JAMA Feature: Sensitive assay detects 'undetectable' troponin linked to mortality risk

Cardiac troponin T (red) and GFP (green) are overlapped on one CM of three in this field (arrow). Image source: Proceedings of the National Academy of Science (Kanno et al)

A highly sensitive assay for cardiac troponin T has been developed that detects levels approximately 10-fold lower than those detectable with the standard assay. Researchers have found that these lower levels of the biomarker are associated with structural heart disease and an increased risk of all-cause death, according to a study in the Dec. 8 issue of the Journal of the American Medical Association.

"In patients with chronic heart failure and chronic coronary artery disease, circulating troponin T is detectable in almost all individuals with the highly sensitive assay, and higher levels correlate strongly with increased cardiovascular mortality," the authors wrote.

"We detected risk that would not have been picked up with the old assay," lead author James A. de Lemos, MD, of the University of Texas Southwestern Medical Center in Dallas, told Cardiovascular Business News. "Before we offer this test routinely, however, we have to determine what we are going to with this new information, how it might impact patient management."

In the study, de Lemos and colleagues studied 3,546 multiethnic individuals, aged 30 to 65 years, enrolled between 2000 and 2002 in the Dallas Heart Study. They determined the prevalence of detectable troponin T in the population using the Elecysys-2010 Troponin T (Roche Diagnostics) highly sensitive assay, as well as the standard assay.

The presence of detectable troponin was 25 percent using the highly sensitive assay and 0.7 percent using the standard assay.

Researchers found large differences in prevalence according to sex and race/ethnicity: Men were three-fold more likely to have detectable levels than women, and black participants had a significantly higher prevalence of detectable troponin than Hispanic or white participants.

The prevalence of detectable troponin also varied with age, ranging from 14 percent in participants aged 40 to 50 years to 57.6 percent in those 60 to 65 years.

Two-thirds of participants in the highest troponin category had undetectable levels with the standard assay. The prevalence of hypertension increased from 27.2 to 70.9 percent and prevalence of diabetes from 7.7 to 41 percent across categories of increasing troponin levels.

Left ventricular (LV) mass increased markedly across troponin categories, as did LV wall thickness, and the proportion of individuals classified as having LV hypertrophy increased from 7.5 percent to 48.1 percent. Self-reported heart failure, coronary heart disease and cardiovascular disease were more frequent with higher levels of troponin.

During a median follow-up of 6.4 years, there were 151 total deaths, including 62 cardiovascular disease deaths. All-cause mortality increased from 1.9 percent to 28.4 percent across higher troponin categories. After adjustment for several factors, troponin category remained independently associated with all-cause mortality.

These associations were consistent in lower-risk subgroups defined by the absence of known cardiovascular disease or a low Framingham risk score category.

"Troponin has been implicated previously with risk of death, but we now see that the risk is associated with much lower levels not detected with assays in current clinical use," de Lemos said.

The researchers noted that if the highly sensitive assay were applied to those with a lower likelihood of MI, but with factors associated with higher troponin levels such as older age, male sex, black race, hypertension, diabetes and LV hypetrophy, "the results of the highly sensitive troponin assays will have lower specificity, and false-positive diagnoses of MI will be more common."

They further noted that because current guidelines recommend more intensive treatment for patients with suspected acute coronary syndromes who have elevated troponin levels, "it is possible that widespread application of highly sensitive assays without integrating new approaches to discriminate acute injury will expose some patients to unnecessary risk and expense."

In a second study in the same issue of JAMA, Christopher R. deFilippi, MD, from the University of Maryland School of Medicine in Baltimore, and colleagues found that two-thirds of nearly 3,000 ambulatory community-dwelling individuals aged 65 years or older had detectable troponin with the highly sensitive assay. Using serial measurements, researchers found an association between troponin levels and a gradient of risk for new-onset heart failure (HF) and cardiovascular death.

The risk, however, was not fixed. "If the troponin levels rose, the risk increased; if they fell, the risk also fell," said de Lemos, a co-author. "It seems to be a potentially modifiable risk."

Investigators noted that the risk associated with troponin was independent of NT-proBNP and CRP levels, as well as other biomarkers such as renal function and ECG evidence of LV hypertrophy.

"More sensitive assays open up new applications for these tests," said de Lemos. "Troponin testing has been limited to the emergency department to test for MI. Now, every outpatient clinic will want to test for heart failure."

The highly sensitive assay used in this research is not yet available in the U.S.