If you have had a heart attack at an early age or one of your parents did but your standard risk factors for coronary heart disease are normal you should consider getting tested for Lipoprotein(a) or Lp(a).
The standard lipid profile that most patients get checks LDL (bad) HDL (good) and total cholesterol along with triglycerides. While these are useful, I have many patients who have normal standard values but have developed advanced coronary heart disease at an early age despite following a perfect lifestyle (not smoking, regular aerobic exercise, healthy diet.)
The skeptical cardiologist tests such patients for Lp(a) (pronounced LP little a) and it is quite frequently elevated.
For patients, these are the facts to know about Lp(a)
It is the strongest single inherited (monogenetic) risk factor for the early development of coronary artery disease, heart attacks and strokes.
In addition to increasing risk of atherosclerosis, high Lp(a) is strongly associated with the development of calcific aortic valve disease which can result in narrowing of the aortic valve and aortic stenosis.
Depending on the cut-off used up to one in five individuals may have elevated Lp(a)
Levels of Lp(a) can be measured with a simple blood test that should cost no more than 50 to 100$. This is not included in standard lipid or cholesterol testing.
Risk for heart attack starts to rise with levels above 30 mg/dl and Canadian guidelines from 2016 (see here)) consider >30 mg/dl to be a risk factor and they recommend measuring Lp(a) in those with a family history of premature CAD or those at intermediate risk.
The European Atherosclerosis Society (EAS, 2010), suggested levels of <50 mg/dl as optimal. The EAS advised measuring Lp(a) once in all patients with premature CVD.
As levels get even higher risk also rises as these graphs show
Treatment For High Lp(a)
The lifestyle changes (both exercise and diet) that improve bad and good cholesterol levels have no effect on Lp(a). Our best drugs, the statins, for reducing risk of heart attack and stroke also don’t lower Lp(a) levels.
Only niacin has been shown to reduce Lp(a) across broad populations but there is no evidence that Lp(a) lowering by niacin lowers cardiovascular risk so it cannot be recommended for treatment.(In the AIM-HIGH study niacin did not reduce cardiovascular events in patients with Lp(a) with levels>50 mg/dl, despite achieving a mean Lp(a) reduction of 39%.)
Cholesteryl ester transfer protein inhibitors which raise HDL levels also reduce lipoprotein(a) concentrations, but three such inhibitors have not shown a clinical benefit.
In fact, currently there are no studies showing that lowering Lp(a) with any drug will effectively lower the associated risk of heart attack, stroke and aortic stenosis.
In the not too distant future, effective therapies may emerge. There are promising newer agents (antisense oligonucleotides or ASOs) currently in clinical trials and in limited populations the PCSK9 inhbitors, mipomersen and estrogen have lowered Lp(a) levels.
Why Test For Lp(a)?
If we have no effective therapies that work by lowering Lp(a) why recommend testing for it?
I test Lp(a) for two reasons.
First, since it is inherited, patients with high levels should consider having first degree relatives tested for Lp(a) to identify those who are going to be at high risk. This provides an early warning of who in the family is most at risk for cardiovascular complications early in life. Such patients should be considered for early screening for subclinical atherosclerosis. In addition, they should be additionally motivated to do everything possible to reduce their elevated risk by lifestyle changes.
Second, I tend to recommend more aggressive cholesterol lowering in patients who have evidence for early plaque build up for atherosclerotic events early in life than I otherwise would be. I tend to agree with the approach diagrammed below:
With this approach for patients who have had events related to atherosclerosis or advanced CAC for age we work super aggressively on optimizing all risk factors. I try to lower LDL to <70 with statins and with the addition of ezetimibe or PCSK9 inhbitors if needed.
If the patient has more problems with atherosclerotic events despite optimizing risk factors and Lp(a) >60 mg/dl, some experts recommend using apheresis a technique which runs the patient’s blood through a filter which removes LDL and Lp(a). Personally, I have not sent any patients for apheresis and await better studies proving its benefit.
For those patients seeking more detailed information and references I recommend Dr. Siggurdson’s excellent post on Lp(a)
Avid readers of the skeptical cardiologist know that he is not an advocate of fish oil supplements.
One of my first posts (1/2013) was devoted to taking down the mammoth OTC fish oil industry because recent scientific evidence was clearly showing no benefit for fish oil pills.
", the bottom line on fish oil supplements is that the most
recent scientific evidence does not support any role for them inpreventing heart attack, stroke, or death. There are potential
down sides to taking them, including contaminants and the impact on the marine ecosystem. I don’t take them and I advise my
patients to avoid them (unless they have triglyceride levels
Despite a lack of evidence supporting taking them, the fish oil business continues to grow, buttressed by multiple internet sites promoting various types of fish oil (and more recently krill oil) for any and all ailments and a belief in the power of “omega-3 fatty acids”.
Another Meta-Analysis Concludes No Benefit To Fish Oil Supplements
A publication this month evaluated the 10 randomized controlled trials involving 77 917 thousand individuals that have studied fish oil supplements in preventing heart disease. The writers concluded that fish oil supplements do not significantly prevent any cardiovascular outcomes under any scenario.
It was written by a group with the ominous title of “The Omega-3 Treatment Trialists’ Collaboration.”
The Omega-3 Treatment Trialists’ Collaboration was established to conduct a collaborative meta-analysis based on aggregated study-level data obtained from the principal investigators of all large randomized clinical trials of omega-3 FA supplements for the prevention of cardiovascular disease, using a prespecified protocol and analysis plan. The aims of this meta-analysis were to assess the associations of supplementation with omega-3 FAs on (1) fatal CHD, nonfatal MI, stroke, major vascular events, and all-cause mortality and (2) major vascular events in prespecified subgroups.
The authors conclusions:
. Randomization to omega-3 fatty acid supplementation (eicosapentaenoic acid dose range, 226-1800 mg/d) had no significant associations with coronary heart disease death (rate ratio [RR], 0.93; 99% CI, 0.83-1.03; P = .05), nonfatal myocardial infarction (RR, 0.97; 99% CI, 0.87-1.08; P = .43) or any coronary heart disease events (RR, 0.96; 95% CI, 0.90-1.01; P = .12). Neither did randomization to omega-3 fatty acid supplementation have any significant associations with major vascular events (RR, 0.97; 95% CI, 0.93-1.01; P = .10), overall or in any subgroups, including subgroups composed of persons with prior coronary heart disease, diabetes, lipid levels greater than a given cutoff level, or statin use.
Nothing. Nada. No benefit.
There is clearly no reason to take fish oil supplements to prevent cardiovascular disease!
American Heart Association Sheepishly Recommends Fish Oil Supplements
If the science was conclusive on this in 2013 why did the American Heart Association (AHA) issue an “advisory” in 2017 suggesting that the use of omega-3 FAs for prevention of coronary heart disease (CHD) is probably justified in individuals with prior CHD and those with heart failure and reduced ejection fractions?
Oddly, this is the study that prompted me to write my first fish oil post in 2013
The AHA advisory totally distorts the completely negative conclusions of the Rizos meta-analysis, writing:
A meta-analysis published in 2012 examined the effects of omega-3 PUFA supplementation and dietary intake in 20 RCTs that enrolled patients at high CVD risk or prevalent CHD and patients with an implantable cardioverter-defibrillator (total n=68 680). That meta-analysis demonstrated a reduction in CHD death (RR, 0.91; 95% CI, 0.85–0.98), possibly as the result of a lower risk of SCD (RR, 0.87; 95% CI, 0.75–1.01).11
Strangely enough, if you look at the conclusions of Rizos, et al. they are
No statistically significant association was observed with all-cause mortality (RR, 0.96; 95% CI, 0.91 to 1.02; risk reduction [RD] -0.004, 95% CI, -0.01 to 0.02), cardiac death (RR, 0.91; 95% CI, 0.85 to 0.98; RD, -0.01; 95% CI, -0.02 to 0.00), sudden death (RR, 0.87; 95% CI, 0.75 to 1.01; RD, -0.003; 95% CI, -0.012 to 0.006), myocardial infarction (RR, 0.89; 95% CI, 0.76 to 1.04; RD, -0.002; 95% CI, -0.007 to 0.002), and stroke (RR, 1.05; 95% CI, 0.93 to 1.18; RD, 0.001; 95% CI, -0.002 to 0.004) when all supplement studies were considered.
Nothing. Nada. No significant benefit!
The AHA was so confused by their own advisory that in the AHA news release on the article they quote Dr. Robert Eckel, a past AHA president as saying he remains “underwhelmed” by the current clinical trials.
“In the present environment of evidence-based risk reduction, I don’t think the data really indicate that fish oil supplementation is needed under most circumstances.”
The end of the AHA news article goes on to quote Eckel as indicating he doesn’t prescribe fish oil supplements and the science advisory won’t change his practice:
Eckel said he doesn’t prescribe fish oil supplements to people who have had coronary events, and the new science advisory won’t change that. “It’s reasonable, but reasonable isn’t a solid take-home message that you should do it,” he said.
AHA: Wrong On Coconut Oil and Fish Oil
It’s hard for me to understand why the AHA gets so many things wrong in their scientific advisories. In the case of the recent misguided attack on coconut oil , their ongoing vilification of all saturated fats, and their support for fish oil supplements I don’t see evidence for industry influence. The authors of the fish oil supplement advisory do not report any financial conflicts of interest.
There is, however, one bias that is very hard to measure which could be playing a role: that is the bias to agree with what one has previously recommended. The AHA issued an advisory in 2002 recommending that people take fish oil. Changing that recommendation would mean admitting that they were wrong and that they had contributed to the growth of a 12 billion dollar industry serving no purpose.
Personally, I am aware of this kind of bias in my own writing and strive to be open to new data and publications that challenge what I personally believe or have publicly recommended.
In the case of fish oil supplements for preventing cardiovascular disease, however, the most recent data supports strongly what I wrote in 2013:
Don’t take fish oil supplements to prevent heart disease.
Americans want a “magic-bullet” type pill to take to ward off aging and the diseases associated with it. There isn’t one. Instead of buying pills and foods manipulated and processed by the food industry which promise better health, eat real food (including fish) eat a lot of plants and don’t eat too much.
N.B. I have no patients on the two prescription fish oil supplements available, Lovaza and Vascepa. I wrote about Vascepa here
Below is an excerpt:
Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides (>500 mg/dl).
This is a very small market compared to the millions of individuals taking fish oil thinking that it is preventing heart disease.
The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.
Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.
After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.
Data do not exist to say that lowering triglycerides in the mild to moderate range by any drug lowers heart attack risk.
In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amarin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.
Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amarin, has stock in the company (Vascepa is the sole drug made by Amrin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amarin.
If he answers no to all of the above then, hopefully, your triglycerides are over 500.
Science continued to progress in the field of cardiology in 2017. Some cardiology interventions were proven to be more beneficial (TAVR) and some less (coronary stents). A class of cholesterol lowering drugs had a big winner and a big loser. A supplement that many thought, based on observational studies, was crucial to prevent heart disease, turned out to be unhelpful. More evidence emerged that saturated fat is not a dietary villain.
From the skeptical cardiologist’s viewpoint, the following were the major scientific studies relevant to cardiology:
1. “Thousands of heart patients get stents that may do more harm than good”
Cardiologists have known for a decade (since the landmark COURAGE study) that outside the setting of an acute heart attack (acute coronary syndrome or ACS), stents don’t save lives and that they don’t prevent heart attacks.
Current guidelines reflect this knowledge, and indicate that stents in stable patients with coronary artery disease should be placed only after a failure of “guideline-directed medical therapy.” Despite these recommendations, published in 2012, half of the thousands of stents implanted annually in the US continued to be employed in patients with either no symptoms or an inadequate trial of medical therapy.
Yes, lots of stents are placed in asymptomatic patients. And lots of patients who have stents placed outside the setting of ACS are convinced that their stents saved their lives, prevented future heart attacks and “fixed” their coronary artery disease. It is very easy to make the case to the uneducated patient that a dramatic intervention to “cure” a blocked artery is going to be more beneficial than merely giving medications that dilate the artery or slow the heart’s pumping to reduce myocardial oxygen demands.
Stent procedures are costly in the US (average charge around $30,000, range $11,000 to $40,000) and there are significant risks including death, stroke and heart attack. After placement, patients must take powerful antiplatelet drugs which increase their risk of bleeding. There should be compelling reasons to place stents if we are not saving lives.
I, along with the vast majority of cardiologists, still recommended stents for those patients with tightly blocked coronary arteries and stable symptoms, which were not sufficiently helped by medications. ORBITA calls into question even this indication for stenting.
The ORBITA study investigators recruited 230 patients to whom most American cardiologists would have recommended stenting. These patients appeared to have a single tightly blocked coronary artery and had chest pain (angina) that limited their physical activity.
They treated the patients for 6 weeks with aspirin/statins/ and medications that reduce anginal symptoms such as beta-blockers, calcium-channel blockers or long-acting nitrates. At this point patients were randomized to receive either a stent or to undergo a catheteriation procedure which did not result in a stent, a so-called sham procedure.
The performance of a sham procedure was a courageous move that made the study truly double-blinded; neither the patients nor the investigators knew which patients had actually received a stent. Thus, the powerful placebo effects of having a procedure were neutralized.
Surprisingly, the study found that those patients receiving stents had no more improvement in their treadmill exercise time, angina severity or frequency or in their peak oxygen uptake on exercise.
ORBITA hopefully will cause more cardiologists to avoid the “oculo-stenotic” reflex wherein coronary artery blockages are stented without either sufficient evidence that the blockage is causing symptoms or that a medical trial has failed.
Although this was a small study with a very narrowly defined subset of patients, it raises substantial questions about the efficacy of coronary stenting. If ORBITA causes more patients and doctors to question the need for catheterization or stenting, this will be a very good thing.
2. Vitamin D Supplementation Doesn’t Reduce Cardiovascular Disease (or fractures, or help anything really).
One of my recurring themes in this blog is the gullibility of Americans who keep buying and using useless vitamins, supplements and nutraceuticals, thereby feeding a $20 billion industry that provides no benefits to consumers (see here and here).
Vitamin D is a prime player in the useless supplement market based on observational studies suggesting low levels were associated with increased mortality and cardiovascular disease
Despite well done studies showing a lack of benefit of Vitamin D supplementation, the proportion of people taking more than 1,000 IU daily of Vitamin D surged from just 0.3 percent in 1999-2000 to 18 percent in 2013-2014.
Most recently a nicely done study showed that Vitamin D supplementation doesn’t reduce the risk of heart disease.
In a randomized clinical trial that included 5108 participants from the community, the cumulative incidence of cardiovascular disease for a median follow-up period of 3.3 years was 11.8% among participants given 100 000 IU of vitamin D3 monthly, and 11.5% among those given placebo.
Aaron Carroll does a good job of summarizing the data showing Vitamin D is useless in multiple other areas in a JAMA forum piece:
Last October, JAMA Internal Medicine published a randomized, controlled trial of vitamin D examining its effects on musculoskeletal health. Postmenopausal women were given either the supplement or placebo for one year. Measurements included total fractional calcium absorption, bone mineral density, muscle mass, fitness tests, functional status, and physical activity. On almost no measures did vitamin D make a difference.
The accompanying editor’s note observed that the data provided no support for the use of any dose of vitamin D for bone or muscle health.
Last year, also in JAMA Internal Medicine, a randomized controlled trial examined whether exercise and vitamin D supplementation might reduce falls and falls resulting in injury among elderly women. Its robust factorial design allowed for the examination of the independent and joined effectiveness of these 2 interventions. Exercise reduced the rate of injuries, but vitamin D did nothing to reduce either falls or injuries from falls.
In the same issue, a systematic review and meta-analysis looked at whether evidence supports the contention that vitamin D can improve hypertension. A total of 46 randomized, placebo controlled trials were included in the analysis. At the trial level, at the individual patient level, and even in subgroup analyses, vitamin D was ineffective in lowering blood pressure.
Finally, if the Vitamin D coffin needs any more nails, let us add the findings of this recent meta-analysis:
calcium, calcium plus vitamin D, and vitamin D supplementation alone were not significantly associated with a lower incidence of hip, nonvertebral, vertebral, or total fractures in community-dwelling older adults.
3. PCSK9 Inhibitors: Really low cholesterol levels are safe and reduce cardiac events
I reported the very positive results for evolocumab and disappointing results for bosocizumab on the physician social media site SERMO in March but never put this in my blog.
As a practicing cardiologist I’ve been struggling with how to utilize the two available PCSK9 inhibitors (Amgen’s Repatha (evolocumab) and Sanofi’s Praluent (alirocumab) in my clinical practice. I would love to use them for my high risk statin-intolerant patients but the high cost and limited insurance coverage has resulted in only a few of my patients utilizing it.
The lack of outcomes data has also restrained my and most insurance companies enthusiasm for using them.
The opening session at this year’s American College of Cardiology Scientific Sessions in DC I think has significantly changed the calculus in this area with two presentations: the first showing Amgen’s “fully humanized” evolocumab significantly lowers CV risk in high risk patients on optimal statin therapy and the second showing that Pfizer’s “mostly humanized” bococizumab loses efficacy over time and will likely never reach the market.
The FOURIER study of evolocumab randomized 27, 564 high risk but stable patients who had LDL>70 with prior MI, prior stroke or symptomatic PAD to receive evolocumab or placebo on top of optimized lipid therapy. 69% of patients were recieving high intensity statin therapy and the baseline LDL was 92. LDL was reduced by 59% to average level of 30 in the treated patients. The reduction in LDL was consistent through the duration of the study.
IN 1/4 of the patients LDL was <20! These are unprecedented low levels of LDL.
Active treatment significantly reduced the primary endpoint by 15% and reduced the secondary endpoinf of CV death, MI, stroke by 20%. absolute difference 2% by 3 years.
There was no difference in adverse effects between placebo and Evo.
The next presentation featured data using Pfizer’s candidate in the PCSK9 wars and the acronym SPIRE (Studies of PCSK9 Inhibition and the Reduction in vascular Events (SPIRE) Bococizumab Development Program).
Paul Ridker presented the outcomes data for bococizumab which was actually similar to evolocumab data but given the declining efficacy and development of antibodies to the Pfizer drug over time these were very disappointing for Pfizer and I would presume their drug will never reach the market.
How will these results impact clinical practice?
I am now more inclined to prescribe evolocumab to my very high risk patients who have not achieved LDL< 70. I’m willing to do what I can to jump through insurance company hoops and try to make these drugs affordable to my patients.
I am less worried about extremely low LDL levels and have more faith in the LDL hypothesis: the lower the LDL the lower the risk of CV disease.
Cost is still going to be an issue for most of my patients I fear and the need for shared decision-making becomes even more important.
4. “Pure Shakes Up Nutritional Field: Finds High Fat Intake Beneficial.”
As one headline put it.
I recorded my full observations on this observational international study here
Here is a brief excerpt:
The Prospective Urban Rural Epidemiology (PURE) study, involved more than 200 investigators who collected data on more than 135000 individuals from 18 countries across five continents for over 7 years.
There were three high-income (Canada, Sweden, and United Arab Emirates), 11 middle-income (Argentina, Brazil, Chile, China, Colombia, Iran, Malaysia, occupied Palestinian territory, Poland, South Africa, and Turkey) and four low-income countries (Bangladesh, India, Pakistan, and Zimbabwe)
This was the largest prospective observational study to assess the association of nutrients (estimated by food frequency questionnaires) with cardiovascular disease and mortality in low-income and middle-income populations,
The PURE team reported that:
-Higher carbohydrate intake was associated with an increased risk of total mortality but not with CV disease or CV disease mortality.
This finding meshes well with one of my oft-repeated themes here, that added sugar is the major toxin in our diet (see here and here.)
I particular liked what the editorial for this paper wrote:
Initial PURE findings challenge conventional diet–disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well designed randomised controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility
I wish for all those following science-based medicine a healthy dose of humility. As science marches on, it’s always possible that a procedure we’ve been using might turn out to be useless (or at least much less beneficial than we thought), and it is highly likely that weak associations turn out to be causally nonsignificant. Such is the scientific process. We must continually pay attention, learn and evolve in the medical field.
Happy New Year to Be from the Skeptical Cardiologist the EFOSC!
The Skeptical Cardiologist was recently contacted by a television reporter working on a segment about statins. and looking for a cardiologist to interview who “is concerned about the cognitive side effects of these drugs.”
Since I regularly prescribe statin drugs to my patients to reduce their risk of heart attack and stroke, I am very concerned about any possible side effects from them, cognitive or otherwise. However, in treating hundreds of patients with statins, I have not observed a consistent significant effect on brain function.
When the U.S. Food and Drug Administration (FDA) issued a statement in 2012 regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use it came as quite a surprise to most cardiologists.
The FDA made a change in the patient information on all statin drugs which stated:
Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken
This FDA statement was surprising because prior observational and randomized controlled trials had suggested that patients who took statins were less likely to have cognitive dysfunction than those who didn’t.
Early studies implied that statins might actually protect against Alzheimer’s disease.
In fact these signals triggered two studies testing if statins could slow cognitive decline in patients with established Alzheimer’s disease One study used 80 mg atorvastatin versus placebo and a second 40 mg simvastatin versus placebo and both showed no effect on the decline of cognitive function over 18 months.
More recently, multiple reviews and meta-analyses have examined the data and concluded that there is no significant effect of statins on cognitive function. Importantly, these have been written by reputable physician-scientists with no financial ties to the pharmaceutical industry.
Data Show No Evidence of Causality Despite Case Reports
The FDA added the warning to statin patient information based on case reports Occasional reports of patients developing memory loss on a statin do not prove that statins are a significant cause of cognitive dysfunction.
Case reports have to be viewed in the context of all the other scientific studies indicating no consistent evidence of negative effects of the statins. Case reports are suspect for several reasons:
First, patients receiving statins are at increased risk for memory loss because of associated risk factors for atherosclerosis and advancing age. A certain percentage of such patients are going to notice memory loss independent of any medications.
Second. The nocebo effect: If a patient taking a statin is told that the drug will cause a particular side effect,that patient will be more likely to notice and report that particular side effect.
A recent study in The Lancet looked at reported side effects in patients taking atorvastatin versus placebo and found substantial evidence for the nocebo effect.
Analysis of the trial data revealed that when patients were unaware whether they were taking a statin or a placebo, the number of side effects reported was similar in those taking the statin and those taking placebo. However, if patients knew they were taking statins, reports of muscle-related side effects in particular increased dramatically, by up to 41 per cent.
Third, a review of the FDA post-marketing surveillance data showed the rate of memory loss with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 per million prescriptions for statins , 1.6 per million prescriptions for losartan) and clopidogrel (1.9 per million prescriptions for clopidogrel.)
What Most Media Prefer: Controversy And Victims
I thought my experience and perspective on statins and cognitive function might be useful for a wider audience of patients to hear so I agreed to be interviewed. After I expressed interest the reporter responded:
I would like to interview you and also a person who has experienced memory and/or thinking problems that they attribute to statin use.
I responded with “let me see what I can find,” although I was concerned that this reporter was searching for a cardiologist to support attention-grabbing claims of severe side effects of statins rather than seeking a balanced, unbiased perspective from a knowledgeable and experienced cardiologist.
If I produced a “victim” of statin-related memory loss this would boost ratings.
I then began racking my brain to come up with a patient who had clearly had statin-related memory loss or thinking problems. I asked my wonderful MA Jenny (who remembers details about patients that I don’t) if she could recall any cases. Ultimately, we both came up without any patients for the interview. (Any patient of mine reading this with definite statin memory loss please let me know and I will amend my post. However, I won’t be posting anecdotes outside of my practice.)
I have had a few patients relate to me that they feel like their memory is not as good as it was and wonder if it could be from a medication they are on. Invariably, the patient has been influenced by one of the statin fear-mongering sites on the internet (or a friend/relative who has been influenced by such a site.)
I wrote about one such site in response to a patient question a while back:
The link appears to be a promotional piece for a book by Michael Cutler, MD. Cutler’s website appears to engage in fear-mongering with respect to statins for the purpose of selling his books and promoting his “integrative” practice. I would refer you to my post entitled “functional medicine is fake medicine”. Integrative medicine is another code word for pseudoscientific medicine and practitioners should be assiduously avoided.
The piece starts with describing the case of Duane Graveline, a vey troubled man who spent the latter part of his life attempting to scare patients from taking statins. Here is his NY Times obituary.
You can judge for yourself if you want to base decisions on his recommendations.
There is no scientific evidence to suggest statins cause dementia.
An Internet-Driven Cult With Deadly Consequences
Steve Nissen recently wrote an eloquent article which accuses statin deniers of being an “internet–driven cult with deadly consequences.” Nissen has done extremely important research helping us better understand atherosclerosis and is known for being a patient advocate: calling out drug companies when they are promoting unsafe drugs.
I have immense respect for his honesty, lack of bias, and his courage to be outspoken . He writes:
“Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search en- gine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled “The Grave Dangers of Statin Drugs—and the Surprising Benefits of Cholesterol”. We are losing the battle for the hearts and minds of our patients to Web sites de- veloped by people with little or no scientific expertise, who often pedal “natural” or “drug-free” remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity— or even worse, dementia.”
He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.
The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:
“The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administra-tion. The bill’s principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies.”
Dealing With Statin Side Effects In My Practice
When a patient tells me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I’ve concluded that in any individual patient, it is possible for any drug to cause side effects. And, chances are that if we don’t address the side effects the patient won’t take the medication.
If the side effect is significant I will generally tell the patient to stop the statin and report to me how they feel after two to four weeks.
If there is no improvement I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.
If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn’t prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.
At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or livalo.) If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.
For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long term therapy.
Today a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I’m sure there is a forum somewhere on the internet where patients have reported this). Fortunately he accepted my expert opinion and will continue taking the drug.
If the symptoms persist and the patient continue to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.
Since statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denials cult thus minimizing the nocebo effect
N.B. It turns out the reporter had an open mind about the issue of statin-related memory loss. We had a good discussion and at some point you may see the skeptical cardiologist on TV being interviewed on the topic.
I could bring to the interview one of my many patients who since starting to take statins have not had a heart attack or stroke and who have taken statins for decades without side effects.
Now that would make for some compelling and exciting TV!
The skeptical cardiologist is frequently asked by patients if it is OK to take certain pain medications.
Yesterday, I got a variation on this when a patient called and indicated that he had been prescribed meloxicam and tramadol by his orthopedic surgeon for arthritic leg joint pain. The orthopedic surgeon said to check with me to see if it was OK to take either of these medications. (Patients, if you want to skip to my answer skip down to the last two sections of the post and avoid the background information.)
What Is The Risk Of Pain Medications?
Cardiologists have been concerned about the increased risk of heart attack and heart failure with non steroidal anti-inflammatory drugs (NSAIDs) since Vioxx was withdrawn from the market in 2004.
NSAIDS have long been known to increase risk of gastrointestinal (GI) bleeding by up to 4-5 fold, Scientists developed Vioxx, a COX-2 inhibitor, hoping to reduce that risk but Vioxx turned out to increase the risk of heart attack.
Since this revelation it has become clear that NSAIDS in general increase the risk of heart problems as well as GI problems
This includes the two over the counter (OTC) NSAIDS:
-ibuprofen (in the US marked most commonly as Motrin or Advil, internationally known as Nurofen). For extensive list of brand names see here.
-naproxen (most commonly sold as Aleve. Per wikipedia “marketed under various brand names, including: Aleve, Accord, Anaprox, Antalgin, Apranax, Feminax Ultra, Flanax, Inza, Maxidol, Midol Extended Relief, Nalgesin, Naposin, Naprelan, Naprogesic, Naprosyn, Narocin, Pronaxen, Proxen, Soproxen, Synflex, MotriMax, and Xenobid. It is also available bundled with esomeprazole magnesium in delayed release tablets under the brand name Vimovo.)
In 2015 the FDA mandated warning labels on all prescription NSAIDs including
1) a “black box” warning highlighting the potential for increased risk for cardiovascular (CV) events and serious life-threatening gastrointestinal bleeding, ulceration, and perforation;
(2) statements indicating patients with, or at risk for, CV disease and the elderly may be at greater risk, and that these reactions may increase with duration of use;
(3) a contraindication for use after coronary artery bypass graft surgery on the basis of reports with valdecoxib/parecoxib;
(4) language that the lowest dose should be used for the shortest duration possible
5) wording in the warning section that there is no evidence that the concomitant use of aspirin with NSAIDs mitigates the CV risk, but that it does increase the GI risk
Since then, hardly a day goes by without me having a discussion with a patient about what drugs they can safely take for their arthritis.
A reasonable approach to using NSAIDS, balancing GI and CV risks, that I have used in the past comes from a 2014 review This table and many authorities recommend naproxen as the NSAID of choice for patients with high CV risk.
Indeed prior to the publication of the PRECISION study in 2016 I believed that naproxen was the safest NSAID for my cardiac patients. I told them it was OK to use from a CV standpoint but to use the least amount possible for the shortest time in order to minimize side effects.
The PRECISION study compared a COX-2 NSAID (celecoxicib or Celebrex) to ibuprofen and naproxen in patients who required NSAIDS for relief of their joint pain.
cardiovascular death (including hemorrhagic death), nonfatal MI, or nonfatal stroke, occurred in 2.3% of celecoxib-treated patients, 2.5% of the naproxen-treated patients, and 2.7% of the ibuprofen group.
There was no placebo in this trial so we can only look at relative CV risk of the three NSAIDS and it did not significantly differ.
GI bleeding was less with celecoxib than the other two NSAIDS.
Although this study has flaws it throws into question the greater CV safety of naproxen and suggests that all NSAIDS raise CV risk.
My Current Patient Advice on Cardiac Safety of Pain Meds
Here is an infographic I came across from the Arthritis Foundation (complete PDF….here)
It’s a reasonable approach for these OTC drugs and I will start handing this out to my patients.
We should consider that all NSAIDS have the potential for increasing the risk of heart attack and heart failure, raising blood pressure, worsening renal function and causing GI bleeding.
Therefore, if at all possible avoid NSAIDS.
Acetaminophen (Tylenol) is totally safe from a heart standpoint and overall if you don’t have liver disease it is your safest drug for arthritis. However, it provides no anti-inflammatory effects and often is inadequate at pain relief.
Treating The Whole Patient
Meloxicam is an NSAID so my patient should , if at all possible, avoid it.
The other drug he was prescribed, tramadol, is an opiod. Opiods have their own set of problems including, most importantly, addiction and abuse.
reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date. Accumulating evidence supports the increased risk for serious harms associated with long-term opioid therapy, including overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction; for some harms, the risk seems to be dose-dependent.
As his cardiologist I am concerned about his heart, of course, but a good cardiologist doesn’t just focus on one organ, he looks at what his recommendations are doing to the whole person.
I certainly don’t want to have him become addicted to narcotics in order to avoid a slightly increased risk of a heart attack. On the other hand, the risks of the NSAIDS involve multiple organs, most of which don’t fall in the domain of the cardiologist.
My patient’s risk of taking either the meloxicam or the tramadol is best assessed by his primary care physician, who has the best understanding of his overall medical condition and the overall risk of dangerous side effects from these drugs.
Ultimately, I think the decision of which pain pill to take for chronic arthritis has to be made by an informed patient in discussion with his informed (and informative) primary care physician. Only the patient can decide how much pain he is having and how much risk he/she wants to assume in relieving that pain.
In an earlier post the skeptical cardiologist introduced Geo, a 61 year old male with no risk factors for heart attack or stroke other than a high cholesterol. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.
His doctor had recommended that he take a statin drug but Geo balked at taking one due to concerns about side effects and requested my input. My first steps were to gather more information.
-I calculated his 10 year risk of stroke or heart attack at 8.4% (treatment with statin typically felt to benefit individuals with 10 year risk >7.5%) and as I have previously noted, this is not unusual for a man over age 60.
-I assessed him for any hidden or subclinical atherosclerosis and found
The vascular ultrasound showed below normal carotid thickness and no plaque and his coronary calcium score was 18, putting him at the 63rd percentile. This is slightly higher than average white men his age.
So Geo definitely has atherosclerotic plaque in his coronary arteries. This puts him at risk for heart attack and stroke but not a lot higher risk than most men his age.
Strictly speaking, since he hasn’t already had a heart attack or stroke, treating him with a statin is a form of primary prevention. However, we know that atherosclerotic plaque has already developed in his arteries and at some point, perhaps years from now it will have consequences.
What is the best approach to reduce Geo’s risk?
It’s essential to look closely at lifestyle changes in everyone to reduce cardiac risk.
The lifestyle components that influence risk are
Cigarette Smoking (by far the strongest)
Obesity (Obviously related to #1 and #2)
Patients who try to change to what they perceive as a heart healthy diet by switching to non-fat dairy and eliminating all red meat will not substantially lower risk (see here.) Even if you are possess the rock-hard discipline to stay on a radically low fat diet like the Esselstyn diet or the Pritikin diet there are no good data supporting their efficacy in preventing cardiac disease.
Geo was not far from theMediterranean diet I recommend but would probably benefit from increased veggie and nut consumption. He was not overweight and he doesn’t smoke. I encouraged him to engage in 150 minutes of moderate exercise weekly.
Low Dose, Intermittent Rosuvastatin
I engaged in shared decision-making with Geo. Informing him, as best I could, of the potential side effects and benefits of statin therapy.
After a long discussion we decided to try a compromise between no therapy and the guideline recommended moderate intensive dose statin therapy.
This approach utilizes a low dose of rosuvastatin taken intermittently with the goal of minimizing any statin side effect but obtaining some of the benefits of statin drugs on cardiovascular risk reduction.
I have many patients who have been unable to tolerate other statin drugs in any dosage due to statin related muscle aches but who tolerate this particular treatment and I see substantial reductions in the LDL (bad) cholesterol with this approach.
Studies have shown that rosuvastatin 5–10 mg or atorvastatin 10–20 mg given every other day produce LDL-C reduction of 20–40 %
Studies have also shown that In patients with previous statin intolerance, rosuvastatin administered once or twice weekly (at a mean dose of 10 mg per week) achieved an LDL-C reduction of 23–29% and was well tolerated by 74–80 % of patients.
In a recent report from a specialized lipid clinic, 90 % of patients referred for intolerance to multiple statins were actually able to tolerate statin therapy, although the majority was at a reduced dose and less-than-daily dosing.
Results in Geo
After several months of taking 5 mg rosuvastatin twice weekly Geo felt fine with no discernible side effects. He obtained repeat cholesterol levels:
His LDL had dropped 52% from 140 to 92.
Hopefully, this LDL reduction plus the non-cholesterol lowering beneficial properties of statins (see here) will substantially lower Geo’s risk of heart attack and stroke.
We need randomized studies testing long-term outcomes using this approach to make it evidence-based. But in medicine we frequently don’t have studies that apply to specific patient situations. In these cases shared decision-making in order to find solutions that fit the individual patient’s concerns and experience becomes paramount.
The diet has the catchy slogan “eat nothing with a face or a mother” and Esselstyn was featured in the vegan propaganda film “Forks Over Knives.”
After detailing the lack of science I concluded:
Any patients who were not intensely motivated to radically change their diet would have avoided this crazy "study" like the plague.
This "study" is merely a collection of 18 anecdotes, none of which would be worthy of publication in any current legitimate medical journal.
Three of the 18 patients have died, one from pulmonary fibrosis, one presumably from a GI bleed, and one from depression. Could these deaths be related to the diet in some way? We can't know because there is no comparison group.
The post garned little attention initially but in the last few months several hundred visitors per day apparently read it and Essesltyn followers have started leaving me testimonials to the diet along with nasty comments.
Here’s are some typical ones (with my comments in red)
“If your (sic) not backed by some meat industry or cardiac bypass group I would be much surprised.”
I am completely free of bias. Nobody is paying me anything to do the research and writing I do. My only purpose is to find the truth about diet in order to educate my patients properly. I have saved many more patients from bypass surgery than I have referred for the procedure.
“it is so arrogant to think the only science could come from clinical studies which may be funded by an interested party.”
Doctors like randomized (and preferably blinded) clinical studies because they minimize the bias introduced by interested parties like patients and zealous investigators (like Dr. E) motivated to see positive outcomes. Small, non-randomized studies can only generate ideas and hypotheses which larger, randomized studies can prove with a greater degree of certainty.
“the entire nentire western medical system is skewed due to the big pharma influence…unfortunately western medicine believes the only science is the pen and the scalpel..whereas …history is the best teacher of all…”
By pen I assume you mean medications. If we examine history as you suggest we see that life expectancy was 50 years in 1945 but today in developed countries it is around 80 years. This advance corresponds to (among other things) advances in vaccines, antibiotics, anti-cancer drugs, cardiac and blood pressure medications and surgery: the pen and the scalpel. It does not correspond to following a vegan diet.
“Your foolishness is the embarrassment.”
Thank you for this insightful comment! I’m considering it as my epitaph.
One man felt that changing to the Esselstyn diet dramatically improved his cardiac situation and commented:
“Nothing like bashing something that works just because you want to eat meat. .”
I do enjoy meat in moderation but I also really enjoy vegetables, nuts, fish, legumes, olive oil and avocados. I looked into Esselstyn’s diet in detail because it stands out as particularly misguided in banning nuts, avocados, fish and olive oil to heart patients.
..”.So sicking (sic) to see people talk trash about something that works so well… It saved my life…”
I’m happy you are doing well with your cardiac condition but it is impossible to know what would have happened to you on a more reasonable diet such as the Mediterranean diet (which actually has legitimate scientific studies supporting it). And again criticizing Esselstyn’s ideas and “study” can hardly be considered trash talk.
“I personally have followed dr. esselstyn’s program for what will be 5 years in 11/17 and have made tremendous gains in my cardio pulmonary function….my cardiologist looks at me in wonder…why are you here? and often says , if everyone did what you have…Id be out of business…so…isnt that telling and sad?”
I’m glad you’re doing well with the program, most patients can’t follow this kind of diet for more than a few months. But perhaps we shouldn’t judge its effectiveness until we make sure you don’t suffer a heart attack next week. Your cardiologist is wrong: see what I wrote about “dealing with the cardiovascular cards you’ve been dealt.” Some individuals inherit genes that guarantee progressive and accelerated atherosclerosis that will kill them at an early age despite the best lifestyle.
“…the phrase “follow the money” comes to mind…and since theres no big money to be made….science will attempt to dispell the results and thousands of years of history that proves this dietary system works…”
Using a scientific approach to analyze Esselstyn’s diet (which tries to claim a scientific basis) seemed appropriate to me but I wasn’t motivated by money. I’m looking for what is best for my patients, pure and simple.
The Plural of Anecdote Is Not Data
One man wrote:
“But since this is only anecdotal evidence – it must be junk science…”
Esseslstyn devotees like to post what their personal experience is with the diet but as skeptical medicine has pointed out “the plural of anecdote is not data.”
One woman described in detail a good response her husband had after starting the diet following a heart attack:
I’m concerned about the skeptical cardiologist going after the person of dr. Esselstyn versus the science, such as quoting how you States dr. Esselstyn came up with the diet. So there may be a personal bias there. I’m sure there are more people out there on the esselstyn diet that are not noted in the study years ago. I hope there is another book coming out
I’ve reviewed in detail my comments about how Esselstyn came up with the diet but I am at a loss to find any ad hominem attack.
This woman went on to say
We will keep you posted, as my husband is willing to get another cardiac Cath and 12 months to visually see the difference after the diet.
I have to point out that if his cardiologist performs a cardiac cath (which carries risks of stroke, heart attack and death) for the sole purpose of checking the effect of the diet he is engaging in unethical medical behavior and likely insurance fraud. By the way, I hope that your husband is on a statin like most of Dr. Esselstyn’s are!:)
and a man wrote
Calling Essylstein ilk shows a little too much biased hatred on your part
Please note the definition of ilk “a type of people or things similar to those already referred to.” No pejorative there. And no ad hominem attack. I wrote:
It is possible that the type of vegan/ultra-low fat diets espoused by Esselstyn and his ilk have some beneficial effects on preventing CAD, but there is nothing in the scientific literature which proves it.
I should be able to criticize the methods and ideas of Dr. E without it being considered an attack on his person
Completely wrong. Esselstyn has saved my life. His book explains it all, how the endothelium cells get ruined, inflammation … heart attack proof (his words). One does not continue as head of the Cleveland Wellness Center if one is a quack.
Words are easy to come by on the interweb but Dr. E’s are not supported by science and as for the “Cleveland Wellness Center” it is probably not wise to get me started. Dr. E ‘s program is listed as being part of the Cleveland Clinic Wellness Center which is an attempt to capitalize on the market for pseudoscientific enterprises. He is not the director. The director recently came under intense criticism for promoting anti vaccine quackery. (See here).
The Wellness Center promotes so-called functional, integrative, complementary and alternative approaches. (Functional medicine is fake medicine!) These are approaches that have not been proven to work and could arguably be called quackery. (Let me be clear, however, I am not calling Dr. Esselstyn a quack but the fact that he is part of the Wellness Center does not add any scientific validity to his work.)
“I’m sure there are more people out there on the esselstyn diet that are not noted in the study years ago. I hope there is another book coming out”
Fake News, Fake Science
As a matter of fact, Dr. E has been hard at work over the last 30 years and has added a grand total of 176 patients who are considered “adherent” to the diet: about 6 per year. The “original research” was published in The Journal of Family Practice in 2014. Unfortunately the bad science present in the original publication has only been amplified.
In addition to any randomization or suitable control group for comparison, the data collection techniques are unacceptable:
“In 2011 and 2012 we contacted all participants by telephone to gather data. If a participant had died, we obtained follow-up medical and dietary information from the spouse, sibling, off-spring or responsible representative.”
In other words, there was no actual systematic review of medical records, autopsies or death certificates, just word of mouth from whomever answered the phone.
“Patients who avoided all meat, fish, dairy, and knowingly, any added oils throughout the program were considered adherent.”
Imagine, if you will, that your husband died 10 years ago and you received a call from Dr. E’s office or perhaps Dr. E himself and he asks you if your husband “avoided all meat, fish, dairy and added oils.” For one thing, it would be very difficult for you to answer that question with any degree of accuracy: was your husband cheating on Dr. E’s diet when you weren’t looking, do you remember his entire diet from 10 years ago?
For another thing, you know that the caller has an agenda. If your husband died of a heart problem the caller is not going to be happy until he/she gets you to admit that your husband had some guacamole on Cinco de Mayo in 2002. If he’s alive and doing well, the caller is likely to be satisfied with a simple answer that , yes, he’s following the diet.
Yes, we have more data from Dr. E but it turns out to be even more incredibly bad than the first lot.
The father of the eternal fiancee’ of the skeptical cardiologist (FOEFOSC, let’s call him “Geo”) is a typical 61 year old white male. A year ago his primary care physician informed him that he needed to start taking a statin drug because his cholesterol was high. The note accompanying this recommendation also stated “work harder on diet and exercise to get LDL<130.” No particulars on how to change his current diet and exercise program were provided.
Neither of Geo’s parents and none of his siblings have had heart problems at an early age and Geo is very active without any symptoms. His diet is reasonably free of processed food and added sugar, he is not overweight and his blood pressures are fine. Due to concern about side effects he had read about on the internet and because he doesn’t like taking medications , Geo balked at taking the recommended statin,
Reluctance to start a new and likely life-long drug is understandable especially when combined with a constant stream of internet-based bashing of statins.
My advice was sought and I suggested a few things that would be helpful in making a more informed decision:
As I’ve pointed out before (here), the vast majority of men over the age of 60 move into a 10 year risk category >7.5%, no matter how great their lifestyle is, and Geo was no exception with a risk of 8.4%. His total cholesterol was 249, LDL (bad) 154, HDL (good) 72 and triglycerides 116.
The vascular ultrasound showed below normal carotid thickness and no plaque and his coronary calcium score was 18, putting him at the 63rd percentile. This is slightly higher than average white men his age.
When Geo presented these findings to his PCP, he seemed unaware of the ASCVD risk estimator (recommended by AHA/ACC guidelines first published in 2013), which no longer suggests LDL levels as goals. His PCP also seemed miffed that he had gotten the coronary calcium scan. Geo felt like the PCP’s attitude was “shut up and do what I tell you.”
Geo’s PCP’s approach exemplifies a not-uncommon traditional doctor-patient relationship, but a better approach is shared decision-making (see here). Geo, like many patients, welcomes more information on the risks and benefits of any recommended treatment so that he can participate in deciding the best course of action.
By giving patients more information on the risks, side effects, and benefits of the statin drugs along with a better understanding of their overall risk of heart disease and stroke, we can hopefully move more patients “off the fence” and onto the most appropriate treatment.
If you’d like to read the recently published recommendations of the US Preventive Services Task Force on statins for primary prevention of cardiovascular disease see here. Importantly this panel of unbiased experts concluded that statin therapy significantly reduced overall mortality and cardiovascular mortality. In addition, the review found no increased risk of diabetes overall with statin therapy. The only trial that identified an increased risk was using high intensity statin therapy (Crestor (rosuvastatin) >20 mg).
And, since the internet is jammed with people who believe statins robbed them of their brain power, I would advise noting that the writers concluded “These findings are consistent with those from a recent systematic review of randomized trials and observational studies that found no adverse associations of statins with incidence of Alzheimer disease, dementia, or decreased scores on tests of cognitive performance.”
When someone who had appeared to be healthy dies suddenly, it is often assumed that he/she died of “a massive heart attack.” Certainly, this was the case in the recent unexpected sudden death of Garry Shandling, the actor and comedian. Shandling, aged 66, died March 24 of this year.
ET online reported:
“His publicist Alan Nierob told the ET that Shandling had no history of heart problems, but that doctors believe he died as the result of a heart attack.”
Although a heart attack resulting in ventricular fibrillation is the most common cause of a sudden, unexpected death in individuals over the age of 40, it is not the only one.
In fact, People magazine reported that Sanders experienced shortness of breath and pain in his legs just a day before his death, and that he spoke to a doctor friend about his symptoms, who stopped by that night to check on him,
Shortness of breath and pain in the legs raise the possibility of a clot or DVT in the leg, which can break loose and embolize into the pulmonary arteries. Such a pulmonary embolism, if massive, can result in swift and sudden death.
The LA Coroner’s office could not get Sanders’ physician to sign his death certificate and the cause of death has still apparently not been determined, pending toxicology testing which typically takes 6 weeks.
What’s On Your Parent’s Death Certificate
More important than what is on Garry Shandling’s death certificate is what is on your parent’s death certificate, and whether it is accurate. If one of your parents died prematurely and suddenly, it is important to know with precision what caused it. If the cause was an heritable cardiovascular condition, hopefully, appropriate testing can determine if you have that condition, and steps can be taken to prevent your premature demise.
Examples of inherited cardiovascular conditions (in addition to heart attack (myocardial infarction) or pulmonary embolism) that can cause sudden and unexpected death include aortic aneurysm dissection, hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasis, and long QT syndrome.
Unfortunately I find that, at least in my patients, uncertainty about the cause of death of one’s parents is the norm.
Many of my patients, for example, tell me one of their parents died of a “massive heart attack” and they assume that they are at increased risk of the same fate. When I press for details, typically no autopsy was performed. Mom or dad may have been found dead at home, or they may have suddenly keeled over but not survived to make it to the hospital for a definitive diagnosis.
Without an autopsy in such circumstances, it is not possible to be sure of the cause of death.
Even if you have a cause of death listed on your parent’s death certificate, there is no guarantee that it is accurate. The doctor that filled it out, without an autopsy in many circumstances, is just speculating on the cause based on what he/she knew about prior medical conditions and the circumstances surrounding the death.
I was recently asked to fill out the death certificate of an elderly patient of mine who had atrial fibrillation and congestive heart failure and was living in a nursing home.
One night she was noted by the staff to be very short of breath and was taken to a local emergency room where she was pronounced dead.
Based on the information available to me, I had no idea what caused her death. Although she had quite signifiant cardiac problems, when I last saw her she was stable and I have numerous patients with the same conditions who live for decades.
I filled out the death certificate, listing all of her conditions, and entered in that the cause of death was unknown.
Although the CDC guide for physicians filling out death certificates clearly states that this is acceptable, I was subsequently informed that the funeral home did not accept unknown cause of death and that they had found another doctor to fill in a cause of death.
I guarantee you, whatever he put on as the cause of death was total speculation.
Shandling mentions “I had hyperparathyroidism,” making a joke that “the symptoms are so much like being an older Jewish man, no one noticed!”
James Fallows, the excellent The Atlantic writer, highlights his own experience with hyperparathyroidism (a disease that leads to high calcium levels and is easily treated with surgery), in a recent Atlantic article. The subtitle of this article, “a rare and under-publicized condition that can sometimes be fatal,” suggests that hyperhyperparathyroidism might have led to Shandling’s death.
I don’t think this is likely because Shandling suggests that the disease is in the past tense (i.e. he has already had the surgery), and sudden death from hyperparathyroidism would be extremely unlikely.
Fortunately, Shandling is getting a full examination and autopsy to fully determine the cause of his death. If he has offspring, this will be extremely helpful to them in understanding what medical conditions they can expect later in life.
If he was not a celebrity, his death, like many of your parents’, most likely would have been ascribed to a “massive heart attack.”
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.