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Extremely Sensitive Troponin Assay Predicts Impending Cardiovascular Events in Patients with Stable Chest Pain

Key findings

  • Among patients with stable chest discomfort and possible coronary artery disease, an extremely sensitive troponin assay predicted cardiovascular events within 1 year, including death, acute myocardial infarction or hospitalization for unstable angina
  • Concentrations of high-sensitivity troponin I were detectable in 99% of study participants
  • The assay was similarly useful in men and women and was particularly prognostic of near-term events (within 90 days)

More than three million ambulatory adults in the U.S. have stable symptoms suggestive of coronary artery disease (CAD), according to the most recent estimates. This is a low-risk population, but some individuals progress to major complications, including acute myocardial infarction (MI) or death. High-risk patients are difficult to identify on clinical grounds alone, and scoring systems tend to overestimate risks.

Therefore, interest has developed in using high-sensitivity troponin I (hsTnI), a blood-based biomarker routinely used to evaluate patients with suspected acute MI, to aid short-term decision making about patients with stable coronary syndromes. Until recently, however, troponin had been studied for prognostic evaluation only in patients already known to have CAD.

James L. Januzzi, MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research, and colleagues report that in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMIS)trial, an extremely sensitive "single-molecule counting" hsTnI assay was prognostic for major cardiovascular events in patients who had stable chest discomfort and no known CAD. They published their observations in the Journal of the American College of Cardiology.

Study Design

Participants in PROMISE were outpatients who needed nonurgent, noninvasive cardiovascular testing. They were randomized to either functional testing or coronary computed tomography angiography. The current analysis involved the 4,021 participants who consented to have a blood sample taken before angiography (if performed) or any acute coronary event, and who had follow-up information available.

From the blood samples the researchers measured concentrations of hsTnI using a highly sensitive method that "counts" individual molecules of troponin. The primary outcome of the analysis was death, acute MI or hospitalization for unstable angina within one year. The median follow-up for that outcome was 735 days.

hsTnI Concentrations

Most study participants had hsTnI concentrations below the limit of detection for conventional troponin assays (0.5 ng/L). The median hsTnI value for the whole group was 1.6 ng/L, yet 99% of participants had measurable hsTnI concentrations.


Within one year, 74 study participants experienced the primary endpoint of death, acute MI or hospitalization for unstable angina, and 28 experienced the composite outcome of cardiovascular death or acute MI. The median baseline hsTnI concentration was significantly higher among patients who experienced any of the events in the primary endpoint than among those who did not.

Likewise, patients who experienced either event in the composite outcome had a significantly higher median hsTnI concentration than those who did not.

In multivariable analysis, hsTnI concentrations were an independent predictor of the primary outcome (HR, 1.54 per increase in log hsTnI interquartile range; 95% CI, 1.33 to 1.78; P < .001) and the composite outcome (HR, 1.52 per increase in log hsTnI IQR; 95% CI, 1.19 to 1.94; P < .001). Of all covariates tested, hsTnI best explained variation in the primary outcome.

Concentrations of hsTnI appeared similarly useful in men and women. Intriguingly, the hsTnI assay most strongly predicted near-term events, those that occurred within 90 days.

Looking Ahead

Patients identified by hsTnI as being at impending risk may represent a unique subset of people who have "high-risk stable angina," the investigators speculate. Unlike functional testing or angiography, the use of a blood test to try to identify such patients would be broadly available, inexpensive and easily interpretable.

The investigators envision a day when patients with stable chest pain syndromes who have relatively higher hsTnI will proceed directly to coronary computed tomography angiography or invasive angiography. They caution that such a recommendation is premature, partly because it is unclear how individual results (e.g., 7 vs. 8 ng/L) should be interpreted.

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