Broader, Primary Prevention Role for High-Sensitivity Troponin Tests Suggested by ARIC Analysis
Serial measurements of high-sensitivity cardiac troponin T identify a population of seemingly healthy individuals who are at higher risk of coronary heart disease, death, and especially heart failure, a new study shows. Conversely, the findings hint that individuals whose troponin levels decline between tests have reduced risk over follow-up.
The findings may have implications for the management of asymptomatic adults unaware they are at higher risk of cardiovascular events down the road, authors say.
“High-sensitivity troponin is an intriguing biomarker in this setting, because we know that it marks patients who are walking around with no symptoms, yet we can detect that they have some myocardial damage,” lead author on the study, John W. McEvoy, MBBCh (Johns Hopkins Bloomberg School of Public Health, Baltimore, MD), told TCTMD.
That early signal of damage has, once again, been shown to be associated with worse outcomes later on, he continued. “In our study, although it wasn't as strong a finding as for increases in troponin being associated with higher risk and subsequent outcomes, we also saw a trend towards reduced risk and reduced outcomes among individuals who had troponin levels [decline]. So it's not just a unidirectional marker, it provides bidirectional information.”
The results were published online this week in JAMA Cardiology.
A Broader Application?
High-sensitivity cardiac troponin T tests (hs-cTNT) have been extensively studied in the setting of chest pain and are approved in Europe and elsewhere as a rule-in/rule-out biomarker for suspected myocardial infarction in the emergency department. Given the sensitivity of the test, which identifies cardiomyocyte injury, hs-cTNT has also been studied in asymptomatic adults with no known heart disease. Prior studies showed that a single elevated hs-cTNT test is associated with increased risks for coronary heart disease, heart failure, and all-cause mortality.
In this latest study, however, investigators explored whether repeat testing of asymptomatic adults improves prediction of cardiovascular events over the long term.
McEvoy and colleagues used two separate blood samples drawn 6 years apart among participants in the Atherosclerosis Risk in Communities (ARIC) study. They then followed subjects for a maximum of 16 years. They found that incident detectable hs-cTNT > 0.005 ng/mL was independently associated with subsequent coronary heart disease, heart failure, and death, as compared with levels of less than 0.005 ng/mL at both visits. Even greater increases were seen among patients when a cutpoint of 0.014 ng/mL was used. Importantly, however, the risk was higher among subjects whose hs-cTNT levels doubled between the two measurements and was lower for subjects whose hs-cTNT levels declined by more than 50% over the same period.
When added to models that included traditional risk factors, baseline hs-cTNT changes, and levels of another cardiac marker—N-terminal pro-brain natriuretic peptide—the change in hs-cTNT provided improved predictive ability for subsequent heart failure and death.
To TCTMD, McEvoy stressed that while the cause of the cardiomyocyte injury picked up by the test is not known, it may still be possible to target that risk, a finding borne out by the fact that a falling hs-cTNT level appeared to be protective in this study. “That’s important, because there are some interventions that are known to reduce high-sensitivity troponin,” McEvoy said, including studies with statins and the new angiotensin receptor-neprilysin inhibitors.
That concept, however, remains “hypothesis-generating” and needs to be studied prospectively, he added.
Part of a Panel of Tests
Commenting on the study for TCTMD, James De Lemos, MD (UT Southwestern Medical Center, Dallas, TX), said that the McEvoy paper “fits with the paradigm” that his own group has been working on for some time, adding that the chief contribution of this new study is in showing the importance of repeat testing.
De Lemos believes hs-cTNT could be measured in healthy adults the same way lipids and glucose are now, during routine doctors’ office visits. “If you get this measured when you get your other annual labs measured, as part of a panel of tests, and if hs-cTNT is surprisingly high for your age and sex, then that suggests you are at higher risk of dying or developing heart failure or another cardiac complication that you would have not otherwise thought about,” he said.
An elevated test might, for example, lead to additional tests that might not have been considered, as well as potentially stepped up diet, lifestyle, and even pharmaceutical interventions, he said.
Going one step further, De Lemos said he believes this may be the true niche for hs-cTNT, adding that he is not convinced that high-sensitivity troponin tests for MI diagnosis offer much in the way of benefit over the troponin tests currently approved for use in chest-pain rule-out. These, he said, are “already very sensitive” for this application.
“In my view,” he said, “the advantage of hs-cTNT sensitivity is that it allows you to ask a completely different host of questions about smaller degrees of smoldering cardiac injury and the conditions that might be associated with that.”
Both McEvoy and De Lemos agreed that further studies are warranted to look at what interventions, if any, might change the course of disease following evidence of an elevated test result or increased hs-cTNT levels on serial testing. The optimal window for repeat tests is also unclear.
In an editorial accompanying the study, James L. Januzzi Jr., MD (Harvard Clinical Research Institute, Boston, MA), also highlights the question of how to intervene in patients with elevated biomarkers, cautioning that a “one-size-fits-all” approach is unlikely to work.
“Currently it seems irrefutable that biomarkers can predict risk in population-based cohorts,” Januzzi writes. “What is needed now are efforts toward developing strategies to upwardly bend the survival curves of those with a biomarker signature of risk, leveraging the knowledge gained from studies such as the report by McEvoy et al to improve public health.”
High-sensitivity troponin tests are currently not approved in the United States. While the abstract for the JAMA Cardiology paper states optimistically that approval could be “soon,” McEvoy conceded in interviews that this biomarker “may not be available in the US quite as soon as we hoped.”
- McEvoy JW, Chen Y, Ndumele CE, et al. Six-year change in high-sensitivity cardiac troponin T and risk of subsequent coronary heart disease, heart failure, and death. JAMA Cardiol. 2016;Epub before print.
- Januzzi JL Jr. Biomarkers to predict risk in appartently well populations. JAMA Cardiol. 2016;Epub before print.
- Troponin, BNP Tests Key to Reducing Perioperative Cardiac Complications After Noncardiac Surgery
- High Troponin T Foretells Poor Outcomes in Patients With Type 2 Diabetes, Stable Heart Disease
- Reagents used in the study were donated by Roche Diagnostics.
- Study authors report receiving National Institutes of Health grant funding.
- De Lemos reports receiving grant support from Roche Diagnostics and serving as a consultant for Roche, Siemens, and Radiometer.
- Januzzi reports receiving grant support from Siemens, Singulex, and Prevencio; receiving support in part from the Hutter Family Professorship at Harvard Medical School; receiving consulting income from Roche Diagnostics, Critical Diagnostics, Sphingotec, Phillips, and Novartis; and participating in clinical endpoint committees for Novartis, Amgen, Janssen, and Boehringer Ingelheim.