Any detectable level of high-sensitivity cardiac troponin T (hs-cTnT) measured in an emergency department (ED) was associated with worse long-term survival—even when not accompanied by acute conditions known to impact troponin levels—according to a Swedish study published in the Journal of the American College of Cardiology.

The detection threshold for hs-cTnT is 5 nanograms per liter. When the researchers analyzed 19,460 patients presenting to the ED with chest pain but no evidence of MI, they found hs-cTnT levels even slightly higher than that threshold were associated with markedly worse survival over the average 3.3 years of follow-up. As hs-cTnT went up, the adjusted hazard ratios increased as follows when compared to levels below 5 ng/L:

• 2.00 for 5-9 ng/L
• 2.92 for 10-14 ng/L
• 4.07 for 15-29 ng/L
• 6.77 for 30-49 ng/L
• 9.68 for ng/L at 50 or above

A 99^th-percentile cutoff point (14 ng/L) has been used to diagnose patients with MI. However, nearly 30 percent of the patients in this study had detectable levels below that threshold but remained at increased risk. Conversely, 7.9 percent of the participants had hs-cTnT levels above that cutoff but no evidence of MI.

“In the absence of clinical guidelines, we strongly believe that persistently elevated hs-cTnT levels may be reason in itself to investigate patients for exclusion of previously undiagnosed heart disease,” wrote Andreas Roos, MD, with the department of medicine at Karolinska Institutet in Stockholm, and colleagues. “In addition, future research should focus on how to mitigate risk for patients with no detectable heart disease that may explain persistently elevated hs-cTnT levels.”

The researchers excluded all patients with end-stage kidney disease and those with MI associated with the visit. They also required at least two hs-cTnT readings to determine if levels were persistently elevated. The mean age of the study population was 54.

In addition to all-cause mortality, Roos et al. noted cardiovascular mortality jumped threefold in patients with ng/L readings of 5 to 9 and 27-fold in patients with ng/L levels above 50. Noncardiovascular mortality also was significantly associated with higher levels of hs-cTnT, but the relationship wasn’t as strong. In addition, increased risks of heart failure and MI were present in individuals with elevated hs-cTnT levels, with the lowest detectable level (5-9 ng/L) showing a nearly fourfold increase in risk of hospitalization for heart failure versus people with undetected hs-cTnT.

“In patients with stable CAD (coronary artery disease), the association between the hs-cTnT level and the risks of all-cause mortality and heart failure is stronger than that between the hs-cTnT level and MI,” Roos and colleagues wrote. “Accordingly, chronic troponin release may be mediated by functional and structural heart diseases rather than by ischemic heart disease. However, further investigation is needed regarding what adverse processes could be mediated by troponin leakage and whether the risk associated with detectable troponin levels in stable patients is modifiable.”

In an accompanying editorial, Marc P. Bonaca, MD, MPH, with Harvard Medical School, said these findings suggest hs-cTnT should be more than simply a diagnostic test for MI or acute coronary syndrome (ACS).

“The data presented by Roos et al. should remind clinicians not to be falsely reassured when ACS is ‘ruled out’ by a lack of dynamic changes or a hs-cTn level that is measurable but below the 99th percentile threshold,” Bonaca wrote. “Even in the presence of apparent clinical stability and no apparent acute condition, these patients remain at heightened intermediate- to long-term risk. We must begin to interpret hs-cTn in this context as an indicator of important subclinical disease that warrants additional evaluation.”