College of American Pathologists
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  A cardiac marker is born




December 2007
Feature Story

Anne Paxton

The discovery of ST2 is actually one of the more interesting developments in cardiac biomarker technology, says James L. Januzzi, MD. "Unlike a lot of markers that are stumbled upon somewhat fortuitously, and we subsequently discover a role for them, ST2 was discovered through good basic science work and transferred over to the clinical side."

Researchers at Brigham and Women's Hospital in Boston under Richard Lee, MD, performed in vitro studies of myocyte stretch and demonstrated that ST2 was one of the genes most powerfully up-regulated in the stretching of the myocyte. "So it was identified initially in a basic science model, and subsequently the protein for ST2 was isolated and an assay was developed for its measurement."

This is the reverse of the typical course of development of cardiac markers. "Frequently we take a biomarker that has been around for a long time and try to shoehorn it into another indication," Dr. Januzzi says. C-reactive protein is an example. "Investigators tried very hard to take a biomarker of inflammation and convince people it's a cardiac marker. But while it does have prognostic value in heart disease, its non-specific nature has left a lot of people feeling dissatisfied."

By contrast, there were genomic studies supporting ST2's plausible link to heart disease. Early clinical studies by Dr. Lee and others demonstrated that ST2 was elevated in a meaningful fashion among patients with heart failure as well as acute coronary syndrome, Dr. Januzzi says. "Concentrations of ST2 appeared to be somewhat prognostic, but after a couple of clinical studies, things sort of dwindled out for a while, and part of that had to do with the fact, I believe, that there was other work demonstrating that ST2 was prognostic in other disease states including pulmonary disease. So the focus seemed to get blurred a little bit with respect to a potential cardiovascular role for ST2."

Following the PRIDE prospective study of NT-proBNP in 2005, (Januzzi JL, et al. Am J Cardiol. 2005;95:948-954), broad interest in ST2 was renewed. It's a perfect example, Dr. Januzzi points out, of how medicine can come full circle from basic science to the patient's bedside.

Anne Paxton is a writer in Seattle.

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