Troponin and CAC Score for Predicting ASCVD Risk

In this podcast, Michael Blaha, MD, MPH, discusses his team’s study on whether troponin levels and coronary artery calcium score can predict future atherosclerotic cardiovascular disease risk, the use of aspirin and statins in patients aged 50 to 79 years, and his team’s future work in this area. 

Additional Resources:

• Sandoval Y, Bielinski SJ, Daniels LB, et al. Atherosclerotic cardiovascular disease risk stratification based on measurements of troponin and coronary artery calcium. J Am Coll Cardiol. 2020;76(4):357-370. https://doi.org/10.1016/j.jacc.2020.05.057 
• Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guidelines on the primary prevention of cardiovascular disease. Circulation. 2019;140(11):e596-e646. https://doi.org/10.1161/CIR.0000000000000678 

Michael Blaha, MD, MPH, is a professor of medicine in epidemiology and director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, Maryland.

TRANSCRIPTION:

Amanda Balbi: Hi everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360 Specialty Network.

Low values of high-sensitivity cardiac troponin and coronary artery calcium scores of zero are associated with a low risk for atherosclerotic cardiovascular disease (or ASCVD). To better understand the relationship between these measurements and future ASCVD risk, a group of researchers evaluated baseline high-sensitivity cardiac troponin and CAC measurements taken from 6749 participants in the MESA study. Participants were aged 45 to 84 years and did not have clinical cardiovascular disease in relationship to incident ASCVD.

Here with us today to discuss his team’s research and their findings is Dr Michael Blaha, who is a professor of medicine in epidemiology and director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, Maryland.

Thank you for joining us today, Dr Blaha. Let’s dive in.

To start, can you tell us more about how the study was conducted and why it is important?

Michael Blaha: Sure. Well, in the primary prevention of cardiovascular disease, we're always looking to conduct risk stratification to figure out who's low risk and who's high risk, because those patients that are low risk may not benefit from our aggressive medical therapies, while patients that are high risk might get more benefit from our therapies.

So, this is a study of risk stratification in middle-ages to older adults. Mean age was about 60, and this is from the Multi-Ethnic Studies of Atherosclerosis, where there's baseline measures of cardiac proponent, of course, serum marker and coronary artery calcium, which is derived from cardiac-gated CT scan.

And really thinking here was to figure out how each marker performed—the troponin and the calcium score—for risk prediction and how they perform together, with a distinct emphasis on low values of each marker—undetectable troponin values and calcium scores of zero—and to what degree those can discriminate patients that are actually low-risk patients.

Amanda Balbi: Your analysis found that detectable CAC and detectable high-sensitivity cardiac troponin was associated with higher rates of ASCVD, compared to undetectable levels. Did any of these findings surprise you?

Michael Blaha: I don't think it would surprise anyone that higher levels of troponin and higher levels of calcium scores predict risk. In fact, these tasks are quite familiar to most clinicians and routinely used to identify higher-risk patients. However, what's not as well known, or perhaps not as often used by clinicians, is these risks markers as so-called “negative risk factors” as markers that drive down a patient's risk compared to what you would have been expecting before the test was done.

On the converse, while the troponin and the calcium score both predicted risk well. What was also notable is that undetectable levels of troponin or calcium scores of zero also predicted extremely low-risk states.

Calcium score and undetectable troponins were associated event rates that were lower than the usual threshold considered for a statin benefit or aspirin benefit in primary prevention. So, the study would suggest that the event rates in patients with undetectable troponin or calcium scores of zero are below which we’d expect there to be a net benefit of preventive pharmacotherapy.

But what's notable also is that when you do a 2 × 2 cross tab of these markers, patients who had both undetectable troponin and a calcium score of zero had the lowest event rates on the order of 2% or 3% over 10 years, which is very low. So, it shows that these markers are both good independent negative risk factors and, when combined, can identify very-low-risk patients.

Amanda Balbi: How might your findings impact clinical practice and how ASCVD can be prevented in the future?

Michael Blaha: Well, we're all looking ways to make preventive practice more precision based. There are strategies that you can apply at the whole population level, but many times we're looking for therapies that are targeted at high-risk individuals so we can spare low-risk individuals the same level of aggressive therapy.

Now in the guidelines—the ACC/AHA prevention guidelines—the calcium score is already in there as a 2a recommendation for patients with borderline to intermediate risk and specific notes on the calcium score zero, for example, that you can defer, postpone, or withdraw therapy in select patients.

So, what’s new here is that the troponin could also be used in a similar way. This is the high-sensitivity modern troponin asset, and if high-sensitivity troponin assay is undetectable, maybe also you can consider being less aggressive with therapy. If you use these 2 markers together, we can come up with more-precision pattern here.

Or if you're negative on both markers, you’re obviously a low-risk patient. But also if you're high on both markers, you're a very, very high-risk patient. And if you're discordant you're somewhere in between. So, we can pinpoint with these two markers patients that are very high risk and patients that are very low risk that are clearly above or clearly below what we think are preventive therapy thresholds for benefit.

So, what's new here is that we might be pointing to a future of using these 2 markers together in future guidelines.

Amanda Balbi: What is the overall key take-home message from your study?

Michael Blaha: The key take home is that we're getting better with risk prediction over time. Really, the combination of the best serum biomarker of vulnerability—troponin—and the best marker of atherosclerosis burden—the calcium score together can do wonders for risk prediction on top of the pooled cohort equations.

So, I think we're pointing toward more of a future where we're going to be more precise with our therapies, not just statins and aspirin, but other more aggressive, expensive preventive therapies can be targeted at the right patients, who maybe have abnormal values of troponin and high calcium scores in primary prevention.

We're going to be more conservative and lifestyle based in patients who are very low risk, rather than a treat-all approach where we treat everyone, for example, with a statin or aspirin. We can be focused.

So that's the take home. We should be in our practice right now thinking about using the calcium score as per guidelines and potentially high-sensitivity troponin when treatment decisions are unclear and primary prevention to really eek out the risk and make more-educated decisions with our patients about who's most likely to benefit from our therapies. In particular, who's most likely to benefit from our more-expensive add-on therapies, for example, non-statin add-on therapies like ezetimibe, [inaudible 7:30], or PCSK9 inhibitors or other therapies that may be coming down the road.

I think it's intriguing. I think also what we're going to see in the future is more emphasis on risk prediction in older adults, where in the past, we might not have done risk prediction. I think that troponins and calcium scores might be particularly valuable in patients even over the age of 60 or 70; which of those patients are actually lower-risk patients, despite their age.

Amanda Balbi: Absolutely, because CAC is more common in older adults, correct?

Michael Blaha: Yeah, both troponins and the calcium score go up with age, and they're more likely to be abnormal the older you are. Therefore, as one ages, if they were able to maintain favorable measures of both of these markers no or low atherosclerosis burden and undetectable troponin.

It really shows that even at an older age we’re able to find patients who are truly low cardiovascular risk. So, I think the future will hold more-precise thinking about risk and therapy, even in very old adults, where the guidelines are relatively mute on risk assessment after the age of, let's say, 75 or 79.

That's coming down the road with, I think, you'll see more data on calcium scores and troponin from future studies in the next couple years.

Amanda Balbi: You also spoke before about aspirin and preventing ASCVD with aspirin. I think it was the AHA guidelines from last year that downgraded low-dose aspirin use for preventing cardiovascular disease. What are your thoughts on the guideline in relation to your study?

Michael Blaha: You're right that the new ACC/AHA guidelines did downgrade aspirin from a 2a recommendation to 2b recommendation in 50 to 70-year-olds who are at higher risk of cardiovascular disease with low bleeding risk. So, it doesn't say don't use aspirin; what they say is use aspirin selectively after careful risk assessment and assessment of bleeding risk.

As some readers and some listeners may know, we've published data that suggests that only those patients with calcium scores above 100 get a net benefit from preventive aspirin therapy. If your calcium score is zero, for example, you're more likely to be harmed from aspirin than helped. And that's in the paper that’s in Circulation from a few months ago.

Now combining these markers—the calcium score and troponin—if you had a calcium score of 100 and a detectable troponin, I think it's even more likely that you were to benefit from an aspirin, and if you're negative values or undetectable values of troponin and a calcium score of zero, you're even more likely to be harmed, rather than helped, with an aspirin.

So we can see how we can use these markers for a therapy like aspirin that has some benefit and has some rest [in order] to tailor who should get it in our practice.

Amanda Balbi: So then what about people younger than 50 years?

Michael Blaha: If you're less than 50, we're going to really selectively use aspirin. However, the calcium score can be particularly helpful here in identifying just those few patients below the age of 50 to do have high calcium scores.

For example, scores above 100 or our data would suggest even scores that are less than that in the young patients might identify patients that have benefited from aspirin. I don't think that high sensitivity troponin is good of a test in the younger patients as it is in middle-aged or older patients, but the calcium score can be particularly helpful in patients with high pre-test probability of atherosclerosis at the young age.

There's good data in the 30- to 50-year-old age group for selective use of calcium score in your direction of statin and aspirin. So I think, really, if you're thinking about the life course, earlier in life I think a calcium score makes sense if you need further risk stratification.

In middle age, high-sensitivity troponin also has some value, and as one ages, if risk assessment is still desired, a combination of a calcium score and troponin can be particularly helpful.

Amanda Balbi: Great. And so, what research are you working on now?

Michael Blaha: Yeah, I think the next step after this study, which shows that the troponin and the calcium score predict risk well, is to actually show if they can identify patients who will get benefit from preventive therapy.

So, what we're looking to do is add calcium score testing and high-sensitivity troponin testing to future clinical trials of aspirin and statins in older adults, some of which are about to start enrolling. If we have those measures of troponin and the calcium score baseline, then at the end of the trial, we can look back and say who benefited from aspirin and who benefited from statins at an older age. Could we have predicted that or sharpen that by use of these biomarkers?

So if these measures are measured in a blinded way at the beginning of a study, it’ll provide immense insight at the end of the study about who actually benefited. So, that's what we're working on next—translating this directly to the bedside just looking at how these tests can be used to derive who gets the most benefit from these preventive therapies in a randomized clinical trial.

Amanda Balbi: Great. We’ll definitely keep an eye out for that research as well. Thank you so much for joining me today and answering my questions.

Michael Blaha: It's my pleasure to join your podcast and talk about our new study.