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Utilizing biomarkers with coronary artery calcium (CAC) scoring for cardiovascular risk (19 min)
00:19:18
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- [00:04]
A
Welcome to Healthier World with Quest Diagnostics. Our goal is to prompt action from Insight as we keep you up to date on current clinical and diagnostic topics in cardiovascular, metabolic, endocrine and wellness medicine. Cardiovascular disease is the number one killer worldwide and for decades, providers have been utilizing a powerful tool called coronary calcium scoring to get ahead of it. This quick and non invasive test that identifies calcified or hardened plaque is used millions of times a year. But what many people may not realize is that a significant portion of dangerous plaque is non calcified. Today's episode features Dr. Mark Penn, founder and chief medical officer for Cleveland Heart Lab, Millicent key nurse practitioner and my fellow clinical education specialist, and myself, Dr. Mason Latsko. And today we talk about how timing plays a role in proper assessment of calcium scoring and how biomarker testing using tests like apolipoprotein B, myeloperoxidase, Lppla2 and high sensitivity CRP can be used in place of or in conjunction with calcium scoring to help guide patient care, especially when a calcium score doesn't tell the full story. Welcome, Dr. Penn. Welcome, Millicent. Thank you so much for joining me today. And let's start by jumping into the basics. Millicent, help us break down what a calcium score is and why it is used in clinic.
- [01:30]
B
A coronary artery calcium score is a score that's going to measure calcified plaque in the arteries using a CT or a CAT scan. And it's going to reflect the burden of atherosclerosis. So it's going to reflect the burden of that buildup of fat and cholesterol in the artery walls. A calcium score is used most often to help us better identify and improve our risk stratification over traditional risk markers for c things like age and smoking status. When we use a coronary artery calcium score, it helps us better improve that risk stratification and also helps us guide our clinical decision making.
- [02:09]
A
Thank you, Billy. So, Dr. Penn, do you have anything to add? Is this also how you've seen calcium scoring evolved in clinic?
- [02:17]
C
Yeah, a lot of folks get calcium scores to either through entre into preventive cardiology to start to determine how much risk they may have and what they want to do. Some may have evidence of risk but not want to be treated with statin therapy or other lipid lowering therapy and they want some proof that they have disease and so they'll get a calcium score. You know, in the old days, quote unquote, it used to be stress testing, right? We would run a stress Test to see if somebody had disease. The identification of disease and stress testing meant you had a blockage of at least 70%, but it was typically a calcified blockage, and you'd have a higher calcium score. The coronary calcium score kind of gives us a bigger picture than just a stress test, because now it's looking at any calcified lesions that may not be 70%, but it says that you had the disease and disease has progressed.
- [03:15]
A
Thank you, Dr. Penn. So you both had several overlapping thoughts there. One that I want to capture here is that calcium scoring is typically run when a patient doesn't have clear high or clear low risk. So, say a person who has very low risk, maybe a young female with no family history or metabolic issues and a clear high risk, an older adult with diabetes, hypertension, and a strong family history. Clearly, there are nuances in using calcium scoring for everyone who falls between those two extremes. Millie, what are some other instances where calcium scoring may not be as accurate or informative?
- [03:54]
B
Yeah, and just like you said, there is a lot of individuals who are going to fall in between those two extremes. They're not clearly low risk, they're not clearly high risk. So it's important to talk about when we best use the coronary artery calcium score in clinic and what it does show us and what it doesn't show. First, it's important to remember that the calcium score is only going to detect calcified plaque. So it's only going to detect that hard plaque. It's not going to reveal the presence or extent of the non calcified or the soft plaque. And we need to keep in mind that that non calcified and soft plaque can rupture. It can lead to cardiovascular events like heart attacks. So a calcium score is considered too early. In general, if it's performed in our younger patients and our patients who are too young and have no or very minimal risk factors for heart disease. And in those patients, the test may not provide meaningful results. For example, the cardia study or the coronary Artery Risk Development in Young Adults study, it showed that only 1 in 10 adults aged 32 to 46 years had a coronary artery calcium score that was greater than zero. So when you're looking at your males less than 40 years old without risk factors, your females who are less than 50 years old without risk factors, in those individuals, the likelihood of a significant coronary artery calcium buildup is very low because again, it's looking for calcified plaque. And as a result, a low or a zero score may provide false reassurance to that individual about their long term cardiovascular risk, while a non zero score could provide unnecessary interventions or evaluations. The coronary score is also not going to assess the blood flow of the coronary arteries or the function of the heart itself. It's not going to give us information about the degree of the narrowing of the coronary arteries. So it has limited utility in some people. It's also absolutely not indicated to evaluate individuals who are having active symptoms like chest pain or shortness of breath. And that needs to be looked at in a different way. So in general, the optimal time for a coronary calcium score is going to be when an individual is between the age of 40 and 70. And it's going to be those patients who have moderate risk factors. So they have elevated high blood pressure or they have high cholesterol, or they're overweight or physically inactive. They have a lot of stress in.
- [06:25]
A
Their life, but they don't have a.
- [06:27]
B
Lot of those other high risk factors that put them in clearly in another category and they're not having any symptoms. Those are going to be the individuals where it's best used.
- [06:39]
A
Interesting. So I want to dig into something that you had mentioned, which is if a patient is at borderline high risk, say they do have high cholesterol or they get a calcium score and it comes back elevated, these are the patients who commonly get placed on a lipid lowering therapy like a statin. Can you help us better understand why those patients should no longer be monitoring their risk using a calcium score?
- [07:02]
C
Sure. If you have somebody who had a high calcium score and you then chose to put them on a statin appropriately, the calcium score goes up. It doesn't go down. And it goes up because any fatty streaks you had or soft plaque that you had gets calcified. That's what you want the statin to do. You want it to slowly leach the lipid, leave the calcium and harden that artery, because again, calcified arteries don't rupture.
- [07:33]
B
Yeah, this is a very good point because in fact, the coronary calcium score may actually increase and can provide the patient a lot of anxiety as a result. They think that they're doing the proper therapy, the proper treatment, and their calcium score is actually going up as a result, when in fact it's really just showing that that statin is stabilizing that soft plaque in that individual.
- [07:58]
A
So now we know that patients who are already on a statin should not be receiving a calcium score because their calcium score inevitably goes up because of the Function of that statin. Now, in a patient who is not on a lipid lowering therapy like a statin, how often can they get calcium scores rerun?
- [08:15]
B
So primarily this is going to be dependent on the clinical judgment of each clinician. However, if the initial coronary artery calcium score is high, say greater than 300, these repeat scans are generally not recommended. Coronary calcium scores are based on percentiles and they are age related. So the likelihood of that individual's score decreasing is low. And monitoring that score as efficacy for therapy is also generally not a good idea. Instead, the focus should shift to preventative measures. So you should be managing that patient's lipid status, lowering their cholesterol. You should be managing that patient's blood pressure, making sure that they're eating well, exercising well, doing all of the things that we know that can over time lower their risk of cbd. If you have a patient who has a coronary calcium score greater than 100, for example, and they're on risk reduction therapy, that's still going to be the same thing. It's really not going to give you much indication about the progression of disease. If you have a patient who's much older and their coronary artery calcium score is 0, really no need to repeat that. You really know where their risk status lies as far as their coronary calcium score goes. And you really just need to address their other risk factors, such as their advanced age. On the other hand, repeat scans may be beneficial if you have an individual who has a moderate coronary artery calcium score, particularly if the results are going to influence treatment decisions. So if they're going to influence, say, the initiation of a statin or the intensification of the statin dose, or if you have individuals with coronary artery calcium score of 0 and they have moderate risk factors, a Repeat scan of 5 to 7 years is really reasonable for those because you're going to be able to reevaluate their long term risk.
- [10:09]
A
Yeah, and that can seem really daunting too, right, to say, okay, you have moderate or high risk per your calcium score or per your other risk factors. Now go on the statin and never check your calcium score again or wait five to seven years and then recheck. So what do we do about it? What is the solution? Are there other beneficial tests that we can be utilizing to assess a patient's risk over time?
- [10:34]
B
Absolutely. And that's such an important factor to note because we are saying, you know, the optimal time to check the initial coronary artery calcium score or the one time Coronary artery calcium score, depending on the patient, is gonna be in that age group of four, 40 to 70. So you've got a lot of years there.
- [10:50]
A
Right.
- [10:51]
B
And we know that age alone is an increasing risk factor for the development of cardiovascular disease. So there are other solutions to assess their risk, and they're equally non invasive, and those include biomarkers. We've touched on these on our earlier podcast, but specifically using assessment of inflammatory markers like HSCRP and myeloperoxidase and Lp, PLA2, using a lipid driven risk assessment like apolipoprotein B. So we could be looking at those routinely and using those biomarkers to evaluate their risk and to also help us with our clinical judgment and to drive treatment decisions.
- [11:37]
A
So outside these ideal windows, say the patient isn't between 50 and 70 or they're already on a statin. These might be patients who would benefit from biomarker testing. Now, I know I delve a little deeper into each of these biomarkers on various other episodes of Healthier World, but Millie, can you walk us through quickly how each of these biomarkers that we mentioned, HSCRP, MPO, LPPLA2, APOB, can tell us a unique story about a patient's risk?
- [12:08]
B
Absolutely. Hscrp, or high sensitivity C reactive protein, is a blood test that measures inflammation in the body. And it's particularly useful as a cardiac marker to look at cardiovascular vascular disease risk. It can indicate disease burden and it actually correlates really well with coronary calcium. So we can use this marker in patients who are outside that appropriate window for calcium scoring, especially in our younger patients, because we can identify that residual inflammatory risk, we can identify that systemic inflammation, and it can still help drive treatment decisions, lifestyle modifications, and clinical judgment when it comes to those patients, MPO or myeloperoxidase and Lp, PLA2, that's going to be looking at that risk of how active that plaque is. If there's soft plaque present, which we've also said before, coronary calcium scoring is not going to properly assess the presence of soft plaque. It's looking for calcified plaque. So when we look at myeloperoxidase and Lppla2, we're looking, okay, is there soft plaque present? If it's present, how active is it? We actually may be able to identify a risk that's present that we would miss if we're only looking at stable calcified plaque using the coronary scoring. And then apob, that's going to be looking at lipid driven risk. For us, we know that APOB is precise and it stratifies risk quite accurately. It gives us a very good indication of dyslipidemia, and it's going to give us those numbers that we can monitor, that we can track before and during lipid lowering therapy. So it's a valuable marker to check, once you have someone on lipid lowering therapy, to look at how effective that therapy is for that individual.
- [13:57]
A
That was great. Thank you so much for reviewing that with us, Millie. So biomarker testing can be a great tool to use when calcium scoring isn't appropriate, say, to track changes more frequently over time or. Or in a patient already on a statin, or to assess inflammatory biomarkers such as MPO and Lp PLA2 in patients who have risk for that soft, non calcified plaque. Dr. Penn, this next question is for you. Do you think that there's a future in biomarker testing and calcium scoring where they can be used in conjunction with each other to assess a patient's risk?
- [14:32]
C
Yeah. The future is like 10 years ago when a lot of studies came out and showed that biomarkers and calcium scoring were synergistic, not redundant. So classically, either whether it's CRP or MPO or LP PLA2, all markers are vulnerable plaque. At some level. If you had an abnormal calcium score, you had risk. If you had an abnormal mpo, you had risk. If you had an abnormal calcium score and an abnormal mpo, you had more risk. The point being, you have calcified plaque, you have vulnerable plaque, and now you have a lot of calcified plaque with a lot of vulnerable plaque. That's worse. And that's true for hcrp, that's true for LP pla, too. There's no question the combination is critical and synergistic.
- [15:22]
A
Great. So I think you alluded to this, but I just want to be explicit in asking this question. So say you have a patient who does decide to do biomarker testing in conjunction with a calcium score, and they get their calcium score back and the score comes back a zero. How do you reconcile that in clinic?
- [15:40]
C
Yeah, so they, they have early fatty streaks, they have early soft plaque. There are, there's certainly a cadre of patients. Just like again, back in the day, we would stress test somebody. Their stress test would be completely normal. They die in the parking lot on their way home of a heart attack. There are patients who have zero calcium scores who go on to have a heart attack because they have fatty lesions. And those fatty lesions Rupture. So they both have equal weight in the initial assessment of a patient. If you have an abnormal MPO or HSCRP but a normal calcium score, it doesn't mean that they don't have risk and you shouldn't be doing something about it. They have an abnormal calcium score, but they're MPO or HSC or P are normal. Doesn't mean you shouldn't be doing something about it. It's what their near term risk is because vulnerable plaque is the nearest term risk we can have compared to a, you know, stable calcified plaque.
- [16:38]
A
Thank you, Dr. Penn. So to round out our conversation today, let's speak a little bit about the utility of a calcium score and biomarker testing in assessing a patient's risk beyond purely cardiovascular. How do these risk markers predict cardiometabolic disease more globally?
- [16:56]
C
Yeah. So, you know, patients who have high calcium scores fall into one of two buckets, in a general sense, maybe three. The first bucket is, you know, some familial driver of cad. So familial hypercholesterolemia, heterozygous high lp, things of that nature. The second bucket is it's really a cardiac problem, which is becoming less and less common these days. Right. So they were a smoker for 30 years. They're hypercharostolemic, they don't exercise things of that nature. And then there's the most common, really driver these days, which is cardiometabolic disease. And if they have cardiometabolic disease, BMI above 27, fasting blood sugar above 100, and A1C above 5, you know, things of that nature. Now we need to really assess the cardiometabolic disease paradigm, which is currently the liver, the heart, and the kidneys. And I would argue one day will be the brain for dementia. And so then in that setting, we really need to look at blood sugars again. A1C above 5 starts to drive increased risk of having a positive insulin resistance score. It drives increased risk of an elevated myeloperoxidase, increased risk of abnormal albumin creatinine ratio in the urine, abnormal fib 4. So we need to take a cardiometabolic approach desilo the assessment, meaning I'm not just looking for heart issues anymore, I'm looking for cardiometabolic issues and then getting aggressively treating those things, which will normalize the biomarkers that started the whole process of cardiovascular disease, but will also prevent the patient from progressing their cardiometabolic disease.
- [18:42]
A
Excellent. Well, thank you both so much for joining me. That was so interesting, and I'm looking forward to the next one.
- [18:48]
C
Super. All right, good seeing you.
- [18:50]
B
Thanks for having me, Mason.
- [18:57]
A
That's a wrap on this episode of Healthier World with Quest Diagnostics. Please follow us on your favorite podcast app and be sure to check out Quest Diagnostics Clinical Education center for more resources, including educational webinars and research publications. Thank you for joining us today as we work to create a healthier world, one life at a time.