Dynamic Troponin Changes Unreliable for MI in Acute Stroke

In patients with acute ischemic stroke and elevated high-sensitivity cardiac troponin (hs-cTn), dynamic changes in hs-cTn are not helpful in identifying myocardial infarction (MI) or distinguishing MI from other causes of acute myocardial injury, results of the PRAISE study showed. 

In contrast, the absolute hs-cTn value on admission provides better diagnostic clarity and was independently associated with atherosclerotic (type 1) MI, which was relatively common in this cohort of patients with acute ischemic stroke and elevated hs-cTn levels.

“We were surprised by the large number of type 1 MI diagnosed by the blinded endpoint adjudication committee,” lead investigator Christian H. Nolte, MD, director, Center for Stroke Research Berlin and Charité-Universitätsmedizin Berlin, Germany, told Medscape Medical News.

“This, of course, has consequences for our patients as MI may both be a cause or consequence of stroke. The source of a substantial portion of embolic strokes of as yet undetermined source could in fact be unrecognized myocardial infarctions,” said Nolte.

Results of the PRAISE study were published online on June 3, 2024, in JAMA Neurology. 

Diagnostic Uncertainty

Elevated levels of hs-cTn are common in patients with acute ischemic stroke and are associated with poor prognosis. Current guidelines recommend routine hs-cTn measurements in patients with acute ischemic stroke, but the implications for subsequent diagnosis and treatment of MI remain unclear. 

The aim of the PRAISE study was to clarify the significance of hs-cTn elevation and its time course for the diagnosis of MI and type 1 MI in acute ischemic stroke. 

The primary hypothesis was that a dynamic change (rise and/or fall) of hs-cTn values (> 50% change at repeated measurements) in patients with acute ischemic stroke and elevated hs-cTn indicates MI.

Participants included 254 patients from 26 sites in Germany admitted for acute ischemic stroke within 72 hours of symptom onset. 

Patients were eligible if they had either highly elevated hs-cTn values on admission above rule-in cutoffs to suspect non–ST-elevation MI (> 52 ng/L) or hs-cTn levels above the upper limit of normal and a > 20% change at repeated measurements. 

All patients underwent cardiac catheterization, and the outcome of acute MI was adjudicated in 247 patients (median age, 75 years; 53% men) by a team of cardiologists blinded to the troponin level.

MI was diagnosed in 126 out of 247 patients (51%), with 50 patients (20%) classified as having type 1 MI. In roughly two thirds (65%) of patients diagnosed with MI, coronary artery disease (CAD) was unknown before coronary angiography.

The predefined change of hs-cTn was detected in 85 patients (34%). A dynamic hs-cTn change > 50% was not associated with the diagnosis of MI (diagnostic odds ratio [OR], 0.76; 95% CI, 0.45-1.28; primary hypothesis).

In sensitivity analyses, dynamic hs-cTn changes with a threshold > 20% (OR, 0.78; 95% CI, 0.47-1.29) or any cutoff between 0% and 100% for relative hs-cTn changes did not improve the association with MI. There was no interaction between receipt of intravenous thrombolysis and a dynamic change in hs-cTn. 

In contrast, baseline absolute hs-cTn values on admission were independently associated with type 1 MI (OR, 1.35; 95% CI, 1.07-1.70; P = .01) with the best cutoffs for predicting type 1 MI being 5-10 times the upper limit of normal.

These findings suggest that in patients with acute ischemic stroke, dynamic hs-cTn changes indicative of acute myocardial injury are “not suitable” for detecting MI, and do not distinguish between different mechanisms of acute myocardial injury, the investigators noted. 

The finding that most patients did not have known CAD suggests a high prevalence of silent CAD in patients with stroke, they added.

“Our data suggest that more patients with acute stroke should be evaluated accordingly. Timely evaluation for and treatment of concomitant CAD and MI may help reduce the risk of future cardiovascular events in these patients,” they wrote.

How to select patients with stroke and elevated hs-cTn for coronary angiography requires further exploration, they added.

“From our point of view, a randomized clinical trial of early cardiac intervention for patients with acute ischemic stroke with elevated troponin vs standard of care is warranted. We are currently working on securing the funds,” said Nolte. 

The investigators acknowledged several limitations of the PRAISE study, including the use of different hs-cTn assays at different study sites and inclusion of patients with predominantly with mild to moderate strokes, which limits generalizability to severe stroke. 

Striking Results, Significant Ramifications

“The most striking finding” of the PRAISE study is the high rate of type 1 MI found in patients with acute ischemic stroke with elevated hs-cTn, Alison Seitz, MD, and Alexander E. Merkler, MD, with Weill Cornell Medicine in New York, noted in an accompanying editorial.

“Regardless of causality, the results of the PRAISE study suggest that a substantial number of patients with acute ischemic stroke have an acute plaque rupture MI. These findings, if replicated, would have significant ramifications as even moderately elevated troponin values are often disregarded or simply ascribed to ‘the effects’ of stroke and not considered to represent an acute MI, which requires both pharmacological and procedural therapy,” Seitz and Merkler said. 

“Put another way, we may be depriving patients with elevated troponin both mechanical thrombectomy of their coronaries and pharmacotherapy to avoid adverse cardiovascular outcomes,” they added. 

Seitz and Merkler agree with the PRAISE study team that a randomized clinical trial of early cardiac intervention for patients with acute ischemic stroke with elevated troponin vs standard of care is warranted.

The PRAISE study was financed by joint funding from the German Centre for Cardiovascular Research and the German Center for Neurodegenerative Diseases. Nolte reported lecture fees and/or consultancies from Abbott, Alexion, AstraZeneca, Bayer Pharma, Bristol Myers Squibb, Daiichi Sankyo, Novartis, Pfizer Pharma, Portola, and Takeda. Seitz and Merkler had no relevant disclosures.