Physician details biomarkers research, clinical applications

James L. Januzzi, MD, is an expert on cardiac biomarker testing with more than 400 publications on the topic, according to his Massachusetts General Hospital profile.

Based on Januzzi’s schedule at the 2017 American Heart Association’s Scientific Sessions, he isn’t exactly slowing down. The cardiologist presented studies on the diagnostic and prognostic utility of highly sensitive cardiac troponin tests for coronary artery disease (CAD), the development of a multi-marker panel for the diagnosis of peripheral artery disease (PAD) and the importance of testing a patient’s biomarkers multiple times rather than just once.

During the conference, Januzzi spoke with Cardiovascular Business about his latest research and where he sees the biomarker field heading in the next few years. Here are three key takeaways from that conversation.

1. Highly sensitive troponin I (hsTnI) testing is underutilized.

Januzzi presented two studies evaluating hsTnI testing—one in patients with stable angina and one in patients who presented with an acute coronary event.

While cardiac troponin is usually measured in cases of MI, Januzzi and colleagues’ research suggests it could be useful to test for hsTnI in patients with stable chest pain as well. In 991 patients without acute MI who had coronary angiography and blood testing performed, those with hsTnI levels at or above the 99^th percentile (6 nanograms per liter) demonstrated 2.68 times the risk of MI and 2.29 times the risk of cardiovascular death over a median 1,486 days of follow-up when compared to patients below that hsTnI cutoff.

In addition, Januzzi and colleagues found the incidence of MI was higher in non-obstructive CAD patients (between 0 and 70 percent stenosis) with hsTnI levels above 6 ng/L than obstructive CAD patients (stenosis of at least 70 percent) with lower hsTnI readings.

“Even in a population of patients without myocardial infarction, the troponin test that we use—which is an extraordinarily highly sensitive assay—was able to identify patients that had significant underlying coronary artery disease and who had a worse prognosis,” Januzzi said. “Troponins may not just be for patients with suspected myocardial infarction. There may be a broader application for these tests even in patients with less acute syndromes.”

2. Biomarkers could have diagnostic utility for PAD.

After considering more than 50 clinical variables and 109 biomarkers, Januzzi and colleagues developed a risk-stratification tool based on seven components: hypertension, midkine, follicle-stimulating hormone, angiopoietin-1, eotaxin-1, kidney injury molecule-1 and interleukin-23.

In a study of 355 individuals, meeting criteria for five of these components was associated with an 86 percent chance of having PAD. The likelihood of PAD was 59 percent with four components, 32 percent with three components, 10 percent with two criteria and 2 percent with just one component. PAD was validated using peripheral angiography.

“We identified a panel of several markers, which together, was very, very accurate for identifying or excluding the presence of obstructive peripheral arterial disease,” Januzzi said. “This provides proof of concept that a multiple-marker diagnostic strategy may be very useful for the clinician seeing patients in the office who may have lower-extremity symptoms. Rather than sending them for a magnetic resonance imaging study, we might be able to send them for a simple blood test and be able to help make that diagnosis.”

Januzzi said his team is currently working on multi-panel tests to diagnose valvular aortic stenosis and to identify the risk for amputation in patients with PAD.

“The era of precision medicine has arrived in cardiology and the use of biomarkers as the precision tool to identify disease and more accurately triage patients to therapy has really arrived,” he said.

3. The next frontier is moving beyond risk stratification and into biomarker-driven preventative medicine.

“We can now measure troponin even in patients without acute symptoms and when we look at the results of those tests, it suggests that an elevated value in an apparently healthy person, which may not be very significant in terms of how high the test is, identifies underlying structural heart disease in these people,” Januzzi said. “This argues for an intervention study now—more aggressively targeting lipids, more aggressive management of blood pressure, blood glucose and other risk factors with the hope that we can prevent an incident event.”

Januzzi predicted the pharmaceutical industry will ultimately contribute to a more widespread adoption of biomarkers in clinical practice.

“What’s making us optimistic in the biomarker world is that multiple sponsors of clinical trials are now looking at the question of precision medicine in cardiology much more seriously,” he said. “For one reason or another over the last several years there’s an increasing recognition of the fact that a one-size-fits-all approach for treating patients with heart disease is no longer going to work and individualizing care on the basis of objective tests like biomarkers would help deliver the right treatment to the right patient at the right time.

“In this regard, I really do envision in the next several years a sea change with respect to how drug companies market their medications, specifically arguing for … targeting their applications and using biomarkers as one way of selecting which patients should be treated.”