Elevated levels of cardiac troponin (cTn) signal an increased risk of cardiovascular events even when the cause of that elevation is unknown, suggests a study published in the Journal of the American College of Cardiology.
“Despite a possibly unidentified etiology of myocardial injury, cTn elevation appears to demask myocardial vulnerability that portends to an increased long-term risk,” wrote lead author Kai M. Eggers, MD, PhD, with Uppsala University in Sweden, and colleagues.
The study included patients who were admitted to Swedish coronary care units between 2005 and August 2013 with suspected acute coronary syndrome but were discharged without a specific diagnosis. That left 48,872 patients, 20.1 percent of whom had cTn levels above the 99th percentile for their specific assays—a cutoff that has traditionally been used to rule-in or rule-out acute myocardial infarction.
Over a median follow-up of 4.9 years, one-quarter of the patients demonstrating that degree of myocardial injury experienced a major adverse event (MAE)—defined as all-cause mortality, nonfatal MI, stroke or readmission for heart failure—compared to only 13 percent of patients with troponin concentrations below the 99th percentile.
Patients in that top percentile were then further divided into tertiles based on their cTn levels, and individuals in the highest category showed a 2.6-fold increased risk of MAE compared to those with normal troponin concentrations. In a subcohort of patients without previous cardiovascular or coronary artery disease, renal dysfunction or left ventricular dysfunction, those in the top tertile of cTn had a 3.6-fold risk of MAE during follow-up versus those with troponin below the 99th percentile.
“Higher cTn levels were associated with constantly increasing MAE rates during long-term follow-up,” the researchers reported. “This was mainly driven by the risks of cardiovascular mortality, MI and readmissions for heart failure. About 1 in 3 patients with cTn levels in the highest assay-specific tertile suffered an event.”
The authors recommended additional workup be performed in patients with an unknown diagnosis but elevated troponin, including retesting with the same or another troponin assay and “liberal referral for echocardiography and invasive or noninvasive coronary imaging, depending on the individual pre-test probability of coronary artery disease.”
Writing in a related editorial, James L. Januzzi Jr., MD, and Cian P. McCarthy, MB BCh, BAO, agreed with the reasoning behind this recommendation but said an elevated cTn shouldn’t be an open license to perform a battery of tests.
“It is logical to consider such an approach, in order to avoid missing unsuspected coronary disease as the cause of injury,” wrote Januzzi and McCarthy, both with Massachusetts General Hospital in Boston. “However, given the many triggers for injury that are not coronary in origin, physicians should consider the cost implications and the risks of overtesting and fact there is currently no evidence (randomized or otherwise), that revascularization would benefit patients with myocardial injury in the absence of obvious coronary ischemia.”
The editorialists and study authors agreed the term “troponinemia,” which has been used to describe unspecified elevations in cTn, trivializes this medically serious scenario and should be avoided. These cases will only become more common as increasingly sensitive troponin assays hit the market and detect some level of the biomarker in a greater proportion of patients.
“As articulated by the fourth universal definition of MI and emphasized by Eggers et al., myocardial injury is not a benign condition and should not be trivialized with awkward and nonsensical monikers such as ‘troponinemia’; it is injury, and should be referred to as such,” Januzzi and McCarthy wrote. “Information on definitive management for these high-risk patients will depend on (the) outcome of much-needed clinical trials currently planned or ongoing.”