For diagnosing high Lp(a) they chose a universal cut point of >100 nmol/L (approximately >50 mg/dl) which is at the 80th percentile in white Americans. This cut-off is not written in stone and may vary depending on risk, ethnicity, and comorbidities. Some labs report out Lp(a) in mg/dl, others in nmol/L. Pay attention to the units.
An individual’s Lp(a) level is 80-90% genetically determined in an autosomal codominant inheritance pattern with full expression by 1-2 years of age and adult-like levels achieved by approximately 5 years of age. Outside of acute inflammatory states, the Lp(a) level remains stable through an individual’s lifetime regardless of lifestyle.
High-quality evidence supports a link between Lp(a) levels and a variety of cardiovascular-related outcomes. See Table 1. The risk of heart attack and aortic stenosis is increased 3 to 4 fold.
4. The following populations should be considered for testing.
5. Neither diet nor lifestyle influences Lp(a) levels.
6. PCSK9 inhibitor drugs and niacin lower Lp(a) levels and but there are no data showing this changes clinical outcomes.
7. Similar to my approach, “the authors recommend initiating a moderate- to high-intensity statin therapy in adults aged 40-75 years with a 10-year ASCVD risk of 7.5% to ≤20% with a Lp(a) ≥100 nmol/L. High-risk patients with LDL-C ≥70 mg/dL (non-HDL-C ≥100 mg/dL) and a Lp(a) ≥100 nmol/L on maximally tolerated statin should be considered for more intensive therapies (ezetimibe and PCSK9 inhibitors) to lower LDL-C.”
8. Currently, novel therapies are being studied that selectively target Lp(a). A phase 2 trial of AKCEA apo(a)-LRx, an apo(a) antisense oligonucleotide, reduced Lp(a) up to 80%. A phase 3 study is being planned. Additionally, an oxPL antibody that binds and inactivates the pro-osteogenic activity of Lp(a) has promising in vitro data. These therapies, while promising, require additional research prior to becoming mainstream therapies.
The cost of the blood test for Lp(a) should be minimal. Medicare reimburses $14 for it. You can order it from Boston Heart Diagnostics for $11. Unfortunately, there is no telling what your local hospital lab will charge.
Since Lp(a) 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.
N.B. In 2018 the Centers for Disease Control and Prevention (CDC) approved two ICD-10 codes for the diagnosis of elevated Lipoprotein(a), or Lp(a). The ICD-10 diagnosis codes help to identify asymptomatic patients with elevated Lipoprotein(a) (E78.41) and a family history of elevated Lipoprotein(a) (Z83.430)
N.B.2. Don’t confuse Lp(a) with Apolipoprotein A1 which is the major protein component of HDL particles in plasma. Also, please note that WordPress converted my little a into a capital A in the title and I have no idea how to prevent that conversion.
For far too long, many patients have undergone a cardiac test that carries grave risks with the misunderstanding that they are getting the definitive assessment of their coronary arteries.
Chances are if you have visited an emergency room in the USA with chest pain and you weren’t clearly having an acute heart attack, you ended up getting one of two tests: a stress test or an invasive coronary angiogram (ICA).
What Is A Cardiac Catheterization?
For decades the ICA (commonly termed “cardiac catheterization or cath”) was considered the “gold standard” for the assessment of the arteries to the heart (the coronary arteries.) This invasive test involves inserting a tube (catheter) into either an artery in the wrist or groin, threading the catheter up the artery to the aorta and injecting contrast dye directly into the coronary arteries.
The x-ray movie images (angiogram) obtained then show the dye within the lumen of the arteries. If the column of dye is impinged upon an obstruction is diagnosed. However, early plaque in the arteries doesn’t necessarily stick into the lumen and typically resides in the wall, hidden from these “lumenograms.”
Below are the freeze-frame images of the left coronary artery invasive angiogram from a man we shall call Jerry who underwent catheterization in his 40s for atypical chest pain. He was told he had normal arteries, that they were “clean”.
Given the news that his arteries had no plaque build-up, he felt no need to modify his lifestyle or take cholesterol medications in order to avoid the fate of early death from myocardial infarction that his father had suffered at age 50.
Limitations Of The Cardiac Cath In Identifying Atherosclerotic Plaque
When I first saw him a year after the cardiac cath I told him that although his previous cardiologist had told him all was fine with his coronary arteries he could, in fact, have significant diffuse subclinical atherosclerosis and still be at high risk for a heart attack.
This came as quite a shock to Jerry as he, like most laypeople, view the cardiac cath as the “gold standard” for assessment of the coronary arteries. For most patients, a normal cath has been viewed as a warranty against heart attack
Although ICA has been the gold standard for the diagnosis of coronary artery disease, lumenography only shows the internal arterial lumen and does not see the vessel wall with its developing atherosclerotic plaque. Previous studies analyzing serial angiograms from patients presenting with acute coronary syndrome (ACS) have suggested that in nearly two-thirds of the culprit lesions, the coronary angiogram obtained a few months before the acute event demonstrated a non-significant stenosis.
Identifying Early Plaque Using Coronary Calcium Scans
I recommended the patient get a coronary artery calcium (CAC) scan to look for early coronary plaque and this demonstrated two small calcific plaques in the proximal portion of his LAD coronary artery. His calcium score was 9 which is higher than 82% of 45-year-old white males.
Now that we had visual proof of the plaque in his arteries he was motivated to change his lifestyle to reduce the risk of suffering his dad’s fate. In addition, he was now willing to take medications to further reduce risk.
A year later he was admitted to our hospital with palpitations and chest tightness. This time as I was his cardiologist we performed a noninvasive test-a coronary CT angiogram (CCTA). This demonstrated the two small areas of calcification in the LAD we had noted on the calcium scan but in addition, we were able to see surrounding those foci of calcification substantial premature build-up of soft plaque.
Following the CCTA and a more definitive assessment of his coronary artery status we were able to tell him there was no significant blockage of the coronaries and therefore no need for any stenting or bypass procedure.
Just as important, however, was the knowledge that he had a substantial plaque in the LAD which puts him at risk for heart attack.
With this knowledge, we were able to convince him to undergo substantial lifestyle changes to reduce his long term risk of heart attack and stroke. In addition, he was started on statin therapy to further reduce those risks.
The CCTA is performed using a special X-ray scanner and the risks are a small amount of radiation plus the risks of administration of intravenous radioiodine contrast. The injected dye material can cause allergic reactions in those predisposed and worsen kidney function in patients with underlying kidney disease.
Cardiac cath is usually very safe. A small number of people have minor problems. Some develop bruises where the catheter had been inserted (puncture site). The contrast dye that makes the arteries show up on X-rays causes some people to feel sick to their stomachs, get itchy or develop hives.
Even the NIH website downplays the risks, terming it a “relatively safe procedure” with rare complications.
However, the procedure is associated with substantial morbidity ranging from internal bleeding requiring surgery to disabling stroke. Although the risk of dying from the procedure has declined over the last 30 years it is still around .05%.
I have included a recent detailed summary of potential complications at the end of this post.
There are definite indications for getting a cardiac catheterization and I refer patients for this procedure on a daily basis. The clearest benefit is in patients presenting with clear evidence for myocardial damage (elevated troponin levels) from a myocardial infarction. In such patients the known benefits of opening tightly blocked coronary arteries outweigh the risks of the procedure.
However, patients should think twice and have an extensive discussion with the cardiologist recommending the test when there has been no evidence for myocardial damage.
Most importantly, patients should know that a declaration of “clean arteries” or “the arteries of a twenty-year-old” from the results of a cardiac cath do not guarantee freedom from cardiac events down the line. To detect early and premature atherosclerotic plaque build-up which corresponds to a very high lifetime risk of heart attack and stroke other techniques that look at the arterial wall and not the lumen are needed.
For the youngish, vascular ultrasound imaging for measurement of carotid IMT and soft plaque detection is useful, whereas CAC or CCTA is more useful in subjects over age 40 years of age.
N.B. As promised a long laundry list of complications for your edification.
The risk of major complications during diagnostic cardiac catheterization procedure is usually less than 1%, and the risk and the risk of mortality of 0.05% for diagnostic procedure. For any patient, the complication rate is dependent on multiple factors and is dependent on the demographics of the patient, vascular anatomy, co-morbid conditions, clinical presentation, the procedure being performed, and the experience of the operator. The complications can be minor as discomfort at the site of catheterization to major ones like death.
But there are very serious complications of the procedure that can result in death or serious disability.
These are among the most common complications seen after cardiac catheterization procedures. Hematomas are usually formed following poorly controlled hemostasis post sheath removal. Most hematomas are self-limiting and benign, but large rapidly expanding hematomas can cause hemodynamic instability requiring resuscitation with fluids and blood. The incidence of this complication is significantly reduced in transradial access. In patients with transfemoral access, retroperitoneal bleeding should be suspected if there is a sudden change in the hemodynamic stability of the patient with or without back pain as there may not be any visible swelling in the groin for some of these patients. The incidence of this complication is less than 0.2%. Strong clinical suspicion along with immediate imaging, usually with CT scan, helps make a diagnosis of this problem. Identification of the bleeding source is essential for patients with continued hemodynamic deterioration. These life-threatening bleeds are more frequent when the artery is punctured above the inguinal ligament. Most patients are managed with a reversal of anticoagulation, application of manual compression and volume resuscitation and observation. Patients with continued deterioration with need coiling of the bleeding source vessel, or balloon angioplasty or covered stents for bleeding from larger vessels.
When the hematoma maintains continuity with the lumen of the artery, it results in the formation of a pulsatile mass locally, defined as a pseudoaneurysm. This will be associated with bruit on examination. They happen following low access in the superficial femoral artery as opposed to the common femoral artery. These are usually diagnosed by ultrasound Doppler imaging or CT angiography. Small pseudoaneurysms of the less than 2 to 3 cm in size may heal of spontaneously and can be followed by serial Doppler examinations. Large symptomatic pseudoaneurysms can be treated by either ultrasound-guided compression of the neck of pseudoaneurysm or percutaneous injection of the thrombin using ultrasound guidance or may need surgical intervention.
Direct communication between the arterial and venous puncture sites with ongoing bleeding from the arterial access site leads to the fistula formation and are associated with a thrill or continuous bruit on examination. These usually will require surgical exploration as they are unlikely to heal spontaneously and may expand with time.
This is an infrequent complication and occurs in patients with an increased atherosclerotic burden, tortuous arteries, or traumatic sheath placement. Non-flow limiting dissections usually heal spontaneously following sheath removal. A flow limiting large dissections could lead to acute limb ischemia and should be treated immediately with angioplasty and stenting. Vascular surgery is usually reserved for patients with failed percutaneous techniques.
Thrombosis and Embolism
This complication is extremely rare with the use of the low profile catheters and predisposing factors include small vessel lumen, and associated peripheral arterial disease, diabetes mellitus, female sex, large diameter sheath, and prolonged catheter dwell time. Treatment involves removal of the occlusive sheath, percutaneous thrombectomy in conjunction with vascular surgery consultation.
Vascular Complications after Transradial Access
The most frequent complication after transradial access is about a 5% risk of radial artery occlusion. This is a clinically insignificant complication if the Allen test is normal. Patients with incomplete palmar arch and abnormal Allen test may have symptoms of hand ischemia after radial artery occlusion.
Radial artery spasm is another frequent complication, and this can be avoided by the use of local vasodilatory medications and systemic anxiolytics. Perforation of the radial artery is an extremely rare complication and is usually managed with prolonged external compression and rarely requires vascular surgery intervention.
Other Major Complications
The incidence of death with cardiac catheterization has decreased progressively and is less than 0.05% for diagnostic procedures. Patients with depressed left ventricular systolic function and those presenting with shock in the setting of acute myocardial infarction are at increased risk. In some subsets of patients, the risk of mortality can be more than 1%. Other factors that would increase the risk include old age, the presence of multivessel disease, left main coronary artery disease, or valvular heart disease like severe aortic stenosis.
The reported incidence of periprocedural myocardial infarction for a diagnostic angiography is less than 0.1%. This is mostly influenced by patient-related factors like the extent and severity of underlying coronary artery disease, recent acute coronary syndrome, diabetes requiring insulin, and technique-related factors.
The overall risk of stroke in recently reported series is low at 0.05% to 0.1% in diagnostic procedures and can increase to 0.18% to 0.4% in patients undergoing intervention. This can be a very debilitating complication associated with a high rate of morbidity and mortality. The risk is higher in patients with extensive atherosclerotic plaque in the aorta and aortic arch, complex anatomy, procedures requiring multiple catheter exchanges or excessive catheter manipulation, or the need for large-bore catheters and stiff wires.
Dissection and Perforation of the Great Vessels
Dissection of the aorta, perforation of the cardiac chambers, perforation of the coronary arteries is an extremely rare complication. The risk is higher in procedures with intervention as opposed to diagnostic procedures only. Patients with type A aortic dissection involving the ascending aorta will require surgical correction. Patients with a cardiac chamber or coronary perforation resulting in the accumulation of the blood in the pericardial space will need urgent pericardiocentesis to restore hemodynamic stability and immediate surgical consultation.
Cholesterol emboli from friable vascular plaques can give rise to distal embolization in multiple vascular beds. These are usually recognized by digital discoloration (blue toes), livedo reticularis. This can also manifest as a neurological squeal or renal impairment. The risk of this complication is minimized by exchanging catheters over a long wire and minimizing the catheter exchanges. Retinal artery occlusion causes Hollenhorst plaque.
Allergic reactions can be related to the use of local anesthetic, contrast agents, heparin or other medications used during the procedure. Reactions to the contrast agents can occur in up to 1% of the patients, and people with prior reactions are pretreated with corticosteroids and antihistamines. Use of iso-osmolar agents decreases the risk compared to high osmolar agents. When severe reactions do occur, they are treated similarly to anaphylaxis with intravenous (IV) epinephrine (initial dose 1 ml of 1:10000 epinephrine).
Acute Renal Failure
The incidence of the reported contrast nephropathy is quite variable (range 3.3% to 16.5%) in the patients undergoing cardiac catheterization resulting in a transient increase in the serum creatinine levels after exposure to contrast material. In the National Cardiovascular Data Registry, the incidence of contrast-induced acute kidney injury was 7.1%, among the patients undergoing elective and urgent coronary intervention. The risk is higher in patients with underlying moderate to severe renal disease, people with diabetes, elderly, females, patients on diuretics, ACEI, and metformin. Adequate pre-hydration, use of iso-osmolar agents, and techniques to minimize the amount of dye used will help prevent this complication. Renal atheroemboli can also cause renal failure and are associated with other signs of embolization.
Cardiac catheterization is performed using sterile technique, and local or systemic infection is extremely rare. Routine prophylaxis for endocarditis is not recommended during cardiac catheterization procedures.
Radiation skin injury can occur if a patient is exposed to excessive doses of radiation to one particular area of the body and manifestation could range from mild erythema to deep ulceration. Skin biopsies should be avoided for these lesions as they would make the underlying condition worse. This complication should be managed by a combined team of cardiologists, dermatologists, and plastic surgeons.
The occurrence of the ventricular fibrillation or ventricular tachycardia during the procedure could be related to irritation or ischemia of the myocardium by the catheter, contrast material or occlusive balloons. These arrhythmias occur more frequently in people presenting with acute ST-elevation myocardial infarction and treatment includes cardioversion along with anti arrhythmic drugs and restoration of the flow to the occluded artery. Atrial tachyarrhythmias can occur following the irritation of the right atrium during right heart catheterization and is usually self-limiting.
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 non-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,
Over the years I’ve had a number of patients tell me that they prefer to take over the counter (OTC) dietary supplements containing “natural” cholesterol lowering ingredients rather than the statin drug I have prescribed.
Red yeast rice (RYR) is a common ingredient in these supplements and is promoted widely and enthusiastically across the internet and in supplement or natural food stores for the purpose of lowering cholesterol and heart disease risk.
RYR has been used for centuries in China for coloring, food and medicine. It is made by fermenting red rice with a specific type of yeast (Monascus purpureus).
Red yeast rice contains chemicals that are similar to prescription statin medications. One of these, called monacolin K, is chemically identical to the statin drug lovastatin (brand name Mevacor).
The History Of Statin Drug Development
The history of the discovery and isolation of lovastatin, the first FDA approved statin, is worthy of a digression here as I think it illustrates the process of discovery, isolation and characterization of a chemical that becomes a safe and effective treatment.
Akin Endo,whose research over decades was crucial to discovering statins, writes that he was inspired by Alexander Fleming, who discovered penicillin in the blue-green mold belonging to the genus Penicillium in 1928.
He writes; “Although no metabolites that inhibited any enzymes involved in cholesterol synthesis had been isolated previously, I speculated that fungi like molds and mushrooms would produce antibiotics that inhibited HMG-CoA reductase. Inhibition of HMG-CoA reductase would thus be lethal to these microbes.”
Endo began analyzing thousands of molds and fungi for biologically active chemicals that would inhibit HMG-CoA reductase.
In 1971, after studying 3800 different strains of fungi he found a promising candidate: citrinin. Unfortunately,
“Citrinin strongly inhibited HMGCoA reductase and, furthermore, lowered serum cholesterol levels in rats. However, the research was suspended because of its toxicity to the kidneys. ”
End spent another 10 years isolating another promising HMG-CoA reductase inhibitor, “compactin, ” from mold and studying it in rats and other animals. Compactin demonstrated marked cholesterol lowering properties in dogs and monkeys and in the few humans who received it but the pharmaceutical company he worked for shut down the project after it appeared that in doses 200 x what were considered appropriate, it increased lymphoma risk in dogs.
The large pharmaceutical company, Merck, got wind of Endo’s studies with compactin, studied his data and realized the potential of similar but safer HMG-CoA reductase inhibitors. Drugs which inhibited HMG-coA reductase were now being termed statins.
Merck set out to find its own statins and in February 1979 isolated a statin very similar to compactin in chemical structure, called mevinolin, from the fungus Aspergillusterreus.
Endo, working separately and also in February 1979, isolated another statin (named monacolin K) from cultures of Monascusruber.(RYR).In the fall of the same year, it was confirmed that monacolin K and mevinolin were the same compound (later both changed to lovastatin).
The drug showed dramatic activity in lowering LDL cholesterol, with very few side effects. This led Merck to begin large-scale clinical trials of lovastatin in patients at high risk and long-term toxicity studies in dogs in 1984. The drug dramatically reduced cholesterol levels and was well tolerated. No tumors were detected. In 1987, Merck gained FDA approval and lovastatin became the first commercial statin.
Since then, six other statin drugs, some of which are synthesized in the laboratory rather than isolated from mold, have been approved for human therapy. These drugs have prevented thousands of heart attacks and contributed to the dramatic drop in cardiovascular deaths seen in developed countries over the last 30 years.
Ryr And Cholesterol Lowering
This brings us back to RYR and its ability to lower cholesterol. Small studies using a version of RYR that contained lovastatin have demonstrated a reduction in cholesterol compared to placebo.
However, because many red yeast rice supplements contained lovastatin (also called monacolin)In May 1998, the FDA ruled that Cholestin (the RYR product used in the studies showing cholesterol lowering benefit) was not a dietary supplement but an unapproved drug.
As a result, Pharmanex removed RYR from Cholestin. Since that ruling, the FDA has written warning letters to several other dietary supplement manufacturers to remove drug claims or eliminate red yeast rice with high lovastatin levels from their products, including Heart and Cholesterol (Mason Vitamins, Miami Lakes, Florida) Cholestrix (Sunburst Biorganics, Baldwin, New York), Red Yeast Rice and Red Yeast Rice/Policosanol Complex , and Red Yeast Rice (Nature’s Way Products Inc, )
A study in 2010, found levels of monacolins varying one-hundred fold in 12 RYR preparations available commercially (total monacolins (0.31-11.15 mg/capsule), monacolin K (lovastatin) (0.10-10.09 mg/capsule), and monacolin KA (0.00-2.30 mg/capsule).
Even more worrisome was that four products had elevated levels of citrinin. You remember citrinin, don’t you? That is the chemical that Endo initially identified as a candidate for cholesterol lowering drug but rejected because it was causing kidney failure in his rats.
Because of limited government oversight and variable manufacturing processes, one can also expect that the same manufacturer will have marked variation of monacolin content and citrinin from batch to batch or bottle to bottle.
Problems With Alternative Medicine In General
These problems with RYR supplements are typical of all supplements.As the the authors wrote
“Our results highlight an important issue with red yeast rice and many other alternative medicines: the lack of standardization of active constituents. Standardization of ingredients is difficult for several reasons: (1) There are variable growth and/or culture conditions and differences in harvesting and processing among manufacturers; (2) medicinal agents from natural sources are complex substances with many chemical constituents, many of which have unclear roles in their pharmacologic activity; and (3) different manufacturers may standardize products to amounts of 1 or 2 chemicals thought to be active ingredients, while other constituents are not standardized and may also have biologic and pharmacologic activity.”
One has to ask, given this background, why would a patient choose to take a “natural” OTC supplement containing an unknown amount of both a). Effective cholesterol lowering chemicals and b)potentially toxic extraneous chemicals over the precisely formulated, carefully regulated, fully studied, pure statin drug available by prescription.
It’s especially baffling to me when one considers that lovastatin comes from RYR. Thus it would have to be considered “natural.”
Akira Endo spent decades carefully identifying the effective and safe chemical portion of RYR. It is now available as a generic costing pennies per pill.
We know exactly how many milligrams you are consuming. We know what benefits to expect and what side effects can occur based on studies in hundreds of thousands of patients who have taken a similar dosage.
You are much better off taking the prescribed statin drug than RYR.