The use of the protein troponin I as a diagnostic for cardiac events is well established. Two news releases that came across my desk in recent weeks suggest that researchers are only beginning to understand the value of troponin as a cardiac biomarker, via the utilization of high-sensitivity tests. In addition to diagnosing heart attack, elevated levels of circulating troponin may predict myocardial infarction years before it occurs. And, rapid testing may both shorten the time to diagnosis and detect more subtle troponin elevation.
Predicting risk for deadly cardiac events
Troponin can be used to identify stable patients at high risk for deadly cardiac events, according to a new study led by researchers at Brigham and Women’s Hospital. Using a test that is more sensitive than what is now used in U.S. hospitals and clinics, the researchers found that nearly 40 percent of patients with type 2 diabetes and stable heart disease had abnormal blood levels of troponin. Patients with elevated levels were twice as likely as their counterparts to die from heart attack, stroke, or other cardiovascular causes within five years. The team also found that a key therapeutic intervention, coronary revascularization, frequently used in patients with heart attack and an abnormal troponin, did not lower stable patients’ elevated troponin levels or risk of deadly cardiac events. The findings are published in The New England Journal of Medicine.
“The patients in our study were not having symptoms of a heart attack, and yet a remarkably high proportion of them had an abnormal troponin, suggesting they were experiencing ongoing injury to their hearts,” says lead author Brendan Everett, MD, MPH. “This test was able to identify patients at increased risk of heart attack, heart failure, or death, even after we accounted for other patient characteristics and risk factors. In the future, if we can understand what causes the abnormal troponin, we may be able to identify new strategies to treat this group of high-risk patients. One strategy we tested—opening the coronary arteries of stable patients with abnormal troponin—did not reduce the risk of future heart attack or death.”
Everett and colleagues measured troponin concentrations from more than 2,200 patients who had both type 2 diabetes and stable heart disease using a highly sensitive test (a high-sensitivity electrochemiluminescence assay) that is currently in use in Europe, and is being studied for use in the U.S. After five years, 27 percent of the patients with abnormal troponin levels went on to die of a heart attack, stroke, or cardiovascular causes, compared to 13 percent of patients with normal troponin levels.
Half of the patients involved in the trial received prompt coronary revascularization—a procedure to open the coronary arteries. However, the procedure did not appear to reduce the risk of cardiovascular-related death in these stable patients with elevated troponin, nor did it reduce troponin levels.
“We know that circulating troponin concentrations reflect ongoing injury to the heart’s muscle tissue, but the causes of this ongoing injury are not completely clear. In the right clinical situation, we would typically interpret the abnormal troponin levels as indicative of an ongoing heart attack, which we often treat by finding the blocked artery and opening it; however, our results indicate that such procedures do not reduce the risk of future heart attack or death in these patients,” says Everett. “We need alternative strategies to improve outcomes.”
Rapid, sensitive tests expedite chest pain triage
Patients arriving at the emergency department with chest pain suggestive of acute myocardial infarction (AMI) can be triaged more quickly and more safely using a new rapid assay with refined cut-offs, German research suggests.
The Biomarkers in Acute Cardiovascular Care (BACC) study suggests this new algorithm can reduce mortality and cut triage times to one hour, compared to the standard three hours.
“There is an urgent need for fast decision-making for this growing patient population,” says principal investigator Dirk Westermann, MD, PhD, from the University Heart Centre Hamburg, and the German Centre for Cardiovascular Research.
“Use of this algorithm in patients with suspected AMI allows for highly accurate and rapid rule-out as well as rule-in, enabling safe discharge or rapid treatment initiation. This rapid algorithm might be applicable to clinical practice without a loss of diagnostic safety.”
For patients with suspected AMI, current guidelines recommend analyzing cardiac troponin I at admission and then three hours later, to determine if the level warrants admission or discharge. This means patients must remain in the hospital for at least three hours before receiving a diagnosis, using resources that are increasingly scarce.
In addition, troponin I levels are now considered abnormal if they are above the 99th percentile from a healthy reference population—in this case 27 ng/L, says Westermann. But highly sensitive troponin I assays can give results more quickly and detect more subtle troponin I elevations that may be important for assessing cardiovascular risk.
The BACC study included 1,045 patients (mean age 65 years) with acute chest pain suggestive of AMI presenting at the emergency room of a university hospital. Patients were assessed using both the standard three-hour assay as well as a highly-sensitive one-hour assay.
Based on the standard approach, 184 patients were diagnosed with AMI and kept in the hospital, while the rest were discharged. All patients were then followed for six months.
Comparing the results of both assays in the cohort, the researchers calculated the best troponin I cut-off value to rule out AMI was 6 ng/L—“far lower than the currently recommended 27 ng/L,” notes Westermann.
They then tested the clinical relevance of this new cut-off for predicting cardiovascular events using data from the BiomarCaRE study—one of the largest studies to include troponin I measurement, in more than 75,000 individuals. The data confirmed that when individuals from the general population had troponin I values higher than 6 ng/L, they were at increased risk of death or cardiovascular disease, whereas patients with levels below this cut-off could be safely discharged.
“This documents that even slightly elevated troponin I values are important predictors of cardiovascular disease,” says Westermann. “At the same time, utilizing a very low cut-off for discharge of patients with suggestive AMI is safe, since these patients are at the lowest possible risk for future events.”
“The standard approach underestimated risk for many patients and resulted in high mortality. In addition, using the rapid, sensitive assay would have reduced usage of the emergency room and scarce medical resources, enabling a faster diagnosis and better treatment.” The algorithm had negative predictive values of 99.7% after one hour and 100% after three hours.