Individuals with higher levels of cardiac troponin in their blood are at greater risk for developing heart failure for the first time, according to a meta-analysis published in JACC: Heart Failure.
Cardiac troponin is a structural protein that is released into the bloodstream upon myocardial damage. It has traditionally been used to diagnosis myocardial infarction (MI), but recent development of highly sensitive assays has expanded its clinical utility.
“High-sensitivity assays have allowed cardiac troponin to be considered as a quantitative measure of cardiac myocyte injury in the setting of myocardial infarction and can measure cardiac troponin at low concentrations in subjects without myocardial infarction, in whom it can be regarded as a marker for myocardial stress,” lead author Jonathan D.W. Evans, MBChB, and colleagues wrote.
The researchers pulled data from 16 studies containing 67,063 people and 4,165 cases of incident heart failure. After multivariate adjustment, participants with baseline high-sensitivity cardiac troponin (hs-cTn) values in the top third demonstrated a 2.09-fold risk of incident heart failure compared to those with hs-cTn values in the bottom third.
Notably, one of the variables adjusted for was natriuretic peptides, another biomarker for heart failure.
“The data suggest that subjects with hs-cTn values in the top third of the population have a less than two-fold increased risk for developing heart failure compared with those in the bottom third,” Evans et al. wrote. “This association was independent of conventional cardiovascular risk factors and natriuretic peptide levels and consistent in the general population and high-risk groups and in men and women. … These data suggest that measurement of hs-cTn may enhance the ability to identify subjects at greater risk for developing heart failure.”
In two studies evaluating types of heart failure separately, hs-cTn levels in the top third were more strongly associated with risk of heart failure with reduced ejection fraction than preserved ejection fraction, although higher troponin levels were linked to increased risk of both conditions.
The authors said it is unknown why cardiac troponin is present in some patients without clinically evident myocardial ischemia, but they offered guesses.
“It is speculated that contributing factors include underlying coronary artery disease, subendocardial ischemia, increased wall stress, and left ventricular hypertrophy,” the researchers wrote. “Another possible mechanism is the cardiac stress characterized by activation of the renin-angiotensin and adrenergic systems, which has been studied in detail in patients with heart failure.”
Evans et al. pointed out only one measurement of hs-cTn was taken for the patients in their analysis. Serial tests and assessment of multiple biomarkers simultaneously are likely to be more informative, they said, “but these approaches are inevitably more resource intensive and costly.”
In a related editorial, Mayo Clinic physicians Allan S. Jaffe, MD, and Wayne L. Miller, MD, PhD, pointed out all hs-cTn assays aren’t of equal sensitivity. They said future analyses should separate studies by assay and contain metrics on sex-specific cutoffs for each assay, among other suggestions.
“As advocates for biomarker use in patients with heart failure and from our previous studies, we appreciate the interesting proof of concept presented by Evans et al., and with which we concur in regard to establishing estimates of those at risk for heart failure going forward,” Jaffe and Miller wrote. “However, we also have tried to use this opportunity to suggest that the field needs to spend additional time and effort refining the specific techniques that might more fully optimize the ability to use summary and meta-analyses that include biomarkers.”