Tag Archives: coronary artery calcium

Are You Taking A Statin Drug Inappropriately Like Eric Topol Because of the MyGeneRank App?

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.

Astoundingly Yours,

-ACP

Ilene Has High Cholesterol With A “Wonderful Ratio” And A Branch Retinal Vein Occlusion: Should She Take A Statin?

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.
Frequent readers of skepcard (especially my posts on statin fence sitters) will know I  plug all these numbers (preferably with the calcium score available) into the MESA coronary calcium risk calculator
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.
More Questions
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?
I’ve generally advocated aspirin in primary prevention for scores >100  so wouldn’t advise it for prevention of cardiovascular events in this situation.
In addition, I have seen nothing in the literature that recommends aspirin for BRVO. These two BRVO experts do not recommend either aspirin or anticoagulants.
Proretinally Yours,
-ACP
N.B. If you have a blockage of the the artery that supplies blood to the retina or a branch retinal artery occlusion ( BRAO)
you might benefit from a statin as this is often caused by a clot or plaque flying out of the heart or the carotid artery.

The Ultimate Guide To The Coronary Artery Calcium Scan (Score) Circa 2019

The skeptical cardiologist’s first post on coronary artery calcium (CAC) scan was posted in 2014 and had the wordy title “Searching for Subclinical Atherosclerosis: Coronary Calcium Score-How Old Is My Heart?”

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?

First, the rationale for using CAC (also known as a coronary calcium score or heart scan) is detection of “subclinical atherosclerosis”, a non-catchy but hugely important process which I describe in an early post on who should take aspirin to prevent heart attack or stroke:

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”.

The updated AHA/ACC Cardiovascular Prevention Guidelines came out in 2013.

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.


The Widowmaker

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.

What We Can Learn From Donald Trump’s CAC?

In 2018 I noted that “Donald Trump Has Moderate Coronary Plaque: This Is Normal For His Age And We Already Knew It.”

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) .

Yesterday it was revealed by the White House doctor , Ronny Jackson, that Trump’s repeat score  was 133.

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?

At a mininum we should consider what is recommended for aircrew to the general 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.

The 2018 guidelines Take A Giant Step Forward

In late 2018 I noted that CAC had been embraced by major guidelines:

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.)

coronary calcium scan with post-processing on a 45 year old white male with very strong history of premature heart attacks in mother and father. The pink indicates the bony structures of the spine (bottom) and the sternum (top). Extensive calcium in the LAD coronary artery is highlighted in yellow and in the circumflex coronary artery in ?teal. His score was 201, higher than 99% of white male his age.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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.

The Importance of Proactivity

In “The MESA App-Estimating Your Risk of Cardiovascular Disease With And Without Coronary Calcium Score” I recently wrote that:

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?

I’ve touched on some of these in the past, including the really tough  question “Should All Patients With A High Coronary Calcium Score Undergo Stress Testing?

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.

Apothanasically Yours,

-ACP


 

Coronary Artery Calcium Scan Embraced By New AHA/ACC Cholesterol Guidelines: Will Insurance Coverage Follow?

The skeptical cardiologist has been utilizing coronary artery calcium (CAC) scans to help decide which patients are at high risk for heart attacks, and sudden cardiac death for the last decade. As I first described in 2014, (see here) those with higher than expected calcium scores warrant more aggressive treatment and those with lower scores less aggrressive treatment.

Although , as I have discussed previously, CAC is not the “mammography of the heart” it is incredibly helpful in sorting out personalized cardiovascular risk. We use standard risk factors like lipids, smoking, age, gender and diabetes to stratify individuals according to their 10 year risk of atherosclerotic cardiovascular disease (ASCVD) but many apparent low risk individuals (often due to inherited familial risk) drop dead from ASCVD and many apparent high risk individuals don’t need statin therapy.

Previously, major guidelines from organizations like the AHA and the ACC did not recommend CAC testing to guide decision-making in this area. Consequently, CMS and major insurers have not covered CAC testing. When my patients get a CAC scan they pay 125$ out of their pocket.. For the affluent and pro-active this is not an obstacle, however those struggling financially often balk at the cost.

I was, therefore, very pleased to read that the newly updated AHA/ACC lipid guidelines (full PDF available here) emphasize the use of CAC for decision-making in intermediate risk patients.

 

 

 

 

 

 

 

 

For those patients aged 40-75 without known ASCVD whose 10 year risk of stroke and heart attack is between 7.5% and 20% (intermediate, see here on using risk estimator) the guidelines recommend “consider measuring CAC”.

If the score is zero, for most consider no statin. If score >100 and/or >75th percentile, statin therapy should be started.

I don’t agree totally with this use of CAC but it is a step forward. For example, how I approach a patient with CAC of 1-99 depends very much on what percentile the patient is at. A score of 10 in a 40 year old indicates marked premature build up of atherosclerotic plaque but in a 70 year old man it indicates they are at much lower risk than predicted by standard risk factors. The first individual we would likely recommend statin therapy and very aggressive lifestyle changes whereas the second man we could discuss  taking off statins.

Neil Stone, MD, one of the authors of the guidelines was quoted  as saying that the imaging technique is “the best tiebreaker we have now” when the risk-benefit balance is uncertain.

“Most should get a statin, but there are people who say, ‘I’ve got to know more, I want to personalize this decision to the point of knowing whether I really, really need it.’ … There are a number of people who want to be certain about where they stand on the risk continuum and that’s how we want to use it,”

Indeed, I’ve written quite a bit about my approach to helping patients “get off the fence” on whether or not to take a statin drug.

I recommend reading “Are you on the fence about taking a statin drug” to understand the details of using CAC in decision-making and the follow up post on a compromise approach to reducing ASCVD risk.

Deriskingly Yours,

-ACP

Full title of these new guidelines includes an alphabet soup of organization acronyms

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol

N.B. For your reading pleasure I’ve copied the section in the new guidelines that discusses in detail coronary artery calcium.

Two interesting sentences which I’ll need to discuss some other time

-When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years

CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.

In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram 

-4.4.1.4. Coronary Artery Calcium

Substantial advances in estimation of risk with CAC scoring have been made in the past 5 years. One purpose of CAC scoring is to reclassify risk identification of patients who will potentially benefit from statin therapy. This is especially useful when the clinician and patient are uncertain whether to start a statin. Indeed, the most important recent observation has been the finding that a CAC score of zero indicates a low ASCVD risk for the subsequent 10 years (S4.4.1.4-1–S4.4.1.4-8). Thus, measurement of CAC potentially allows a clinician to withhold statin therapy in patients showing zero CAC. There are exceptions. For example, CAC scores of zero in persistent cigarette smokers, patients with diabetes mellitus, those with a strong family history of ASCVD, and possibly chronic inflammatory conditions such as HIV, may still be associated with substantial 10-year risk (S4.4.1.4-9–S4.4.1.4-12). Nevertheless, a sizable portion of middle-aged and older patients have zero CAC, which may allow withholding of statin therapy in those intermediate risk patients who would otherwise have a high enough risk according to the PCE to receive statin therapy (Figure 2). Most patients with CAC scores ≥100 Agatston units have a 10-year risk of ASCVD≥7.5%, a widely accepted threshold for initiation of statin therapy (S4.4.1.4-13). With increasing age, 10- year risk accompanying CAC scores of 1 to 99 rises, usually crossing the 7.5% threshold in later middle age (S4.4.1.4-13). When the CAC score is zero, some investigators favor remeasurement of CAC after 5 to 10 years (S4.4.1.4-14–S4.4.1.4-16). CAC measurement has no utility in patients already treated with statins. Statins are associated with slower progression of overall coronary atherosclerosis volume and reduction of high-risk plaque features, yet statins increase the CAC score (S4.4.1.4-17). A prospective randomized study of CAC scoring showed improved risk factor modification without an increase in downstream medical testing or cost (S4.4.1.4-18). In MESA (Multi-Ethnic Study of Atherosclerosis), CAC scanning delivered 0.74 to l.27 mSv of radiation, which is similar to the dose of a clinical mammogram (S4.4.1.4- 19). CAC scans should be ordered by a clinician who is fully versed in the pros and cons of diagnostic radiology.

Downloaded from http://ahajournals.org by on November 11, 2018

from Grundy SM, et al.
2018 Cholesterol Clinical Practice Guidelines

What You Should Know About Lipoprotein(a) And Heart Attack Risk

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)

  1. It is the strongest single inherited (monogenetic) risk factor for the early development of coronary artery disease, heart attacks and strokes.
  2. 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.
  3. Depending on the cut-off used  up to one in five individuals may have elevated Lp(a)
  4. 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.
  5. 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.
  6. 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.
  7. 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.

Antiproatherogenically Yours,

-ACP

For those patients seeking more detailed information and references I recommend Dr. Siggurdson’s excellent post on Lp(a)

There is a Lipoprotein(a) Foundation with reasonably informative and accurate website you can peruse here for more information.

Finally, if you want to delve deeply into the data check out this recent JACC review here.

The graphs above and this figure
showing the proposed pro-inflammatory, pro-atherogenic and pro-thrombotic pathways of Lp(a) are from that article.

 

Calcium Supplements: Would You Rather Have a Hip Fracture or a Heart Attack?

ct_calcium
Does taking extra calcium pills contribute to the deposition of calcium into the coronary arteries that we see in CT scans like this?

Since I’ve been utilizing coronary calcium CT scans to detect early atherosclerotic plaque (see here) in my patients, I have frequently been asked about the relationship between calcium supplements and heart attack risk.

For example, Mrs. Jones has just found out that she has a very high calcium score and that it reflects the amount of atherosclerotic plaque lining and potentially clogging the coronary arteries to her heart. She has also been taking calcium and Vitamin D supplements recommended to her to prevent bone thinning and fractures in the future.

Did all that extra calcium she was consuming end up depositing in her coronary arteries, thus increasing her risk of heart disease?

This is a complex and not fully settled issue, however, there is enough evidence to suggest that we be cautious about calcium supplements.

A recent meta-analysis (Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691) of cardiovascular events in randomized, placebo controlled trials of calcium supplements (without vitamin D co-administration) showed that calcium supplements significantly increased the risk of myocardial infarction by 31% in five trials involving 8151 participants.

A recent meta-analysis of trials involving calcium and Vitamin D supplements found a similar increased risk of cardiovascular disease in the subjects randomized to taking calcium and Vitamin D.

These authors concluded

“in our analysis, treating 1000 patients with calcium or calcium and vitamin D for five years would cause an additional six myocardial infarctions or strokes (number needed to harm of 178) and prevent only three fractures (number needed to treat of 302”

How Might Calcium Supplements Increase Cardiovascular Risks?

Calcium supplements acutely and chronically  increase serum calcium concentration. Higher calcium levels are associated with more carotid artery plaque, aortic calcification, and  a higher incidence of heart attack and death.

Just like atherosclerosis, the process of calcium deposition into the arteries is very complex. Higher calcium levels could alter certain regulators of the process, such as fetuin A, pyrophosphate and bone morphogenic protein-7 or bind to calcium receptors on vascular smooth muscle cells lining the arteries

Higher calcium levels may also promote clot formation.

Bone Fracture versus Heart Attack

The informed doctor would have to tell Mrs. Jones that her calcium supplements may have contributed to her advanced coronary calcium and raised her risk of heart attack and stroke.

As with all medications, she and her doctor are going to have to discuss the relative risks and benefits.

If she has great concerns about fractures and has very low bone mineral bone density (osteoporosis) along with no family history of premature heart disease then the calcium supplementation may be appropriate.

Conversely, if she has high risk factors for coronary heart disease and/or a strong family history of premature coronary heart disease and only slightly low bone mineral density, avoiding the calcium supplements would be appropriate.

Preventing Fractures and Heart Attacks

It’s best to get calcium from the foods we eat rather than a sudden concentrated load of a supplement. Full fat dairy products like yogurt and cheese are heart healthy (see here and here) and they are an excellent source of calcium.

Weight-bearing exercise (such as running/jogging/hiking) and strength-building exercise (lifting weights, resistance machines, etc.) are also important for strengthening bones.

Thus, eating full fat dairy and aerobic exercise will help prevent both a fracture and a heart attack.

Searching for Subclinical Atherosclerosis: Coronary Calcium Score-How Old Is My Heart?

Heart attacks and most sudden cases of sudden death are due to rupture of atherosclerotic plaques. Thus, it makes sense to seek out  such plaques, a process I call searching for subclinical atherosclerosis. I’ve talked about using high frequency ultrasound of the carotid arteries to the brain to look for plaque and for carotid IMT in earlier posts here and here.

There is a third method that looks directly at the coronary arteries, which supply blood to the heart.  It is variously called a heart scan, coronary calcium score, or cardioscan, and it is more widely utilized amongst physicians who are serious about preventing cardiovascular disease.

This technique utilizes the ionizing radiation inherent in X-rays to perform a CT examination of the chest. It does not require injection of any dye or the puncture of any arteries; thus, it is considered noninvasive and has no risk or pain associated with it.

When atherosclerosis first begins to form in the arteries, it generally takes the form of “soft” plaques. Soft plaques are initially full of lipids, but after a period of time, the plaques undergo change: calcium begins to deposit into this plaque.

There is a direct relationct_calciumship between coronary artery calcium (CAC) and the amount of atherosclerotic plaque in the coronary arteries.

CT scans are very accurate in identifying small amounts of calcium in the soft tissue of the body. Calcium score tests essentially look for blobs of calcium that are felt to be within the coronary arteries, count up the intensity and distribution of them, and calculate a total score that reflects the entire amount of calcium in the coronary arteries.

A large body of scientific literature has documented that higher calcium scores are associated with higher risk of significantly blocked coronary arteries and of heart attack.

You can read the NHLBI clinic’s info for patients here on the test.

How Is The Calcium Score Used To Help Patients?

The calcium score can be utilized (in a manner similar to the carotid IMT and plaque) to help determine whether a given individual has more advanced atherosclerosis than we would predict based on their risk factor profile. A score of zero is consistent with a very low risk of significantly blocked arteries and confers an excellent prognosis. On the other hand, scores of >400 indicate extensive atherosclerotic plaque burde , high risk of heart attack, and high likelihood of a significantly blocked coronary artery.

The calcium score (similar to the carotid IMT) increases with age and is higher in males versus females at any given age. We have very good data on age and gender normals. The average 50-59 year old woman has a zero score, whereas a man in that age range has a score of 30. The average man has developed some CAC by the fourth decade of life whereas the average woman doesn’t develop some until the sixth decade. More advanced CAC for age and gender is a poor prognostic sign. You can plug your own age, gender, race and CAC score into a calculator on the MESA (Multi-ethnic Study of Atherosclerosis) website here.

2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk says the following

 If, after quantitative risk assessment, a risk based treatment decision is uncertain, assessment of 1 or more of the following—family history, hs-CRP, CAC score, or ABI—may be considered to inform treatment decision making

This guideline recommended utilizing a  CAC score of >300 Agatson Units or >75th percentile for age, gender and ethnicity as a cut-off.

CAC Score Identifies Those At Very High  Risk

A forty-something year old man came to see me for palpitations. He had a stress echo which was normal except for the development of frequent PVCs and a brief run of non sustained ventricular tachycardia.  His risk factor profile was not particularly bad: no diabetes, hypertension, or cigarette smoking and an average lipid profile. When I calculated his 10 year risk of ASCVD using my iPhone app it came out at 7%: below the level at which statin treatment would be recommended.  Because his father had a coronary stent in his fifties (this does not qualify as a family history of heart disease according to the new guideline, by the way)  I recommended he get a CAC test done.

His CAC score came back markedly elevated, almost 1000.  .  A subsequent cardiac catheterization demonstrated a very high-grade coronary blockage iwhich was subsequently stented. I started him on high intensity statin therapy and he has done well.

CAC score identifies Those At Very Low Risk

Many individuals with high cholesterol values do not develop atherosclerosis.  A zero CAC score in a male over 50 or a woman over 65 (or non-zero CAC score that is <25th percentile for age, gender, ethnicity) indicates that they are not developing atherosclerosis and makes it less likely that they will benefit from statin therapy to lower cholesterol.

Some Caveats About CAC score testing

-Like carotid vascular screening, there is no reason to get a CAC test if you already have had problems related to blocked coronary arteries such as a heart attack or coronary stents or coronary bypass surgery.

-CAC score testing is not covered by insurance (except in Texas) and costs somewhere between $125 and $300 out of pocket.

-The CT scan leads to a small amount of radiation exposure-approximately 1 – 2 milliseiverts of radiation (mSv). To puts things in perspective, the annual radiation dose we receive from natural sources is around 3 mSV per year.

Some of the other approximate radiation doses for tests commonly used in medicine are:

Chest X-ray ( )            0.1 mSV
Routine CT chest:  10 mSV
CT abdomen: 10 mSV
Nuclear stress test: 10 to 20 mSV