This story has been updated to correct a quote citing a BG official saying BNP is a marker of inflammation. In fact, he said that it was a marker of "loading and stretch."
Researchers from the National Heart, Lung and Blood Institute's Framingham Heart Study have published data suggesting the protein galectin-3 could serve as a prognostic biomarker for heart failure, but the clinical utility of the marker is still uncertain.
Results from the 3,353-patient study, detailed in a paper published last week in the online edition of the Journal of the American College of Cardiology, showed that elevated galectin-3 levels were linked to an increased risk of heart failure. The study also found, however, that adding galectin-3 to existing risk models did little to improve predictions of heart failure or mortality.
Galectin-3 "was statistically significant in identifying people at high risk for heart failure, but… it didn't add so much above conventional [models] that it is something we would predict today to be clinically useful," Daniel Levy, director of the FHS and author on the study, told ProteoMonitor.
The result will likely be of interest to the cardiology community in general, but it is particularly significant for protein diagnostics firm BG Medicine, which is currently developing a galectin-3 test for use in screening for heart failure risk.
The company already offers a galectin-3 test – its BGM Galectin-3 product – for use in monitoring patients with chronic heart failure. A manual version of that test has received US Food & Drug Administration 510(k) approval and a CE mark from the EU, and in July the company filed a 510(k) application for an automated version of the test to be run on Abbott Laboratories' Architect platform (PM 7/27/2012).
In May, BG announced that it had obtained a CE mark and filed a 510(k) submission for an expanded use of the Galectin-3 test that could be used for predicting risk of heart failure in the general adult population (PM 5/17/2012). According to BG CEO Eric Bouvier, this additional use would significantly expand the market for the test – taking it from around 20 million patients in the US and Europe to roughly 200 million.
The FHS results offer something of a mixed message regarding these plans – indicating that galectin-3 is in fact predictive of increased heart failure risk but also that it adds little prognostic value above clinical factors that are currently used to predict risk.
The study found that the standard clinical model – a collection of factors including age, sex, blood pressure, and body mass – predicted future development of heart failure with an area under the curve of .855. Adding galectin-3 to this clinical model upped the AUC to .859. On the other hand, the standard clinical model plus levels of brain natriuretic peptide – another heart failure marker – gave an AUC of .869. Adding galectin-3 to this clinical model plus BNP combination raised the AUC slightly to .871.
Similar trends held for prediction of mortality. In that case, the clinical model alone had an AUC of .785; the clinical model plus galectin-3 was .786; the clinical model plus BNP was .785; and the clinical model with BNP and galectin-3 was .786.
Levy noted, however, that although galectin-3 added relatively little to established methods of predicting heart failure, it was too early to say what its ultimate utility might be.
"In the last year or two, galectin-3 has emerged as a promising biomarker for people with heart failure, to predict their outcome," he said. "So we hypothesized that if this is a marker that predicts outcomes in people with heart failure, perhaps… it would predict the risk of developing heart failure in the first place."
"To our surprise, it did predict the occurrence of heart failure, so this is a starting point," Levy said. "But right now I think it's too early to say exactly what [its clinical role] might be."
Aram Adourian, vice president of scientific affairs at BG, suggested that the marker could prove important in giving physicians a better idea of the processes underlying a patient's heart failure.
The study's results, he told ProteoMonitor, suggests galectin-3's independence from the other variables taken into account via BNP measurements and the standard clinical model. This, he added, indicates the protein could be useful in helping physicians distinguish the processes underlying a patient's disease.
"As a clinician, you want to know what's going on with the pathophysiology, and myocardial dysfunction involves a lot of different aspects, among them some aspects that are reflected by biomarkers like BNP that are reflective of loading and stretch, and others [like galectin-3] that are reflective of cardiac remodeling and fibrogenesis," Adourian said. "So I think it's kind of a holistic picture that one needs to have to asses the degree to which a patient may or may not be experiencing subclinical myocardial dysfunction."
The FHS study used BG's BGM Galectin-3 assay for measuring galectin-3 levels in its samples, but the company was not involved in any other aspects of the work, such as sample collection or data analysis, Levy said.
The FHS researchers are now pursuing an additional 3,000-plus-patient galectin-3 study tracking patient levels over time, he added, noting that the recently published study measured galectin-3 levels at only one time point.
"Hopefully we will learn a few things from this study," Levy said. "How stable are galectin-3 levels? Do they change over time? What are the predictors of that change? How do galectin-3 changes relate to changes in structure and function of the heart?"
The hope, he said, is that this data "might give us some perspective regarding in which patients galectin-3 might be particularly useful to monitor."
Levy added that he expected additional studies would provide further insight into the protein's potential clinical usefulness and role in heart failure.
"This is the first study to look at it in this way, and we're hopeful now that other studies will look at this further," he said. "We want to see if other studies can corroborate our findings. Additional studies could [also] provide insights into … [whether] there is a subset of individuals in which measuring galectin-3 could be useful clinically."
Adourian said BG is also pursuing its own research into the protein's usefulness as a marker for broad heart failure risk screening, although he declined to offer specifics on any studies currently underway.