Association Between Changes in Serial Values of hsTn, Subsequent Cardiovascular Events

In this podcast, Robert P. Guigliano, MD, SM, discusses the findings from a secondary analysis from the IMPROVE-IT study on the association of serial high-sensitivity cardiac troponin T with subsequent cardiovascular events in patients stabilized after acute coronary syndrome, including if it is worthwhile to measure troponin and how often.

Additional Resource:

• Patel SM, Qamar A, Giugliano RP, et al. Association of serial high-sensitivity cardiac troponin t with subsequent cardiovascular events in patients stabilized after acute coronary syndrome: a secondary analysis from IMPROVE-IT. JAMA Cardiol. 2022;7(12):1199-1206. doi:10.1001/jamacardio.2022.3627

Robert P. Giugliano, MD, SM, is a senior investigator at the TIMI Study Group at the Brigham and Women’s Hospital, a staff physician in the Cardiovascular Division at Harvard Medical School, and an associate professor of medicine at Harvard Medical School (Boston, Massachusetts). 

TRANSCRIPTION:

Jessica Bard:

Hello, everyone. And welcome to another installment of Podcast360, your go-to resource for medical news and clinical updates. I'm your moderator, Jessica Bard, with Consultant360, a multidisciplinary medical information network. Dr Robert Guigliano is here to speak with us today about the findings from a secondary analysis from the IMPROVE-IT study on the association of serial high-sensitivity cardiac troponin T with subsequent cardiovascular events in patients stabilized after acute coronary syndrome.

Dr Robert P. Guigliano:

Thank you for the invitation today. My name is Robert Guigliano. I'm a cardiologist at the Brigham and Women's Hospital and a senior investigator with the TIMI Study Group here in Boston. And I not only see patients in the CCU, but also have an outpatient clinic at the Brigham and Women's Hospital and a professor at Harvard Medical School. So glad to be here today.

Jessica Bard:

Thank you for joining us today, Dr. Guigliano. Could you please provide us with an overview of your team's analysis?

Dr Robert P. Guigliano:

Right. Sure, no, I'm happy to spend a few minutes talking about this paper, which was published originally online in October of 2022 and came out in JAMA Cardiology in print in December 2022. This is one of many secondary papers from the IMPROVE-IT Trial, which many of the audience will know well. IMPROVE-IT stands for improved reduction of outcomes Vytorin efficacy international trial. And it was a study in over 18,000 patients hospitalized for an acute coronary syndrome who were randomized to either simvastatin alone or ezetimibe plus simvastatin. And it was placebo-controlled, double-blinded, and showed that ezetimibe reduced LDL cholesterol and reduced cardiovascular events during a meeting in a six years follow-up.

Now, as part of a large clinical trial, we collected blood samples, have been doing many secondary analyses and papers. And so this particular paper we're discussing today was an analysis of over 6,000 patients who had their blood collected at one month and four months into the trial. And high-sensitivity troponin was measured. This was a troponin T assay. And we just asked the question, do the troponin T levels at one and four months after a clinical trial, are they important or helpful for prognostication? And we ended up focusing in really on the change in troponin, which was an important predictor of worse outcomes, worse cardiovascular outcomes. If your troponin was rising, particularly if there was a large rise, that was a bad sign for the patient.

Jessica Bard:

So of course we're talking about, is it worthwhile to measure troponin? What would you say? Could you elaborate more on the results of this analysis?

Dr Robert P. Guigliano:

Yeah, sure. So I would say first in standard practice, at least in my area, it's not standard or routine in outpatients to measure troponin for prognostication. We use it in the emergency department to identify myocardial infarction or myocardial injury. We obviously use it in the hospital to understand who's having an infarct or where they are in the infarct, and are they recovering? But now we're talking about measuring it in stable outpatients who have had a recent acute coronary syndrome. And in fact, if you try to do that at our institution, you'll even get a warning saying, "Do you really want to measure the troponin in an outpatient? It's not designed for that." So we're breaking new ground here by measuring it one and four months post-ACS. And noticed that, first of all, high troponin even in stabilized patients is not a good thing, higher rates of cardiovascular events.

And furthermore, if you look at the change between month one and month four, those who had no change had pretty low event rates, those who had a moderate change on this particular assay between three and seven nanograms per liter had worse cardiovascular outcomes. And the group that really had the highest event rates were those who had an increase of more than seven nanograms per liter. And we analyzed it in all different ways, different cut points, and so forth, and found pretty consistent results that the larger the absolute increase, the worst the prognosis. And then there were some patients who had a decrease, and those patients tended to do better with lower event rates than those that increased. So kind of an interesting novel application of a troponin assay in outpatients after acute coronary syndromes.

Jessica Bard:

Now, you mentioned that it's not always common to measure troponin. What would you say are the gaps in the research of troponin and subsequent cardiovascular events? And what would you say is next for research on this topic?

Dr Robert P. Guigliano:

Yeah. Well, troponin was designed to help us identify patients who are having a myocardial infarction, and then has been proven useful in other cardiovascular diagnoses like a pulmonary embolism to identify high-risk PE, to identify patients who have other causes of myocardial injury or necrosis, like myopericarditis, acute cardiomyopathies, takotsubo syndrome. So it's very useful in the ED and in the inpatient setting. This is one of the first applications in an outpatient setting and with the use of serial troponins. And so we have in this paper a little over 6,000 patients with values at month one and month four. But is this something we ought to be measuring at month 12, yearly thereafter? Is it a marker you want to continue to follow? And in which patients? And how do you interpret that? All that remains to be determined. But this is kind of just the first chapter in the outpacing use of serial troponins to say, "Hey, this biomarker could be useful to follow in patients with chronic coronary disease."

Jessica Bard:

What would you say are the overall take-home messages from this analysis and from our conversation today?

Dr Robert P. Guigliano:

Yeah. I would say the take-home message would be these cardiac biomarkers, like troponin, and we didn't discuss BNP because that wasn't in this paper, but there's BNP, and there are other novel markers. Keep an eye on this space because we're beginning to see that the biomarkers we use and research and in the hospital may also play an important role in the outpatient setting. And specifically, the take-home message from this paper is, if you have a stable patient following acute coronary syndrome, measuring serial troponin, and here we did it at month one and four, but I think likely you could expand that out, that changes in troponin are associated with a gradient of risk. And if you start low and remain low, then that's a low-risk situation. If you're low to high or you start high and you remain high, particularly if you're increasing, that indicates a patient who is at high risk for additional cardiovascular events in the future. And in the future means, in this trial, a six-year average follow-up.

Jessica Bard:

Now, we know there are several secondary analyses from IMPROVE-IT. Is there anything that you'd like to talk about that's next in the analysis of the data or other important papers that you'd like to mention?

Dr Robert P. Guigliano:

Yes. Well, IMPROVE-IT was one of the many large TIMI trials that we have run, this one in partnership with Duke Clinical Research Institute. And like many of the trials, large cardiovascular outcome trials, there's a wealth of data. You have lots of patients in order to maximize the experience. And being in a clinical trial, we'll often measure blood samples including genetics and look at various biomarkers or look at other types of imaging studies, what have you. This phase of IMPROVE-IT, which is a trial that started, geez, now we're talking about 17 years ago, enrolled and then followed for six years and reported out about a decade ago. We've certainly published many papers and we're now focusing on novel biomarkers, so the blood samples we have. And in particular, the genetics because that's a field that's very exciting and novel. And we're continuing to learn from analyzing genetics and tying those into the clinical outcomes.

Jessica Bard:

Well, thank you so much for all of your work on this and for joining us in the podcast. Is there anything else that you'd like to add that you think we missed?

Dr Robert P. Guigliano:

I mean, I would just say that, for the listeners, this is a two-way street. That we're very happy to participate in these types of discussions and share with you the new data. But a lot of the listeners will have interesting ideas. And a lot of the advances in science occur when you're in clinical practice and you have a question that's related to a patient. And certainly, feel free to share those either with me or other members of our group. And who knows, we may work together on one of your ideas one day.

Jessica Bard:

Well, thank you Dr. Guigliano. It was a pleasure speaking with you.

Dr Robert P. Guigliano:

All right, thank you