Blood biomarker predicts severity of pulmonary arterial hypertension

By John Murphy, MDLinx
Published June 21, 2016

Key Takeaways

Elevated serum levels of a specific protein—hematoma derived growth factor (HDGF)—predicted the severity and survival for patients with pulmonary arterial hypertension (PAH), according to a study published June 2, 2016 in American Journal of Respiratory and Critical Care Medicine.

This discovery may lead to a more specific, noninvasive test that could help doctors to detect and monitor PAH, as well as decide the best treatment for a patient with the progressive, incurable disease. Currently, patients often aren’t diagnosed until they’re in the final stages of the disease.

“This has the potential to be a much more specific readout for the health of the lungs than what we currently measure using invasive cardiac catheterization,” said senior study author Allen Everett, MD, Professor of Pediatrics and Director of the Pediatric Proteome Center at the Johns Hopkins University School of Medicine, in Baltimore, MD.

“It could really have value in making decisions about when to escalate therapy and when to ease it because, at present, it’s difficult to determine whether someone’s disease is getting better or worse, especially in children,” Dr. Everett added.

HDGF is a protein involved in new blood vessel formation, which is known to occur in the lungs of patients with PAH. For this study, the researchers developed a new enzyme-linked immunosorbent assay (ELISA) to measure serum levels of HDGF.

The investigators collected blood samples from 39 patients with severe PAH who had failed conventional treatment and were waiting for lung transplants. They compared these with a control group of 39 age-, gender-, and race-matched healthy volunteers.

Results showed that PAH patients had median HDGF levels that were about 7 times higher (1.93 ng/ml) than HDGF levels in control subjects (0.29 ng/ml).

The researchers investigated further by testing HDGF levels in a validation cohort of 73 additional patients with PAH. The results were dramatic, Dr. Everett said. Patients with an HDGF level greater than 0.7 ng/ml had more extensive heart failure and couldn’t walk as far in the 6-minute walking test.

“Thus, patients with higher HDGF had worse functional status and diminished functional capacity,” the authors wrote.

HDGF was also higher in non-survivors (1.4 ng/ml) than in survivors (0.2 ng/ml). Even after adjusting for age, PAH subtype, and other factors, elevated levels of HDGF were associated with a 4.5-fold increased risk of death.

These findings suggest that HDGF has a distinct advantage over current clinical measures for predicting survival in patients with pulmonary hypertension, Dr. Everett noted.

“This could be a cheap and easy way to say, ‘Oh, good, your levels are going down. Let’s try to take away one of your medicines and see how that works,’” he said. “Or if you know from the very beginning of their treatment that someone isn’t responding to any medicines, you can get them on the list for a lung transplant much sooner.”

More research is needed to find out whether HDGF levels change as drug treatment eases symptoms, whether the results hold true in children with PAH, and whether HDGF can be used to predict PAH in patients at risk of developing the disease in the future, the researchers acknowledged.

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