In October, 2016 the skeptical cardiologist predicted that Donald Trump’s coronary calcium score, if remeasured, would be >100 . At that time I pointed out that this score is consistent with moderate coronary plaque build up and implies a moderate risk of heart attack and stroke.
Trumps’ score gave him a seven-fold increase risk of a cardiovascular event in comparison to Hilary Clinton (who had a zero coronary calcium score) .
I was able to predict this score because we knew that Trump’s coronary calcium was 98 in 2013 and that on average calcium scores increase by about 10% per year.
I pointed out that his previous score was average for white men his age and his repeat score is also similar to the average white male of 71 years.
Entering Trump’s numbers into the MESA coronary calculator shows us he is at the 46th percentile, meaning that 46% of white men his age have less calcium.We can also calculate Trump’s 10 year risk of heart attack and stroke using the app from the ACC (the ASCVD calculator) and entering in the following information obtained from the White House press briefing:
Total Cholesterol 223
LDL Cholesterol 143
HDL Cholesterol 67
Systolic Blood Pressure 122
Never Smoked Cigarettes
Taking aspirin 81 mg and rosuvastatin (Crestor) 10 mg.
His 10 year risk of heart attack or stroke is 16.7%.
Given that his calcium score is average it doesn’t change his predicted risk and the conclusion is that his risk is identical to the average 71 year old white man-moderate.
We also know that Trump had an exercise stress echocardiogram which was totally normal and therefore can be reasonably certain that the moderate plaque build up in his arteries is not restricting the blood flow to his heart.
Here is what Dr. Jackson said about the stress echo:
He had an exercise stress echocardiogram done, which demonstrated above-average exercise capacity based on age and sex, and a normal heart rate, blood pressure, and cardiac output response to exercise. He had no evidence of ischemia, and his wall motion was normal in all images. the stress echo:
The New York Times article on this issue, entitled “Trump’s Physical Revealed Serious Heart Concerns, Outside Experts Say” however, presents a dramatically worrisome and misleading narrative.
It quotes several cardiologists who were very concerned about Trump’s high LDL level, weight and diet.
It’s interesting that some of the experts quoted in the NY Times piece feel that Trump’s Crestor dose should be increased in light of the recent NY Times piece questioning whether the elderly should take statins at all.
If we have serious concerns about Trump’s heart then we should have the same concerns about every 71 year old white man because he is totally average with regard to cardiac risk. In addition he is on a statin and on aspirin, the appropriate drugs to reduce risk.
In contrast to the average 71 year old male he has had a battery of cardiac tests which show exactly where he stands cardiac wise.
Most of these cardiac tests we would not recommend to an asymptomatic individual of any age. Jackson revealed that Trump had an EKG and an echocardiogram.
His ECG, or commonly EKG, was normal sinus rhythm with a rate of 71, had a normal axis, and no other significant findings.
He had a transthoracic echocardiogram done, which demonstrated normal left ventricular systolic function, an ejected fraction of 60 to 65 percent, normal left ventricular chamber size and wall thickness, no wall motion abnormalities, his right ventricle was normal, his atria were grossly normal, and all valves were normal.
So our President has a normal heart for a 71 year old white male. This automatically puts him at moderate risk for heart attack and stroke over the next 10 years but he is being closely monitored and appropriately treated and should do well.
N.B. I see that Trump’s LDL was reported previously as 93. The current LDL of 143 suggests to me that he has not been taking his Crestor.
N.B. Below is an excerpt from my prior post which explains coronary calcium
Regular readers of the skeptical cardiologist should be familiar with the coronary calcium scan or score (CAC) by now. I’ve written about it a lot (here, here, and here) and use it frequently in my patients, advocating its use to help better assess certain patient’s risk of sudden death and heart attacks.
The CAC scan utilizes computed tomography (CT) X-rays, without the need for intravenous contrast, to generate a three-dimensional picture of the heart. Because calcium is very apparent on CT scans, and because we can visualize the arteries on the surface of the heart that supply blood to the heart (the coronary arteries), the CAC scan can detect and quantify calcium in the coronary arteries with great accuracy and reproducibility.
Calcium only develops in the coronary arteries when there is atherosclerotic plaque. The more plaque in the arteries, the more calcium. Thus, the more calcium, the more plaque and the greater the risk of heart attack and death from heart attack.
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.
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.
In the last year, several of my patients have asked me whether it is safe for them to take testosterone for “low T.” They were responding to media reports suggesting that testosterone therapy raised heart attack risk by one-third.
I must admit, I had been skeptical of the legitimacy of the “low T” diagnosis. Many of the symptoms attributed to testosterone (T) deficiency, it seemed, were just part of normal male aging: decreased libido, fatigue, weight gain, and loss of muscle mass.
Perhaps, I thought, men should just be more willing to exercise regularly and lose weight and accept the indignities of aging that result despite our best efforts.
On the other hand, in the back of mind was the idea that perhaps I, as a sixty-something male with declining strength and endurance, could somehow forestall the ravages of aging by taking T.
I googled “low T” and immediately found some sponsored sites, including “is it low T.com,” which appears to be an educational site for patients. However, the one treatment option that they provide links to is made by Abbvie, the somewhat hidden host of the site. Abbvie is a pharmaceutical company that makes Androgel, the most widely prescribed testosterone cream.
I answered yes to the 3 questions I thought were just uniform consequences of aging:
1. Reduction in strength and/or endurance.
2. Loss of height.
3. Deterioration in your ability to play sports.
After taking the quiz, I was told that answering yes to 3 of the 10 questions strongly suggests you have low T.
In addition, according to the site, if you answered yes to question 1 (decreased libido) or 7 (less strong erections) you have low T.
Based on this quiz, I and 99% of men my age must have low T!!
In the last 10 years, the use of testosterone therapy has quadrupled, driven by better formulations for testosterone delivery and by direct-to-consumer marketing campaigns that suggest that treating low T will reverse these normal consequences of aging.
As a result, in 2013, 2.3 million American men received testosterone therapy and 25% of these men had no baseline testosterone levels tested.
A year ago, the New York Times editorial board opined on the dangers of overprescribing testosterone and the influence of pharmaceutical companies in over-promoting the drug, in a piece entitled “Overprescribing testosterone, dangerously.” Articles like this are what have raised patients’ concerns about T therapy and increased risk of heart attack.
Testosterone and Mortality
There is a large body of evidence that shows an association between lower T levels and increased mortality and coronary artery disease. Lower T levels are also associated with higher risk of diabetes and the metabolic syndrome. Studies also show that T therapy in T-deficient men increase lean mass and reduce fat mass and are associated with a reduction in mortality. A recent review article by Morgenthaler, et al in Mayo Clinic Proceedings, provides a detailed and meticulous summary of these studies and data.
Two recent studies contradict this large body of evidence and gained enormous media attention. The first, by Vigen et al in JAMA 2013, was a retrospective analysis of VA patients which has received extensive criticism for its statistical technique and has been corrected twice. The second study was by Finical, et al in PLoS One 2014, suggesting increased mortality in patients for 90 days after receiving their prescription for T. This study also contains methodologic issues and is hardly conclusive.
Is it Safe to Take T for low T
My recommendation to patients who want to take T after looking at all the data is as follows:
-Make sure that you really have low T. Your total T levels should be less than 300 ng/dL done in a reliable, certified lab.
-At this time, I don’t see solid evidence that taking T, if you definitely have T deficiency, increases the risk of cardiovascular complications or death.
As with all medications, the shortest duration and smallest effective amount is what you should take. All medications have side effects, some that we know and some that we don’t know. Most of the studies that have been published were on small numbers of patients for short periods of time.
-If you are overweight and/or sedentary, there is good evidence that losing weight and exercising will improve many of the symptoms ascribed to low T. These will also improve your life expectancy and lower your risk of heart attack.
…And you won’t have to worry about any side effects!
Do I have low T? Like all sixty-somethings my T levels are lower than when I was 30. My endurance is less. I’m losing height. Fat wants to build up in my abdomen, despite my best efforts.
It’s only going to get worse, but I’m willing to accept these as normal consequences of the aging process, rather than introduce external T into my system with its unknown consequences.
I will not go gentle into that good night but will continue to rage against the dying of the light without the wonders of pharmaceutical grade T.
Since I’ve been utilizing coronary calcium CT scans to detect early atherosclerotic plaque (see here) in my patients, I have frequently been asked about the relationship between calcium supplements and heart attack risk.
For example, Mrs. Jones has just found out that she has a very high calcium score and that it reflects the amount of atherosclerotic plaque lining and potentially clogging the coronary arteries to her heart. She has also been taking calcium and Vitamin D supplements recommended to her to prevent bone thinning and fractures in the future.
Did all that extra calcium she was consuming end up depositing in her coronary arteries, thus increasing her risk of heart disease?
This is a complex and not fully settled issue, however, there is enough evidence to suggest that we be cautious about calcium supplements.
A recent meta-analysis (Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691) of cardiovascular events in randomized, placebo controlled trials of calcium supplements (without vitamin D co-administration) showed that calcium supplements significantly increased the risk of myocardial infarction by 31% in five trials involving 8151 participants.
A recent meta-analysis of trials involving calcium and Vitamin D supplements found a similar increased risk of cardiovascular disease in the subjects randomized to taking calcium and Vitamin D.
These authors concluded
“in our analysis, treating 1000 patients with calcium or calcium and vitamin D for five years would cause an additional six myocardial infarctions or strokes (number needed to harm of 178) and prevent only three fractures (number needed to treat of 302”
How Might Calcium Supplements Increase Cardiovascular Risks?
Calcium supplements acutely and chronically increase serum calcium concentration. Higher calcium levels are associated with more carotid artery plaque, aortic calcification, and a higher incidence of heart attack and death.
Just like atherosclerosis, the process of calcium deposition into the arteries is very complex. Higher calcium levels could alter certain regulators of the process, such as fetuin A, pyrophosphate and bone morphogenic protein-7 or bind to calcium receptors on vascular smooth muscle cells lining the arteries
Higher calcium levels may also promote clot formation.
Bone Fracture versus Heart Attack
The informed doctor would have to tell Mrs. Jones that her calcium supplements may have contributed to her advanced coronary calcium and raised her risk of heart attack and stroke.
As with all medications, she and her doctor are going to have to discuss the relative risks and benefits.
If she has great concerns about fractures and has very low bone mineral bone density (osteoporosis) along with no family history of premature heart disease then the calcium supplementation may be appropriate.
Conversely, if she has high risk factors for coronary heart disease and/or a strong family history of premature coronary heart disease and only slightly low bone mineral density, avoiding the calcium supplements would be appropriate.
Preventing Fractures and Heart Attacks
It’s best to get calcium from the foods we eat rather than a sudden concentrated load of a supplement. Full fat dairy products like yogurt and cheese are heart healthy (see here and here) and they are an excellent source of calcium.
Weight-bearing exercise (such as running/jogging/hiking) and strength-building exercise (lifting weights, resistance machines, etc.) are also important for strengthening bones.
Thus, eating full fat dairy and aerobic exercise will help prevent both a fracture and a heart attack.
A recent paper in JAMA and a Seinfeld episode shed some light on the change in diet and fat consumption in Americans initiated by national nutritional recommendations beginning in the 1970s.
Based on weak to nonexistent scientific evidence Americans were told to consume less total fat and cut saturated fat consumption to less than 10% of calories.
The paper shows that women in the St. Paul-Minneapolis area followed this advice and cut fat consumption as a % of total calories from 38.4% in 1980-1982 to 30.6% in 1995-1997. Saturated fatty acids dropped from 13.5 to 10.5%. (Since then, total fat % and SFA % has drifted slightly upward and calories downward )(for the full table see fat consumption table (PDF))
Media summaries and reports on this paper have emphasized that Americans have failed to cut their saturated fat consumption to meet recommendations of the USDA (<10%) and the American Heart Association (<6%) with a call for more promotion of these (mis)guidelines.
The skeptical cardiologist has a different take.
Interestingly total calories during these time intervals went up from 1645 to 1851. Thus, in replacement of the fat calories, the women were consuming the carbohydrates and sugars the food industry had obligingly added to food to make it more palatable, “heart healthy” and comply with guidelines.
The authors discuss the fact that during these time intervals, despite slashing fat consumption, overall rates of obesity substantially rose. Their explanation was that the women were “underreporting” fat consumption.
A simpler and more compelling explanation is that replacement of fat with carbohydrates along with overall increase in calorie consumption was the culprit.
The Non-Fat Yogurt Scam and Seinfeld
One ongoing contributor to the phenemon of replacing healthy real food fats with engineered, highly processed and highly sugared foods is the yogurt industry.
I wrote about the non fat yogurt scam about a year ago in this post.
I happened to see the fantastic Seinfeld episode “The Non-Fat Yogurt” last night . In this episode Jerry, Elaine and George eat at a non-fat frozen yogurt shop. Everyone concurs that the yogurt is surprisingly delicious given that it is “non-fat” and begin eating it regularly. Jerry and Elaine gain weight and begin suspecting that the yogurt is not truly “non-fat”.
This episode aired in 1993 during the height of the shift toward unhealthy low fat, processed substitutes. An analysis of the yogurt revealed that it was not non-fat and this is why they were gaining weight. In reality, people get fat on truly non-fat yogurt (even Greek Yogurt) and non-fat cookies and non-fat smoothies and anything with added sugar.
Fat consumption doesn’t make you fat.
Enjoy this snippet from the episode (and please excuse the bad language)
The skeptical cardiologist dislikes running. When I start running my whole body seems to be telling me I am making a serious mistake. After running, my knees hurt (worse than the normal level of pain) and if I do enough of it, my hips hurt too.
Despite this, I have incorporated running into my exercise routine over the last few years since I stopped playing tennis. I primarily get my aerobic exercise now by using elliptical type devices and I try to get at least 150 minutes of vigorous elliptical work per week. About once a week, I run a mile on a treadmill at 6 MPH.
My current patient exercise recommendation is for 150 minutes of moderate intensity aerobic exercise. I have advised patients in the past, that walking at a moderate pace was adequate exercise, and I’ve felt, based on prior studies, that running was not necessary to achieve the cardiovascular benefits of exercise.
Any Running Associated With Lower Risk of Dying
A new study published recently in JACC has made me reconsider this advice.
As part of a prospective longitudinal cohort study at the Cooper Clinic in Dallas, Texas, Lee, et al. looked at data from a group of 55,137 adults on whom they had information on running or jogging activity during the previous 3 months.
To reduce confounding bias in the association between running and mortality, the total amount of other physical activities except running was adjusted in all multivariable regression models.
They obtained information on death from The National Death Index and over 15 years found 3,413 all-cause death and 1,217 deaths from cardiovascular disease.
Those individuals who described themselves as having done any running in the last 3 months had a 30% lower risk of all-cause mortality and a 45% lower cardiovascular mortality.
As you might expect, the non-runners were older, smoked more and were fatter. The investigators ran analyses that controlled for the differences in these factors. The protective effect of running, even a small amount, persisted, regardless of age, gender, body mass index, smoking or alcohol consumption.
Amazingly, it didn’t matter how much you ran.
This finding is quite remarkable.
Those who ran <51 minutes per week did just as well as those who ran >176 minutes per week.
Of the 20,67 that had two examinations, those who were runners at both examinations had the best outcomes with a 50% lower risk of CVD mortality.
These findings are not definitive. We need more studies in this area but they are food for thought.
Why Would Running Be A Better Form of Exercise For Your Heart
Perhaps the person who doesn’t want to run has a fundamentally different mindset about his/her health than the person who is willing to run just a little bit. Does this inclination to run mirror the person’s overall approach to their health? We can assess factors like cigarette smoking, obesity, diabetes and cholesterol but there are likely (so far) intangible factors that contribute to our health that tend to cluster with a pro-active health attitude.
Why do I run? After all, I don’t like it, it hurts my knees and I didn’t think it was contributing to my overall health. I did the mile run for a few reasons:
Running a mile in 10 minutes served as a milestone, a fixed goal if you will, for my cardiovascular fitness. I can get a very good idea of where I’m at by measuring my heart rate. I’m 60 years old and my predicted maximal heart rate (220 minus age) is 160. When I’m out of shape, my heart rate will get as high as 155 BPM during the mile, when in shape it is 10 BPM lower. 145 BPM is 91% of my predicted maximal HR.
My sense is that a good goal for cardiovascular fitness is to get the heart rate up to 90% or so of your predicted maximal. It may be that running more reliably gets you to that threshold than other activities.
Also, as the significant other of the skeptical cardiologist points out, “you can’t cheat at running.” There’s a certain amount of effort you have to put into it and there’s no way to escape it as there is on a bicycle or an elliptical. With walking you could choose a speed ranging from the snail-like up to 4 MPH or so.
Those who don’t run may also have orthopedic limitations (plantar fasciitis, osteoarthritis, rheumatoid arthritis) or pulmonary problems (COPD, asthma) or undiagnosed heart problems (heart failure, valve defects, rhythm problems) that are not captured by the examinations the investigators performed.
These findings, the authors of the paper suggest, may make people more likely to run:
“Because time is one of the strongest barriers to participate in physical activity, this study may motivate more people to start running and continue to run as an attainable health goal for mortality benefits. Compared with moderate-intensity activity, vigorous-intensity activity, such as running, may be a better option for time efficiency, producing similar, if not greater, mortality benefits in 5 to 10 min/day in many healthy but sedentary individuals who may find 15 to 20 min/day of moderate-intensity activity too time consuming.”
Some Possible Mechanisms For The Benefits of Running
As I was putting the finishing touches on this post I notice that the Sept 23 issue of the Journal of the American College of Cardiology sitting in front of me has two articles that are directly relevant to this issue. I haven’t had time to analyze these in detail but the conclusions of the first study are that
“low doses of casual, lifelong exercise do not prevent the decreased compliance and distensibility observed with healthy, sedentary aging. In contrast, 4 to 5 exercise sessions/week throughout adulthood prevent most of these age-related changes”
Thus, the mechanism through which running or more “committed” exercising improves survival could be mediated through improving the diastolic properties of the heart.
I spent most of my academic cardiology career studying diastolic function and it is an incredibly complicated and poorly understood area. Simply put, the heart has to contract to pump out blood (we call this systole) then it has to fill back up with blood (we call this diastole). With aging, the heart’s ability to contract doesn’t change but its ability to fill changes dramatically. Thus, diastolic properties become impaired with aging and this study suggests that dedicated regular exercise prevents that.
The other study showed that regular exercise helps to slow age-related increase in blood pressure. Lower blood pressure with aging could be a mechanism for preventing the age-related decline in diastolic performance of the heart.
Changing Exercise Prescription
From now on when I talk to my patients about exercise, I will inquire about running specifically and I’ll mention these studies which suggest a little running may go along way toward forestalling the aging process of the heart and lowering their risk of dying.
The Skeptical Cardiologist is not just researching low carb diets in The Big Easy. He has also been investigating the effects of marriage on cardiovascular risk.
I and the significant other of the skeptical cardiologist stayed at the wonderful Terrell House, a bed and breakfast nestled among the magnolias on Magazine Street in the Garden District of New Orleans. There, we participated in the marriage of our close friends, Dave and Barb.
Was marrying a heart healthy choice for Dave? for Barb?
Science seems to tell us yes. Marriage has been associated with a lower risk of cardiovascular disease compared to being single or divorced in multiple studies and for both sexes.
A study of the rate at which individuals in Finland developed what are termed acute coronary syndromes or ACS (think of these as heart attacks or heart attacks about to happen) showed that ACS events were approximately 58–66% higher among unmarried men and 60–65% higher in unmarried women, than among married men and women in all age groups.
The chance of dying within 28 days of an ACS were even worse for the unmarried. These mortality rates were found to be 60–168% higher in unmarried men and 71–175% higher in unmarried women, than among married men and women.
This meant a rate of death of 26% in the 35-64-year-old married men, 42% in men who had previously been married, and 51% in never-been-married men. Among women, the corresponding figures were 20%, 32%, and 43%.
As with all such observational studies, association does not prove causation.
How on earth does being married confer a lower risk of developing cardiac problems and halving of the death rate once one has an ACS?
Some speculation from the authors:
1. Perhaps a poor health status leads to not getting married or getting divorced more frequently.
2. Perhaps married people have better health habits and enjoy higher levels of social support than the unmarried which promotes lower risk
3. Perhaps prospects in the pre-hospital phase are better because of earlier intervention (wife bugging husband to get that indigestion checked out)
Do I believe that Dave and Barb have suddenly halved their risk of dying from cardiovascular disease because they tied the knot last night? Not at all!
Nothing has fundamentally changed in their lives that I can see that will have any significant impact on either one’s risk of a heart attack.
If Dave were a true bachelor and not in a committed monogamous relationship I can see certain factors that marriage would modify: perhaps unmarried Dave would be more inclined to engage in risky behaviors such as binge drinking, cigarette smoking, unhealthy food consumption or staying out late partying and listening to wild music. Perhaps married Dave’s wife will be watching over him carefully for any signs or symptoms of heart disease and encouraging an early visit to the doctor to get checked out.
Perhaps the presence of kids limits the married parents engagement in risky or unhealthy behaviors either because the parents are spending more time parenting than partying or because they are trying to serve as role models.
Perhaps, and this is likely unmeasurable, it is the “love” in the relationship (and the associated change in neurohormonal milieu) that lowers stress and inflammation and is crucial in stopping atherosclerosis.
Two individuals living together in a committed and loving relationship would seem to have these same factors on their side and I can’t fathom how the legal or religious sanctioning of their union modifies those factors favorably.
Unfortunately, the myriad studies that have been published on this topic totally fail to capture the important distinction between single and unattached and single but living in a committed and loving relationship.
In any event, in the immortal words from my toast to them last night:
“May your fights be short and your apologies many
May your desire to be in each other’s company grow stronger every year
And may all your bartenders look like Alan Alda”
Here’s to Barb and Dave and marriage and less death!