New findings show the addition of easily identified circulating proteins can provide a more accurate risk assessment.
James Januzzi, MD
A new study planned for presentation at the ACC.20 Together with Word Congress of Cardiology (ACC/WCC) Scientific Sessions this year showed a novel approach to assessing the risk of acute myocardial infarction in at-risk patients
The study, which found circulating proteins that could be used in combination with patient troponin levels to better identify myocardial event risk, bucked the normative expectation that troponin alone could confidently and consistently serve as a risk biomarker.
In an interview with HCPLive® on the study, study author James Januzzi, MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Massachusetts General Hospital, explained the continued refinement of myocardial risk assessment, the state of understood biomarkers, and how more pragmatic testing could benefit primary care.
HCPLive: What is the basis of the study? What was being sought?
Januzzi: So, the standard approach for evaluating patients with suspected acute myocardial infarction is a history and physical examination, as well as a 12-lead electrocardiogram. The problem is that standard meetings to evaluate patients for MI are limited. We've also turned to the use of blood tests of myocardial injury to identify the presence of myocardial injury as a reflection of the presence of a myocardial infarction. And, of course, the troponins are what we use for that indication.
The problem with troponin testing is that, number 1, there are a lot of things that may cause a myocardial injury besides a myocardial infarction. In addition, there are patients whose troponin results are ambiguous. They may be abnormal, but they may not be entirely diagnostic. And then lastly, there are patients who present with cardiac-related chest pains from a blocked-up artery who don't have abnormal troponin because they haven't had an MI—but they still have unstable angina. So, for all those reasons, we recognize that there is room for opportunity to improve the performance of troponin.
So, in that effort, we sought to identify, using targeted proteomics, circulating proteins that may be added together with troponin to improve this performance. And we did this with a population of patients presenting to the Massachusetts General Hospital Center for coronary angiogram. So, we knew who did and who did not have the presence of obstructed coronaries. And we measured over 109 proteins in the blood of these patients, as well as high-sensitivity troponin.
And what we did was we identified several proteins that were associated with the presence of blocked up coronary arteries, which when added together with troponin resulted in a very sensitive, very specific set of results to identify the presence of narrowed coronary arteries, far and away better than tripling alone, and actually helped to improve the diagnostic performance of troponin in those patients with ambiguous results. So this really sort of provides important evidence that troponin testing may be improved through the measurement of other circulating proteins that could be easily identified.
HCPLive: And this is a follow-up from a similar test results presented at AHA 2019?
Januzzi: That is exactly right. This is the next step off of the results that we discussed previously. What we recognized is that troponin is measured so widely, that it would make perfect sense to evaluate whether we could do the same approach, but utilize troponin as part of that story.
HCPLive: What sort of breakthrough would this mean, in terms of assessing risk? What does this mean in terms of being able to be more pragmatic about treatment approach, and understanding diagnoses a little bit better?
Januzzi: It illustrates the the inadequacies of troponin. While it is still the gold standard for identifying myocardial infarction, what we're doing is we're approaching the question differently. We're not asking, 'Is there myocardial injury present?' What we're asking is, 'Is there a blocked up artery?' Because really, that's why we're testing troponin in people with chest discomfort, right? We're looking for people with blocked up arteries. And so, our approach was to basically start with that answer and work backwards, and identify the predictors of a blocked artery. And it turns out that troponin was one of them. That actually provides useful information supporting the use of measurement of troponin in the setting, but we can do better. By adding other proteins together we can actually sharpen the performance.
HCPLive: What does preventive care currently look like for myocardial infarction?
Januzzi: I think it's fair to say that if we had the ability to identify non-invasively—the presence and severity of coronary disease—we can more precisely apply the therapies that we know are beneficial for preventing complications from coronary disease. So, for example, I would not as a non-evasive cardiologist—if I knew my patient had coronary artery disease, but they had no symptoms—I would not advocate for stress testing, I would not advocate for an anatomic definition. In other words, I would not get a coronary CT or an invasive coronary angiogram.
But, I would sit down and review all of the risk factors that we could treat in this patient, including diabetes, hypercholesterolemia, hypertension. We'd get them exercising, really do the things that may negate risk from coronary disease, that we know can change outcome. So, this really serves to more precisely guide the application of beneficial therapies in patients with coronary artery disease.
HCPLive: These findings, the development of refined assays, and individualized risk management—how exactly does this benefit primary care physicians?
Januzzi: It's a huge benefit, right? In people with stable coronary artery disease, I would be emphatic about pointing out that revascularisation strategies and stable coronary disease have actually not been shown to be superior to medical management. On the other hand, medical therapies to reduce risk in coronary disease are grossly under-deployed.
So, this allows for managing physicians to more confidently identify patients at risk for complications from their coronary artery disease and get those preventative measures on board. Not every patient with coronary disease needs to see a cardiologist. If they've got a primary care or family practice caregiver, comfortable in the preventative means to treat coronary disease in an asymptomatic person, then that would be a win for everybody.