High-Sensitivity Troponin May Help Uncover Heart Failure Risk

Elevated levels are strongly related to risk of later heart failure, but how to use this information remains unclear.

High-Sensitivity Troponin May Help Uncover Heart Failure Risk

Considering high-sensitivity cardiac troponin (hs-cTn) concentrations in addition to conventional risk factors may help improve the identification of people who are at risk for developing heart failure and may benefit from preventive treatments, a meta-analysis affirms.

In pooled results from 16 studies, patients with baseline troponin levels in the top third versus the bottom third were more than twice as likely to have a new-onset heart failure event during follow-up (adjusted HR 2.09; 95% CI 1.76-2.48), a finding little changed with further adjustment for B-type natriuretic peptide. Lead author Jonathan Evans, MBChB (University of Cambridge, England), and colleagues report their results in a study published online January 10, 2018, ahead of print in JACC: Heart Failure.

“We show that troponin, because of this positive association, might be useful for identifying people at high risk of developing heart failure, and this could help to target preventive interventions in these patients,” senior author Peter Willeit, PhD (Medical University of Innsbruck, Austria), told TCTMD.

Noting high heterogeneity across studies, however, Willeit said further research—ideally using patient-level data from the studies included in the meta-analysis—is needed to clarify how best to incorporate high-sensitivity troponin assays into risk prediction using traditional risk factors.

Commenting for TCTMD, Vijay Nambi, MD, PhD (Michael E. DeBakey Veterans Affairs Hospital and Baylor College of Medicine, Houston, TX), said the meta-analysis confirms the link between elevated troponin levels and future risk of heart failure, but added that there remains a question about how that information can inform clinical practice.

Research has begun to focus on that question. In fact, Nambi is the principal investigator for a study in which patients with detectable troponin T using a high-sensitivity assay, an estimated 10-year risk of heart failure hospitalization exceeding 5%, and reasonably well-controlled blood pressure are randomized to usual care or one of two antihypertensive regimens. The primary outcome is the surrogate measure of cardiac strain, which is associated with heart failure risk.

What strategies might be used to reduce the risk of developing heart failure in patients found to be at high risk remains a fertile area for research, Nambi said. He pointed out that if he were to see a patient with elevated troponin currently, however, he would consider taking a more intensive approach to controlling traditional risk factors and following the patient more closely to look for early signs of heart failure.

“These are things that have to be determined through clinical trials, but at least within the norms of what we think are reasonable standards of care of the traditional risk factors at this point in time, perhaps we should be more aggressive,” Nambi said.

Broader Application for Hs-cTn

High-sensitivity troponin assays have been used for several years outside of the United States to help clinicians diagnose MI, and the first such test was finally approved by the US Food and Drug Administration about a year ago.

Several studies, though, have suggested that the assays might be useful in other settings. A previous meta-analysis by Evans’ and Willeit’s group, for example, showed that high-sensitivity troponin levels are associated with long-term risks of coronary heart disease or stroke in patients without obvious cardiovascular disease.

In this new meta-analysis, the investigators sought to better understand the potential role for high-sensitivity troponin assays in predicting risk of new-onset heart failure. They pooled results from 16 prospective cohort studies—10 in the general population and six in high-risk groups—that included a total of 67,063 patients and 4,165 incident heart failure events.

High troponin levels were strongly associated with new-onset heart failure, although heterogeneity was high across studies (I2 of 80%).

The relationship was consistent regardless of sex, type of troponin measured, and other study characteristics, but it was stronger for heart failure with reduced versus preserved ejection fraction in the two studies with available data.

Two studies also reported the association between troponin increases over time and risk of new-onset heart failure, showing a roughly 60% relative increase in risk for patients who had detectable troponin T at baseline and a more than 50% increase in levels at 2 to 3 years and at 6 years. In one of those studies, patients with undetectable troponin T at baseline had nearly double the risk of incident heart failure if they had a detectable level at 6 years (HR 1.96; 95% CI 1.62-2.37).

Evans et al also found that adding hs-cTn values to conventional risk factors improved risk discrimination, with increases in the C-index mostly in the range of 1% to 3%.

Elevated Hs-cTn: What Next?

In an accompanying editorial, Allan Jaffe, MD, and Wayne Miller, MD, PhD (Mayo Clinic, Rochester, MN), say that the meta-analysis supports the hypothesis that high-sensitivity troponin assays can be used to identify patients at risk for developing heart failure, but also reveals substantial heterogeneity across studies.

“So, rather than helping to clarify how to proceed based on the findings of the meta-analysis, uncertainty is extended,” they write. “This marked heterogeneity may be why the increase in C-statistic for the analysis is so small (0.03).”

Jaffe and Miller detail several potential explanations of the observed heterogeneity, including differences in sensitivity across assays, variation in the values of troponin used to define risk, use of different cutoff values for the 99th percentile upper reference limit, issues around imprecision, and lack of consideration of sex-specific cutoffs.

“These issues do not invalidate the present meta-analysis, which suggests that hs-cTn should be helpful in identifying patients who are at risk for the development of HF,” they say. “However, this and other meta-analyses should call attention to the need for biomarker studies to improve the quality of their summary analyses.”

In an email, Sheryl Chow, PharmD (Western University of Health Sciences, Pomona, CA), told TCTMD that the use of biomarkers for the prediction of new-onset heart failure “is an interesting and emerging area of practice.”

She said that use of high-sensitivity troponin assays to identify patients at risk for developing heart failure varies across centers. “However,” she added, “our [American Heart Association] statement recently published in 2017 suggests that TnI or TnT alone may add prognostic value to standard risk factors for predicting new-onset HF.”

“Moving forward, we anticipate a multimarker strategy using biomarkers of injury (troponin) in addition to natriuretic and fibrotic markers, which may enhance prognosis more than any biomarker alone, but more prospective data are needed,” Chow continued. “Certainly, a randomized study is needed to determine whether or not early intervention could delay the onset of HF and improve long-term outcomes in such patients.”

Sources
Disclosures
  • Evans reports being supported by a clinical research fellowship from the British Heart Foundation Cambridge Centre of Research Excellence.
  • Willeit reports being supported by the excellence initiative (Competence Centers for Excellent Technologies) of the Austrian Research Promotion Agency FFG: Research Center of Excellence in Vascular Ageing – Tyrol, VASCage, funded by Bundesministerium für Verkehr, Innovation und Technologie, Bundesministerium für Wissenschaft, Forschung und Wirtschaft, Wirtschaftsagentur Wien, and Standortagentur Tirol.
  • Jaffe reports consulting for most of the major diagnostic companies either currently or in the past.
  • Nambi reports being a co-investigator on a provisional patent (# 61721475) entitled, “Biomarkers to Improve Prediction of Heart Failure Risk,” filed by Baylor College of Medicine and Roche; receiving an honorarium from Siemens for event adjudication for a study of a hs-cTn assay; and being supported by an investigator-initiated research grant from the Department of Veterans Affairs Clinical Science Research & Development.
  • Miller and Chow report no relevant conflicts of interest.

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