Unless you live in Texas you will have to pay out of pocket for a coronary artery calcium (CAC) scan. Insurers and Medicare won’t pay a dime for this simple test which progressive preventive cardiologists and primary care docs rely on to better determine who is at risk for heart attacks and sudden death.
But as we approach 2020 perhaps this failure to cover our best tool to detect subclinical atherosclerosis can be reversed. To my surprise, earlier this week, a patient of mine revealed to me that United Health Care had reimbursed him for the CAC he had done earlier this year.
It wasn’t easy or straightforward but his process may work for others so I asked him to email me the letter he sent that resulted in coverage which I have copied below.
As discussed in your office today, I was able to get my insurance company (United Healthcare) to reimburse me from the Cardiac Calcium Scoring costs of $125 after filing an appeal through my former employer. Below, as requested, is the simple write up I provided to them.
I visited a cardiologist (Dr. Anthony Pearson) in May 2019 regarding heart palpitations I had with increasing frequency. He performed a variety of diagnostic tests (blood work, Holter monitor, echo stress test), which were all covered by UHC. Because these tests did not show any issues, he suggested I have a Cardiac Calcium Scoring Test, which I completed on May 24, 2019. The test showed that I had serious coronary artery disease (score of over 800), which caused the cardiologist to prescribe a daily baby aspirin and a statin medicine (also covered by UHC). While I was told that the Cardiac Calcium Scoring Test cost is not covered by insurance, this is the one and only test that indicated I was at a severe risk for a coronary artery event (significant or total blockage) and, per the cardiologist, may have saved my life or perhaps avoided an unexpected significant cost (e.g. bypass surgery) by catching the issue early.
To recap, St. Luke’s Hospital did not submit a claim for the $125 cost of the Cardiac Calcium Scoring Test because they said no insurance company pays for this test. This test was ordered by my cardiologist, Dr. Anthony Pearson, and was performed at St. Luke’s Hospital in St. Louis. I am requesting reimbursement for the cost of this test for the reasons stated above
The United Health Care EOB contained this claims summary:
It would appear the mighty wall that insurers and CMS have put up against paying for CAC scans is crumbling and can be breached.
I highly recommend all patients who have gotten an appropriately ordered CAC go through this process with their insurers to attempt to obtain reimbursement.
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.
With the recent recall of valsartan due to carcinogenic Chinese contaminants the issue of where one’s generic medication is manufactured has become more important.
I take two generics: ramipril for my hypertension and rosuvastatin for my cholesterol/atherosclerosis and I had no idea where they came from when I discussed the rise of generics manufactured in China recently.
Where Is My Ramipril Made?
I called my St. Lukes pharmacist, Robert, and asked him if he could give me information on the origin of these pills.
Robert told me that my 10 mg ramipril capsule was distributed by a company called West-Ward located in New Jersey. West-Ward was an independent Columbus, Ohio company but was purchased in 2016 by a very large pharmaceutical company , Hikma, based in Aaman, Jordan. Now the Hikma web site indicates West-Ward is no more and is simply called Hikma in the US.
Hikma Pharmaceuticals Plc projects it will end 2017 with about $2 billion revenue, about $600 million of which is from generic drugs made by its U.S. subsidiary West-Ward. In the spring, the company had projected $800 million in generics sales.
Customer service at Hikma informs me that my ramipril was made in their Columbus, Ohio plant.
Where Is My Rosuvastatin Made?
My rosuvastatin (generic of Crestor) was made by Glenmark Pharmaceuticals which, per wikipedia
Glenmark received FDA approval to market their generic rosuvastatin in the US in July, 2016. and at that time had 115 products authorized for distribution in the US market and 61 drugs pending approval with the US FDA.
My rosuvastatin according to Robert was made in India although the Glenmark product catalog does not reveal this information.
Generic versus Brand Name
I’ve talked about Crestor/rosuvastatin a few times on this blog and the development of a generic version has been very helpful for many of my patients. Looking online today I see that generic rosuvastatin goes for about 10$ per month compared to 260$ for Crestor.
Is it worth paying an extra 250$ per month to get brand name Crestor if, let’s say it was manufactured in the US? For most people it isn’t. For one thing, there is no guarantee of where your brand name drug is manufactured.
Crestor used to be made in a factory in Bristol, UK but this was shut down in 2017 and now I can’t tell where Astra-Zeneca makes the stuff. Frankly, I’m surprised that they are selling any of the drug which used to account for 5 billion dollars of their annual sales.
So my cholesterol drug is made in India by an Indian company and my blood pressure drug is made in Columbus, Ohio by a Jordanian company.
I never realized how globalized the pharmaceutical industry has become. Hopefully, the FDA is doing a good job of monitoring the safety and quality of products we rely on for our wellbeing which are manufactured all over the globe.
Addendum: I have an updated post which includes more generic ARB recalls here
Many of the skeptical cardiologist’s patients managed to quit cigarette smoking by using e-cigarettes . They often continue to vape, prolonging their addiction to nicotine but overall I felt they were probably better off than smoking cigarettes. However, a couple of recent articles have me very concerned about the overall effect of e-cigarettes on public health.
The first article came from the PR department at UCSF with the headline:
Smoking E-Cigarettes Daily, Doubles Risk Of Heart Attacks”
It focused on an abstract presented in Baltimore in February 2018 by Stanton Glantz, UCSF professor of medicine and director of the UCSF Center for Tobacco Control Research and Education. The abstract (paper yet to be published) was an observational study of about 70,000 individuals. Since it was observational the causality implied by the headline is not justified but the findings are still worrisome:
When adjusted for other risk factors, daily e-cigarette use was associated with significantly increased odds (Odds Ratio: 1.79) of having had a heart attack (myocardial infarction), as was daily conventional cigarette smoking (OR: 2.72). Former and occasional e-cigarette use were not associated with significant changes in the odds of having had a heart attack, while the same categories of cigarette smoking were associated with smaller increases in risk than for current smokers.
So e-cigarettes might be safer than real cigarettes but if you don’t quit smoking you are worse off:
“E-cigarettes are widely promoted as a smoking cessation aid, but for most people, they actually make it harder to quit smoking, so most people end up as so-called ‘dual users’ who keep smoking while using e-cigarettes,” said Glantz. “The new study shows that the risks compound. Someone who continues to smoke daily while using e-cigarettes daily has an increased risk of a heart attack by a factor of five.
Juul and The Rise In Teenage Vaping
The second article was from The New Yorker and is fascinating. Entitled “The Promise of Vaping and the Rise of Juul.” , it details an alarming rise in teenage vaping which often involves a particular brand of e-cigarette, Juul, which resembles a flash drive.
To Juul (the brand has become a verb) is to inhale nicotine free from the seductively disgusting accoutrements of a cigarette: the tar, the carbon monoxide, the garbage mouth, the smell. It’s an uncanny simulacrum of smoking. An analyst at Wells Fargo projects that this year the American vaporizer market will grow to five and a half billion dollars, an increase of more than twenty-five per cent from 2017. In the latest data, sixty per cent of that market belongs to Juul.
Scientists Warn of E-cigarette Health Risks
In March, a congressionally mandated report on the health effects of e-cigarettes from the National Academies of Sciences, Engineering, and Medicine concluded:
Evidence suggests that while e-cigarettes are not without health risks, they are likely to be far less harmful than conventional cigarettes, the report says. They contain fewer numbers and lower levels of toxic substances than conventional cigarettes, and using e-cigarettes may help adults who smoke conventional cigarettes quit smoking.
With respect to cardiovascular diseases, their conclusions were:
There is good evidence that in the short term the nicotine in e-cigarettes raises systolic and diastolic blood pressure and heart rate
There is limited evidence that e-cigarettes increase biomarkers of oxidative stress, increase endothelial dysfunction and arterial stiffness. All of these factors are known to contribute to the development of atherosclerosis.
Long term, it is anyone’s guess what the consequences of vaping on the cardiovascular system will be.
As the New Yorker article makes abundantly clear, however, the youth of America are taking up vaping and Juuling increasingly and the National Academies are appropriately worried:
However, their long-term health effects are not yet clear. Among youth — who use e-cigarettes at higher rates than adults do — there is substantial evidence that e-cigarette use increases the risk of transitioning to smoking conventional cigarettes
Are Your Kids Vaping?
In 2015 there was a 40% chance your middle school or high school child had used e-cigarettes. The chart below from the CDC shows how rapidly rates are climbing.
The surgeon general/CDC issued a warning in 2016, writing:
E-cigarette use among U.S. youth and young adults is now a major public health concern. E-cigarette use has increased considerably in recent years, growing an astounding 900% among high school students from 2011 to 2015. These products are now the most commonly used form of tobacco among youth in the United States, surpassing conventional tobacco products, including cigarettes, cigars, chewing tobacco, and hookahs. Most e-cigarettes contain nicotine, which can cause addiction and can harm the developing adolescent brain.
Compared with older adults, the brain of youth and young adults is more vulnerable to the nega- tive consequences of nicotine exposure. The effects include addiction, priming for use of other addic- tive substances, reduced impulse control, deficits in attention and cognition, and mood disorders. Furthermore, fetal exposure to nicotine during pregnancy can result in multiple adverse consequences, including sudden infant death syndrome, altered corpus callosum, auditory processing deficits, effects on behaviors and obesity, and deficits in attention and cognition. Ingestion of e-cigarette liquids con- taining nicotine can also cause acute toxicity and possibly death if the contents of refill cartridges or bottles containing nicotine are consumed.
Stealth Vaping Devices
Vaping devices no longer clearly look like cigarettes. Here are some examples from the CDC report.
Note, however, that the Juul is not depicted.
It doesn’t look like a cigarette or a device that would be facilitating your child’s addiction to nicotine. And it has a USB port so it can be recharged from a laptop.
This wasn’t an issue as far as I can tell when my children were teens but I’m pretty sure if I had teenagers I would ban vaping and would confiscate anything that resembled an e-cigarette including flash or thumb drives that aren’t flash or thumb drives.
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!
It is a reasonable question. If statins are a treatment for abnormally high cholesterol levels why would we start them on a patient with normal or low levels.
The answer is that we are not concerned with cholesterol levels. What we are concerned with is atherosclerotic cardiovascular disease (ASCVD) and its downstream consequences including heart attack and stroke.
Thus, the new guidelines recommend calculating a patient’s 10 year risk of heart attack and stroke due to ASCVD ( see here for my discussion of smart phone app that makes this calculation) and if it is over 7.5% to consider starting a statin drug to reduce ASCVD risk.
Cholesterol is just one of many factors that effect the risk but we know that irrespective of cholesterol level, starting a statin will substantially lower the risk.
A patient who has smoked cigarettes lifelong asked me this question recently.
When I plugged the patient’s excellent cholesterol values into the ASCVD app, the 10 year risk of heart attack or stroke was quite high, 14.9%. Bad cholesterol (LDL) was 90, well below what is considered optimal. Good cholesterol (HDL) was 60, well above what is considered optimal.
Studies have demonstrated that even patients with cholesterol numbers this good benefit from statin therapy. Their risk of heart attack and stroke will be substantially reduced over time.
My patient has not yet had a heart attack or stroke and it is likely that despite engaging in the extremely damaging behavior of cigarette smoking , the genetically programmed excellent cholesterol values have somewhat protected from ASCVD.
However, a vascular screening study has demonstrated that early atherosclerotic plaque in both the patients carotids. The patient has ASCVD and it is only a matter of time if the patient keeps smoking before the patient has a clinical event related to it.
I told my patient that if he/she stopped smoking cigarettes his/her estimated 10 year risk would drop to 9.7% and I would not recommend statin therapy.
We discussed methods to help quit and the patient indicated that the patient would start using a nicotine patch and try to quit in the next few months.
Unfortunately, at follow up smoking was ongoing.
Thus, my recommendation to start statin therapy despite her excellent cholesterol values.
Other groups of patients besides cigarette smokers can have advanced or premature ASCVD with excellent or “normal” cholesterol values. Diabetics often have low bad cholesterol values associated with low good cholesterol and high triglycerides.
Sometimes, ASCVD develops prematurely even in patients who have a low 10 year risk based on standard risk factors. This is usually in patients with a strong family history of ASCVD who have an inherited atherogenic abnormality of lipid metabolism that is not manifested in the standard cholesterol parameters (see Dealing With the Cardiovascular Cards You’ve Been Dealt).
To identify these patients a search for subclinical atherosclerosis by vascular screening or coronary calcium scan is necessary. When advanced plaque is identified statin therapy is often warranted even with a low estimated 10 year risk and normal cholesterol values.
So some patients can have very high cholesterol values and I don’t recommend any therapy, some have low and I do. I’m much more focused on the presence or absence of ASCVD in my treatment decisions.
Ultimately we are not treating “high cholesterol” when we start cholesterol lowering therapy we are working to prevent or slow the progression of ASCVD,
A year ago one of my patients began experiencing chest pain when he walked up hills. Subsequent evaluation revealed that atherosclerotic plaque (95% narrowing of a major coronary artery ) was severely reducing the blood flow to his heart muscle and was the cause of his chest pain. When this blockage was opened up with a stent he no longer had the pain.
Along with other medications (aspirin and plavix to keep his stent open) I had him start atorvastatin, the generic version of Lipitor, a powerful statin drug that has been shown to prevent progression of atherosclerotic plaque and thereby reduce subsequent heart attacks, strokes and death in patients like him
I saw him in the office the other day in follow up and he was feeling great . He asked me “Doc I read your post yesterday.s Since you say that cholesterol in the diet doesn’t matter anymore, does that mean I don’t have to take my cholesterol drug anymore.?”
His question gets at the heart of the “diet-heart hypothesis”. The concept that dietary modification, with reduction of cholesterol and fat consumption can reduce coronary heart disease.
The science supporting this hypothesis has never been strong but the concept was foisted on the American public and was widely believed. It was accepted I would say because it has a beautiful simplicity which can be summarized as follows:
“If you eat cholesterol and fat it will enter your blood stream and raise cholesterol levels. This excess cholesterol will then deposit in your arteries, creating fatty plaque , clogging them and leading to a heart attack.”
This concept was really easy to grasp and simplified the public health recommendations.
However, cholesterol blood levels are determined more by cholesterol synthesized in the liver and predicting how dietary modifications will effect these levels is not easy.
Since the public has had the diet-heart hypothesis fed to them for decades and given its beautiful simplicity it is hard to reverse this dogma. My patient’s question reflects a natural concern that if science/doctors got this crucial question so wrong, is everything we know about cholesterol treatment and heart disease wrong?
In other words, are doctors promoting a great cholesterol hoax?
Evidence Strongly Supports Statins in Secondary Prevention
For my patient the science supporting taking a cholesterol-lowering statin drug is very solid. There are multiple excellent studies showing that in patients with established coronary artery disease taking a statin drug substantially reduces their risk of heart attack and dying.
These studies are the kind that provide the most robust proof: randomized, prospective and blinded.
When cardiologists rate the strength of evidence for a certain treatment (as done for lifestyle intervention here) we use a system that categorizes the evidence as Level A, B, or C quality.
LeveleA quality (or strong) evidence consists of multiple,large, well-done, randomized trials such as exist for statins in patients with coronary heart disease.
Level B Evidence comes from a single randomized trial or nonrandomized studies.
Level C evidence is the weakest and comes from “consensus opinion of experts, case studies or standard of care.”
When treatment recommendations are based on Level C evidence they are often reversed as more solid data is obtained. Level A recommendations almost always hold up over time.
The level of evidence supporting restricting dietary cholesterol and fat to reduce heart attacks and strokes has always been at or below Level C and now it is clear that it is insufficient and should be taken out of guideline recommendations.
Evidence Strongly Supports Atherogenic Cholesterol is Related to Coronary Heart Disease
There are other lines of evidence that strongly support the concept that LDL cholesterol (bad cholesterol) or an atherogenic form of LDL cholesterol is strongly related to the development of atherosclerosis. If you are born with really high levels you are at very high risk for coronary heart disease, conversely if you are born with mutations that cause extremely low levels you are highly unlikely to get coronary heart disease.
Thus, the cholesterol hypothesis as it relates to heart disease is very much till intact although the diet-heart hypothesis is not.
Conflating the Diet-Heart Hypothesis and the Cholesterol Hypothesis
There is an abundance of misinformation on the internet that tries to conflate these two concepts. Sites with titles like “The Great Cholesterol Lie” , “The” Cholesterol Hoax”, The Cholesterol Scam” abound .
These sites proclaim that cholesterol is a vital component of cell membranes (it is) and that any attempt by diet or drugs to lower levels will result in severe side effects with no benefit
Doctors, according to these types of sites, in collusion with Big Pharma, have inflated the benefits of statin drugs and overlooked the side effects in the name of profit. Often, a “natural” alternative to statins is promoted. In all cases a book is promoted.
The Great Cholesterol Truths
It’s unfortunate that nutritional guidelines have promoted restriction of cholesterol and fat for so long. These guidelines (like most of nutritional science) were based on flawed observational studies. They should not have been made public policy without more consensus from the scientific community. The good news is that ultimately the truth prevails when enough good scientific studies are done.
It is right to question the flimsy foundation of nutritional recommendations on diet and heart disease but the evidence for statin benefits in patients with established coronary heart disease is rock solid.
Hopefully, the less long-winded explanation I provided my patient in the office will persuade him to keep on taking his atorvastatin pills while simultaneously allowing him to eat eggs, shrimp and full fat dairy without guilt.
Important findings from the IMPROVE-IT trial were presented at the American Heart Association meeting yesterday. They demonstrate for the first time that the cholesterol lowering drug ezetimibe (brand name Zetia) lowers the risk of heart attack and stroke when added to a statin drug in high risk patients (those who have sustained a heart attack or had unstable angina) over a statin drug plus placebo.
That study showed
The primary endpoint of CV death/MI/UA/coronary revascularization beyond 30 days/stroke was significantly lower in the ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up (32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99; p = 0.016).
Prior to this study, Zetia had been prescribed to millions of patients since 2002 garnering Merck, its maker, profits of 30 billion dollars despite there being no evidence that it reduced heart attack or stroke.
Dr. Melissa Walton-Shirley wrote an excellent article on the status of Zetia at the beginning of 2014, summarizing thusly:
Perhaps the lesson to be learned is that starting in 2014, let’s not put compounds on the market for human ingestion without knowing if they help or hurt. Let’s make it unacceptable for a company to make tens of billion dollars from the sale of a compound without knowing if it lowers mortality or improves quality of life
I have previously bashed Zetia on this site and I only prescribe it in very rare cases. These new data may change my approach.
Before embracing Zetia, though, I want to see the full paper in published form and examine the data in detail. Many questions need to be answered. For example, the addition of the drug to simvastatin lowered heart attack and stroke compared to simvastatin alone but there was no difference in overall death rates or cardiovascular death rates. That raises a red flag.
In addition, this study does not support the use of Zetia in patients who have not had heart attacks or near heart attacks (primary prevention).
Science moves slowly but inexorably toward the truth if done properly. It’s important that public policy and drug prescribing not get in front of the science as it did with this drug.
The skeptical cardiologist was in Atlanta recently visiting his Life Coach (LCOSC). Oddly enough, the wife of the LCOSC (who I’ll call Lisa) had just undergone a coronary calcium scan and it came back with a high score. Most women her age (58 years old) have a zero score but hers came back at 208 .
What is the significance of a calcium score of 208 in this case?
The CT scan for calcium (discussed by me in more detail here) focuses entirely on quantifying the intense and very specific kind of x-ray absorption from calcium. The three-dimensional resolution of the scan is such that the coronary arteries which supply blood to the heart can be accurately located and the amount of calcium in them very accurately and reproducibly added up. Calcium is not in the arteries normally and only accumulates as atherosclerotic plaque builds up over time. The build up of fatty plaque (atherosclerosis) is the major cause of coronary artery disease (CAD, sometimes termed coronary heart disease (CHD)) which is what causes most heart attacks and most death in both men and women in the U.S.
We can enter Lisa’s numbers into the online MESA calculator to see how she compares to other white 59 year old women. The calculator tells us that 72% of her peers have a zero calcium score and a score of 208 is higher than 95% of her peers. Although the 95th percentile is a good place to be for SAT scores it is not for atherosclerosis. This means substantial amount of fatty atherosclerotic plaque has built up in the arteries and puts the individual at significantly greater risk for heart attack and stroke. A calcium score of 100-300 confers a 7.7 times increased risk compared to an individual with similar risk factors with a zero calcium score.
Most of the risk factors that we can measure to assess one’s risk of heart attack (blood pressure, diabetes, smoking) were absent in Lisa. Her cholesterol levels had risen in the last 10 years but when I entered her numbers (total cholesterol 221, HDL 68) into the ASCVD risk estimator her 10 year risk came back at 2.5%. This is considered low and no treatment of cholesterol would be advised by the new guidelines.
The only clue that her cardiologist would have that Lisa has advanced premature atherosclerosis is that her mother had coronary heart disease at an early age, something we call premature CAD. Her mom at the age of 62 suffered a heart attack and had a stent placed in one of her coronary arteries. The occurrence of significant premature CAD in a parent or sibling substantially increases the chances that a patient will have premature CAD and the earlier it occurred in the parent or sibling the higher the risk.
Some of this excess risk is transmitted by measurable risk factors such as hypertension and hyperlipidemia and some through lifestyle factors but the majority of it is through genetic factors that we haven’t fully identified.
How much of an individual’s risk for heart attack is determined by genetics versus lifestyle?
A large Swedish study found that adopted men and women with at least one biological parent with CHD were 1.5 times more likely to have CHD than adoptees without. In contrast, men and women with one adoptive parent were not at increased risk.
Since 2007 an intense project to identify genetic factors responsible for CAD has been underway at multiple academic centers. Thus far 50 genetic risk variants have been identified. According to Dr. Robert Roberts
” All of these risk variants are extremely common with more than half occurring in >50% of the general population. They increased only minimally the relative risk for coronary artery disease. The most striking finding is that 35 of the 50 risk variants act independently of known risk factors, indicating there are several pathways yet to be appreciated, contributing to the pathogenesis of coronary atherosclerosis and myocardial infarction. All of the genetic variants seem to act through atherosclerosis, except for the ABO blood groups, which show that A and B are associated with increased risk for myocardial infarction, mediated by a prolonged von Willebrand plasma half life leading to thrombosis”
How well do the standard risk factors capture the individuals risk for heart attack?
The standard approach to estimating risk fails in about 25% of individuals as it does not accurately convey the high risk of the patient with family history and it overestimates risk in many elderly individuals who have an excellent family history.
It is in these patients that testing for the actual presence of atherosclerosis, either by vascular screening or coronary calcium is helpful.
Reducing The Excess Risk of Premature CAD
For many individuals there are clear-cut lifestyle changes that can be implemented once advanced CAD is identified: cigarette smoking cessation, weight loss through combinations of diet and exercise with resulting control of diabetes, However, many patients like Lisa, are non-smokers, living a good lifestyle, eating an excellent diet with plenty of fresh fruit, vegetables, fish and healthy oils and without obesity or diabetes. There is no evidence that modifying lifestyle in this group is going to slow down an already advanced progression of atherosclerosis.
Patients like Lisa have inherited predisposition to CAD, it is not due to their lifestyle.
Lisa’s cardiologist suggested she get a copy of Dr. Esselstyn’s book “Prevent and Reverse Heart Disease”. This book, based on the author’s experience in treating 18 patients with advanced CAD espouses an ultra low fat diet. The author declares that “you may not eat anything with a face or a mother (meat/poultry/fish)” and bans full fat dairy products and all oil (“not even a drop”)
Such “plant-based diets” (codeword for vegan or vegetarianism) lack good scientific studies supporting efficacy and are extremely hard to maintain long term. There is nothing to suggest that Lisa’s long term risk of heart attack and stroke would be modified by following such a Spartan dietary regimen.
Her cardiologist did recommend two things proven to be beneficial in patients with documented advanced CAD: statins and aspirin.
Taking a statin drug will arrest the atherosclerotic process and reduce risk of heart attack and stroke by around 30% as I’ve discussed here and here.
An aspirin is now indicated since significant atherosclerosis has now been documented to be present as I’ve discussed here.
We can blame a lot of heart disease on lifestyle: poor diets and lack of exercise are huge factors leading to obesity, diabetes, hypertension and hyperlipidemia, but in many patients I see who develop heart disease at an early age, lifestyle is not the issue, it is the genetic cards that they have been dealt.
Until we develop reliable genetic methods for identifying those at high risk it makes sense to utilize methods such as vascular screening or coronary calcium to look for atherosclerosis in individuals with a family history of premature CAD.
Once advanced atherosclerosis is identified, we have extremely safe and effective medications that can help individuals like Lisa deal with the cardiovascular cards they have been dealt.