of heart attacks, raising the HDL would lower that risk. Similarly, lowering the triglycerides would improve cardiovascular risks.

While niacin certainly improved the cholesterol profile, there was no good evidence that starting it in a patient already on statin would improve cardiovascular outcomes. The cholesterol profile is a surrogate endpoint: the actual treatment goal is reducing cardiovascular disease.

In 2011, the AIM-HIGH study proved there was no benefit to adding niacin to good statin therapy despite increasing HDL from 35 to 42 mg/dl, lowering triglycerides and lowering LDL. This and other studies showing no benefit of niacin therapy (and worrisome adverse effects) should have resulted in the total cessation of niacin prescriptions, especially  in patients on statins.

Unfortunately, old habits die hard amongst physicians, and the allure of raising HDL and lowering triglycerides with niacin persisted despite a lack of evidence of any benefit in lowering cardiovacular risk.

Yesterday, the FDA announced it was removing from the market two  drugs made by Abbvie, Advicor and Simcor, which are combinations of extended release niacin plus lovastatin or simvastatin, and removed its approved indication for niacin ER plus statin for lowering CHD risk stating:

“Based on the collective evidence from several large cardiovascular outcome trials (Refs. 1-3), the Agency has concluded that the totality of the scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events. Consistent with this conclusion, FDA has determined that the benefits of niacin ER tablets and fenofibric acid DR capsules for coadministration with statins no longer outweigh the risks, and the approvals for this indication should be withdrawn.”

This is good news for patients whose physicians were keeping them on the unproven brand name combination drugs, Advicor and Simcor.

There are still legitimate uses of niacin to prevent vitamin deficiencies but If you are still taking some form of niacin ER for the purpose of preventing heart disease with or without a statin I recommend presenting your doctor with the link to the FDA pronouncement above and having a good discussion with him about the rationale for staying on it.

The other drug mentioned in the announcement, fenofibric acid,  is far less often prescribed and is not available as a combination. It is the most effective drug we have for extremely high triglyceride levels over 500 mg/dl which can cause pancreatitis. I have a few patients on the generic fenofibric acid strictly for the purpose of lowering their dangerously high triglycerides but not for the indication of lowering their cardiovascular risk.

Nonsurrogateingly Yours



Red Yeast Rice: Let’s Lower Our Cholesterol With Unknown Amounts of a Statin Drug

Red Yeast Rice sits atop the "Heart Healthy" shelves at Whole Foods, surrounded by other useless "natural" supplements like ubiquinol (Coenzyme Q-10) and reservatrol.
Red Yeast Rice sits atop the “Heart Healthy” shelves at Whole Foods, surrounded by other useless “natural” supplements like ubiquinol (Coenzyme Q-10) and reservatrol.

Over the years I’ve had a number of patients tell me that they prefer to take over the counter (OTC) dietary supplements containing “natural” cholesterol lowering ingredients rather than the statin drug I have prescribed.

Red yeast rice (RYR)  is a common ingredient in these supplements and is promoted widely and enthusiastically across the internet and in supplement or natural food stores for the purpose of lowering cholesterol and heart disease risk.

RYR  has been used for centuries in China for coloring, food and medicine. It is made by fermenting red rice with a specific  type of yeast (Monascus purpureus).

Red yeast rice contains chemicals that are similar to prescription statin medications. One of these, called monacolin K, is chemically identical to  the statin drug lovastatin (brand name Mevacor).

The History Of Statin Drug Development

The history of the discovery and isolation of lovastatin, the first FDA approved statin, is worthy of a digression here as I think it illustrates the process of discovery, isolation and characterization of a chemical that becomes a safe and effective treatment.

Akin Endo,whose research over decades was crucial to discovering statins, writes that he was inspired by Alexander Fleming, who discovered penicillin in the blue-green mold belonging to the genus Penicillium in 1928.

He writes; “Although no metabolites that inhibited any enzymes involved in cholesterol synthesis had been isolated previously, I speculated that fungi like molds and mushrooms would produce antibiotics that inhibited HMG-CoA reductase. Inhibition of HMG-CoA reductase would thus be lethal to these microbes.”

Endo began analyzing thousands of molds and fungi for biologically active chemicals that would inhibit HMG-CoA reductase.

In 1971, after studying 3800 different strains of fungi he found a promising candidate: citrinin. Unfortunately,

“Citrinin strongly inhibited HMGCoA reductase and, furthermore, lowered serum cholesterol levels in rats. However, the research was suspended because of its toxicity to the kidneys. ”

End spent another 10 years isolating another promising HMG-CoA reductase inhibitor, “compactin, ” from mold and studying it in rats and other animals. Compactin demonstrated marked cholesterol lowering properties in dogs and monkeys and in the few humans who received it but the pharmaceutical company he worked for shut down the project after it appeared that in doses 200 x what were considered appropriate, it increased lymphoma risk in dogs.

The large pharmaceutical company, Merck, got wind of Endo’s studies with compactin, studied his data and realized the potential of similar but safer HMG-CoA reductase inhibitors.  Drugs which inhibited HMG-coA reductase were now being termed statins.

Merck set out to find its own statins and in February 1979 isolated a statin very similar to compactin in chemical structure, called mevinolin, from the fungus Aspergillus terreus.

Endo, working separately and also in February 1979, isolated another statin (named monacolin K) from cultures of Monascus ruber.(RYR).In  the fall of the same year, it was confirmed that monacolin K and mevinolin were the same compound (later both changed to lovastatin).

The drug showed dramatic activity in lowering LDL cholesterol, with very few side effects. This led Merck to begin large-scale clinical trials of lovastatin in patients at high risk and long-term toxicity studies in dogs in 1984. The drug dramatically reduced cholesterol levels and was well tolerated. No tumors were detected. In 1987, Merck gained FDA approval  and lovastatin became the first commercial statin.

Since then, six other statin drugs, some of which are synthesized in the laboratory rather than isolated from mold, have been approved for human therapy. These drugs have prevented thousands of heart attacks and contributed to the dramatic drop in cardiovascular deaths seen in developed countries over the last 30 years.

Ryr And Cholesterol Lowering

This brings us back to RYR and its ability to lower cholesterol. Small studies using a version of RYR that contained lovastatin have demonstrated a reduction in cholesterol compared to placebo.

However, because many red yeast rice supplements contained lovastatin (also called monacolin)In May 1998, the FDA ruled that Cholestin (the RYR product used in the studies showing cholesterol lowering benefit) was not a dietary supplement but an unapproved drug.

As a result,  Pharmanex removed RYR from Cholestin. Since that ruling, the FDA has written warning letters to several other dietary supplement manufacturers to remove drug claims or eliminate red yeast rice with high lovastatin levels from their products, including Heart and Cholesterol (Mason Vitamins, Miami Lakes, Florida)  Cholestrix (Sunburst Biorganics, Baldwin, New York), Red Yeast Rice and Red Yeast Rice/Policosanol Complex , and Red Yeast Rice (Nature’s Way Products Inc, )

A study in 2010, found levels of monacolins varying one-hundred fold in 12 RYR preparations available commercially (total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule).

Even more worrisome was that four products had elevated levels of citrinin. You remember citrinin, don’t you? That is the chemical that Endo initially identified as a candidate for cholesterol lowering drug but rejected because it was causing kidney failure in his rats.

Because of limited government oversight and variable manufacturing processes, one can also expect that the same manufacturer will have marked variation of monacolin content and citrinin from batch to batch or bottle to bottle.

Problems With Alternative Medicine In General

These problems with RYR supplements are typical of all supplements.As the the authors wrote

“Our results highlight an important issue with red yeast rice and many other alternative medicines: the lack of standardization of active constituents. Standardization of ingredients is difficult for several reasons: (1) There are variable growth and/or culture conditions and differences in harvesting and processing among manufacturers; (2) medicinal agents from natural sources are complex substances with many chemical constituents, many of which have unclear roles in their pharmacologic activity; and (3) different manufacturers may standardize products to amounts of 1 or 2 chemicals thought to be active ingredients, while other constituents are not standardized and may also have biologic and pharmacologic activity.”

One has to ask, given this background, why would a patient choose to take a “natural” OTC supplement containing an unknown amount of both a). Effective cholesterol lowering chemicals and b)potentially toxic extraneous chemicals over the precisely formulated, carefully regulated, fully studied, pure statin drug available by prescription.

It’s especially baffling to me when one considers that lovastatin comes from RYR. Thus it would have to be considered “natural.”

Akira Endo spent decades carefully identifying the effective and safe chemical portion of RYR. It is now available as a generic costing pennies per pill.

We know exactly how many milligrams you are consuming. We know what benefits to expect and what side effects can occur based on studies in hundreds of thousands of patients who have taken a similar dosage.

You are much better off taking the prescribed statin drug than RYR.

Skeptically yours,