High-Sensitivity Troponin T May Offer Glimpse Into Future HF Risk: ARIC Analysis

High-sensitivity cardiac troponin T (hs-cTnT) measurements are highly predictive of diastolic dysfunction in people with no preexisting CVD, researchers say, raising the possibility that the simple test could one day be part of routine screening for early detection and prevention of heart failure (HF).

The intriguing data come from the community-based ARIC study, which began measuring hs-cTnT levels in community-based participants between 1990 and 1992, when they were between 45 and 64 years of age, and continued to follow them with repeated measurements over two decades. In the new analysis, the average age of the participants at the final visit was 75.

“It was an opportunity to look not only at how troponin relates to the heart and heart failure risk, but also at how your history of troponin in midlife also may have an influence on those outcomes,” Amil M. Shah, MD, MPH (Brigham and Women’s Hospital, Boston, MA), the study’s senior author, told TCTMD. “I think one of the things that was unique for our study and helps fill a gap in terms of the understanding about troponin and heart failure risk, especially in late life, is being able to relate it to measures of diastolic function.”

Shah added that it is too early to draw broad conclusions about the value of screening individuals with no CVD risk for future HF risk with a hs-cTnT assay.

However, the findings are consistent with several other studies that also have shown troponin’s potential as a predictor of future HF, including an analysis from MESA that connected troponin levels in patients with no overt CVD to progressive dilation of the left ventricle and LV mass.

Inherently, although we're identifying people who are at elevated risk of heart failure, they're clearly not people who have the same risk as individuals who actually have heart failure. Amil M. Shah

Christopher R. deFilippi, MD (Inova Heart and Vascular Institute, Falls Church, VA), senior author of that MESA analysis, told TCTMD the new ARIC data help to “connect the dots” in this emerging area of research.

“It's an important incremental study in really identifying that the troponin levels, the biochemical measure, is associated with functional structural evidence of diastolic dysfunction,” he noted. However, deFilippi agreed that the next steps in this area should be done carefully before concluding that hs-cTnT screening should become as routine as a lipid panel.

Early Marker of Predisposition to HF

For the study, published online September 4, 2019, ahead of print in JAMA Cardiology with lead author Peder Myhre, MD, PhD (Brigham and Women’s Hospital), the investigators analyzed data on 4,111 participants in ARIC. Their multiple troponin measurements were assessed cross-sectionally against echocardiographic measurements and incident HF.

Individuals with the highest levels of hs-cTnT (14 ng/L and above for women and 22 ng/L and above for men) had greater LV mass index, cavity size, wall thickness, and prevalence of hypertrophy; all remained statistically significant after multivariable adjustment.

HF occurred at a rate of 2.8%. Those with high hs-cTnT levels had greater risk of incident HF (HR 2.58; 95% CI 1.87-3.57), as well as of incident HF with preserved ejection fraction (HR 2.23; 95% CI 1.39-4.35). After adjustment, however, elevated troponin levels were associated with increased risk of HF with preserved ejection fraction only among those who also had diastolic dysfunction. Furthermore, the associations between hs-cTnT levels and diastolic function were independent of LV mass. There was no association seen between elevated troponin and measures of LV systolic function.

We are definitely at that point where the evidence says we're ready to test a therapy, or a couple of different therapies, because the risk-benefit ratio in an older adult should be considered acceptable for a prevention strategy. Christopher R. deFilippi

The predicament now, Shah said, is that there is little evidence to answer the question of how to proceed in patients like these.

“Inherently, although we're identifying people who are at elevated risk of heart failure, they're clearly not people who have the same risk as individuals who actually have heart failure,” he said.

Looking ahead, it will be important to ensure that any proposed intervention has a large benefit-to-risk ratio, Shah added. These may range from aggressive lifestyle modifications and comorbidity control as the initial efforts to various pharmacologic interventions. “But, that’s still an open question,” he observed.

DeFilippi added that low-risk drugs that may make sense in this population include sacubitril/valsartan (Entresto; Novartis) and spironolactone. But, he cautioned that more questions remain, such as how often troponin levels should be monitored, what changes in the levels might mean, and whether any intervention will ultimately prevent HF from occurring.

“The landscape is littered with great pathophysiologic mechanisms that would seem to make a lot of sense but failed to interrupt the progression of disease,” deFilippi said. “But I think we are definitely at that point where the evidence says we're ready to test a therapy, or a couple of different therapies, because the risk-benefit ratio in an older adult should be considered acceptable for a prevention strategy.”