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)
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!
While in Paris recently, allegedly researching the French Paradox, the skeptical cardiologist and his Eternal Fiancee’ participated in a Food Tour (Paris By Mouth). Along with 2 other American couples, we were guided and educated by a Parisian food/wine expert as we wandered from one small shop to another in the St. Germain district of the Left Bank.
We collected the perfect Baguette Monge from Eric Kayser, delicious rillettes, terrine, and saucisson from Charcuterie Saint Germain, amazing cheese from Fromager Laurent Dubois, delightful pastries from Un Dimanche a Paris, and unique and delicious chocolate from Patrick Roger.
The tour ended at La Cave du Senat wine shop, where we descended into a stone cellar and tasted all of the delicious foods while drinking wonderful wines.
The French Paradox refers to the fact that the French are among the world’s highest consumers of saturated fat, but have among the world’s lowest rates of cardiovascular disease. For those nutritional experts still obsessed with the dangers of all saturated fats, this poses a conundrum.
Cheese And The French Paradox
France consumes more cheese (27 kg per person per year) than any other country in the world (the US only consumes 16 kg per capita). Unlike Americans who have embraced low fat or skim versions of cheese, the French predominantly consume full fat cheese.
I wrote In Defense of Real Cheese in 2014 and extolled the heart-healthy virtues of eating full fat , non factory-processed cheese.
Perhaps the French are protected against heart disease by their high consumption and love of real cheese ?
Chocolate And The French Paradox
Whereas cheese contains saturated fat and has been unfairly stigmatized as unhealthy, chocolate, similarly with high saturated fat content, seems to have been coronated as the king of food that is yummy but paradoxically is also heart healthy.
Could chocolate be the enigmatic protector of the hearts of the French?
Back on Boulevard Saint-Germain we entered the shop of Patrick Roger, who won the coveted Meilleur Ouvrier de France, in the craft of chocolate in 2000. The MOF is France’s way of recognizing the best artisans in various fields and occurs every 4 years. The standards are so high that in 2015 none of the 9 chocolatier competitors were felt to merit receiving the award.
The French clearly take their chocolate seriously but they don’t top the international charts at per capita consumption.
The Swiss consume 20 pounds of chocolate per year, whereas the French and US are tied for 9th, consuming 9.3 and 9.5 lbs. (Infographic from Forbes
Chocolate And The Heart
I’ve been meaning to write a post on chocolate and the heart since my encounter with high end chocolatiers in Paris and Bruges, and especially since May when there was much fanfare over a Danish study showing less atrial fbrillation in high chocolate consumers.
A NYTimes piece stimulated by the Danish study and entitled “Why Chocolate May Be Good For The Heart” typified the media headlines and summarized the study thusly:
Scientists tracked diet and health in 55,502 men and women ages 50 to 64. They used a well-validated 192-item food-frequency questionnaire to determine chocolate consumption.
After controlling for total calorie intake, smoking, alcohol consumption, body mass index and other factors, they found that compared with people who ate no chocolate, those who had one to three one-ounce servings a month had a 10 percent reduced relative risk for atrial fibrillation, those who ate one serving a week had a 17 percent reduced risk, and those who ate two to six a week had a 20 percent reduced risk.
Previous large, well done observational studies also show that high chocolate consumption compared to no consumption is associated with a lower risk of cardiovascular disease.
Of course these being observational studies with only weak (but significant) associations, we cannot conclude that chocolate consumption actually lowers the risk of developing afib or cardiovascular disease (causation.)
My favorite graph to hammer home this point is below and plots how much each country consumes in chocolate, versus the number of nobel laureates.
There is a good correlation here (Pearson’s (no relation unfortunately) correlation coefficient or r value) which is highly significant (p value <.0001). But does anyone seriously think a country can boost its Nobel Laureate production by promoting chocolate consumption?
The authors of the Danish afib trial, admit the possibility of residual or unmeasured confounding variables as a limitation in their discussion:
Although we had extensive data on diet, lifestyle and comorbidities, we cannot preclude the possibility of residual or unmeasured confounding. For instance, data were not available on renal disease and sleep apnoea. However, after adjusting for age, smoking status and other potential confounders, the association was somewhat attenuated but remained statistically significant.
Most chocolate authorities proclaim the health benefits of dark chocolate over milk chocolate but in this Danish study:
We did not have information on the type of chocolate or cocoa concentration. However, most of the chocolate consumed in Denmark is milk chocolate. In the European Union, milk chocolate must contain a minimum of 30% cocoa solids and dark chocolate must contain a minimum of 43% cocoa solids; the corresponding proportions in the USA are 10% and 35%.16 Despite the fact that most of the chocolate consumed in our sample probably contained relatively low concentrations of the potentially protective ingredients, we still observed a robust statistically significant association, suggesting that our findings may underestimate the protective effects of dark chocolate.
Despite the fact that the participants in the Danish AFib study were likely mostly consuming milk chocolate rather than dark chocolate, the lead author of the study has been quoted as saying “dark chocolate with higher cocoa content is better… because it is the cocoa, not the milk and sugar, that provides the benefit.”
Here at Vox, we examined 100 Mars-funded health studies, and found they overwhelmingly drew glowing conclusions about cocoa and chocolate — promoting everything from chocolate’s heart health benefits to cocoa’s ability to fight disease. This research — and the media hype it inevitably attracts — has yielded a clear shift in the public perception of the products.
“Mars and [other chocolate companies] made a conscious decision to invest in science to transform the image of their product from a treat to a health food,” said New York University nutrition researcher Marion Nestle (no relation to the chocolate maker). “You can now sit there with your [chocolate bar] and say I’m getting my flavonoids.”
Flavonols and Blood Pressure
Dark chocolate and cocoa products are rich in chemical compounds called flavanols. Flavanols have attracted interest as they might help to reduce blood pressure, a known risk factor for cardiovascular disease. The blood pressure-lowering properties of flavanols are thought to be related to widening of the blood vessels, caused by nitric oxide.
Studies were short, mostly between two and12 weeks, with only one of 18 weeks. The studies involved 1804 mainly healthy adults. They provided participants with 30 to 1218 mg of flavanols (average of 670 mg) in 1.4 to 105 grams of cocoa products per day in the active intervention group. Seven of the studies were funded by companies with a commercial interest in their results, and the reported effect was slightly larger in these studies, indicating possible bias.
This graph from Volluz’s Vox article demonstrates how much chocolate you would need to consume to get the average amount of flavanols that participants in these studies received:
The Cochrane review felt there was
moderate-quality evidence that flavanol-rich chocolate and cocoa products cause a small (2 mmHg) blood pressure-lowering effect in mainly healthy adults in the short term.
Thus, for a very small drop in blood pressure you would have to make chocolate the main source of calories in your daily diet.
Consuming such large amounts of chocolate, even dark chocolate, would drastically increase your sugar consumption.
Further weakening any conclusions on the benefit of chocolate are that these are very short-term studies with markedly different baseline BPs, ages, and large variations in flavanol dosage.
Is Your Chocolate Produced By Slaves?
After reading the Danish AFib article, I purchased several bars of Tony’s Chocolonely chocolate that caught my eye at the Whole Foods checkout counter. The bars had interesting wrappers and on the inside of the wrapper I discovered that Tony’s Chocolonely’s claim to fame is that it is “slave-free.”
The slogan of the company is: “Crazy about chocolate, serious about people“.
I was previously unaware of the problem of child slavery and cocoa production. If you’d like to read more about it start here.
The Tony’s Chocoloney was so tasty I ended up consuming vast quantities of it at the end of the day and it disappeared rapidly. Currently the skeptical cardiologist’s house is chocolate free.
Should Chocolate Be Considered A Super Food or A Slave Food?
I can’t recommend chocolate to my patients as a treatment for high blood pressure or to reduce their risk of heart attack or stroke on the basis of the flimsy evidence available.
If you like chocolate, the evidence suggests no adverse effects of consuming it on a regular basis.
As far as flavanols obtained from cocoa and their benefits for cardiovascular disease, I eagerly awaiit the result of the ongoing Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), a randomized trial looking at whether daily supplements of cocoa extract and/or a standard multivitamin reduces the risk of developing cardiovascular disease and cancer.
Patients and readers should recognize that there is an ongoing research/media campaign by Big Chocolate to convince them that chocolate is a SuperFood which can also be a dessert.
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.
In March , 2016, Garry Shandling died suddenly and unexpectedly. At the time, TMZ reported that “Sources familiar with the situation tell TMZ Shandling died from a massive heart attack, with no prior warning whatsoever”
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.
What Did Shandling Die Of?
In a post dated 12/27/2016 (which I was unaware of until last week) TMZ reported the details of Shandling’s medical examination .
It turns out that Shandling did not die of a massive heart attack or an explosion of his heart.
His autopsy revealed that he died from a pulmonary embolism, the disease I had raised as a likely alternative cause of his sudden death in my post in April, 2016. The actual death certificate can be viewed here.
The medical report on his death reveals that Shandling had a prior history of clots in the leg (s) (DVT) and that previously he had had an IVC filter implanted.
An IVC filter is an umbrella shaped device that is inserted into the major vein draining blood from the the lower half of the body (the inferior vena cava) to physically obstruct the vein and thereby prevent clots from reaching the pulmonary artery. These are used in cases where the normal medical treatment for blood clots (anticoagulants or blood thinners) can’t be utilized due to bleeding risk or have proven ineffective.
Although effective 95% of the time in preventing legs clots from migrating to the pulmonary artery there are reported failures and Shandling was clearly one.
Risk factors for DVT and PE include cancer, surgery and immobility. Shandling, it appears, was recently in Hawaii and long plane flights like the one he must have taken back to LA are notorious causes of immobility that can lead to DVT.
What Can We Learn From Shandling’s Death
Some take home points
-When some one dies suddenly and unexpectedly it is not automatically due to a massive heart attack. Do not assume your family member or spouse who was found dead in bed suffered a myocardial infarction.
-Unless the victim was quite old or had advanced cancer consider asking for an autopsy to find out the true cause of death. Whatever disease caused the death could be inherited by the victim’s offspring.
-Pulmonary embolism can be a rapidly lethal disease. Consider a medical evaluation for it if you are experiencing leg pain/swelling, sudden, unexplained shortness of breath or chest pain which worsens upon taking a breath. If you have risk factors for leg clots or prior leg clots be even more vigilant.
N.B. Carrie Fisher was also reported to have suffered a “massive heart attack” by Radar Online (a most despicable website) and multiple other media outlets:
The Star Wars star, 60, suffered a massive heart attack on a United Airlines Flight from London on December 2, 2016, and was rushed to the hospital in LA upon landing, where she died four days later. Her death certificate was released by the Los Angeles County Department of Health and her cause of death was listed as “cardiac arrest/deferred,” which means it was likely a heart attack, but the final result is pending investigation.
No Radar Online! Cardiac arrest is the final mechanism of almost all deaths no matter what the cause. It does not mean she had a heart attack.
The CDC does not want cardiac arrest listed as a cause on death certificates:
In Part I, the immediate cause of death is reported on line (a). This is the final disease, injury, or complication directly causing the death. An imme diate cause of death must always be reported on line (a). It can be the sole entry in the cause-of-death section if that condition is the only condition causing the death.
The immediate cause does not mean the mechanism of death or terminal event (for example, cardiac arrest or respiratory arrest).The mechanism of death (for example, cardiac or respiratory arrest) should not be reported as the immediate cause of death as it is a statement not specifically related to the disease process, and it merely attests to the fact of death. Therefore, the mechanism of death provides no additional information on the cause of death.
We may never know the cause of carrie Fisher’s death because the autopsy (with accompanying toxicology) may never be released.
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.