It is available online and through an app for Apple and Android (search in the app store on “MESA Risk Score” for the (free) download.)
The MESA tool allows you to easily calculate how the CACS effects you or your patient’s 10 year risk of ASCVD.
The Multi-Ethnic Study of Atherosclerosis (MESA) is a study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. MESA researchers study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Approximately 38 percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent.
To use the score you will need information on the following risk factors:
age, gender, race/ethnicity, diabetes (yes/no), current smoker (yes/no), total and HDL cholesterol, use of lipid lowering medication (yes/no), systolic blood pressure (mmHg), use of anti-hypertensive medication (yes/no), any family history of heart attack in first degree relative (parent/sibling/child) (yes/no), and a coronary artery calcium score (Agatston units).
In many cases the CACS dramatically lowers or increases the risk estimate.
In this example a 64 year old man with no discernible risk factors has a CACS of 175 The 10 year risk of a CHD event almost doubles from 4.7% to 7.6% when the CACS is added to the standard risk factors and moves into a range where we need much more aggressive risk factor modification.
On the other hand if we enter in zero for this same patient the risk drops to a very low 1.9%.
It’s also instructive to adjust different variables. For example, if we change the family history of heart attack (parents, siblings, or children) from no to yes, this same patient’s risk jumps to 7.2% (2.6% with zero calcium score and to 10.4% with CACS 175.)
It can also be used to help modify risk-enhancing behaviors. For example if you click smoker instead of non-smoker the risk goes from 4.7% to 7.5%. Thus, you can tell your smoking patient that his risk is halved if he stops.
Discussions on the value of tighter BP control can also be informed by the calculator. For example, if our 64 year old’s systolic blood pressure was 160 his risk has increased to 6.8%.
How Does Your CACS Compare To Your Peers?
A separate calculator let’s you see exactly where your score stands in comparison individuals with your same age, gender, and ethnicity
The Coronary Artery Calcium (CAC) Score Reference Values web tool will provide the estimated probability of non-zero calcium, and the 25th, 50th, 75th, and 90th percentiles of the calcium score distribution for a particular age, gender and race. Additionally, if an observed calcium score is entered the program will provide the estimated percentile for this particular score. These reference values are based on participants in the MESA study who were free of clinical cardiovascular disease and treated diabetes at baseline. These participants were between 45-84 years of age, and identified themselves as White, African-American, Hispanic, or Chinese. The current tool is thus applicable only for these four race/ethnicity categories and within this age range.
The calculator tells us that 75% of 64 year old white males have a zero CACS and that the average CACS is 61.
Unlike SAT scores or Echo Board scores you don’t want your CACS percentile status to be high. Scores >75th percentile typically move you to a higher risk category, whereas scores <25th percentile move you to a lower risk category, often with significant therapeutic implications.
Scores between the 25th and 75th percentile typically don’t significantly change the risk calculation.
Exploring Gender Differences In CACS
If we change the gender from male to female on our 64 year old the risk drops considerably from 4.7% down to 3.3%. This graph demonstrates that over 20% of women between the ages of 75 and 84 years will have zero calcium scores.
The graph for men in that same range shows that only around 10% will have a zero CACS.
I’ve been asked what the upper limit is for CACS but I don’t think there is one. I’ve seen numerous patients with scores in the high two thousands and these graphs show individuals in the lowest age decile having scores over 2981.
If you want to be proactive about the cardiovascular health of yourself or a loved one, download the MESA app and evaluate your risk. Ask your doctor if a CACS will help refine that risk further.
Since 1/3 of Americans die from atherosclerotic cardiovascular disease (ASCVD, mostly heart attacks and strokes) and dropping dead is often the first symptom of ASCVD it’s incredibly important to identify early, “subclinical” ASCVD and begin measures to reduce risk.
How early to begin that process is open to debate. The recent sudden death of the 41-year old son of a patient of mine, however, has reinforced to me how crucial it is to begin risk assessment and potential treatments as early as possible, especially in individuals with a strong family history of premature ASCVD.
We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of ASCVD (using this online risk calculator) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals have no subclinical ASCVD and don’t need preventive therapy.
Recent studies provide compelling support for the early utilization of cardiac imaging in to identify high risk individuals.
Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out such plaques, a process I call searching for subclinical atherosclerosis. There are a number of ways to search for sublinical plaques but the two most widely studied are carotid ultrasound screening and coronary artery calcification (CAC) measurement.
I’ve been utilizing CAC (also termed heart scan, coronary calcium score, or cardioscan) to help assess my patient’s risk of ASCVD for years although the procedure is not covered by insurance and until recently was not strongly endorsed by major guidelines. (For a complete description of the test and the risks/benefits see here). As I pointed out here, in November the new ACC/AHA guidelines finally embraced CAC for
adults 40 to 75 years of age without diabetes mellitus and with LDL-C levels ≥70 mg/dL- 189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5% to 19.9%, if a decision about statin therapy is uncertain
Typically, if we have calculated (using the ASCVD risk estimator) a 10 year risk >7.5% we have a discussion with the patient about beginning drug treatment to reduce risk.
To inform the decision and help us “get off the fence” I usually recommend a CAC. To see how this works in a typical sixty something see my posts here and here.
Significant Of CAC Score
As the new ACC/AHA guidelines state:
If CAC is zero, treatment with statin therapy may be withheld or delayed, except in cigarette smokers, those with diabetes mellitus, and those with a strong family history of premature ASCVD.
A duo of studies from Walter Reed Army Hospital have provided more support for the value of the zero CAC for risk prediction and identifying who should get treatment for prevention of both heart attacks and strokes.
Over 10,00 subjects underwent CAC and were assessed for the primary outcomes of all-cause mortality, incident MI, stroke, and the combination of major adverse cardiovascular events (MACE), defined as stroke, MI, or cardiovascular death over an average 11.4 years
Patients were classified on the basis of the presence or absence of calcium and further subdivided into CAC score groups of 0, 1 to 100, 101 to 400, and >400
Patients without a zero CAC had a very low number of events , with a 1.0% rate of mortality and 2.7% rate of MACE over a 10-year period.
On the other hand subjects without any traditional risk factors (n = 6,208; mean age 43.8 years), the presence of any CAC (>0) was associated with a 1.7 fold increased risk of MACE after adjustment for traditional risk factors.
The red line of the >400 score individuals has a much higher risk of death, stroke and heart attack (myocardial infarction) than the blue (CAC 1-100) or the gray line of the zero CAC scorers.
Furthermore, when these investigators looked at outcomes in those individuals who received statins versus those who didn’t, the zeros didn’t benefit from statin therapy over the 10 year follow-up.
But there was a tremendous reduction in bad CV events in those with scores >100 who received statin (red line) versus those who did not (blue line).
Here’s the figure which encapsulates both the risk prediction power of the CAC (and the benefits of statin treatment restricted to those with >0 (blue lines)
Benefits of CAC Testing In The Young
So these new studies provide powerful data supporting the use of CAC in younger individuals to help us refine risk estimates and target the individual at high risk of MI and sudden death. It seems highly appropriate to consider CAC testing beginning at age 40 years as the AHA/ACC guidelines suggest.
But what about the individual who has a strong family history of premature CAD and is age say 35 or 39 years of age. Do we ignore advanced risk assessment? Very few individuals die in their 30s from ASCVD but I have a number of patients who suffered heart attacks in their forties. In addition, the earlier we can start risk modification the better as the process begins very early in life and accumulates over time.
The Coronary Artery Risk Development in Young Adults (CARDIA) Study published in 2017 has demonstrated the early development of nonzero CAC score in the youngish and the predictive value of the high CAC score for mid life ASCVD events. It was a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014.
Any CAC in early adult life, even in those with very low scores, indicates significant risk of having and possibly dying of a myocardial infarction during the next decade beyond standard risk factors and identifies an individual at particularly elevated risk for coronary heart disease for whom aggressive prevention is likely warranted.
I read CAC scans every day and it is not uncommon to see a non-zero scores in individuals in their late 30s or early 40s.
The two sons of another one of my patients both in their late 50s with unremarkable risk factor profiles and both developing anginal type symptoms limiting their activities each underwent multi vessel stent procedures in the last month. If I had seen them 10 to 20 years ago we would have identified the subclinical atherosclerosis building up in their coronaries, started treatment and avoided the need for invasive, expensive procedures.
Other Risk-Enhancing Factors To Consider In The Young
The ACC/AHA guidelines list some “risk-enhancing factors” some of which I find useful.
Clearly family history of premature ASCVD is important but the devil is in the details. What relatives count? What was the event in the family member? If it was sudden death was an autopsy done?
What about nontraditional lipid/biomarkers? I consider an assessment of Lp(a) and some more sophisticated measurement of atherogenic dyslipidemia (apoB, LDL-P) and inflammation (CRP) essential.
Interestingly the guidelines include ABI (which I do not find helpful) but not carotid vascular screening which has frequently guided me to earlier therapy in youngish individuals with abnormal biomarkers or strong family history.
Vascular screening in young subjects may detect subclinical atherosclerosis as measured by thickening of the carotid wall (IMT) or early carotid plaque prior to the formation of calcium in the coronary arteries. Advanced IMT precedes the formation of soft plaque in arteries and only later is calcium deposited in the plaque.
It’s never too early to start thinking about your risk of cardiovascular disease. If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.
Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.
Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.
There is still no reason to take over the counter fish oil supplements.
In fact, a study published Saturday found that fish oil supplementation (1 g per day as a fish-oil capsule containing 840 mg of n−3 fatty acids, including 460 mg of eicosapentaenoic acid [EPA] and 380 mg of docosahexaenoic acid [DHA]
did not result in a lower incidence than placebo of the primary end points of major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type.
However, another study published Saturday (REDUCE-IT) and presented at the annual American Heart Association Scientific Sessions to great fanfare found that an ethyl-ester formulation (icosapent ethyl) of eicosapentanoic acid (EPA, one of the two main marine n-3 fish oils) reduced major cardiovascular events by 25% in comparison to placebo.
When I wrote about Icosapent ethyl (brand name Vascepa) in a previous blog post in 2015 there was no data supporting its use:
A fish oil preparation, VASCEPA, available only by prescription, was approved by the FDA in 2012.
Like the first prescription fish oil available in the US, Lovaza, VASCEPA is only approved by the FDA for treatment of very high triglycerides(>500 mg/dl).
This is a very small market compared to the millions of individuals taking fish oil thinking that it is preventing heart disease.
The company that makes Vascepa (Amrin;$AMRN)would also like to have physicians prescribe it to their patients who have mildly or moderatelyelevated triglycerides between 200 and 500 which some estimate as up to 1/3 of the population.
Given the huge numbers of patients with trigs slightly above normal, before approving an expensive new drug, the FDA thought, it would be nice to know that the drug is actually helping prevent heart attacks and strokes or prolonging life.
After all, we don’t really care about high triglycerides unless they are causing problems and we don’t care about lowering them unless we can show we are reducing the frequency of those problems.
Data do not exist to say that lowering triglycerides in the mild to moderate range by any drug lowers heart attack risk.
In the past if a company promoted their drug for off-label usage they could be fined by the FDA but Amarin went to court and obtained the right to promote Vascepa to physicians for triglycerides between 200 and 500.
Consequently, you may find your doctor prescribing this drug to you. If you do, I suggest you ask him if he recently had a free lunch or dinner provided by Amarin, has stock in the company (Vascepa is the sole drug made by Amarin and its stock price fluctuates wildly depending on sales and news about Vascepa) or gives talks for Amarin.
If he answers no to all of the above then, hopefully, your triglycerides are over 500.
And although elevated triglycerides confer an elevated CV risk nearly all prior trials evaluating different kinds of triglyceride-lowering therapies, including extended-release niacin, fibrates, cholesteryl ester transfer protein inhibitors, and omega-3 fatty acids have failed to show reductions in cardiovascular events
REDUCE-IT, Amarin trumpeted widely in September (before the actual data was published) now provides impressive proof that it prevents cardiovascular disease. Has the skeptical cardiologist changed his mind about fish oil?
Vascepa Is Not Natural Fish Oil
Although Amarin’s marking material states “VASCEPA is obtained naturally from wild deep-water Pacific Ocean fish” the active ingredient is an ethyl ester form of eicosapentoic acid (EPA) which has been industrially processed and distilled and separated out from the other main omega-3 fatty acid in fish oil (DHA or docosohexanoieic acid).
Natural fish oil contains a balance of EPA and DHA combined with triacylglycerols (TAGS).
So even if the REDUCE-IT trial results can be believed they do not support the routine consumption of over the counter fish oil supplements for prevention of cardiovascular disease.
Does REDUCE-IT Prove The Benefit of Purified High Dose EPA?
REDUCE-IT was a large (8179 patients) randomized, double-blind placebo controlled trial
Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter and had been receiving a stable dose of a statin for at least 4 weeks. In 2013 the protocol was changed and required a triglyceride level>200 mg/dl.
Participants were randomized to icosapent ethyl (2 g twice daily with food [total daily dose, 4 g]) or a placebo that contained mineral oil to mimic the color and consistency of icosapent ethyl and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group.
More importantly, the hard end-points of CV death, nonfatal stroke and heart attack were also significantly lower in the Vascepa arm compared to the “placebo” arm.
These results are almost unbelievably good and they are far better than one would have predicted given only a 17% reduction in triglycerides.
This makes me strongly consider prescribing Vascepa (something I heretofore have never done) to my higher risk patients with triglycerides over 200 after we’ve addressed lifestyle and dietary contributors.
Perhaps the high dose of EPA (4 grams versus the 1 gram utilized in most trials) is beneficial in stabilizing cell membranes, reducing inflammation and thrombotic events as experimental data has suggested.
Lingering Concerns About The Study
Despite these great results I have some concerns:
The placebo contained mineral oil which may not have been neutral in its effects. In fact, the placebo arm had a significant rise in the LDL cholesterol.
Enrolled patients were predominantly male and white. No benefit was seen in women.
Higher rates of serious bleeding were noted in patients taking Vascepa
Atrial fibrillation developed significantly more often in Vascepa patients (3.1%) versus the mineral oil patients (2.1%)
Finally, the trial was sponsored by Amarin Pharma. This is an aggressive company that I don’t trust. The steering committee consisted of academic physicians (see the Supplementary Appendix), and representatives of the sponsor developed the protocol, and were responsible for the conduct and oversight of the study, as well as the interpretation of the data. The sponsor was responsible for the collection and management of the data. All the data analyses were performed by the sponsor,
After i wrote my negative piece on Vascepa in 2015 a number of Amarin investors attacked me because Vascepa is the only product Amarin has and any news on the drug dramatically influences its stock price. Here is the price of Amarin stock in the last year.
The dramatic uptick in September corresponds to the company’s announcement of the topline results of REDUCE-IT. Since the actual results have been published and analyzed the stock has dropped 20%.
High Dose Purified and Esterified EPA-Yay or Nay?
I would love to see another trial of high dose EPA that wasn’t totally under the control of Amarin and such trials are in the pipeline.
Until then, I’ll consider prescribing Amarin’s pills to appropriate patients* who can afford it and who appear to have significant residual risk after statin therapy*.
But, I will continue to tell my patients to stop paying money for useless OTC fish oil supplements.
N.B.* Appropriate patients will fit the entry criteria for REDUCE-IT described below.
Patients could be enrolled if they were 45 years of age or older and had established cardiovascular disease or were 50 years of age or older and had diabetes mellitus and at least one additional risk factor. Eligible patients had a fasting triglyceride level of 150 to 499 mg per deciliter (1.69 to 5.63 mmol per liter) and a low-density lipoprotein (LDL) cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter) and had been receiving a stable dose of a statin for at least 4 weeks;
So either secondary prevention (prior heart attack or stroke) or primary prevention in patients with diabetes and another risk factor.
The skeptical cardiologist has been utilizing coronary artery calcium (CAC) scans to help decide which patients are at high risk for heart attacks, and sudden cardiac death for the last decade. As I first described in 2014, (see here) those with higher than expected calcium scores warrant more aggressive treatment and those with lower scores less aggrressive treatment.
Although , as I have discussed previously, CAC is not the “mammography of the heart” it is incredibly helpful in sorting out personalized cardiovascular risk. We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of atherosclerotic cardiovascular disease (ASCVD) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals don’t need statin therapy.
Previously, major guidelines from organizations like the AHA and the ACC did not recommend CAC testing to guide decision-making in this area. Consequently, CMS and major insurers have not covered CAC testing. When my patients get a CAC scan they pay 125$ out of their pocket.. For the affluent and pro-active this is not an obstacle, however those struggling financially often balk at the cost.
I was, therefore, very pleased to read that the newly updated AHA/ACC lipid guidelines (full PDF available here) emphasize the use of CAC for decision-making in intermediate risk patients.
For those patients aged 40-75 without known ASCVD whose 10 year risk of stroke and heart attack is between 7.5% and 20% (intermediate, see here on using risk estimator) the guidelines recommend “consider measuring CAC”.
If the score is zero, for most consider no statin. If score >100 and/or >75th percentile, statin therapy should be started.
I don’t agree totally with this use of CAC but it is a step forward. For example, how I approach a patient with CAC of 1-99 depends very much on what percentile the patient is at. A score of 10 in a 40 year old indicates marked premature build up of atherosclerotic plaque but in a 70 year old man it indicates they are at much lower risk than predicted by standard risk factors. The first individual we would likely recommend statin therapy and very aggressive lifestyle changes whereas the second man we could discuss taking off statins.
Neil Stone, MD, one of the authors of the guidelines was quoted as saying that the imaging technique is “the best tiebreaker we have now” when the risk-benefit balance is uncertain.
“Most should get a statin, but there are people who say, ‘I’ve got to know more, I want to personalize this decision to the point of knowing whether I really, really need it.’ … There are a number of people who want to be certain about where they stand on the risk continuum and that’s how we want to use it,”
Indeed, I’ve written quite a bit about my approach to helping patients “get off the fence” on whether or not to take a statin drug.
Full title of these new guidelines includes an alphabet soup of organization acronyms
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol
N.B. For your reading pleasure I’ve copied the section in the new guidelines that discusses in detail coronary artery calcium.
Two interesting sentences which I’ll need to discuss some other time
-When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years
–CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.
–In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram
-22.214.171.124. Coronary Artery Calcium
Substantial advances in estimation of risk with CAC scoring have been made in the past 5 years. One purpose of CAC scoring is to reclassify risk identification of patients who will potentially benefit from statin therapy. This is especially useful when the clinician and patient are uncertain whether to start a statin. Indeed, the most important recent observation has been the finding that a CAC score of zero indicates a low ASCVD risk for the subsequent 10 years (S126.96.36.199-1–S188.8.131.52-8). Thus, measurement of CAC potentially allows a clinician to withhold statin therapy in patients showing zero CAC. There are exceptions. For example, CAC scores of zero in persistent cigarette smokers, patients with diabetes mellitus, those with a strong family history of ASCVD, and possibly chronic inflammatory conditions such as HIV, may still be associated with substantial 10-year risk (S184.108.40.206-9–S220.127.116.11-12). Nevertheless, a sizable portion of middle-aged and older patients have zero CAC, which may allow withholding of statin therapy in those intermediate risk patients who would otherwise have a high enough risk according to the PCE to receive statin therapy (Figure 2). Most patients with CAC scores ≥100 Agatston units have a 10-year risk of ASCVD≥7.5%, a widely accepted threshold for initiation of statin therapy (S18.104.22.168-13). With increasing age, 10- year risk accompanying CAC scores of 1 to 99 rises, usually crossing the 7.5% threshold in later middle age (S22.214.171.124-13). When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years (S126.96.36.199-14–S188.8.131.52-16). CAC measurement has no utility in patients already treated with statins. Statins are associated with slower progression of overall coronary atherosclerosis volume and reduction of high-risk plaque features, yet statins increase the CAC score (S184.108.40.206-17). A prospective randomized study of CAC scoring showed improved risk factor modification without an increase in downstream medical testing or cost (S220.127.116.11-18). In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram (S18.104.22.168- 19). CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.
I mentioned at that time that Honey-Nut Cheerios was the #1 selling ready-to-eat breakfast cereal and Cheerios #4. This update indicates little has changed in the rankings or consumption of breakfast cereal since then despite a more widespread recognition that added sugar is the major toxin in our diet and that these food items are basically a vehicle for sugar.
Apparently, Americans believe honey is not sugar. But Honey Nut Cheerios contain 9 times as much sugar as cheerios. Here are the top ingredients:
General Mills tries to emphasize the healthiness of Honey Nut Cheerios, focusing on their close relationship with bees and the natural goodness of honey in its advertising along with other factors that we now know are not important (low fat, 12 vitamins and minerals, source of iron).
Little has changed with respect to the science supporting fiber consumption to reduce cardiovascular disease since 2014. It is still weak and based on observational studies and surrogate biomarkers.
Between the lines below is my original post with current annotations in red.
The skeptical cardiologist usually eschews the breakfast offerings in the Doctor’s lounge. I’m not really interested in consuming donuts, muffins, or bagels with their high carbohydrate load. As I’ve ranted out about previously, the only yogurt available is Yoplait low fat , highly sugared-up yogurt which is arguably worse than starting the day with a candy bar.
A selection of breakfast cereals is available including Cheerios, Raisin Bran, and Frosted Flakes. Occasionally, when I have neglected to bring in my own full-faty yogurt, granola and/or fruit I will open up one of the Cheerios containers and consume a bowl mixed with 2% milk (full-fat, organic milk which I passionately advocate here and here is not available) (2018 update, I have said “cheerio” to all breakfast cereals and no longer eat Cheerios in the doctor’s lounge).
Pondering the Cheerios packaging and the cute little O’s made me wonder whether this highly processed and packaged food with a seemingly endless shelf life was truly a healthy choice.
The “Ready-To-Eat” And Allegedly Heart-Healthy Cereal
Cheerios and Honey-nut cheerios were the #4 and #1 breakfast cereals in the US in 2013, generating almost a billion dollars in sales. Both of these General Mills blockbusters undoubtedly have reached their popularity by heavily promoting the concept that they are heart healthy.
The Cheerios label is all about the heart. The little O’s sit in a heart-shaped bowl. A prominent red heart with a check inside it attests to the AHA having certified Cheerios as part of its checkmark.heart.org program. Additional text states “low in Saturated fat and cholesterol” and “diets low in saturated fat and cholesterol may reduce the risk of heart disease.”
Is The Fiber In Cheerios “Heart-Healthy” ?
Beta-glucan is a soluble fiber primarily located in the endosperm cell wall of oats. Early studies showed that oats and beta-glucan soluble fiber could reduce total and LDL (bad cholesterol) levels. The mechanism isn’t really known. (see the end of post for possible mechanisms). The Quaker oats web site oversimplifies the mechanism thusly :
“In your digestive tract, it acts as a sponge, soaking up cholesterol and carrying it out of the body”
This narrative fits with the oversimplified and now discredited descriptions of atherosclerosis which attribute it directly to consumption of cholesterol and fatty acids. See here if you’d like to appreciate how complex the process truly is.
The FDA Sanctions Oats As Heart Healthy
In 1997, the FDA reviewed 33 studies (21 showing benefit and 12 not) and decided to allow a health claim for foods that contain oats and soluble fiber. A minimum dose of 3 grams/day of oat beta-glucan was suggested for a beneficial reduction in blood cholesterol and (presumably, although never documented) a subsequent decline in coronary heart disease.
In 1998 Johnson, et al, published the results of a study funded by a grant from General Mills that showed that inclusion of whole grain oat ready to eat cereal providing 3 grams of beta-glucan as part of a low fat diet reduced LDL cholesterol by 4% after 6 weeks. HDL was unchanged. Patients in this study consumed 45 grams (1.5 oz) of cheerios at breakfast and then again in the evening. There was a total of 3 grams of soluble fibre in this amount of Cheerios. A control group consumed corn flakes in a similar fashion without change in LDL.
General Mills took this weak data and ran with it and began posting on Cheerios the following statements
“Did you know that in just 6 weeks Cheerios can reduce bad cholesterol by an average of 4 percent? Cheerios is … clinically proven to lower cholesterol. A clinical study showed that eating two 1 1/2 cup servings daily of Cheerios cereal reduced bad cholesterol when eaten as part of a diet low in saturated fat and cholesterol.”
Although the FDA had approved verbiage indicating oats may reduce heart disease “when eaten as part of a diet low in saturated fat and cholesterol” the agency objected to General Mills claiming that Cheerios lowers cholesterol “when eaten as part of a diet low in saturated fat and cholesterol”.
The FDA issued a warning letter to General Mills in 2009 in which the agency alleged “serious violations” of the FDC Act in the label and labeling of Cheerios cereal.
Based on claims made on your product’s label, we have determined that your Cheerios® Toasted Whole Grain Oat Cereal is promoted for conditions that cause it to be a drug because the product is intended for use in the prevention, mitigation, and treatment of disease.
Lowering Cholesterol Is Not The Same As Preventing Heart Disease
The FDA was telling General Mills that it was OK to say that Cheerios may reduce heart disease but not that it can reduce cholesterol because that made it a drug. It makes no sense.
The only thing that had been demonstrated for oat soluble fiber and Cheerios in particular was a reduction in cholesterol. There has never been a study with oats showing a reduction in heart disease..
It’s the heart disease, the atherosclerosis clogging our arteries and causing heart attacks and strokes that we want to prevent. We could care less about lowering cholesterol if it doesn’t prevent atherosclerosis.
A recent review of studies since the FDA ruling shows that 70% of studies show some reduction in LDL with beta-glucan. Interstingly, the studies which added beta-glucan to liquids were generally positive whereas addition to solids such as muffins usually did not show benefit.
I’m going to accept as evidence-based the claim that whole oats can lower your LDL about 7% if you consume a very large amount of them on a daily basis.
However, the critical question for any drug or dietary intervention is does it prevent atherosclerosis, the root cause of heart attacks and strokes. There has been in the past an assumption that lowering cholesterol by any means would result in lowering of atherosclerosis.
This theory has been disproven by recent studies showing that ezetimibe and niacin which significantly lower LDL do not reduce surrogate markers of atherosclerosis or cardiovascular events any more than placebo when added on to statin drugs. (There is now weak evidence that ezetimibe does lower cardiovascular events ). The recently revised cholesterol guidelines endorse the concept of treating risk of atherosclerosis rather than cholesterol levels.
I do like the food writer Michael Pollan’s simple rules to “Eat Food. Mostly Plants. Not Too Much.” and this NY Times piece summarizes much of what is in his short, funny and helpful Food Rules book:
you’re much better off eating whole fresh foods than processed food products. That’s what I mean by the recommendation to eat “food.” Once, food was all you could eat, but today there are lots of other edible foodlike substances in the supermarket. These novel products of food science often come in packages festooned with health claims, which brings me to a related rule of thumb: if you’re concerned about your health, you should probably avoid food products that make health claims. Why? Because a health claim on a food product is a good indication that it’s not really food, and food is what you want to eat.
If you follow Pollan’s dictum you will get plenty of fiber, soluble or otherwise and you will avoid the necessity to obsess over the macronutrients in your diet, fiber or otherwise. Throw in some Cheerios and oatmeal every once in a while if you like them; in their unadulterated state they are a heart-healthy food choice.
This brief post from the British Journal of Sports Medicine blog nicely presents the rationale for using strength training to improve the overall health of the elderly. I have reblogged it below.
Americans spend billions on useless supplements and vitamins in their search for better health but exercise is a superior drug, being free and without drug-related side effects
I’ve spent a lot of time on this blog emphasizing the importance of aerobic exercise for cardiovascular health but I also am a believer in strength and flexibility training for overall health and longevity.
As we age we suffer more and more from sarcopenia-a gradual decrease in muscle mass.
Scientific reviews note that loss of muscle mass and muscle strengh is quite common in individuals over age 65 and is associated with increased dependence, frailty and mortality
Specific information on progressive resistance training for the elderly is sparse but I found this amusing and helpful video on a Canadian site that provides some guidance for beginners.
And below is the referenced blog post:
Resistance training – an underutilised drug available in everybody’s medicine cabinet
As we get older we begin to lose muscle mass, approximately 1% every year. But more importantly, the decline in muscle strength declines at a rate 3-times greater . The consequences of this decline in strength are significant, with lower muscle strength being associated with an increased risk dementia, needing care, and mortality. But should we accept this as our fate, or is there anything we can do prevent, reverse or at least slow this age-related decline?
In 1990, a type of exercise called progressive resistance training, commonly known as strength training, was introduced to 9 nonagenerians living in a nursing home, specifically to treat the loss of muscle mass and strength, and the functional consequences of disability . After just 8 weeks, these older adults saw average strength gains of 174%, with 2 individuals no longer needing a cane to walk. In addition, one out of the three individuals who could not stand from a chair, was now able to stand up independently. Just take a moment to think about the results of that study. If I told you there was a medicine that you or a loved one could take, and it could make either of you strong enough to now get out of a chair, would you take it?
What if you or a loved one had a hip fracture, and I told you that same medicine could help reduce the risk of mortality by 81%, and the risk of going in to a nursing home by 84%, as was shown in this study . Currently, the only way to take this medicine is by lifting weights, or pushing against resistance.
A recent study from Britain,  showed an association between adults who participated in 2 days per week of strength training and a 20% reduction in mortality from any cause, and a 43% reduction in cancer mortality. Data from the Women’s Health Study in the US published at a similar time were very similar, with women reporting up to 145 minutes per week of strength training having a 19-27% reduced risk of mortality from any cause .
So where does the benefit of strength training come from? First and foremost, it is anabolic in nature (meaning that it can stimulate muscle growth) making it the only type of exercise that can address the age-associated decline in muscle mass and strength. Within our laboratory at the University of Sydney, we have shown that we can use this type of exercise to improve cognitive function in adults who have subjective complaints about their memory . What’s important though, is that there was a direct relationship between strength gains and improvements in cognition, and so maximizing strength gains should be a key focus if you want to maximize your benefit . This type of exercise has even been taken into hospitals and used in adults with kidney failure undergoing haemodialysis, where it was shown to reduce inflammation, and improve muscle strength and body composition .
Other laboratories around the world have also used strength training to increase bone strength in postmenopausal women , help manage blood sugar levels in adults with type 2 diabetes , as well as to counteract the catabolic side effects of androgen-deprivation therapy for men with prostate cancer . Not to mention its benefits to sleep , depression  and recovery from a heart attack .
So it is no surprise to see that the Australian  and UK  public health guidelines for physical activity recommend we take part in activities such as strength training 2-to-3 days per week. Unfortunately however, these recommendations lack detail and guidance on intensity and frequency.
A key theme in all the randomized controlled studies discussed above, is that not only were exercises performed at least 2 days per week, but they were fully supervised, used machine and/or free weights, and were done at a high intensity, which is commonly set to 80% of an individual’s peak strength. It is for this reason I like to focus on the guidelines put forward by The American College of Sports Medicine (ACSM) . The ACSM advises that everyone, including older adults do at least 2 days of progressive resistance training, which is to be performed at a moderate (5 – 6) to high/hard (7 – 8) intensity on a scale of 0 to 10, involving the major muscle groups of the body.So if you are looking to maximise the benefit from your time in the gym, or looking to make a positive change to your lifestyle, remember that there is medicine you can take; Try lifting some weights or doing other forms of strength training, 3 days a week, and importantly, make sure it feels moderate to hard. Not only will it add years to your life, but life to your years.
Since college I have regularly done weight training 3 times per week As I get dangerously close to age 65 and joining the ranks of the “elderly” I have ramped up the intensity of my workouts, working hard to forestall the sarcopenia that will ultimately be my fate.
Video credit: Produced for the University of British Columbia’s (UBC) Department of Physical Therapy, the Aging, Mobility, and Cognitive Neuroscience Laboratory, the Centre for Hip Health and Mobility and the Brain Research Centre at Vancouver Coastal Health and UBC hiphealth.ca/news/preventing-dementia
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.