I've noticed that there are many comments on my post which take the viewpoint that either
1) LDL/apo B is not important in the development of ASCVD
2) Statins don't reduce the risk of ASCVD
Clearly, if you believe these 2 points, there is no point in doing CAC
When I became the skeptical cardiologist in 2013 I systematically challenged all that I had been taught about ASCVD. At that time, the hypothesis that lowering LDL would invariably lead to reduced ASCVD in my mind was not fully established. Since then it has been. Basic scientific investigation, prospective longitudinal cohorts, mendelian randomization and randomized clinical trials have all established that apo B is the particle that triggers atherosclerosis and that drugs that lower apo B reduce or eliminate atherosclerotic plaque formation and its consequences including heart attack and stroke.
"despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs"
We have the ability to eliminate ASCVD, the biggest killer of humans in the world.
CAC is how we identify subclinical atherosclerosis.
We now have multiple very safe and effective medications beyond statins that lower apo B/LDL and reduce the devastation of ASCVD.
The only serious scientific question at this point is how aggressive to be without pharmacologic treatment in the individual sitting in front of us in the office
You’ve cited supposed knowns - and the vast majority of experts out there believe these claims - but calcium and cholesterol share something really interesting:
Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification
This enzyme is essential for the on-site biosynthesis of menaquinone-4, a hormone. MK- 4 is the most prevalent form of VK2 in our bodies and, in rodents, it is highest in thyroids (over other tissues/organs), but it is unknown how this translates to humans. I mentioned that T3 creation, its gene, directly relates to creation of matrix gla protein, which, upon activation, is the most potent anti-calcification substance known. In arteries, in endothelial cells, MGP has the role of preventing inappropriate calcium deposition. It prevents arterial ossification, noted to increase with age, and previously viewed as inevitable, but which can now be seen as a process over which we may have more control than previously appreciated.
It’s important to believe in one’s integrity, in one’s ability to accurately identify true cause and effect and interpret data correctly, and I am sure that you truly believe these statements to which I am responding. I am showing that there really are other ways to interpret what you state, but they question dogma and are contrary to A LOT of what we do and have been doing in medicine (and nutrition). Is CAC a way to ID subclinical atherosclerosis or is it an indicator of calcium dysregulation? Instead of lipids, what if it’s really calcium dysregulation that causes the “…biggest killer of humans in the world?” PS We will all die.
After all:
A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9715 individuals
Since statins increase CAC, a scan after taking them is not advised. And a very small reduction in events - artificially inflated by using RR instead of AR - by taking statins is cited as success. But, are these drugs, reducing serum LDLc, the BEST way? I think not. The best way is to prevent plaque and I’m showing that plaque etiology may well be initiated via calcium dysregulation, which just happens to share that enzyme, UBIAD1, with cholesterol. Reducing serum cholesterol has been observed with supplemental VK (and insulin sensitivity is increased), but good RCTs are called for, obviously:
“To test this theory, he ran a small pilot trial giving vitamin K supplements to a few subjects and found it lowered LDL or the bad cholesterol, triglycerides and total cholesterol comparably to lipid-lowering medications.”
Yes, anecdotal, not RCT, but there are more similar findings and supportive data*, but the sheer enormity of money, careers, inertia make for focusing on certain biomarkers and seeing them rather linearly, not holistically, and certainly Dear Peter Toth…how you see this is much like
1) menarche is earlier these days bc of our better nutrition
2) obesity is caused by greater energy intake than expenditure
3) excessive cholesterol causes plaques/CVD and not meeting guidelines by way of drugs is killing folks (poor Toth thinks this, apparently)
[Evidence for these are missing, but these are stories we have embraced/medical societies have embraced]
CAC, if used in trials, would be an interesting biomarker bc of this. In medical practice, facing people with events, symptoms, and all the data published so far, it’s risky to go against this Titanic of thought that we must use certain drugs and meet certain biomarkers , but just look into what I am showing. Look at calcium dysregulation as found in concomitant diseases: CVD, T2D, CKD, obesity, dementia, hypertension. Not tons of data, but they are increasing daily.
This is an entirely different paradigm, it connects the various diseases that tend to be concomitant, it truly questions guidelines/dogma bc: statins increase CAC, beta cells of pancreas have newly discovered vitamin K-dependent proteins that control calcium via carboxylation, those who eat more VK2 have fewer cardiovascular events/weigh less, kidney disease and calcium dysregulation co-exist.
The risk factor paradigm for atherosclerosis and cardiovascular disease has gotten us nowhere over the past 70 years that it has dominated research into these areas. No scientifically valid study of risk factor modification has ever shown any significant benefit beyond the small differences that could easily be due to chance. One problem is that atherosclerosis and the problems said to result from it (primarily heart attack and stroke) are related but not in any really consistent pattern. Atherosclerosis is found in all long lived animal species albeit with varying degrees of severity and rates of development. Heart attack and stroke are sudden events which often occur without warning. It has been pretty well established (at least for heart attack) that the common pathophysiology is a break in the endothelial lining of an artery that triggers a blood clotting cascade. As mentioned by a number of other commentors here, there have been a number of studies where angiograms shortly before the MI and soon after show that the changes often are seen in parts of the arteries that were not seen to be significantly diseased in the pre-MI angiogram. The relationship of calcification to actual stenosis has also not been definitively determined. In many years of practice with a fairly high percentage of elderly patients I saw quite a few with carotid arteries so heavily calcified that a plain x-ray would show much of the length of the artery. But the majority of these had no episodes of stroke or even TIA despite being of advanced age and had lived with this condition for many years. Any attempt to attach a risk figure based on this or any other risk factor(s) is tenuous at best. To prescribe "preventive" medications or advise invasive procedures is unwarranted as it is a pretense of knowledge that we don't have any evidence to support.
I’m 73, Asymptomatic, in great shape but calcifications on the coronaries were incidentally ID’d during a CT AoAngio 4 years ago. So AHA doesn’t help me. I’m coincidentally seeing the Cardiologist tomorrow to discuss this. Thanks!!!!
I feel the author erroneously sets aside the absence of RCT in his defence of CAC. It’s the simple burden of proof.
If proponents of CAC suggest that the test ADDS diagnostic value to the status quo, and meaningfully alters treatment strategies that may be triggered downstream of CAC testing which ultimately improves clinical outcomes (again above and beyond what would currently be done absent CAC), they are welcome to roll up their sleeves and prove it. It’s seems to be the epitome of hand-waving to say “yeah I require high quality evidence…but for this thing I’m a proponent of, I’m willing to look the other way”.
It’s disingenuous to compare CAC with echo (disclosure: I read echo). No one gets an echo just to order an echo. They are done in response to symptoms, and are not “screening tests”. That already fundamentally sets it apart from CAC, which is meant to screen asymptomatic people. (If someone orders CAC in a pt with symptoms, that’s next-level head-scratcher territory. ). Furthermore, in HF, downstream therapies are predicated on EF, which echo easily, relatively cheaply, and non-invasively provides, relative to others diagnostic modalities. So echo as part of a diagnostic and therapeutic strategy that results in reduction in hard clinical outcomes is already well established in numerous landmark RCT. The same cannot nearly be said for CAC. And for me, that’s all that needs to be said.
If you come at it from a shared decision-making thought process approach, I think both John and Anthony are correct in their own interpretations as to what should be done with CAC. They both have a solid interpretation of the evidence, they know the “risks/benefits/harms” and they come to a different decision. They are allowed to have different personal opinions.
Just like my experience with talking to people with statins – some think a 2% absolute benefit over 10 years is pretty good – some think it is ridiculously small. They are both correct.
However, what do practicing primary care clinicians (and likely most cardiologists) do when you have 2 thoughtful and smart academic cardiologists coming to what looks like, opposite opinions.
Well in my opinion they need to have access to simple tools that explain what the result of an intervention – in this case a test – will do to risk/benefit discussions for an individual person.
The link below is the best simple table I could put together. It shows in a 60-year-old person how knowing their CAC could inform a risk benefit discussion.
As with all tests you need to consider whether or not it would change what you would do BEFORE you order a test.
So, before you order a CAC test, discuss with the patient what the patient might do with the result. The bottom line is knowing a CAC test in a 60-year-old with somewhat elevated risk factors helps you/them refine the estimate of the 10-year benefit from a statin from a low of ~0.5% up to ~2% in a non-diabetic, and from between ~1% to ~5% in a diabetic. So, if those ranges would elicit a different decision, then the test may have value for that patient.
Here is a link to the table that gives those numbers.
Just want to add how often I am surprised by the decisions that my patients make when using this process. People I was sure would say" " No way I am taking that therapy" instead opt in and vice-versa.
Totally agree - which is why a discussion is essential. We need to allow people the freedom (if they wish) to make a decision. And it's not that difficult to do. And I believe it is more rewarding than simply following the "guideline du jour".
I have found CAC useful in providing additional information to patients with "intermediate" scores on lipid profile and ACC/AHA risk calculators helpful - but I would also point out it is most used and seems most useful for patients that are ambivalent about what to do. So - CAC does not need to be used as a "screening" test. I see no reason why any population should all routinely have this test (and I don't see it purported to be used that way). Statins are a unique niche of medicines that many patients/people feel strongly about in either a very positive or a very negative/suspicious way. If a patient is highly motivated to want a statin, no reason for this CAC. Patients who are highly negative about statins don't really feel more compelled to take statins with this add'l information. It is useful in patients who seem to fit many of the higher risk criteria, but still have a general inclination NOT to take medicines, but are open to information. What I'm saying is that it is not a "screening", mass-use test but one that can add to a clinician and patient decision-making. This falls into a category of the "art of medicine" - an astute clinician who can assess a patient's risk, assess a patient's willingness/interest in taking medication, and knows that this will be helpful in some way. Unfortunately, in today's medical world, the 10-minute office appointment does not afford for this type of assessment, review, discussion, and "artful medicine" application by good clinicians. (but again, I find this a useful test in the right patient).
I did read JMM's rebuttal against routine use of CAC - one interesting thing he pointed out was that lots of CAC testing would drive a certain amount of "incidental" findings and information about coronary arteries that would end up driving anxiety in patients. I have not seen that with CAC testing as much as other areas of medical tests. One area I DO see an alarming level of unnecessary anxiety is in the frequency of "borderline aortic aneurysms" being found on various cardiac tests: Echo being a big one. I have many patients who live in fear of the "ticking time bomb" in their chests - MANY patients mention this. They get pulled into yearly cardiac testing (Echo or CT, MRI) - for a problem that is not very common (the rate of death due to thoracic aortic aneurysm is quite low!). I'd love to see JMM do a review of this situation!
Agree, should not be universally applied but adds greatly to decision-making for many of my patients and that process requires a considerable mastery of the "art of medicine."
But I find it often changes our approach even in those who are highly motivated to take a statin (for example if we find >75th percentile for age/gender and decide to treat to secondary prevention apo B targets which require combo therapy whereas <25th percentile we would use much more lenient targets and lower statin dosing)
On the other hand, those highly disinclined to take statin who are found to be very high risk often agree to take other agents (zetia, PCSK9i) and both patient and physician can feel relieved and comfortable with the decision if very low risk or zero score is identified.
As to incidental findings, I've discovered several seriously large aortas by CAC (2 of whom required surgery . The lung spots are what drive me crazy which are identified all the time on chest CTs ordered for other reasons and cause much angst.
I agree. I will point out that the last CAC I ordered had an incidental finding of a lung nodule and the radiologist recommended follow up Chest CT in my patient without risk factors for lung cancer. I inwardly groaned.... Any test we order has the possibility of these incidental findings and it is good to acknowledge that.
Absolutely)! I am not a fan of incidental findings in any way, shape, or form. And I've got the same issue I have to advise a patient about right now, sitting in my "to do" box. Incidental finding (lung nodule) in patient with no risks and she wants to know what we should do (and this was on a test done in 2020 that I did not order! Nothing has been done till now, but she wants my advice). And I agree with your suggestion we acknowledge the downsides to our tests. Exactly why I would not think this is a good screening test.
After awhile, you start to wonder how much of anything we do is very helpful and adds anything much beyond a focus on healthy lifestyle and healthy habits! (and more focus on trying to spread that information to high risk populations with low health-literacy and general unhealthy habits)...
Thanks for the post. I am a family doctor with 20 years of experience and am most passionate about motivating patients to make lifestyle changes for their health. I personally had a CAC done last year since my LDL and Apo B and coronary inflammatory markers were slightly above normal...despite everything I knew to do lifestyle wise. The CAC was a useful tool for further risk stratification to help med decide if I needed a statin for the rest of my life. Fortunately my CAC was zero and so I felt reassured to not take a statin and continue with my healthy lifestyle. I have found I'm not alone. I tend to target patients age 45-60 who have borderline lab results. We talk about the pros/cons of simply starting a statin, making lifestyle interventions or getting more information with a CAC. Most of my patients elect to start lifestyle interventions and monitor their numbers first. There have been a handful of times I've ordered a CAC and found the results useful to better counsel my patient.
Just because CAC is misused does not mean that it's useless.
I've found that it's a great way to open discussions about overall risk, overall "how's aging going for you?" conversations. When used this way, I've seen most people take a greater interest in the health ... whether that's through lifestyle, drugs, or a combination ... and isn't that the goal when we go to work?
As a family physician, I have not seen this lead to an inappropriate intervention ... but maybe that's where I live. (Rural Wyoming doesn't have a lot of invasive cardiologists!)
Side note: this whole debate points out that I don't realize how much momentum certain departments in academic centers have ... glad I'm not practicing there!
I’m 69 years old, cycle 150+ miles a week, swim daily and weight lift 3x a week. I’m a clean eater 80% of the time ( no red meat for 40+ years) My internist ordered a CAC for me when I was 63, because my father had a massive heart attack at 56 (lived to 89). When the test came back - zero! However, a 17x16mm nodule was noted in posterior position of left lower lobe. This started down a rabbit hole of CT scans, X-rays, etc, visits with pulmonary specialist. Bottom line, probably had Valley Fever at one point and didn’t know. Doc wanted to repeat again last year and I refused! Did I make a mistake???
First, I think you were wise to get the CAC. Your dad had an MI at age 56 and could have dropped dead from it at that time. It is essential, IMO, with that kind of family history to know with certainty the level of atherosclerosis in your coronary arteries and make an informed decision on how to best handle the identified risk.
The zero score indicates you are in a very very low risk category and didn't inherit your dad's ASCVD risk and should be incredibly reassuring.
As to repeating the CAC, I would be fine with not repeating it.
The lung nodule will still be there. If you are still nonzero you know that you are still at incredibly low risk for ASCVD.
If it is nonzero it the score will tell you precisely where you stand in comparison with other 69 year old women and I suspect it will be less than the 25th percentile still and even more reassuring.
Learn about overdiagnosis or incidentilomas. I happen to like H Gilbert Welch’s coverage of this.
He did a cute video about an elderly patient who came in bc of hoarseness. With a subsequent test, cancer was found in a kidney - totally bc they did scans, etc, not bc of symptoms - and the patient balked at surgery.
He pointed out that he came bc he was hoarse and now they want to remove his kidney?
He declined.
He died of pneumonia 10 years later, and Welch was hyper-alert to his autopsy. Yep, cancer still there and it never really affected him.
Seriously, see Welch’s videos about overdiagnosis.
Thanks, Micki. I was glad I did the CAC test, but the path of three years being followed for the lung spot was crazy - pet scans, CT scans, X-rays, pulmonary appts., etc.
I'll have to search for the Welch video. Thanks for your comment.
I agree with much of your criticism. My comment is truncated in that the various aspects of potential proof are omitted…and “true” proof is very elusive, even in all the supposed “knowns” upon which we’ve based so much in our rather clunky modern medicine. I didn’t even cite some of the articles, studies, trials upon which I am offering evidence, maybe not technically “TRUTH,” but definitely questioning what we think we know and offering alternative narratives of both etiology and treatment of common chronic diseases, including CVD.
I mean, where’s the proof that cholesterol causes plaques? Is this true? (nope)
Actually, no proof, and when faced with purely fatty plaques, cardiologists figure they’re bad, in spite of evidence to the contrary. Without calcium, they are benign.
Sooo much money, hubris, careers, reputations are based in really misguided ideas.
How do we reconcile that most folks who suffer an event have so-called “normal” cholesterol levels?
A search of the literature regarding such as CAC, calcium, microcalcifications, vitamin K/K2, matrix gla protein, UBIAD1, etc - alone and in combination - offer some real insights.
See: Historical Review of the Use of Relative Risk Statistics in the Portrayal of the Purported Hazards of High LDL Cholesterol and the Benefits of Lipid-Lowering Therapy (2023)
Or here’s a fun, new alternative diabetes insight:
Revisiting the interconnection between lipids and vitamin K metabolism: insights from recent research and potential therapeutic implications: a review
Once cholesterol was blamed for plaques, we were stuck. Stuck, stuck, stuck. We hit on an answer to a problem: statins. Only this was and is incorrect. Statins suffer the statistical manipulations cited in that Historical Review mentioned above and harms are understated. There are clues about real causes of cardiovascular events bc we know that a zero CAC offers a 15 year warranty from death by all causes (!). But no drugs address CAC, so there’s push back against measuring that; no answer, why look? Contrarily, even if the answer is “bad,” we can be persuaded to believe and I could cite several specifics in a variety of specialties as examples.
Instead of seeing this CAC as something to attack, let’s understand its etiology. That will, upon enough literature searching, lead to microcalcifications. Which will lead to the hugely important and vastly misunderstood topic of vitamin K. Huge. Complex. Inchoate. But once we saw vitamin K as only about coagulation, we got stuck (see a pattern?).
We are now facing some huge health woes by way of epidemic non communicable diseases and modern medicine, stuck as it is, is not addressing them.
As a small add-on : cancer.
A Japanese man with HCC quit responding to conventional therapy, had many metastases. So they gave him a vitamin K2 analogue. No bad effects. All metastases disappeared…complete response.
Search cancer and vitamin K2. Crazy.
“Truth [and proof] may be found at the bottom of a bottomless well.”
This is an important topic. Our entire system is arranged around blockages in heart arteries and opening those blockages even though we have had hard evidence for almost 30 years that those stable blockages don't cause a heart attack. They are a marker for the presence of cholesterol deposits that don't block the artery. 68% of heart attacks occur in a heart artery that was less than 50% blocked prior to the heart attack. That means it would not have caused symptoms and it would not meet the 70% blockage criteria required to justify a stent. Only 14% of the arteries that cause a heart attack have a 70% chronic blockage beforehand. The coronary calcium score tells you how much plaque you have.
Heart attack may happen in an artery that was totally open with cholesterol deposites that had remodeled the artery outward. Large cholesterol deposits can happen in an artery that is totally open. Heart attack happens when one of these cholesterol deposits breaks open and initiates the clotting process. A person can go from wide open to totally blocked in a matter of seconds to minutes. That is why a person with no history of chest pain or shortness of breath can have a heart attack out of the blue or drop dead on the sidewalk. Traditional risk factors don't identify everyone at risk. The calcium score identifies people with a lot of plaque who need optimal medical therapy very inexpensively. Women are even more likely to have a heart attack with no stable blockage beforehand
Thank you for these citations, but both are from 1995.
Newer technology has been invented that shows those microcalcifications I mentioned.
We continue to tweak measuring the various fats in serum (and by inference, plaques?) and now acknowledge Lp(a), as well as try to develop ratios among them that offers risk accuracy.
If CAC is such an accurate biomarker of risk (a zero represents 15 years warranty from death by all causes!), what makes it appear? Really…what makes CAC happen? What mechanisms? And how can we reconcile that lipophilic statins increase CAC and yet consider this good?
Are centenarians taking lots of drugs?
How does nature make the pathways that you cite (mTOR and AMPK) happen?; how does nature maintain homeostasis? Why are multiple drugs better than how nature accomplishes this?
We’ve spent a lot of time and effort on the wrong things and turning around the metaphorical Titanic of current medical dogma is daunting, threatening, and important.
Nature maintains homeostasis via genetics, epigenetics, and the related molecular biology. Genes that should be quiet are reactivated by abdominal fat, cigarette smoking, and age itself to increase oxidant production, inflammation, make us sick and kill us. The drugs that matter in chronic disease block oxidant production that leads to mTOR activation and AMPK deactivation. There were many fewer centenarians in 1900 when the average lifespan was 40. Good science has dramatically extended life span. It is not the calcium that kills us. It is the soft inflammed cholesterol plaque and atorvastatin reduces soft plaque, inflammation, and stabilizes it that so it does not rupture and cause a clot. Yes these studies are almost thirty years old. this link is almost twenty, but they answer questions that should change the way we treat artery disease.
The story about statins making for plaque stabilization has been widely embraced; lots of articles about plaque stability exist - discussing shear forces, flexibility - and this has been a large arm of thinking in cardiology. (If you bend the statistics of statin benefits by way of RR, you also need to cite mechanisms to explain…it’s a whole tapestry of stories that evolve over time, thanks to pharma)
There is evidence to the contrary.
Look for it!
I seek info that discounts what I claim, and I recommend it for all.
(e.g. several VK interventions haven’t changed CAC, but arterial flexibility was maintained in middle-aged women who supplemented, HCC was cured in one man, VK is a known anti-inflammatory and anti-tumor agent, MANY vitamin K-dependent proteins are being increasingly appreciated for myriad roles beyond coagulation, but single interventions with VK have yielded mixed results)
Statins appear to create CAC. Especially lipophilic ones.
Mechanisms are known that could explain this dysregulation of calcium via statins; they directly affect VK actions with negative effects, which we tend to shuffle under the rug bc we’ve obsessed over cholesterol and ignored calcium.
We could test this if diabetics w/o CAC were prescribed a statin (guidelines…and I disagree) and then monitor if CAC subsequently appears.
But if this happened, could the statin/plaque stability story even be questioned?
Could we see mechanisms differently?
I would suggest we’re in too deep.
Calcium is a signaling messenger as well as a huge component of hydroxyapatite.
When hydroxyapatite goes awry (bones lose it while arteries accumulate it), bad things happen.
Ossification in arteries. Crappy bones.
Mammograms look for calcium.
Cancer is addicted to calcium. (Search that phrase)
I just showed about beta cells having newly discovered VKDPs and that article explained that the stress of age increases the calcium dysregulation, explaining why age increases risk AND THAT VK reduces that stress. Nature’s way. Go check out the VK/VK2 intake of so-called Blue Zones. And they aren’t stomping on VKactions with drugs like statins, bisphosphonates, warfarin, even antibiotics. CAC increases with them.
This claim misses some things…and I suspect that you know this:
“There were many fewer centenarians in 1900 when the average lifespan was 40. Good science has dramatically extended life span”
Hygiene, antibiotics, vaccines…I mean, not statins, not metformin, not screening, but those other medical advances were beneficial.
In my lifetime, the obesity has exploded in our population, T2D has also, but the answers have failed miserably.
Clearly, diseases happen and people need help. Medicines save lives…but not all, and certainly our understanding of the common chronic diseases that tend to be concomitant is chasing the proverbial cow long out of the barn. Not drugs, but true understanding of etiology, of mechanisms, offers true answers.
I will stick with the optimal medical therapy approach which is not about relative reductions in risk but about massively better outcomes. Patients on optimal medical therapy who have had a heart attack are ten times as likely to be alive in five years as those receiving usual care. Diabetics on optimal medical therapy have one fourth as many heart attacks, one fifth as many strokes, and one sixth as many go on dialysis. If you can show me something that approaches those results, I am all ears.
When it comes to RCT's of screening in general, it seems like there is less money to do them, since there are no drug companies willing to fund them. Another problem is the very large sample size needed to show changes in mortality as described by Dr. Peter Attia when talking about breast cancer screening, which I imagine also applies to CAC screening. I posted the link below with my comment on Dr. Cifu's piece about blood biopsies but in case you didn't see it....
I tend to think of "screening" as something that's applied to all patients, but I'm not sure if CAC needs to be given to all patients. But I can attest to the fact that it's helpful with some patients: myself and my spouse. Both of us fell in the "moderate risk" category based on traditional PCE scores, and neither of us wanted to go on a statin. Once we saw that there was plaque in our coronary arteries via CAC, we both decided to start a statin. (We were already good with lifestyle). So for people in our situation, I think it's very helpful. BTW, I was never impressed by the ARR of statins, but after listening/reading Peter Attia's explanation of cumulative risk over decades, along with a masterclass in lipidology by Thomas Dayspring, statins make more sense to me, but the CAC scores are what really got us there.
His thesis on cumulative risk over decades sure sounds convincing, The question is, is it correct? If it were, one would imagine the data at least pointing to it would be much more convincing...
Feb 28·edited Feb 28Liked by The Skeptical Cardiologist
Maybe I'm gullible, but I find this evidence persuasive enough that I'm taking no more chances with my high LDL-C, given that I know I have atherosclerosis thanks to the CAC.
I posted 3 articles and you already read them? Wow! Speed reader! I don't know which one of the 3 articles you're referring to, but it doesn't matter if all you bothered to read were the footnotes.
Interesting perspective. Except for the part about “lack of RCT’s”! This retired EBM teacher and medical generalist has heard this argument about every single screening test in existence. The CAC score is indeed a “screening test”. Regardless of baseline risk, it is attempting to “find” a disease in patient who may or may lt have it. The results do change probabilities, it does not make the diagnosis! It is not a credible gold standard, merely another thing to plug into risk calculations. The results trigger another therapeutic and investigational cascade that have their own risks and benefits.
One can “believe” it changes meaningful outcomes, and that the harms are trivial. The same occurred with every other medical intervention… where RCT’s demonstrated reality. In many cases it was only the RCT data that allowed physicians to communicate risks and benefits to patients … so that THEY could decide what to do with their lives. That is true “personalized medicine”.
This 70 year old retired doc, with 12% body fat, lifelong endurance exercise, parents and well into their 90’s, BP of 90/60 and strikingly high LDL and non-reassuring Apo B, will give this a miss! It’s my one precious life, and only data from RCT’s will allow me to decide what to do.
I remain dismayed how we keep making the same errors over and over again.
That said, heterodox viewpoints are critical, and this was important reading. We must all leave our opinion silos, and you both demonstrate how it is done.
I can't tell you how many active, asymptomatic patients I've seen with your lifestyle , BP and lipids who were status post PCI, CABG or MI that came without warning.
I do think having parents in their 90s without documented CAD strongly mitigates the risk.
But, if you were my friend and colleague I would be constantly bugging you to get a 10 minute painless test for $100 that could better determine the risk created by the "non-reassuring apo B"
I too have seen many similar patients. I do understand both your assessment of risks, and, as a result of your excellent article, the reasons for your beliefs about the utility of this inadequately studied screening test.
Lastly, I suspect that all of this is embedded within a desire to mitigate patient risk and likely an empathetic worldview. Unlike many, I see no sinister motives (financial or otherwise).
I have had many conversations on this topic, as well as related ones (PSA screening, FOB screening and many others).
Each of us has biases, and we must do the best we can with all of these confounders. Both of us are not exceptions.
My reply to you would be “Thank you for your concern and well-intentioned advice, but although I think about this issue from time to time, even the most non-reassuring Calcium score will not change my current decisions about treatment of my one modifiable risk factor”.
Patients and friends are funny that way, they make decisions very different from us.
Again, I thank you for your article and viewpoint. It’s important and I am grateful for your concern for my wellbeing!
Female, 70 years old, CAC score zero, BP 122/76, BMI 24.3, LDL 172, Apo B 125, hs-CRP 2.6, long-lived parents and grandparents on both sides. My doctor who advised no statin has retired; zoom cardiologist consult advised statin; new doctor advises statin. It was two experts against one, so I just started rosuvastatin 20 mg. Sheesh! I guess I'll keep getting exercise and drinking a lot of water.
I've seen lots of 70 year old women with lipids that high who have zero CAC scores of zero. With such derisking we don't recommend statins unless the patient wants to be super proactive. If we do start, we start low.
I'm not sure what drinking a lot of water will accomplish :)
I'm 62 with very high LDL but also good HDL and triglycerides, CAC = 0 and did well on the treadmill, no symptoms of anything, ever. I have no interest in statins and can't tolerate them, and really tried to when prescribed. My husband developed focal necrotizing myositis on statins. No thank you.
Drinking plenty of water is just good general advice with next to no arguments on the other side! It has been great to read these divergent opinions. Thank you; and especially thank you for your website, particularly the coverage of AFib + alcohol. My "irregular heartbeat" has been observed since age six. I have gone two months with almost zero alcohol and my exercise bicycle, which recently alarmed twice during very mild exertion (post-holiday alcohol excesses perhaps), has not alarmed once since! Tell your AFib patients that alcohol-free beer is pretty good (wine not so much).
Jennifer, thanks for your post. It saddened me that two doctors “advised” taking a statin. Might it be more helpful for them to state something like “despite considerable uncertainty, in patients similar to you, evidence from RCT’s suggests that the use of a statin at your age will change your absolute (not relative) risk of an adverse clinical outcome (MI, Angina, stoke, dementia or whatever the RCT outcomes assessed), from X to Y. The risks (myopathy, $, sick-role etc) occur at Z frequencies. “
“Given this information, can you decide what course of action you wish to take”, because you need to know that if you leave it to me, I am likely to play it safe because of my biases”.
If physicians cannot do this in what is the most evidence informed area of medicine, we are in big, big trouble. Vote counting is a sad state of affairs.
Steve, this is such a great example of how to do good shared decision making. Could you clarify what you mean by ‘change your absolute (not relative) risk’? I assume this means give someone what their individual absolute risk reduction would be given an estimation of their risk. Dr Pearson writes that CAC is a good additional factor to clarify an individual’s baseline risk
Also, it has been published in peer reviewed journal that a lifetime of statins increases life time by about 4 days.
Statin naive patients had muscle biopsies before statins and then subsequently after taking them. Muscle damage was shown in these biopsies, though symptom complaints were inconsistent.
Harms are mostly denied, but they are there. Pharma cites benefits outweighing harms, uses RR to cite benefits and AR to cite ‘side effects’*
Sure. It’s the same issue with reporting outcomes in the mega-trials… often reported as relative risk reductions (often in the 20-50% range). Tell a patient “your relative risk will drop 40%, and you get buy-in for therapy. Tell them the (also true)
“ your risk of an MI will drop from 1% to 0.6% and all you have to do is take this drug for X years at a cost of $1000 per year” and one might get a different answer.
Thanks. One thing I worry about and talk to my learners about is how much of an impact the way we frame information has on how patients make decisions and being aware of how much our own biases inform how we do choice architecture.
What is missing here is that CAC begins as microcalcifications, invisible by way of CT, but now we can see them with new technology.
Once it's visible as CAC, calcium dysregulation has advanced and those microcalcifications are growing.
Can we lessen it; can we move it?
That's one criticism of a CAC scan (that there's no drug known to do this), but instead of falsely chasing cholesterol, triglycerides, we need to understand what leads to CAC; how do microcalcifications begin and what enables
them to advance to measurable CAC?
Here's a fun insight:
The so-called active thyroid hormone, T3, is directly involved in creating matrix gla protein, the most active anti calcification agent - when properly activated by vitamin K - known.
T3 is created on site, mostly, by deiodinases, and if enough matrix gla protein isn't present in endothelial cells, or if they aren't properly activated, calcium deposits.
THAT is the beginning of plaques.
Not cholesterol, a really bogus biomarker that has dominated thinking and is very inaccurate.
Statins are NOT the answers to anything.
Their reductions in absolute risk of an event are poor, but trials have been statistically manipulated to use relative risks to describe benefits and absolute risks to describe harms. In short, they lie.
Further, statins interfere with an intermediary of both cholesterol creation AND menaquinone-4 creation, which leads to increased risk of T2D bc this essential process of creating MK-4 is important in insulin sensitivity and is a hormone affecting expression of many genes.
CAC is the hint of what causes plaques and someone stinking needs to look there!
Statins - especially lipophilic ones - increase CAC
I sure posted a lot, didn’t I? So not sure what you’re interested in learning more about. I gave some links that support some of my claims here in subsequent posts, but these are a few supportive articles about claims for which I didn’t post anything to date:
1) microcalcifications are newly seen via new technology and appear to lead to what will be CAC
Thyroid Hormone Targets Matrix Gla Protein Gene Associated With Vascular Smooth Muscle Calcification (2005)
[This is where the various medical specialties tend to communicate amongst themselves poorly, not really understanding how they are akin to the story about the blind men and the elephant. Endocrinologists have assumptions about T3 by way of conversion by deiodinases, they know how thyroid patients are at increased risk of cardiovascular events, they even know that calcium dysregulation is coexisting with thyroid diseases, but how many cardiologists and endocrinologists know what this paper implies? We can’t measure on-site T3, so we assume serum levels tell us that. But, since rodents are ‘willing’ to die, so we can test this assumption, we know that T4 to T3 conversion differs among tissues and is the diversity is not represented by serum levels. Humans? And hypothyroid patients on standard-of-care T4 monotherapy have different serum ratios of T3/T4 compared to euthroid patients. Cardiologists figure endocrinology knows thyroid functioning, based largely on TSH guidelines, but:
Micki, how do you know this is “true”? It’s an interesting hypothesis, and may be true, in whole or part, but assertions of truth do not move me.
Much of the divisive stuff on Twitter starts with statements of certainty and absolutism where none exists. One of the fantastic things about this Substack is the acknowledgment and acceptance of uncertainty.
Great food for thought. Thanks for your time.
I've noticed that there are many comments on my post which take the viewpoint that either
1) LDL/apo B is not important in the development of ASCVD
2) Statins don't reduce the risk of ASCVD
Clearly, if you believe these 2 points, there is no point in doing CAC
When I became the skeptical cardiologist in 2013 I systematically challenged all that I had been taught about ASCVD. At that time, the hypothesis that lowering LDL would invariably lead to reduced ASCVD in my mind was not fully established. Since then it has been. Basic scientific investigation, prospective longitudinal cohorts, mendelian randomization and randomized clinical trials have all established that apo B is the particle that triggers atherosclerosis and that drugs that lower apo B reduce or eliminate atherosclerotic plaque formation and its consequences including heart attack and stroke.
As Peter Toth has as written recently (https://www.sciencedirect.com/science/article/pii/S2666667722000551)
"despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs"
We have the ability to eliminate ASCVD, the biggest killer of humans in the world.
CAC is how we identify subclinical atherosclerosis.
We now have multiple very safe and effective medications beyond statins that lower apo B/LDL and reduce the devastation of ASCVD.
The only serious scientific question at this point is how aggressive to be without pharmacologic treatment in the individual sitting in front of us in the office
Dr P
Dear Skeptical Cardiologist,
Thank you.
You’ve cited supposed knowns - and the vast majority of experts out there believe these claims - but calcium and cholesterol share something really interesting:
the enzyme UBIAD1.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149639
Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification
This enzyme is essential for the on-site biosynthesis of menaquinone-4, a hormone. MK- 4 is the most prevalent form of VK2 in our bodies and, in rodents, it is highest in thyroids (over other tissues/organs), but it is unknown how this translates to humans. I mentioned that T3 creation, its gene, directly relates to creation of matrix gla protein, which, upon activation, is the most potent anti-calcification substance known. In arteries, in endothelial cells, MGP has the role of preventing inappropriate calcium deposition. It prevents arterial ossification, noted to increase with age, and previously viewed as inevitable, but which can now be seen as a process over which we may have more control than previously appreciated.
It’s important to believe in one’s integrity, in one’s ability to accurately identify true cause and effect and interpret data correctly, and I am sure that you truly believe these statements to which I am responding. I am showing that there really are other ways to interpret what you state, but they question dogma and are contrary to A LOT of what we do and have been doing in medicine (and nutrition). Is CAC a way to ID subclinical atherosclerosis or is it an indicator of calcium dysregulation? Instead of lipids, what if it’s really calcium dysregulation that causes the “…biggest killer of humans in the world?” PS We will all die.
After all:
A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9715 individuals
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537357/#:~:text=CAC%3D0%20confers%20a%2015,unaffected%20by%20age%20or%20gender.
Since statins increase CAC, a scan after taking them is not advised. And a very small reduction in events - artificially inflated by using RR instead of AR - by taking statins is cited as success. But, are these drugs, reducing serum LDLc, the BEST way? I think not. The best way is to prevent plaque and I’m showing that plaque etiology may well be initiated via calcium dysregulation, which just happens to share that enzyme, UBIAD1, with cholesterol. Reducing serum cholesterol has been observed with supplemental VK (and insulin sensitivity is increased), but good RCTs are called for, obviously:
https://www.augustachronicle.com/story/lifestyle/health-fitness/2016/10/06/vitamin-k-tested-diabetes-high-cholesterol/14279990007/
“To test this theory, he ran a small pilot trial giving vitamin K supplements to a few subjects and found it lowered LDL or the bad cholesterol, triglycerides and total cholesterol comparably to lipid-lowering medications.”
Yes, anecdotal, not RCT, but there are more similar findings and supportive data*, but the sheer enormity of money, careers, inertia make for focusing on certain biomarkers and seeing them rather linearly, not holistically, and certainly Dear Peter Toth…how you see this is much like
1) menarche is earlier these days bc of our better nutrition
2) obesity is caused by greater energy intake than expenditure
3) excessive cholesterol causes plaques/CVD and not meeting guidelines by way of drugs is killing folks (poor Toth thinks this, apparently)
[Evidence for these are missing, but these are stories we have embraced/medical societies have embraced]
CAC, if used in trials, would be an interesting biomarker bc of this. In medical practice, facing people with events, symptoms, and all the data published so far, it’s risky to go against this Titanic of thought that we must use certain drugs and meet certain biomarkers , but just look into what I am showing. Look at calcium dysregulation as found in concomitant diseases: CVD, T2D, CKD, obesity, dementia, hypertension. Not tons of data, but they are increasing daily.
This is an entirely different paradigm, it connects the various diseases that tend to be concomitant, it truly questions guidelines/dogma bc: statins increase CAC, beta cells of pancreas have newly discovered vitamin K-dependent proteins that control calcium via carboxylation, those who eat more VK2 have fewer cardiovascular events/weigh less, kidney disease and calcium dysregulation co-exist.
* More info available, just ask
I’m interested in learning more about effective alternatives to statins. That they exist is new to me.
So many.
Ezetimibe.
Repatha/Praluent. PCSK9inhibitors
Bempedoic Acid
The risk factor paradigm for atherosclerosis and cardiovascular disease has gotten us nowhere over the past 70 years that it has dominated research into these areas. No scientifically valid study of risk factor modification has ever shown any significant benefit beyond the small differences that could easily be due to chance. One problem is that atherosclerosis and the problems said to result from it (primarily heart attack and stroke) are related but not in any really consistent pattern. Atherosclerosis is found in all long lived animal species albeit with varying degrees of severity and rates of development. Heart attack and stroke are sudden events which often occur without warning. It has been pretty well established (at least for heart attack) that the common pathophysiology is a break in the endothelial lining of an artery that triggers a blood clotting cascade. As mentioned by a number of other commentors here, there have been a number of studies where angiograms shortly before the MI and soon after show that the changes often are seen in parts of the arteries that were not seen to be significantly diseased in the pre-MI angiogram. The relationship of calcification to actual stenosis has also not been definitively determined. In many years of practice with a fairly high percentage of elderly patients I saw quite a few with carotid arteries so heavily calcified that a plain x-ray would show much of the length of the artery. But the majority of these had no episodes of stroke or even TIA despite being of advanced age and had lived with this condition for many years. Any attempt to attach a risk figure based on this or any other risk factor(s) is tenuous at best. To prescribe "preventive" medications or advise invasive procedures is unwarranted as it is a pretense of knowledge that we don't have any evidence to support.
I’m 73, Asymptomatic, in great shape but calcifications on the coronaries were incidentally ID’d during a CT AoAngio 4 years ago. So AHA doesn’t help me. I’m coincidentally seeing the Cardiologist tomorrow to discuss this. Thanks!!!!
I feel the author erroneously sets aside the absence of RCT in his defence of CAC. It’s the simple burden of proof.
If proponents of CAC suggest that the test ADDS diagnostic value to the status quo, and meaningfully alters treatment strategies that may be triggered downstream of CAC testing which ultimately improves clinical outcomes (again above and beyond what would currently be done absent CAC), they are welcome to roll up their sleeves and prove it. It’s seems to be the epitome of hand-waving to say “yeah I require high quality evidence…but for this thing I’m a proponent of, I’m willing to look the other way”.
It’s disingenuous to compare CAC with echo (disclosure: I read echo). No one gets an echo just to order an echo. They are done in response to symptoms, and are not “screening tests”. That already fundamentally sets it apart from CAC, which is meant to screen asymptomatic people. (If someone orders CAC in a pt with symptoms, that’s next-level head-scratcher territory. ). Furthermore, in HF, downstream therapies are predicated on EF, which echo easily, relatively cheaply, and non-invasively provides, relative to others diagnostic modalities. So echo as part of a diagnostic and therapeutic strategy that results in reduction in hard clinical outcomes is already well established in numerous landmark RCT. The same cannot nearly be said for CAC. And for me, that’s all that needs to be said.
If you come at it from a shared decision-making thought process approach, I think both John and Anthony are correct in their own interpretations as to what should be done with CAC. They both have a solid interpretation of the evidence, they know the “risks/benefits/harms” and they come to a different decision. They are allowed to have different personal opinions.
Just like my experience with talking to people with statins – some think a 2% absolute benefit over 10 years is pretty good – some think it is ridiculously small. They are both correct.
However, what do practicing primary care clinicians (and likely most cardiologists) do when you have 2 thoughtful and smart academic cardiologists coming to what looks like, opposite opinions.
Well in my opinion they need to have access to simple tools that explain what the result of an intervention – in this case a test – will do to risk/benefit discussions for an individual person.
The link below is the best simple table I could put together. It shows in a 60-year-old person how knowing their CAC could inform a risk benefit discussion.
As with all tests you need to consider whether or not it would change what you would do BEFORE you order a test.
So, before you order a CAC test, discuss with the patient what the patient might do with the result. The bottom line is knowing a CAC test in a 60-year-old with somewhat elevated risk factors helps you/them refine the estimate of the 10-year benefit from a statin from a low of ~0.5% up to ~2% in a non-diabetic, and from between ~1% to ~5% in a diabetic. So, if those ranges would elicit a different decision, then the test may have value for that patient.
Here is a link to the table that gives those numbers.
https://therapeuticseducation.org/wp-content/uploads/2024/02/CAC-statin-benefit-table-768x432.jpg
If you have ideas for improvement, please let me know.
Excellent table. This would be a useful tool both before and if the patient chose to undergo the test, after ordering the CAC.
"So, before you order a CAC test, discuss with the patient what the patient might do with the result"
Excellent suggestion. Personally, I would have used it to demand LAD arterial intervention prior to experiencing acute cardiogenic shock.
Just want to add how often I am surprised by the decisions that my patients make when using this process. People I was sure would say" " No way I am taking that therapy" instead opt in and vice-versa.
Totally agree - which is why a discussion is essential. We need to allow people the freedom (if they wish) to make a decision. And it's not that difficult to do. And I believe it is more rewarding than simply following the "guideline du jour".
I have found CAC useful in providing additional information to patients with "intermediate" scores on lipid profile and ACC/AHA risk calculators helpful - but I would also point out it is most used and seems most useful for patients that are ambivalent about what to do. So - CAC does not need to be used as a "screening" test. I see no reason why any population should all routinely have this test (and I don't see it purported to be used that way). Statins are a unique niche of medicines that many patients/people feel strongly about in either a very positive or a very negative/suspicious way. If a patient is highly motivated to want a statin, no reason for this CAC. Patients who are highly negative about statins don't really feel more compelled to take statins with this add'l information. It is useful in patients who seem to fit many of the higher risk criteria, but still have a general inclination NOT to take medicines, but are open to information. What I'm saying is that it is not a "screening", mass-use test but one that can add to a clinician and patient decision-making. This falls into a category of the "art of medicine" - an astute clinician who can assess a patient's risk, assess a patient's willingness/interest in taking medication, and knows that this will be helpful in some way. Unfortunately, in today's medical world, the 10-minute office appointment does not afford for this type of assessment, review, discussion, and "artful medicine" application by good clinicians. (but again, I find this a useful test in the right patient).
I did read JMM's rebuttal against routine use of CAC - one interesting thing he pointed out was that lots of CAC testing would drive a certain amount of "incidental" findings and information about coronary arteries that would end up driving anxiety in patients. I have not seen that with CAC testing as much as other areas of medical tests. One area I DO see an alarming level of unnecessary anxiety is in the frequency of "borderline aortic aneurysms" being found on various cardiac tests: Echo being a big one. I have many patients who live in fear of the "ticking time bomb" in their chests - MANY patients mention this. They get pulled into yearly cardiac testing (Echo or CT, MRI) - for a problem that is not very common (the rate of death due to thoracic aortic aneurysm is quite low!). I'd love to see JMM do a review of this situation!
Agree, should not be universally applied but adds greatly to decision-making for many of my patients and that process requires a considerable mastery of the "art of medicine."
But I find it often changes our approach even in those who are highly motivated to take a statin (for example if we find >75th percentile for age/gender and decide to treat to secondary prevention apo B targets which require combo therapy whereas <25th percentile we would use much more lenient targets and lower statin dosing)
On the other hand, those highly disinclined to take statin who are found to be very high risk often agree to take other agents (zetia, PCSK9i) and both patient and physician can feel relieved and comfortable with the decision if very low risk or zero score is identified.
As to incidental findings, I've discovered several seriously large aortas by CAC (2 of whom required surgery . The lung spots are what drive me crazy which are identified all the time on chest CTs ordered for other reasons and cause much angst.
I agree. I will point out that the last CAC I ordered had an incidental finding of a lung nodule and the radiologist recommended follow up Chest CT in my patient without risk factors for lung cancer. I inwardly groaned.... Any test we order has the possibility of these incidental findings and it is good to acknowledge that.
Agree. Radiologist called a lung nodule from my abdominal CT which necessitated a follow up chest CT and had disappeared.
Absolutely)! I am not a fan of incidental findings in any way, shape, or form. And I've got the same issue I have to advise a patient about right now, sitting in my "to do" box. Incidental finding (lung nodule) in patient with no risks and she wants to know what we should do (and this was on a test done in 2020 that I did not order! Nothing has been done till now, but she wants my advice). And I agree with your suggestion we acknowledge the downsides to our tests. Exactly why I would not think this is a good screening test.
After awhile, you start to wonder how much of anything we do is very helpful and adds anything much beyond a focus on healthy lifestyle and healthy habits! (and more focus on trying to spread that information to high risk populations with low health-literacy and general unhealthy habits)...
Thanks for the post. I am a family doctor with 20 years of experience and am most passionate about motivating patients to make lifestyle changes for their health. I personally had a CAC done last year since my LDL and Apo B and coronary inflammatory markers were slightly above normal...despite everything I knew to do lifestyle wise. The CAC was a useful tool for further risk stratification to help med decide if I needed a statin for the rest of my life. Fortunately my CAC was zero and so I felt reassured to not take a statin and continue with my healthy lifestyle. I have found I'm not alone. I tend to target patients age 45-60 who have borderline lab results. We talk about the pros/cons of simply starting a statin, making lifestyle interventions or getting more information with a CAC. Most of my patients elect to start lifestyle interventions and monitor their numbers first. There have been a handful of times I've ordered a CAC and found the results useful to better counsel my patient.
Just because CAC is misused does not mean that it's useless.
I've found that it's a great way to open discussions about overall risk, overall "how's aging going for you?" conversations. When used this way, I've seen most people take a greater interest in the health ... whether that's through lifestyle, drugs, or a combination ... and isn't that the goal when we go to work?
As a family physician, I have not seen this lead to an inappropriate intervention ... but maybe that's where I live. (Rural Wyoming doesn't have a lot of invasive cardiologists!)
Side note: this whole debate points out that I don't realize how much momentum certain departments in academic centers have ... glad I'm not practicing there!
I’m 69 years old, cycle 150+ miles a week, swim daily and weight lift 3x a week. I’m a clean eater 80% of the time ( no red meat for 40+ years) My internist ordered a CAC for me when I was 63, because my father had a massive heart attack at 56 (lived to 89). When the test came back - zero! However, a 17x16mm nodule was noted in posterior position of left lower lobe. This started down a rabbit hole of CT scans, X-rays, etc, visits with pulmonary specialist. Bottom line, probably had Valley Fever at one point and didn’t know. Doc wanted to repeat again last year and I refused! Did I make a mistake???
First, I think you were wise to get the CAC. Your dad had an MI at age 56 and could have dropped dead from it at that time. It is essential, IMO, with that kind of family history to know with certainty the level of atherosclerosis in your coronary arteries and make an informed decision on how to best handle the identified risk.
The zero score indicates you are in a very very low risk category and didn't inherit your dad's ASCVD risk and should be incredibly reassuring.
The incidentaloma is an annoyance. I hate these and asked a radiologist friend to write a guest post for me (https://theskepticalcardiologist.com/2017/10/15/what-is-the-significance-of-a-spot-on-the-lung-the-three-eyed-radiologist-on-incidental-pulmonary-nodules/) on the topic which should be of some help in understanding the implications.
As to repeating the CAC, I would be fine with not repeating it.
The lung nodule will still be there. If you are still nonzero you know that you are still at incredibly low risk for ASCVD.
If it is nonzero it the score will tell you precisely where you stand in comparison with other 69 year old women and I suspect it will be less than the 25th percentile still and even more reassuring.
Learn about overdiagnosis or incidentilomas. I happen to like H Gilbert Welch’s coverage of this.
He did a cute video about an elderly patient who came in bc of hoarseness. With a subsequent test, cancer was found in a kidney - totally bc they did scans, etc, not bc of symptoms - and the patient balked at surgery.
He pointed out that he came bc he was hoarse and now they want to remove his kidney?
He declined.
He died of pneumonia 10 years later, and Welch was hyper-alert to his autopsy. Yep, cancer still there and it never really affected him.
Seriously, see Welch’s videos about overdiagnosis.
Thanks, Micki. I was glad I did the CAC test, but the path of three years being followed for the lung spot was crazy - pet scans, CT scans, X-rays, pulmonary appts., etc.
I'll have to search for the Welch video. Thanks for your comment.
It seems that patients and medical professionals must do the best we can amid considerable uncertainty! Thanks to all for a terrific discussion.
I agree with much of your criticism. My comment is truncated in that the various aspects of potential proof are omitted…and “true” proof is very elusive, even in all the supposed “knowns” upon which we’ve based so much in our rather clunky modern medicine. I didn’t even cite some of the articles, studies, trials upon which I am offering evidence, maybe not technically “TRUTH,” but definitely questioning what we think we know and offering alternative narratives of both etiology and treatment of common chronic diseases, including CVD.
I mean, where’s the proof that cholesterol causes plaques? Is this true? (nope)
Actually, no proof, and when faced with purely fatty plaques, cardiologists figure they’re bad, in spite of evidence to the contrary. Without calcium, they are benign.
Sooo much money, hubris, careers, reputations are based in really misguided ideas.
How do we reconcile that most folks who suffer an event have so-called “normal” cholesterol levels?
A search of the literature regarding such as CAC, calcium, microcalcifications, vitamin K/K2, matrix gla protein, UBIAD1, etc - alone and in combination - offer some real insights.
See: Historical Review of the Use of Relative Risk Statistics in the Portrayal of the Purported Hazards of High LDL Cholesterol and the Benefits of Lipid-Lowering Therapy (2023)
Or here’s a fun, new alternative diabetes insight:
https://pubmed.ncbi.nlm.nih.gov/37171959/
Vitamin K-dependent carboxylation regulates Ca2+ flux and adaptation to metabolic stress in β cells
(Note new, larger than usual, vitamin K-dependent proteins in the ER of those beta cells)
Or this:
https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-023-00779-4
Revisiting the interconnection between lipids and vitamin K metabolism: insights from recent research and potential therapeutic implications: a review
Once cholesterol was blamed for plaques, we were stuck. Stuck, stuck, stuck. We hit on an answer to a problem: statins. Only this was and is incorrect. Statins suffer the statistical manipulations cited in that Historical Review mentioned above and harms are understated. There are clues about real causes of cardiovascular events bc we know that a zero CAC offers a 15 year warranty from death by all causes (!). But no drugs address CAC, so there’s push back against measuring that; no answer, why look? Contrarily, even if the answer is “bad,” we can be persuaded to believe and I could cite several specifics in a variety of specialties as examples.
Instead of seeing this CAC as something to attack, let’s understand its etiology. That will, upon enough literature searching, lead to microcalcifications. Which will lead to the hugely important and vastly misunderstood topic of vitamin K. Huge. Complex. Inchoate. But once we saw vitamin K as only about coagulation, we got stuck (see a pattern?).
We are now facing some huge health woes by way of epidemic non communicable diseases and modern medicine, stuck as it is, is not addressing them.
As a small add-on : cancer.
A Japanese man with HCC quit responding to conventional therapy, had many metastases. So they gave him a vitamin K2 analogue. No bad effects. All metastases disappeared…complete response.
Search cancer and vitamin K2. Crazy.
“Truth [and proof] may be found at the bottom of a bottomless well.”
A Civil Action
This is an important topic. Our entire system is arranged around blockages in heart arteries and opening those blockages even though we have had hard evidence for almost 30 years that those stable blockages don't cause a heart attack. They are a marker for the presence of cholesterol deposits that don't block the artery. 68% of heart attacks occur in a heart artery that was less than 50% blocked prior to the heart attack. That means it would not have caused symptoms and it would not meet the 70% blockage criteria required to justify a stent. Only 14% of the arteries that cause a heart attack have a 70% chronic blockage beforehand. The coronary calcium score tells you how much plaque you have.
Heart attack may happen in an artery that was totally open with cholesterol deposites that had remodeled the artery outward. Large cholesterol deposits can happen in an artery that is totally open. Heart attack happens when one of these cholesterol deposits breaks open and initiates the clotting process. A person can go from wide open to totally blocked in a matter of seconds to minutes. That is why a person with no history of chest pain or shortness of breath can have a heart attack out of the blue or drop dead on the sidewalk. Traditional risk factors don't identify everyone at risk. The calcium score identifies people with a lot of plaque who need optimal medical therapy very inexpensively. Women are even more likely to have a heart attack with no stable blockage beforehand
https://pubmed.ncbi.nlm.nih.gov/7634481/
https://www.ahajournals.org/doi/full/10.1161/01.CIR.91.11.2844
Thank you for these citations, but both are from 1995.
Newer technology has been invented that shows those microcalcifications I mentioned.
We continue to tweak measuring the various fats in serum (and by inference, plaques?) and now acknowledge Lp(a), as well as try to develop ratios among them that offers risk accuracy.
If CAC is such an accurate biomarker of risk (a zero represents 15 years warranty from death by all causes!), what makes it appear? Really…what makes CAC happen? What mechanisms? And how can we reconcile that lipophilic statins increase CAC and yet consider this good?
Are centenarians taking lots of drugs?
How does nature make the pathways that you cite (mTOR and AMPK) happen?; how does nature maintain homeostasis? Why are multiple drugs better than how nature accomplishes this?
We’ve spent a lot of time and effort on the wrong things and turning around the metaphorical Titanic of current medical dogma is daunting, threatening, and important.
Nature maintains homeostasis via genetics, epigenetics, and the related molecular biology. Genes that should be quiet are reactivated by abdominal fat, cigarette smoking, and age itself to increase oxidant production, inflammation, make us sick and kill us. The drugs that matter in chronic disease block oxidant production that leads to mTOR activation and AMPK deactivation. There were many fewer centenarians in 1900 when the average lifespan was 40. Good science has dramatically extended life span. It is not the calcium that kills us. It is the soft inflammed cholesterol plaque and atorvastatin reduces soft plaque, inflammation, and stabilizes it that so it does not rupture and cause a clot. Yes these studies are almost thirty years old. this link is almost twenty, but they answer questions that should change the way we treat artery disease.
https://jamanetwork.com/journals/jama/fullarticle/202629
These are facts we have known for decades and thousands of people are dying because we have not change what we do.
https://pubmed.ncbi.nlm.nih.gov/20973686/
what would you recommend we do differently?
The story about statins making for plaque stabilization has been widely embraced; lots of articles about plaque stability exist - discussing shear forces, flexibility - and this has been a large arm of thinking in cardiology. (If you bend the statistics of statin benefits by way of RR, you also need to cite mechanisms to explain…it’s a whole tapestry of stories that evolve over time, thanks to pharma)
There is evidence to the contrary.
Look for it!
I seek info that discounts what I claim, and I recommend it for all.
(e.g. several VK interventions haven’t changed CAC, but arterial flexibility was maintained in middle-aged women who supplemented, HCC was cured in one man, VK is a known anti-inflammatory and anti-tumor agent, MANY vitamin K-dependent proteins are being increasingly appreciated for myriad roles beyond coagulation, but single interventions with VK have yielded mixed results)
Statins appear to create CAC. Especially lipophilic ones.
Mechanisms are known that could explain this dysregulation of calcium via statins; they directly affect VK actions with negative effects, which we tend to shuffle under the rug bc we’ve obsessed over cholesterol and ignored calcium.
We could test this if diabetics w/o CAC were prescribed a statin (guidelines…and I disagree) and then monitor if CAC subsequently appears.
But if this happened, could the statin/plaque stability story even be questioned?
Could we see mechanisms differently?
I would suggest we’re in too deep.
Calcium is a signaling messenger as well as a huge component of hydroxyapatite.
When hydroxyapatite goes awry (bones lose it while arteries accumulate it), bad things happen.
Ossification in arteries. Crappy bones.
Mammograms look for calcium.
Cancer is addicted to calcium. (Search that phrase)
I just showed about beta cells having newly discovered VKDPs and that article explained that the stress of age increases the calcium dysregulation, explaining why age increases risk AND THAT VK reduces that stress. Nature’s way. Go check out the VK/VK2 intake of so-called Blue Zones. And they aren’t stomping on VKactions with drugs like statins, bisphosphonates, warfarin, even antibiotics. CAC increases with them.
This claim misses some things…and I suspect that you know this:
“There were many fewer centenarians in 1900 when the average lifespan was 40. Good science has dramatically extended life span”
Hygiene, antibiotics, vaccines…I mean, not statins, not metformin, not screening, but those other medical advances were beneficial.
In my lifetime, the obesity has exploded in our population, T2D has also, but the answers have failed miserably.
Clearly, diseases happen and people need help. Medicines save lives…but not all, and certainly our understanding of the common chronic diseases that tend to be concomitant is chasing the proverbial cow long out of the barn. Not drugs, but true understanding of etiology, of mechanisms, offers true answers.
Calcium dysregulation does kill us.
I will stick with the optimal medical therapy approach which is not about relative reductions in risk but about massively better outcomes. Patients on optimal medical therapy who have had a heart attack are ten times as likely to be alive in five years as those receiving usual care. Diabetics on optimal medical therapy have one fourth as many heart attacks, one fifth as many strokes, and one sixth as many go on dialysis. If you can show me something that approaches those results, I am all ears.
When it comes to RCT's of screening in general, it seems like there is less money to do them, since there are no drug companies willing to fund them. Another problem is the very large sample size needed to show changes in mortality as described by Dr. Peter Attia when talking about breast cancer screening, which I imagine also applies to CAC screening. I posted the link below with my comment on Dr. Cifu's piece about blood biopsies but in case you didn't see it....
I tend to think of "screening" as something that's applied to all patients, but I'm not sure if CAC needs to be given to all patients. But I can attest to the fact that it's helpful with some patients: myself and my spouse. Both of us fell in the "moderate risk" category based on traditional PCE scores, and neither of us wanted to go on a statin. Once we saw that there was plaque in our coronary arteries via CAC, we both decided to start a statin. (We were already good with lifestyle). So for people in our situation, I think it's very helpful. BTW, I was never impressed by the ARR of statins, but after listening/reading Peter Attia's explanation of cumulative risk over decades, along with a masterclass in lipidology by Thomas Dayspring, statins make more sense to me, but the CAC scores are what really got us there.
https://peterattiamd.com/life-extension-from-cancer-screening/
His thesis on cumulative risk over decades sure sounds convincing, The question is, is it correct? If it were, one would imagine the data at least pointing to it would be much more convincing...
Maybe I'm gullible, but I find this evidence persuasive enough that I'm taking no more chances with my high LDL-C, given that I know I have atherosclerosis thanks to the CAC.
https://jamanetwork.com/journals/jamacardiology/fullarticle/2784038
https://www.jacc.org/doi/10.1016/j.jacc.2020.07.059
https://academic.oup.com/eurheartj/article/44/Supplement_2/ehad655.1366/7392932
the footnotes in that article speak loudly
I posted 3 articles and you already read them? Wow! Speed reader! I don't know which one of the 3 articles you're referring to, but it doesn't matter if all you bothered to read were the footnotes.
Dr. Mandrola please post a link to your rebuttal, or to your perspective on CAC, so that we may see both sides of the debate. Thanks.
There’s a hyperlink in my introduction
Interesting perspective. Except for the part about “lack of RCT’s”! This retired EBM teacher and medical generalist has heard this argument about every single screening test in existence. The CAC score is indeed a “screening test”. Regardless of baseline risk, it is attempting to “find” a disease in patient who may or may lt have it. The results do change probabilities, it does not make the diagnosis! It is not a credible gold standard, merely another thing to plug into risk calculations. The results trigger another therapeutic and investigational cascade that have their own risks and benefits.
One can “believe” it changes meaningful outcomes, and that the harms are trivial. The same occurred with every other medical intervention… where RCT’s demonstrated reality. In many cases it was only the RCT data that allowed physicians to communicate risks and benefits to patients … so that THEY could decide what to do with their lives. That is true “personalized medicine”.
This 70 year old retired doc, with 12% body fat, lifelong endurance exercise, parents and well into their 90’s, BP of 90/60 and strikingly high LDL and non-reassuring Apo B, will give this a miss! It’s my one precious life, and only data from RCT’s will allow me to decide what to do.
I remain dismayed how we keep making the same errors over and over again.
That said, heterodox viewpoints are critical, and this was important reading. We must all leave our opinion silos, and you both demonstrate how it is done.
Thank you both.
I can't tell you how many active, asymptomatic patients I've seen with your lifestyle , BP and lipids who were status post PCI, CABG or MI that came without warning.
I do think having parents in their 90s without documented CAD strongly mitigates the risk.
But, if you were my friend and colleague I would be constantly bugging you to get a 10 minute painless test for $100 that could better determine the risk created by the "non-reassuring apo B"
I too have seen many similar patients. I do understand both your assessment of risks, and, as a result of your excellent article, the reasons for your beliefs about the utility of this inadequately studied screening test.
Lastly, I suspect that all of this is embedded within a desire to mitigate patient risk and likely an empathetic worldview. Unlike many, I see no sinister motives (financial or otherwise).
I have had many conversations on this topic, as well as related ones (PSA screening, FOB screening and many others).
Each of us has biases, and we must do the best we can with all of these confounders. Both of us are not exceptions.
My reply to you would be “Thank you for your concern and well-intentioned advice, but although I think about this issue from time to time, even the most non-reassuring Calcium score will not change my current decisions about treatment of my one modifiable risk factor”.
Patients and friends are funny that way, they make decisions very different from us.
Again, I thank you for your article and viewpoint. It’s important and I am grateful for your concern for my wellbeing!
Steve
10 likes!
Female, 70 years old, CAC score zero, BP 122/76, BMI 24.3, LDL 172, Apo B 125, hs-CRP 2.6, long-lived parents and grandparents on both sides. My doctor who advised no statin has retired; zoom cardiologist consult advised statin; new doctor advises statin. It was two experts against one, so I just started rosuvastatin 20 mg. Sheesh! I guess I'll keep getting exercise and drinking a lot of water.
I've seen lots of 70 year old women with lipids that high who have zero CAC scores of zero. With such derisking we don't recommend statins unless the patient wants to be super proactive. If we do start, we start low.
I'm not sure what drinking a lot of water will accomplish :)
I'm 62 with very high LDL but also good HDL and triglycerides, CAC = 0 and did well on the treadmill, no symptoms of anything, ever. I have no interest in statins and can't tolerate them, and really tried to when prescribed. My husband developed focal necrotizing myositis on statins. No thank you.
Drinking plenty of water is just good general advice with next to no arguments on the other side! It has been great to read these divergent opinions. Thank you; and especially thank you for your website, particularly the coverage of AFib + alcohol. My "irregular heartbeat" has been observed since age six. I have gone two months with almost zero alcohol and my exercise bicycle, which recently alarmed twice during very mild exertion (post-holiday alcohol excesses perhaps), has not alarmed once since! Tell your AFib patients that alcohol-free beer is pretty good (wine not so much).
Speaking of lipidologists, there are some really interesting Japanese lipidologists worth a look.
See:
https://pubmed.ncbi.nlm.nih.gov/25655639/
Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms
Follow up on articles from first author in this.
They are often published in the journal, Calcium.
Here, in the US, we don’t subscribe.
We’re in the thrall….
Sorry, Jennifer, for their advice.
You are kicking it at 70, so you have years of experience, but apparently they got to you. Two against one is not insurmountable, but it can be scary.
Sigh for all of us….
Jennifer, thanks for your post. It saddened me that two doctors “advised” taking a statin. Might it be more helpful for them to state something like “despite considerable uncertainty, in patients similar to you, evidence from RCT’s suggests that the use of a statin at your age will change your absolute (not relative) risk of an adverse clinical outcome (MI, Angina, stoke, dementia or whatever the RCT outcomes assessed), from X to Y. The risks (myopathy, $, sick-role etc) occur at Z frequencies. “
“Given this information, can you decide what course of action you wish to take”, because you need to know that if you leave it to me, I am likely to play it safe because of my biases”.
If physicians cannot do this in what is the most evidence informed area of medicine, we are in big, big trouble. Vote counting is a sad state of affairs.
I empathize with your dilemma.
Steve, this is such a great example of how to do good shared decision making. Could you clarify what you mean by ‘change your absolute (not relative) risk’? I assume this means give someone what their individual absolute risk reduction would be given an estimation of their risk. Dr Pearson writes that CAC is a good additional factor to clarify an individual’s baseline risk
To bolster Steve’s very accurate statements:
https://www.cureus.com/articles/141648-historical-review-of-the-use-of-relative-risk-statistics-in-the-portrayal-of-the-purported-hazards-of-high-ldl-cholesterol-and-the-benefits-of-lipid-lowering-therapy#!/
[read this!!!]
Also, it has been published in peer reviewed journal that a lifetime of statins increases life time by about 4 days.
Statin naive patients had muscle biopsies before statins and then subsequently after taking them. Muscle damage was shown in these biopsies, though symptom complaints were inconsistent.
Harms are mostly denied, but they are there. Pharma cites benefits outweighing harms, uses RR to cite benefits and AR to cite ‘side effects’*
* yet another example of propaganda:
Benefits v harms
or the more disingenuous version
Benefits v side effects (side effects? meh)
Sure. It’s the same issue with reporting outcomes in the mega-trials… often reported as relative risk reductions (often in the 20-50% range). Tell a patient “your relative risk will drop 40%, and you get buy-in for therapy. Tell them the (also true)
“ your risk of an MI will drop from 1% to 0.6% and all you have to do is take this drug for X years at a cost of $1000 per year” and one might get a different answer.
Thanks. One thing I worry about and talk to my learners about is how much of an impact the way we frame information has on how patients make decisions and being aware of how much our own biases inform how we do choice architecture.
Thank you Steve!
What is missing here is that CAC begins as microcalcifications, invisible by way of CT, but now we can see them with new technology.
Once it's visible as CAC, calcium dysregulation has advanced and those microcalcifications are growing.
Can we lessen it; can we move it?
That's one criticism of a CAC scan (that there's no drug known to do this), but instead of falsely chasing cholesterol, triglycerides, we need to understand what leads to CAC; how do microcalcifications begin and what enables
them to advance to measurable CAC?
Here's a fun insight:
The so-called active thyroid hormone, T3, is directly involved in creating matrix gla protein, the most active anti calcification agent - when properly activated by vitamin K - known.
T3 is created on site, mostly, by deiodinases, and if enough matrix gla protein isn't present in endothelial cells, or if they aren't properly activated, calcium deposits.
THAT is the beginning of plaques.
Not cholesterol, a really bogus biomarker that has dominated thinking and is very inaccurate.
Statins are NOT the answers to anything.
Their reductions in absolute risk of an event are poor, but trials have been statistically manipulated to use relative risks to describe benefits and absolute risks to describe harms. In short, they lie.
Further, statins interfere with an intermediary of both cholesterol creation AND menaquinone-4 creation, which leads to increased risk of T2D bc this essential process of creating MK-4 is important in insulin sensitivity and is a hormone affecting expression of many genes.
CAC is the hint of what causes plaques and someone stinking needs to look there!
Statins - especially lipophilic ones - increase CAC
I'm interested in learning more about this.
Hi KittyB,
I sure posted a lot, didn’t I? So not sure what you’re interested in learning more about. I gave some links that support some of my claims here in subsequent posts, but these are a few supportive articles about claims for which I didn’t post anything to date:
1) microcalcifications are newly seen via new technology and appear to lead to what will be CAC
https://www.sciencedirect.com/science/article/abs/pii/S1050173818300574?via%3Dihub
Coronary arterial calcification: A review of mechanisms, promoters and imaging (2018)
https://www.sciencedirect.com/science/article/pii/S1936878X1731001X?via%3Dihub
Coronary Artery Calcification and its Progression: What Does it Really Mean? (2018)
https://www.mdpi.com/2075-4418/9/4/125
Coronary Artery Microcalcification: Imaging and Clinical Implications (2019)
2) matrix gla protein synthesis is directly related to the transformation of the thyroid hormone, T4, into the active hormone, T3:
https://www.ahajournals.org/doi/10.1161/01.RES.0000181431.04290.bd?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
Thyroid Hormone Targets Matrix Gla Protein Gene Associated With Vascular Smooth Muscle Calcification (2005)
[This is where the various medical specialties tend to communicate amongst themselves poorly, not really understanding how they are akin to the story about the blind men and the elephant. Endocrinologists have assumptions about T3 by way of conversion by deiodinases, they know how thyroid patients are at increased risk of cardiovascular events, they even know that calcium dysregulation is coexisting with thyroid diseases, but how many cardiologists and endocrinologists know what this paper implies? We can’t measure on-site T3, so we assume serum levels tell us that. But, since rodents are ‘willing’ to die, so we can test this assumption, we know that T4 to T3 conversion differs among tissues and is the diversity is not represented by serum levels. Humans? And hypothyroid patients on standard-of-care T4 monotherapy have different serum ratios of T3/T4 compared to euthroid patients. Cardiologists figure endocrinology knows thyroid functioning, based largely on TSH guidelines, but:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287526/
Is a Normal TSH Synonymous With “Euthyroidism” in Levothyroxine Monotherapy? (2016)]
Other claims, with supportive links, are in my other posts.
I hope this answers your request!
“ THAT is the beginning of plaques.”
Micki, how do you know this is “true”? It’s an interesting hypothesis, and may be true, in whole or part, but assertions of truth do not move me.
Much of the divisive stuff on Twitter starts with statements of certainty and absolutism where none exists. One of the fantastic things about this Substack is the acknowledgment and acceptance of uncertainty.