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.
While campaigning in Las Vegas last October, Vermont Senator Bernie Sanders began experiencing tightness in his chest. He was rushed to a hospital where he was diagnosed with a heart attack and had two stents implanted to open blocked arteries.
Despite little details about his cardiac condition, the event cast a cloud over his candidacy.
At the time I asked (and answered) a few questions): Is it appropriate for voters to lose confidence in Sanders at this point? He was already the oldest candidate in the race at age 78 years. Would he survive a 4 year term in the grueling position of head of the free world?
We now have more details to better answer these questions.
On December 30 of 2019, a letter from Brian P. Monahan, MD MACP on a letter head which reads in all caps “THE ATTENDING PHYSICIAN:Congress of the United States” to The Honorable Bernard Sanders was released.
This letter summarized Sanders’ “general health history and current medications” as Sanders had requested
Monahan, an oncologist by training, examined Sanders on 12/19/2019 at which time he found the senator was:
” 6 feet tall and 174 pounds. His blood pressure was 102/56, with a pulse of 62 beats per minute. His total cholesterol was 117 milligrams per deciliter of blood, HDL cholesterol (or “good” cholesterol) was 32 milligrams, and LDL cholesterol (or “bad” cholesterol) was 58 milligrams.”
With the exception of the low HDL these are good numbers and they indicate that Sanders LDL/bad cholesterol was at the appropriate goal post MI of <70 mg/dl. I would be a little concerned about the lowish BP of 102/56 in a 78 year old man but this likely reflects to some extent medications he is receiving to strengthen and protect his heart muscle.
Past Medical History
Next, Monahan summarizes Sanders’ past medical history
Over the years you have been treated for medical conditions including gout, hypercholesterolemia, diverticulitis, hypothyroidism, laryngitis secondary to esophageal reflux, lumbar strain, and complete removal of superficial skin lesions. Your colorectal cancer screening is up to date. Your past surgical history consists of repair of left and right-side inguinal hernias by laparoscopic technique and a right true vocal cord cyst excision. In November 2019, a follow-up ENT evaluation of your vocal cords for hoarseness was stable. You have no history of tobacco use, exercise regularly, and seldom drink alcohol.
Now we know some Bernie’s characteristic voice is due to a vocal cord cyst and that he is following a healthy lifestyle with regular exercise and no cigarette smoking.
What Happened In Vegas: The Myocardial Infarction
Monahan’s description of the heart attack (myocardial infarction or MI) Sanders suffered in Las Vegas gives more information than I had seen previously but is still lacking in details which I felt were important to know: troponin level and ejection fraction
The most significant event in your recent health was your admission to the Desert Springs Hospital in Las Vegas Nevada on October 19 2019. You experienced myocardial infarction due to an acute blockage of a coronary artery. In the initial hours of your evaluation, you were found to have an elevation of cardiac muscle proteins in your blood accompanied by diminished heart muscle strength and chamber wall motion reduction as determined by echocardiogram. You underwent prompt cardiac catheterization with identification of the narrowed segment of the midportion of the left anterior descending coronary artery. The narrowed segment was re-opened followed by the placement of two drug-eluting stents, a procedure that is referred to as primary percutaneous coronary intervention (Per). You received standard treatment with medications to improve your heart function and provide antiplatelet therapy required by your stents. You were released from the hospital three days later and returned home.
The exact elevation of the cardiac muscle protein, aka troponin, level is not reported.
He indicates “diminished heart muscle strength” determined by an echocardiogram and this is the ejection fraction (EF) but the exact percent EF is not given.
The size of Sanders’ heart attack is an important determinant of his prognosis. The more myocardial cells that died the larger the damage. We can detect and quantify heart attacks with a blood test using a cardiac specific protein called troponin.
Some heart attacks are tiny and only detected by very slight increases in the troponin in the blood whereas larger ones result in large increases in the troponin. What kind did Sanders have?
The more damage to the main pumping chamber of the heart, the left ventricle, the weaker the pumping action as measured by the ejection fraction. The lower the ejection fraction the more likely the development of heart failure. What is Sanders ejection fraction? Does he have any evidence of heart failure?
Heart Failure?: Signs Or Symptoms?
Later in his letter Monahan indicates
You have never had symptoms of congestive heart failure
This is an interesting turn of phrase. The doctor is not stating clearly that Sanders did not have congestive heart failure (CHF)
We diagnose CHF by eliciting certain symptoms such as shortness of breath or fatigue and observing certain signs such as crackles in the lungs, distention of the jugular veins, or swelling in the legs. These findings are combined with lab tests (BNP or pro BNP) and imaging studies (chest x-ray, echocardiography).
Given Monahan’s phrasing I suspect there were signs and/or abnormal labs that suggested CHF on his presentation with chest pain. The good news is that subsequent testing indicates no CHF.
Monahan goes on to describe current medications:
Your current daily medications include atorvastatin, aspirin, clopidogrel, levothyroxine, and lisinopril
The aspirin and clopidogrel are anti-platelet agents which are standard after implantation of drug-eluting stents like the two Sanders received at the time of his MI. They help keep the stents from stenosing or clogging up.
The atorvastatin is a statin/cholesterol lowering drug which should be given post MI in high dosages (40 to 80 mg daily) to reduce the risk of progression of the atherosclerotic plaque in Bernie’s coronaries which caused his MI. The atorvastatin has lowered his LDL to <70.
Lisinopril is an ACE inhibitor which is likely being utilized in this case to help strengthen and protect his heart muscle after the MI. Typically this would be used in conjunction with a beta-blocker however later in the letter, Dr. Monahan indicates Sanders was taken off a beta-blocker:
Several of the medications you initially required (blood-thinner, beta blocker) were stopped based on your progress. Your heart muscle strength has improved
Why Was The Beta-Blocker Stopped?
I see two possibilities, one portending a good prognosis and the other a bad prognosis.
Beta-blockers have been shown to significantly improve outcomes post MI in patients with depressed EF. The normal EF is >55%. Did Sanders’ EF improve to the point where the doctors felt beta-blockers would no longer be beneficial? This would be a good prognostic sign.
The other possibility is that Sanders’ blood pressure was so low on the beta-blockers that he was weak or dizzy. This would be a bad prognostic sign.
A third possibility seems less likely to me: excessive heart rate slowing on a beta-blocker. Given his resting heart of 62 bpm on no beta-blocker he should have been able to tolerate at least a low dose of beta blocker.
Cardiac Testing Post MI
After Sanders returned to his home in Vermont he saw his personal cardiologist Martin LeWinter and underwent further testing which according to Monahan showed the following
The heart chamber sizes, wall thickness, estimated pressures, and heart valves are normal.
I’m presuming this information comes from an echocardiogram. One of the key pieces of information that would come from this same echocardiogram is the ejection fraction. Why doesn’t he mention the EF?
Several 24-hour recordings of your heart electrical activity indicated no significant heat rhythm abnormality.
So Senator Sanders had at least two Holter monitors. This is not the norm post MI and I have to think he must have had some significant arrhythmias on telemetry while hospitalized to prompt these investigations. What rhythm abnormalities prompted multilple Holter monitor studies?
Sanders also underwent a treadmill stress test in December which is the norm post MI. Findings were summarized by Monahana
a successful graded exercise treadmill examination monitoring your heart function, muscular exertion, and oxygen consumption that indicated a maximal level of exertion to 92% of your predicted heart rate without any evidence of reduced blood flow to your heart or symptoms limiting your exercise performance. Your overall test performance was rated above average compared to a reference population of the same age. The cardiac exercise physiologist who evaluated your results determined that you are fit to resume vigorous activity without limitation.
A letter from Dr. Phillip Ades indicates this was a cardiopulmonary exercise test and it appears maximal aerobic capacity was measured directly but this number is not revealed.
However, this type of stress test is not capable of monitoring “heart function” and Monahan’s statement that there was no “evidence of reduced blood flow to your heart” can only mean there were no EKG changes as blood flow to the heart was not directly measured.
Fitness To Continue Campaigning And Serve As President
Senator Sanders’ doctors conclude based on all the evidence they have that he is fit and able.
In addition to the letters referenced above, Mr. Sanders’s personal cardiologist, Martin LeWinter wrote a letter (which I can’t locate) which states that Mr. Sanders had experienced “modest heart muscle damage” but that his heart function was now “stable and well-preserved.”
Once more, the two things I would like to know are not being precisely described.
Heart muscle damage would be precisely assessed by the maximal troponin level during his MI. Modest is defined as “not large” in the Cambridge English dictionary.
Heart function would be precisely assessed by the ejection fraction. Well-preserved is most frequently used to describe older things or people that are in good condition or don’t appear as old as they really are. It’s often used to describe left ventricular function but is vague. Why not just state the ejection fraction?
It would also be nice to know what coronary artery was stented and what was the status of the other coronary arteries that weren’t stented.
Dr. LeWinter concludes
“At this point, I see no reason he cannot continue campaigning without limitation and, should he be elected, I am confident he has the mental and physical stamina to fully undertake the rigors of the presidency,”
I have a lot of confidence in Dr. LeWinter’s (see below) integrity and judgement and therefore would agree with his conclusions. I’d feel even more confident if I had access to all of Senator Sanders’ relevant data.
N.B. I recognized Dr. LeWinter’s name as he has been a prominent figure in the area of pericardial disease and heart failure research.
His CV is very impressive.
Dr. LeWinter is Professor of Medicine and Molecular Physiology and Biophysics and Director of the Heart Failure and Cardiomyopathy Program at the University of Vermont. He received his undergraduate degree from Columbia University, his M.D. from New York University and sub-specialty training in Cardiovascular Disease at University of California, San Diego. In addition to heart failure, cardiac hypertrophy and myocardial dysfunction Dr. LeWinter has had a longstanding interest in pericardial disease. Dr. LeWinter has received continuous research support from the NIH for over 35 years and is the author of over 190 original research papers, over 60 book chapters and review articles, and the Editor of two books. He is a Fellow of the American Heart Association, the American College of Cardiology, the Cardiovascular Section of the American Physiological Society and the International Academy of Cardiovascular Sciences, and a member of the Association of University Cardiologists. Dr. LeWinter has served on numerous Editorial Boards and research review committees and is an Associate Editor of the journals Circulation and Coronary Artery Disease.
Despite this, a common concern of my patients when we discuss potentially utilizing statin drugs to reduce their long term risk of heart attack and stroke is that the drug will rob them of their memory.
More studies have been published in this area and they continue to show absolutely no evidence for adverse association between statins and cognition.
A recent summative review found no beneficial or detrimental associations between statins and cognition in elderly cohorts with normal baseline cognition, impaired cognition or with incident dementia.
Finally, and most recently we have reassuring evidence from Australian researchers who meticulously studied over a thousand participants aged 70-90 years in the Sydney Memory and Ageing Study.
-no difference in the rate of decline in memory or global cognition between statin users and never users.
-Statin initiation during the observation period was associated with blunting the rate of memory decline.
-Exploratory analyses found statin use was associated with attenuated decline in specific memory test performance in participants with heart disease and apolipoprotein Eε4 carriage.
-There was no difference in brain volume changes between statin users and never users.
For those who see statins as part of a conspiracy please note that there was absolutely no connection between the researchers and the statin pharmaceutical industry.
This study was supported by the Australian Government’s National Health and Medical Research Council (Dementia Research Grant 510124). Dr. Brodaty has served on the Nutricia Australia Advisory Board. Dr. Sachdev has served on the Australian Advisory Board of Biogen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
My 2017 post was triggered by a call from a reporter who wanted to discuss the “cognitive side effects” of statins. It goes into a fair amount of detail about media and internet fear-mongering and how this contributes to the nocebo effect which makes it more likely patients will experience adverse side effects from medicine.
At the end I discuss how we handle potential side effects in my practice.
I’ve copied it below as it remains highly relevant 2 years later.
Since I regularly prescribe statin drugs to my patients to reduce their risk of heart attack and stroke, I am very concerned about any possible side effects from them, cognitive or otherwise. However, in treating hundreds of patients with statins, I have not observed a consistent significant effect on brain function.
When the U.S. Food and Drug Administration (FDA) issued a statement in 2012 regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use it came as quite a surprise to most cardiologists.
The FDA made a change in the patient information on all statin drugs which stated:
Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken
This FDA statement was surprising because prior observational and randomized controlled trials had suggested that patients who took statins were less likely to have cognitive dysfunction than those who didn’t.
Early studies implied that statins might actually protect against Alzheimer’s disease.
In fact these signals triggered two studies testing if statins could slow cognitive decline in patients with established Alzheimer’s disease One study used 80 mg atorvastatin versus placebo and a second 40 mg simvastatin versus placebo and both showed no effect on the decline of cognitive function over 18 months.
More recently, multiple reviews and meta-analyses have examined the data and concluded that there is no significant effect of statins on cognitive function. Importantly, these have been written by reputable physician-scientists with no financial ties to the pharmaceutical industry.
Data Show No Evidence of Causality Despite Case Reports
The FDA added the warning to statin patient information based on case reports Occasional reports of patients developing memory loss on a statin do not prove that statins are a significant cause of cognitive dysfunction.
Case reports have to be viewed in the context of all the other scientific studies indicating no consistent evidence of negative effects of the statins. Case reports are suspect for several reasons:
First, patients receiving statins are at increased risk for memory loss because of associated risk factors for atherosclerosis and advancing age. A certain percentage of such patients are going to notice memory loss independent of any medications.
Second. The nocebo effect: If a patient taking a statin is told that the drug will cause a particular side effect,that patient will be more likely to notice and report that particular side effect.
A recent study in The Lancet looked at reported side effects in patients taking atorvastatin versus placebo and found substantial evidence for the nocebo effect.
Analysis of the trial data revealed that when patients were unaware whether they were taking a statin or a placebo, the number of side effects reported was similar in those taking the statin and those taking placebo. However, if patients knew they were taking statins, reports of muscle-related side effects in particular increased dramatically, by up to 41 per cent.
Third, a review of the FDA post-marketing surveillance data showed the rate of memory loss with statins is not significantly higher than for other non-statin cardiovascular medications (1.9 per million prescriptions for statins , 1.6 per million prescriptions for losartan) and clopidogrel (1.9 per million prescriptions for clopidogrel.)
What Most Media Prefer: Controversy And Victims
I thought my experience and perspective on statins and cognitive function might be useful for a wider audience of patients to hear so I agreed to be interviewed. After I expressed interest the reporter responded:
I would like to interview you and also a person who has experienced memory and/or thinking problems that they attribute to statin use.
I responded with “let me see what I can find,” although I was concerned that this reporter was searching for a cardiologist to support attention-grabbing claims of severe side effects of statins rather than seeking a balanced, unbiased perspective from a knowledgeable and experienced cardiologist.
If I produced a “victim” of statin-related memory loss this would boost ratings.
I then began racking my brain to come up with a patient who had clearly had statin-related memory loss or thinking problems. I asked my wonderful MA Jenny (who remembers details about patients that I don’t) if she could recall any cases. Ultimately, we both came up without any patients for the interview. (Any patient of mine reading this with definite statin memory loss please let me know and I will amend my post. However, I won’t be posting anecdotes outside of my practice.)
I have had a few patients relate to me that they feel like their memory is not as good as it was and wonder if it could be from a medication they are on. Invariably, the patient has been influenced by one of the statin fear-mongering sites on the internet (or a friend/relative who has been influenced by such a site.)
I wrote about one such site in response to a patient question a while back:
The link appears to be a promotional piece for a book by Michael Cutler, MD. Cutler’s website appears to engage in fear-mongering with respect to statins for the purpose of selling his books and promoting his “integrative” practice. I would refer you to my post entitled “functional medicine is fake medicine”. Integrative medicine is another code word for pseudoscientific medicine and practitioners should be assiduously avoided.
The piece starts with describing the case of Duane Graveline, a vey troubled man who spent the latter part of his life attempting to scare patients from taking statins. Here is his NY Times obituary.
You can judge for yourself if you want to base decisions on his recommendations.
There is no scientific evidence to suggest statins cause dementia.
An Internet-Driven Cult With Deadly Consequences
Steve Nissen recently wrote an eloquent article which accuses statin deniers of being an “internet–driven cult with deadly consequences.” Nissen has done extremely important research helping us better understand atherosclerosis and is known for being a patient advocate: calling out drug companies when they are promoting unsafe drugs.
I have immense respect for his honesty, lack of bias, and his courage to be outspoken . He writes:
“Statins have developed a bad reputation with the public, a phenomenon driven largely by proliferation on the Internet of bizarre and unscientific but seemingly persuasive criticism of these drugs. Typing the term statin benefits into a popular Internet search en- gine yields 655 000 results. A similar search using the term statin risks yields 3 530 000 results. One of the highest-ranking search results links to an article titled “The Grave Dangers of Statin Drugs—and the Surprising Benefits of Cholesterol”. We are losing the battle for the hearts and minds of our patients to Web sites de- veloped by people with little or no scientific expertise, who often pedal “natural” or “drug-free” remedies for elevated cholesterol levels. These sites rely heavily on 2 arguments: statin denial, the proposition that cholesterol is not related to heart disease, and statin fear, the notion that lowering serum cholesterol levels will cause serious adverse effects, such as muscle or hepatic toxicity— or even worse, dementia.”
He goes on to point out that this misinformation is contributing to a low rate of compliance with taking statins. Observational studies suggest that noncompliance with statins significantly raises the risk of death from heart attack.
The reasons for patient noncompliance, Nissen goes on to say, can be related to the promotion of totally unproven supplements and fad diets as somehow safer and more effective than statin therapy:
“The widespread advocacy of unproven alternative cholesterol-lowering therapies traces its origins to the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). Incredibly, this law places the responsibility for ensuring the truthfulness of dietary supplement advertising with the Federal Trade Commission, not the U.S. Food and Drug Administra-tion. The bill’s principal sponsors were congressional representatives from states where many of the companies selling supplements are headquartered. Nearly 2 decades after the DSHEA was passed, the array of worthless or harmful dietary supplements on the market is staggering, amounting to more than $30 billion in yearly sales. Manufacturers of these products commonly imply benefits that have never been confirmed in formal clinical studies.”
Dealing With Statin Side Effects In My Practice
When a patient tells me they believe they are having a side effect from the statin they are taking (and this applies to any medication they believe is causing them side effects), I take their concerns very seriously. After 30 years of practice, I’ve concluded that in any individual patient, it is possible for any drug to cause side effects. And, chances are that if we don’t address the side effects the patient won’t take the medication.
If the side effect is significant I will generally tell the patient to stop the statin and report to me how they feel after two to four weeks.
If there is no improvement I have the patient resume the medication and we generally reach a consensus that the side effect was not due to the medication.
If there is a significant improvement, I accept the possibility that the side effect could be from the drug. This doesn’t prove it, because it is entirely possible that the side effect resolved for other reasons coincidentally with stopping the statin. Muscle and joint aches are extremely common and they often randomly come and go.
At this point, I will generally recommend a trial at low dose of another statin (typically rosuvastatin or livalo.) If the patient was experiencing muscle aches and they return we are most likely dealing with a patient with statin related myalgias. However, most patients are able to tolerate low dose and less frequent administration of rosuvastatin or Livalo.
For all other symptoms, it is extremely unusual to see a return on rechallenge with statin and so we continue statin long term therapy.
Today a patient told me he thought the rosuvastatin we started 4 weeks ago was causing him to have more diarrhea. I informed him that there is no evidence that rosuvastatin causes diarrhea more often than a placebo and had no reason based on its chemistry to suspect it would. (Although I’m sure there is a forum somewhere on the internet where patients have reported this). Fortunately he accepted my expert opinion and will continue taking the drug.
If the symptoms persist and the patient continue to believe it is due to the statin, we will go through the process I described above. And, since every patient is unique, it is possible that my patient is having a unique or idiosyncratic reaction to the statin that only occurs in one out of a million patients and thus is impossible to determine causality.
Since statins are our most effective and best tolerated weapon in the war against our biggest killer, it behooves both patients and physicians to have a high threshold for stopping them altogether. Having such a high threshold means filtering out the noise from attention-seeking media and the internet-driven denials cult thus minimizing the nocebo effect
The ISCHEMIA (International Study of Comparative Health Effectiveness With Medical And Invasive Approaches) study presented at the AHA meeting this week provides further evidence that a conservative approach utilizing optimal medical therapy is an acceptable strategy for most patients with stable coronary disease (CAD).
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), coronary 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 stabilize atherosclerotic plaque, dilate the coronary artery or slow the heart’s pumping action 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.
What Did ISCHEMIA Prove?
ISCHEMIA (paper unpublished but slides available here) showed that an invasive strategy (employing cardiac catheterization with resulting stenting or coronary bypass surgery (CABG)) offered no benefit over optimal medical therapy in preventing cardiovascular events in patients with moderate to severe CAD.
Rates of all-cause death were nearly superimposable over the years studied, reaching 6.5% and 6.4% at 4 years for the invasive and conservative groups,
Inclusions and exclusion criteria are listed below. Patients with unnaceptable angina despite optimal medical therapy were not included. These patients clearly benefit symptomatically from revascularization (as long as their chest pain is actually angina and not from another cause.)
All patients had stress imaging studies demonstrating moderate to severe amounts of ischemia. Such patients with very abnormal stress tests in the past have typically been sent immediately to the cath lab.
Based on ISCHEMIA we now know in these patients there is no need to do anything urgently other than institute OMT.
These patients were on good medical therapy which likely explains the very good outcomes in both conservative and invasive arms. The “high level of medical therapy optimization” is what cardiologists should be shooting for with LDL<70, on a statin with systolic blood pressure <140 mm Hg, on an antiplatelet drugg and not smoking.
Interestingly coronary CT angiography (CCTA) was utilized prior to patients receiving catheterization. I’ve been utilizing this noninvasive method for visualizing the coronary arteries increasingly prior to committing to an invasive approach.
Quality Of Life
Finally, in a separate presentation the ISCHEMIA trial showed that the invasive strategy did improve symptoms and quality of life modestly. It did not improve quality of life in those without angina symptoms.
The ORBITA study (which I wrote about here) showed that a large amount of the symptomatic improvement in patients following stenting may be a placebo effect.
Importance Of ISCHEMIA
Hopefully the results of ISCHEMIA will cut down on the number of unnecessary catheterizations, stents and bypass operations performed. This, in turn, will save our health system millions of dollars and prevent unnecessary complications.
Outside the setting of an acute heart attack the best approach to patients with blocked coronary arteries is a calm, thoughtful, and measured one which allows ample time for shared decision-making between informed patients and knowledgeable physicians. Such decisions should carefully consider the ISCHEMIA, COURAGE and ORBITA results.
N.B. Ischemia is a fantastic acronym for this study. Doctors use it a lot to describe the absence of sufficient blood flow to tissues.
N.B.2 Although I deplore the number of unnecessary caths and stents performed in the US, especially in patients without symptoms and those with noncardiac chest pain, I still utilize them in my patients with flow-limiting coronary stenoses and unacceptable anginal chest pain with symptoms despite optimal medical therapy and have noticed outstanding results. This angiogram shows a tight, eccentric LAD blockage in such a patient who now, post stent, has had complete resolution of the chest pain that limited him from even short walks.
While campaigning in Las Vegas on Tuesday of last week, Vermont Senator Bernie Sanders began experiencing tightness in his chest. He was rushed to a hospital where he was diagnosed with a heart attack and had two stents implanted to open blocked arteries.
Little to nothing beyond these bare details of his health condition is known but, as Politico put it, this event has “cast a cloud over his candidacy.”
Is it appropriate for voters to lose confidence in Sanders at this point? He was already the oldest candidate in the race at age 78 years. Would he survive a 4 year term in the grueling position of head of the free world?
An American Federation of Aging white paper, Longevity and Health of U.S. Presidential Candidates for the 2020 Election, used data from national vital statistics to estimate lifespan, healthspan (years of healthy living), disabled lifespan, and four- and eight-year survival probabilities for U.S. citizens with attributes matching those of the 27 then candidates for Presidency.
Given the favorable health and longevity trajectories of almost all of the presidential candidates relative to the average member of the same age and gender group in the U.S., and the apparent current good health of all of the candidates, there is reason to question whether age should be used at all in making judgments about prospective presidential candidates
I would agree that individual health is more important than chronological age in evaluating longevity and in Sanders’ case the heart attack may be an indicator of a poor prognosis and an inability to withstand the rigors of campaigning for and serving as president.
Unfortunately we need to know a lot more about Sanders’ heart attack and overall health to make this determination.
Big Heart Attack Or Little Heart Attack?
A heart attack or myocardial infarction (MI) occurs when heart muscle does not get enough blood/oxygen to keep the myocardial cells alive. This typically is due to a tight blockage in one of the coronary arteries supplying blood to the heart, thus constricting the blood flow to a segment of heart muscle (myocardium).
The size of Sanders’ heart attack is an important determinant of his prognosis. The more myocardial cells that died the larger the damage. We can detect and quantify heart attacks with a blood test using a cardiac specific protein called troponin.
Some heart attacks are tiny and only detected by very slight increases in the troponin in the blood whereas larger ones result in large increases in the troponin. What kind did Sanders have?
The more damage to the main pumping chamber of the heart, the left ventricle, the weaker the pumping action as measured by the ejection fraction. The lower the ejection fraction the more likely the development of heart failure. What is Sanders ejection fraction? Does he have any evidence of heart failure?
Stunned or Hibernating Myocardium?
With some heart attacks the heart muscle doesn’t die but becomes stunned-weakened but still living. Under other circumstances a tightly blocked coronary artery doesn’t cause a heart attack but the reduced oxygen supply causes the muscle to stop working-in effect hibernating. Thus, 3 months from now Sanders’ heart muscle function may improve as these stunned or hibernating myocardial cells come back to full function. What will Sanders’ ejection fraction be 3 months from now.? Will he have evidence of heart failure at that time?
Troponin levels and EF are just two of many factors that will determine Sanders’ prognosis.
A recent review of such factors on the one year post MI prognosis concluded
Secular trends showed a consistent decrease in mortality and morbidity after acute MI from early to more recent study periods. The relative risk for all-cause death and cardiovascular outcomes (recurrent MI, cardiovascular death) was at least 30% higher than that in a general reference population at both 1–3 years and 3–5 years after MI. Risk factors leading to worse outcomes after MI included comorbid diabetes, hypertension and peripheral artery disease, older age, reduced renal function, and history of stroke.
Hopefully, prior to the Iowa caucases all the candidates will release their medical records for the public to review. Only by learning more details about Senator Sanders’ heart attack and his overall medical condition can we answer whether he is fit to serve as President. Similarly, heretofore unknown individual health conditions could markedly effect the prognosis of any of the other candidates and their medical records should be equally scrutinized.
Big tobacco had successfully blocked such labels but yesterday the FDA announced a proposed rule which would post new graphic health warnings on cigarette packages if approved:
The 13 proposed warnings, which feature text statements accompanied by photo-realistic color images depicting some of the lesser-known health risks of cigarette smoking, stand to represent the most significant change to cigarette labels in 35 years.
Here are some of the proposed graphics which aren’t quite as attention-grabbing as the ones I saw in Europe.
Cigarette smoking is by far the worse thing my patients do to compromise their health and I’m in favor of hammering home the horrible complications smokers face.
Do you want feet like this?
Or Lungs like these?
Or a scar on your chest from open heart surgery?
All this and more can be yours if you keep smoking!
I’ve reposted below my initial blog on the topic.
While strolling the delightful (and typically debris-free) streets of Haarlem in The Netherlands the skeptical cardiologist espied an unusual cigarette pack on the ground.
In comparison to the typical American cigarette pack I noted a very prominent and disgusting picture of a leg which had been ravaged by peripheral artery disease.
The large print translates “smoking clogs your arteries.”
This is one of many potential warnings on Dutch cigarette packs. My favorite is
Roken kan leiden tot een langzame, pijnlijke dood
(Smoking can lead to a slow, painful death)
Perhaps, if such warning had been on American cigarette packs in the 1990s my mother would have been able to walk without severe pain in her legs (claudication) from the severe blockages caused by her decades of cigarette smoking.
When cigarette smoking patients tell me that “you have to die from something” I tell them that although they are greatly increasing their chance of dying from lung and cardiac disease, the smoking may not kill them but leave them miserable and unable to walk or breath.
Experts on tobacco control note that these large, graphic and direct warnings are much more effective than the first small boxed warnings:
After the implementation of the first warning labels in 1966, the FTC’s 1981 report concluded that the original warning labels were not novel, overexposed and too abstract to remember and be personally relevant.46 Warning labels, like advertisements, wear out over time.47 Written warning labels wear out faster than graphic ones.48,49 In response, Congress passed a law mandating four rotating warnings. Studies on them began appearing in the late 1980s, demonstrating that several years after the implementation, those written labels on cigarette packs were also not noticed and not remembered by smokers and adolescents.50–53 Since then, the diffusion and evolution of tobacco warning labels have been propelled by observational and experimental studies showing the effectiveness of large graphic warning labels in informing consumers about the health harms of smoking and reducing their smoking behavior.45,54
Here’s how Australia’s warnings have evolved
In 2011 the US Congress passed legislation moving America towards such effective graphic warnings:
However, the law was challenged by Big Tobacco and has never been enacted. From the FDA site:
The Family Smoking Prevention and Tobacco Control Act requires the FDA to include new warning labels on cigarette packages and in cigarette advertisements. On June 22, 2011, the FDA published a final rule requiring color graphics depicting the negative health consequences of smoking to accompany the nine new textual warning statements. However, the final rule was challenged in court by several tobacco companies, and on Aug. 24, 2012, the United States Court of Appeals for the District of Columbia Circuit vacated the rule on First Amendment grounds and remanded the matter to the agency. On Dec. 5, 2012, the Court denied the government’s petition for panel rehearing and rehearing en banc. In 2013, the government decided not to seek further review of the court’s ruling.
The FDA has been undertaking research related to graphic health warnings since that time.
 R.J. Reynolds Tobacco Co., et al., v. Food & Drug Administration, et al., 696 F.3d 1205 (D.C. Cir. 2012)
More than 100 countries/jurisdictions worldwide have now required pictorial warnings, with fully 105 countries/jurisdictions having done so. This represents a landmark global public health achievement.
Increasingly, the United States stands alone, because of a constitutional doctrine privileging commercial speech above public health.
Here are the countries requiring pictorial warnings courtesy of that Canadian Cancer Society report.
The skeptical cardiologist was listening to a podcast discussion between Sam Harris and Eric Topol recently and became flabbergasted.
Topol, the “world-renowned cardiologist” who is seemingly everywhere in media these days was discussing what he considers the overuse of imaging technology during the podcast which Harris’s website describes as follows:
In this episode of the Making Sense podcast, Sam Harris speaks with Eric Topol about the way artificial intelligence can improve medicine. They talk about soaring medical costs and declining health outcomes in the U.S., the problems of too little and too much medicine, the culture of medicine, the travesty of electronic health records, the current status of AI in medicine, the promise of further breakthroughs, possible downsides of relying on AI in medicine, and other topics.
Personally, I have been amazed at the hype and promotion that artificial intelligence (AI) has been getting given the near total absence in cardiology of any tangible benefits from it and I wanted to hear what the man who wrote ” Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again ” had to say about it.
About 28 minutes into the podcast, Harris, who has lately been preoccupied with promoting meditation as a cure for all ills, begins describing a procedure he underwent:
I’ve had a few adventures in cardiology. CT scan, calcium score scan.
Harris, who in neuroscience and philosophy might speak precisely, here is very vague. Did he get a coronary calcium scan (CAC) or a coronary CT angiogram? There is a huge difference and he is conflating the two imaging procedures.
Apparently he is unhappy with having undergone it but:
I might be telling a different story if my life was saved by it.
And his doctor’s rationale for getting the scan was lacking:
The way this was dispensed to me. We now have this new tool, let’s use it.
Let me just say at this point that if your doctor’s rationale for performing a test is that he has a machine that performs the test just say no. Or demand an explanation of how the results will change your management or prognosis.
Apparently the scan that Harris had didn’t turn out either horrifically worse than expected or remarkably better and didn’t change management:
In my case at the end it didn’t make sense.
Now, I can forgive Sam Harris for being somewhat naive and misguided when it comes to coronary artery scans or coronary CT angiograms but Eric Topol , the world’s leading talking cardiology head should fully understand the value of coronary artery calcium scans.
This is where I first become flabbergasted.
Topol says in response at this point that coronary artery calcium scans are “terribly overused” and that “I’ve never ordered one.”
Eric, you cannot be serious!
Are you telling me that you wouldn’t order one on your 60 year old airline pilot friend whose father dropped dead of a massive MI at age 50 but whose lipids look fine?
Why doesn’t Eric order CACs?
Because “There are so many patients who have been disabled by the results of their calcium score even though they have no symptoms.”
This is where the degree of my flabbergastment increased by an order of magnitude.
Our job as preventive cardiologists is to identify those at high risk and lead them to lifestyle choices and medicine that dramatically lowers that risk. We educate them that the large build up of subclinical atherosclerosis we identified does not have to result in sudden death, crippling heart attacks or strokes. We reassure them that with the right tools we can help them live a long, productive and happy life.
Eric, what do you tell these people? The calcium score is irrelevant? You’re fine. You shouldn’t have gotten it. Surely not! This would be the preventive cardiology equivalent of sticking one’s head in the sand.
This is not the first time Topol has opined on the dangers of CAC. An excerpt from his book, ‘The Patient Will See You Now: The Future of Medicine Is in Your Hands” posted on Scientific American describes the ills created in a 58 year old man who had a CAC score of 710.
My patient was told that he had a score of 710—a high calcium score—and his physician had told him that he would need to undergo a coronary angiogram, a roadmap movie of the coronary anatomy, as soon as possible. He did that and was found to have several blockages in two of the three arteries serving his heart. His cardiologists in Florida immediately put in five stents (even though no stress-test or other symptoms had suggested they were necessary), and put him on a regimen of Lipitor, a beta-blocker, aspirin and Plavix.
This case is not an example of inappropriate usage of CAC it is an example of really bad doctoring and failure to utilize the CAC information properly.
One should never order a cardiac catheterization/coronary angiogram solely on the basis of a high CAC score. Even ordering a stress test in this situation is debatable as I discuss here.
And Topol’s patients symptoms were most likely related to a beta-blocker that he didn’t need (see here).
My Gene Rank
Later in the podcast I reached maximum flabbergast levels when Topol announced that as a result of a high score for CAD risk he received using an iPhone app called MyGeneRank he had started taking a statin drug.
He enthusiastically promoted the app which his Scripps Translational Science Institute developed and urged listeners to utilize this approach to better refine the estimate of their risk of heart attack and stroke.
Per the Scripps website:
The MyGeneRank mobile app is built using Apple’s ResearchKit, an open source framework that enables researchers and programmers to build customized mobile apps for research purposes. With user permission, the app connects with the 23andMe application program interface and automatically calculates and returns a genetic risk score for coronary artery disease.
In addition, the app calculates a 10-year absolute risk estimate for an adverse coronary event, such as heart attack, using a combination of genetic and clinical factors. Users are able to adjust behavioral risk factors to see the influence of lifestyle habits on their overall risk.
Elsewhere, Topol, has stated
“We are excited to launch a unique study that combines an iOS app and genomics to help guide important health decisions,” says Eric Topol, MD, Founder and Director of the Scripps Translational Science Institute and Professor of Molecular Medicine at The Scripps Research Institute. “Not only does participating in the study arm individuals with their own data, but it also gives them the opportunity to participate in new type of research – one that is driven by and for patients.”
Curious, I downloaded the MyGeneRank app, answered some questions and gave it permission to access my 23 and Me data. After requiring me to complete a survey on my health it then yielded my coronary artery disease risk score.
Oh, no! My genetic risk score was at the 81st percentile! In the red zone. According to Eric Topol I should take a statin like him. Based on these results I probably should be incredibly anxious and crippled by fears of cardiac death.
Fortunately, I have superior information to allay my fears. I’ve had CAC scans in the past which are well below average for men my age. Despite my dad’s history of early CAD, a recent coronary CT angiogram showed minimal plaque. I know exactly where I stand risk-wise.
How many cardiac cripples has Topol’s MyGeneRank inappropriately created?
Is the data that MyGeneRank utilizes superior to that from CAC scans?
For coronary artery calcium scanning there is a wealth of data supporting improved risk prediction and we are looking directly at the atherosclerotic process that eventually causes the diseases we want to prevent.
It’s interesting that a recent study looking at a polygenetic risk score’s ability to predict cardiac events was comparing the risk score’s ability to predict subclinital atherosclerosis:
Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque.
In the Scientific American article Topol quotes Mark Twain:, “To a man with a hammer, a lot of things looks like nails that need pounding.”
Topol’s hammer is artificial intelligence. We eagerly await the day he discovers a nail that he can bang on that significantly advances medical care.
In the meantime I and the vast majority of progressive preventive cardiologists will be utilizing CAC scores intelligently to identify both those patients at high risk for cardiovascular events who need more aggressive treatment and those at low risk who can be reassured and have treatment de-escalated.
Polygenetic CAD risk scores do show promise to improve our predictive powers but more study is needed in this are before we make clinical treatment decisions based on the results.
Recently the skeptical cardiologist was asked by Ilene, a reader with an HDL almost as high as her LDL and a history of branch retinal vein occlusion (BRVO) whether she should take the statin her cardiologist had prescribed.
I enjoy reading your articles and would appreciate your opinion on my situation. I recently took a lipid panel blood test: total cholesterol: 244 HDL:112 LDL:121 VLDL:11 CRP: 1.77 Triglycerides: 57. Also my Cardiac Agatston score is 21.
I had a Branch Retinol Vein Occlusion a year ago in my left eye (it’s healing beautifully) and as a precaution am now taking Amlodipine 5mg daily (my blood pressure was never too high to begin with) along with a daily baby aspirin.
I am otherwise a healthy 72 year old woman, exercise and eat healthy.
My regular doctor (Integrative MD) says my cholesterol ratio is wonderful….my cardiologist wants me to take a statin (Atorvastatin) in a low dose. The ONLY med I take is Amlodipine and I am not one to be taking a plethora of meds for the rest of my life (unless “absolutely” necessary. What is your suggestion…take a statin or not.
While I can’t provide medical advice to Ilene specifically it is worthwhile to ponder the general aspects of her case and how I would approach it as it likely applies to thousands of other patients including many of my own.
In my mind there are two questions here: 1) Should Ilene and patients like her take a statin to prevent future heart attacks and strokes and 2) Do statins effect the Branch Retinal Vein Occlusion (BRVO)?
Although I’m not a fan of integrative or functional medicine Ilene’s integrative MD is correct in saying that her ratio of total cholesterol to HDL cholesterol is wonderful. Perhaps that high HDL is protecting her from a build-up of atherosclerotic plaque.
On the other hand, Ilene tells me that “My father did have a heart attack in his 60’s”. Perhaps she inherited something from him that puts her in a higher than average risk category.
With the information from the CAC we don’t have to guess about the influence of the high HDL and the family history of CAD. Her score is at the 48th percentile, slightly below average for white women her age, thus it would appear she is not destined for her father’s fate.
In this case, the CAC score does not significantly alter our risk estimate as it is so close to the average for her age
Even if we count her as having hypertension because she is on the amlodipine her 10 year risk of heart attack and stroke is low at 3.2%.
Guidelines don’t recommend statin treatment unless risk is >7.5%.
Also, note that I answered yes to “Family history heart disease” but most studies generally only consider this a risk factor if father had heart attack prior to age 55 years. If we make that a no the risk drops to <3%.
Now that we’ve answered Ilene’s real question let’s see if the BRVO warrants statin therapy.
Branch Retinal Vein Occlusion
BRVO is the blockage of a vein from the retina and the second most
common cause of vision loss from retinal vascular disease, following diabetic retinopathy. It typically results in the painless loss of vision in one portion of one eye due to hemorrhage and edema in the retina.
A reasonable summary of BRVO provided by the American Academy of Ophthalmology can be found here.
BRVO is not clearly related to atherosclerosis or hyperlipidemia and there is no evidence that taking a statin would prevent recurrence or help the condition.
The leading theory for what causes BRVO is that the more delicate and distensible retinal veins are squished or compressed at points where the stiffer and thicker retinal arteries cross them. Up to Date notes:
Whereas branch retinal vein occlusion (BRVO) appears to be related to compression of the branch vein by retinal arterioles at the arteriovenous crossing points, central retinal vein occlusion (CRVO) is usually associated with primary thrombus formation.
Although BRVO is more common in patients with hypertension and atherosclerosis it is not clear that one causes the other or that treatment of hypertension or atherosclerosis diminishes the risk of BRVO. So statins are not recommended.
Every patient case for me leads to more questions, more investigations and more knowledge. Here are some questions that occurred to me from ilene’s case.
-Why would someone with no symptoms and no heart problems be seeing a cardiologist?
(“I started seeing a cardiologist just to make sure all systems were “go” and stayed that way!… we take care of our cars so why not my body. )
I kind of like this answer and I definitely see lots of patients with that philosophy but if we extrapolate the car analogy: going to a cardiologist would be like taking your car to a mechanic who only works on engines or perhaps one specific part of the engine (help me out here people who know about cars.)
-Why was Ilene unwilling to take a statin? (I pretty much know the answer to this (see here) for most patients.
‘m just afraid of the horrible muscle related side effects of statin drugs…and that’s why I’m taking Berberine 500mg twice a day.
Yep. I feel a post abut Berberine may be in the works!
-Finally, should a 72 year old with a CAC score of 21 and BRVO be taking a baby aspirin?
This post still serves as a good introduction to the test (rationale, procedure, risks) but in the 5 years since it was published there has been a substantial body of data published on CAC and in 2018 it was embraced by major organizations.
Overall, I’ve written 20 posts in which CAC plays a predominant role since then and I feels it’s time to put the most important changes and concepts in one spot.
Detection Of Subclinical Atherosclerosis: What’s Your Risk of Dropping Dead?
We have the tools available to look for atherosclerotic plaques before they rupture and cause heart attacks or stroke. Ultrasound screening of the carotid artery, as I discussed here, is one such tool: vascular screening is an accurate, harmless and painless way to assess for subclinical atherosclerosis.
In my practice, the answer to the question of who should or should not take aspirin is based on whether my patient has or does not have significant atherosclerosis. If they have had a clinical event due to atherosclerotic cardiovascular disease (stroke, heart attack, coronary stent, coronary bypass surgery, documented blocked arteries to the legs) I recommend they take one 81 milligram (baby) uncoated aspirin daily. If they have not had a clinical event but I have documented by either
vascular screening (significant carotid plaque)
coronary calcium score (high score (cut-off is debatable, more on this in a subsequent post)
Incidentally discovered plaque in the aorta or peripheral arteries (found by CT or ultrasound done for other reasons)
then I recommend a daily baby aspirin (assuming no high risk of bleeding).
Help In Deciding Who Needs Aggressive Treatment
Second, CAC is an outstanding tool for further refining risk of heart attack and stroke and helping better determine who needs to take statins or undergo aggressive lifestyle reduction, something I described in detail in my post “Should All Men Over Sixty Take a Statin Drug”.
After working with them for 9 months and using the iPhone app to calculate my patients’ 10 year risk of atherosclerotic cardiovascular disease (ASCVD, primarily heart attacks and strokes) it has become clear to me that the new guidelines will recommend statin therapy to almost all males over the age of 60 and females over the age of 70.
As critics have pointed out, this immediately adds about 10 million individuals to the 40 million or so who are currently taking statins.
By identifying subclinical atherosclerosis, CAC scoring identifies those who do or don’t need statins.
This is particularly important for patients who have many reservations about statins or who are “on the fence” about taking them when standard risk factor calculations suggest they would benefit.
In 2015 I wrote about a documentary entitled “The Widowmaker” (see here and here) which is about the treatment and prevention of coronary artery disease and what we can do about the large number of people who drop dead from heart attacks, some 4 million in the last 30 years:
The documentary, as all medical documentaries tend to do, simplifies, dumbs down and hyperbolizes a very important medical condition. Despite that it makes some really important points and I’m going to recommend it to all my patients.
At the very least it gets people thinking about their risk of dying from heart disease which remains the #1 killer of men and women in the United States.
Perhaps it will have more patients question the value of stents outside the setting of an acute heart attack. This is a good thing.
Perhaps it will stimulate individuals to be more proactive about their risk of heart attack. This is a good thing.
Although CAC has some similarities to mammography (both utilize low dose radiation, 0.5 mSV) I concluded that CAC was not “the mammography of the heart” as the documentary proclaims.
In October, 2016 the skeptical cardiologist predicted that Donald Trump’s coronary calcium score, if remeasured, would be >100 . At that time I pointed out that this score is consistent with moderate coronary plaque build up and implies a moderate risk of heart attack and stroke.
Trumps’ score gave him a seven-fold increase risk of a cardiovascular event in comparison to Hilary Clinton (who had a zero coronary calcium score) .
I was able to predict this score because we knew that Trump’s coronary calcium was 98 in 2013 and that on average calcium scores increase by about 10% per year.
What is most notable about the Trump CAC incident is that Trump, like all recent presidents and all astronauts underwent the screening. If the test is routine for presidents why is it not routine for Mr and Mrs Joe Q Public?
A three-phased approach to coronary artery disease (CAD) risk assessment is recommended, beginning with initial risk-stratification using a population-appropriate risk calculator and resting ECG. For aircrew identified as being at increased risk, enhanced screening is recommended by means of Coronary Artery Calcium Score alone or combined with a CT coronary angiography investigation.
I was very pleased to read that the newly updated AHA/ACC lipid guidelines (full PDF available here) emphasize the use of CAC for decision-making in intermediate risk patients.
For those patients aged 40-75 without known ASCVD whose 10 year risk of stroke and heart attack is between 7.5% and 20% (intermediate, see here on using risk estimator) the guidelines recommend “consider measuring CAC”.
If the score is zero, for most consider no statin. If score >100 and/or >75th percentile, statin therapy should be started.
A Few Final Points On CAC
First, it’s never too early to start thinking about your risk of cardiovascular disease. I have been using CAC more frequently in the last few years in individuals <40 years with a strong family of early sudden death or heart attack and often we find very abnormal values (see here for my discussion on CAC in the youngish.)
If heart disease runs in your family or you have any of the “risk-enhancing” factors listed above, consider a CAC, nontraditional lipid/biomarkers, or vascular screening to better determine were you stand and what you can do about it.
Included in my discussions with my patients with premature ASCVD is a strong recommendation to encourage their brothers, sisters and children to undergo a thoughtful assessment for ASCVD risk. With these new studies and the new ACC/AHA guideline recommendations if they are age 40-75 years there is ample support for making CAC a part of such assessment.
Hopefully very soon, CMS and the health insurance companies will begin reimbursement for CAC. As it currently stands, however, the 125$ you will spend for the test at my hospital is money well spent.
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.
There are many other questions to answer with regard to CAC-should they be repeated?, how do statins influence the score?, is there information in the scan beyond just the score that is important? Is a scan helpful after a normal stress test?
Like most things in cardiology we have a lot to learn about CAC. There are many more studies to perform. Many questions yet to be answered.
A study showing improved outcomes using CAC guided therapy versus non CAC guided therapy would be nice. However, due to the long time and thousands of patients necessary it is unlikely we will have results within a decade.
I don’t want to wait a decade to start aggressively identifying who of my patients is at high risk for sudden death. You only get one chance to stop a death.