CAC Scores, Lp(a), CRP: CV Screening in Real Life

This transcript has been edited for clarity.

Matthew J. Budoff, MD: Welcome and thank you, everybody, for joining us today. I am Matt Budoff, a preventive cardiologist at the UCLA School of Medicine, and my primary practice is at the Lundquist Institute in Torrance, California. I'm joined today by Seth Baum, a cardiologist and clinical lipidologist in Boca Raton, Florida. He is a professor at the Florida Atlantic University College of Medicine and past president of the American Society for Preventive Cardiology. Today we would like to discuss screening for heart disease, including updates from the prevention and cholesterol guidelines.

New American College of Cardiology/American Heart Association guidelines came out in 2018. They more strongly advocated for screening and recommended generally lower lipid targets than 2013. They more strongly advocated for identifying patients at high risk and getting them on appropriate lipid-lowering therapies and potentially more aggressive lipid-lowering therapies. So with that in mind, I wanted to start by briefly discussing where coronary artery calcium (CAC) score may fit in and then open it up to Dr Baum to discuss some clinical cases and where such things as C-reactive protein (CRP), lipoprotein(a) (Lp[a]), and other screening tests may fit into the algorithm.

Coronary Artery Calcium Screening

Budoff: On the basis of the guidelines and a 2A recommendation, CAC screening is supposed to be used now in a pretty broad-based population: those between 5% and 20% cardiovascular risk where there is any discrepancy over whether or not patients should be on therapy. On the basis of a physician-patient discussion, if there is some indecision left about whether or not the patient would benefit from statin therapy, then a CAC score is more actively and more highly advocated for than it has been in the past. That is very appropriate because seeing the plaque in the coronary arteries is not only a great way to adjudicate whether somebody has atherosclerosis, but more important, it acts as a great motivator for the patient to start their preventive therapies. It goes beyond taking a statin therapy; it's diet, it's exercise, it's healthy living in general. There may be blood pressure medications or antiplatelet therapies that are considered. Patients can undertake a host of things once they have identified themselves as having atherosclerosis and have been shown that, although they feel fine, they have some plaque in their coronaries. This is really eye-opening for a lot of patients.

Let me turn it over to Dr Baum and see whether he has comments on how he has been using coronary calcium scoring and other tests in his practice as well.

Seth J. Baum, MD, FACC, FACPM, FAHA, FNLA, FASPC: First of all, your discussion was wonderful. I agree with everything you just said, especially the aspect of it being a motivator for patients if they see calcium in their coronaries. It clearly does that. It's also been documented in clinical studies that this happens. But on a personal note, I've seen it happen many times where patients see the calcium in their coronaries and become very activated.

Another aspect of our 2018 guidelines is that they have added some clinical dimensions and have definitely personalized our approach to medicine. They made it more of precision medicine, or however you want to call that. But interestingly, in my practice for a number of years, outside the guidelines I've been doing coronary CT angiography on my patients as I would CAC scoring. We get a CAC score and a CT angiogram as long as the patient does not have renal impairment or a history of allergies to contrast. And what that has done for me at times is identify the very small percentage of people who have soft plaque and no calcium, or sometimes you'll get a greater flavor than just a calcium score. You can see mixed plaquing. You can see high-risk plaque with positive remodeling or specific patterns of calcification.

I'll share a couple of examples with you that I'm sure you have seen many times in your own practice. I had one patient with what I thought was familial hypercholesterolemia (FH). Her low-density lipoprotein (LDL) cholesterol was only in the 150s, but from a family standpoint, it seemed that she had FH. This woman did not want to take statins; she was adamant that no way was a statin going to cross her lips. I got a calcium score with CT angiogram, and lo and behold, the calcium score was zero. But there were multiple soft large plaques in the right coronary artery (RCA) and the left anterior descending (LAD) artery, which were very motivating. Now I was able to get her on therapy. Interestingly, she actually did have an FH mutation on the allele receptor. So here is somebody who would have fit potentially in a calcium score category of zero, meaning maybe don't treat, although the family history would push you to treat anyway. But some might interpret it differently. A couple other patients come to mind with calcium scores of zero. It's always the "not wanting statin" people with significant soft plaque and associated hypertension in a couple of other patients. That is where I am. I'd love to hear your opinion about adding CT angiography to your calcium score.

Budoff: As you outlined, calcium scores are not a perfect test. It has a high sensitivity for plaque, but it's not 100%. We do low-dose radiation CT angiography in younger patients where we know a calcium score may not be the best test. [Younger being] age under 40; some people even say age under 45 years old. You might get a false-negative calcium score (it will be zero), but they have plaque or even stenosis. So, I have less confidence in a calcium score in the young.

These patients whom you described either with FH or bad family history where I'm nervous about their atherosclerotic burden, I can rely on a calcium score alone. If the calcium score is positive that is pretty good, because I don't need to know if they have a 50% lesion in the mid-LAD. I'm not going to put a stent in that anymore. That was something that we did a while ago, and I don't think it's as necessary unless they are having angina. So, for our asymptomatic patient, I'm pretty comfortable if the calcium score is positive to get therapy started.

Baum: Would you add women to your calculus there? You said younger patients, but how about women?

Budoff: Before menopause for sure. Maybe that 10-year lag. For premenopausal women or men under the age of 45, I'm a little bit more nervous about a zero CAC score.

C-Reactive Protein and Lipoprotein(a)

Budoff: Where do you put CRP and Lp(a)?

Baum: I like CRP. Obviously we have a lot of data, but certainly CRP is so variable. You can get a CRP on somebody and it's 2 mg/L but the next week, it's 0.1 mg/L. It's not nearly as strong as the calcium score. Lp(a) is very valuable, especially if you have an unexplained family history. But even absent that, it helps in a holistic risk assessment, because if you have an elevated Lp(a) in addition to LDL and hypertension or whatever, it certainly dramatically increases your risk. We know we can't do anything other than treat risk factors very aggressively. Right now, the current major trial does not include primary prevention so you don't even have that option. So that is really it — you are going to maximize therapy even more. And it's a motivator, just like you said. That is how I use it.

Budoff: Both are so easy to get now relative to when they used to be fairly complicated or not always available at your local labs. I do like them both. I sometimes get a Lp(a) after I get a calcium score that is positive and kind of an unexplained high calcium score. Sometimes I'll go looking for the cause. And you are right, it's still a bit problematic because we don't have all of these new therapies that are being developed yet available for the primary prevention population. But I do think identifying them with Lp(a) at least gets me motivated to get that LDL even lower than I might have otherwise pushed it. In primary prevention, I'll now push the LDL well below 70 mg/dL. Whereas, if everything else was okay, I might just leave it a little bit higher than that if they are doing well. So it does get me aiming lower for my LDL.

Aspirin

Baum: Does that also increase the likelihood that you are going to use aspirin in a primary prevention patient?

Budoff: I definitely like aspirin for a calcium score above 100 Hounsfield units (HU). The data are quite good. Their short-term risk is higher, and their short-term risk exceeds their bleeding risk. I think the risk benefit is there. So, a calcium score above 100 HU for me is an easy cut point. I think for those patients with Lp(a), because it does elevate risk for heart attack a stroke, a baby aspirin probably is a good idea. For patients with more risk factors or higher CV risk, I can calculate the risk benefit of being on a low-dose aspirin.

Interpreting the CAC Score

Baum: I use it that way as well. You are one of the world's authorities on the calcium score. What do you say to a patient who has a calcium score of 1, and the patient says, "It's just 1; it doesn't mean anything."

Budoff: It obviously depends on the host as well. If they are older, I agree with them. If they are after menopause or men in their 60s or even in their 50s, I would say, "One is a good number. Let's check it again in a few years just to make sure we're not starting some rapid progression process." If they are younger, I'd say that 1 is a bad number. I would say that they should have zero and 1 is now the beginning of atherosclerosis. If there is still a lot of back and forth, that might be a good place to get a CT angiogram. If you can get a low-dose CT angiogram and you see a lot of soft plaque, then 1 is the tip of the iceberg. If you see everything is clear as a bell and there is just a speck somewhere or you don't even see the speck anymore, then you know there is not much going on. Sometimes it does take a little adjudication. A score of 1 to 5 is a little bit of a tough place right now to be adamant one way or the other.

Radiation Exposure in Testing

Baum: You keep mentioning low-dose CT. My understanding was that pretty much around the country, all CTs — or most — are now low-dose.

Budoff: Most. A few centers are still using some of the older technology and old 64-slice scanners without dose reduction software. You could be giving the dose that is equivalent to a nuclear test if you do it wrong. I would just make sure that wherever you are sending your patient, it's at least reasonable. A 64-slice scanner is great because they have dose-reduction software. You can get a scan for 2 millisieverts (mSv), which is less than background radiation for a year. But if the center that you are sending them is averaging 15 mSv, kind of like a nuclear scan, I might not be as cavalier. I'd certainly think twice about giving a younger person 15 mSv without more provocation.

Baum: Right. That brings home the point of the nuclear stress test. A lot of patients think that the nuclear stress test is okay from a radiation standpoint and coronary CT angiography is not. Whereas in a good low-dose center, you can do it for a mSv or even less and 15 mSv for a nuclear scan. Patients are shocked by that. Sometimes clinicians are surprised by that as well. What are your thoughts on that?

Budoff: CT angiography never averaged over about 15 mSv. It was always the same as nuclear back in the early days. And then it just kept getting better, and nuclear didn't come down quite as much. It's just old thinking. Some older docs out there have it in their head that CT angiography is really high-dose and nuclear is "safe" because they have been doing it for so long, yet they don't even know the radiation exposures. If you ask them what is their average nuclear exposure, they have no idea. They would guess low; they would guess single digits and they would be way off probably unless somebody is doing a PET scan, which would be a very expensive way to work up a primary prevention case. But you could keep the dose down with PET.

We're coming up on the on the end of the session here. I wanted to thank everybody for joining us today. Thanks to Dr Baum for his clinical insights. It's always great to see him, at least virtually, and hopefully we will all be back together soon enough. Again, thank you, everybody, for joining us today.

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