Higher Levels of sST2 Protein Linked to Poorer Outcomes in PH, Study Finds

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Higher levels of a protein involved in certain immune responses, called soluble suppression of tumorigenicity-2 (sST2), are associated with more severe pulmonary hypertension (PH) and heart dysfunction, a study found.

This protein’s potential use as a prognostic biomarker for PH, however, seems to be limited.

The study, “The Prognostic Value of Soluble ST2 in Adults with Pulmonary Hypertension,” was published in the Journal of Clinical Medicine.

PH is a rare disorder caused by a narrowing of the arteries in the lungs, often coupled with heart dysfunction, leading to high pulmonary arterial pressure (PAP).

Previous studies have found that sST2 — a protein that has emerged in recent years as a biomarker of heart failure because its levels rise markedly when the heart is under stress — is involved in alterations occurring in lung blood vessels of patients with idiopathic pulmonary arterial hypertension (PAH).

Other studies also found a direct correlation between sST2 levels and the degree of right heart dysfunction in PAH patients. This suggested that, in addition to being a valuable biomarker of heart failure, sST2 may also be a useful indicator of heart and lung blood vessel deterioration in PH.

To explore this possibility, researchers at Erasmus University Medical Center in the Netherlands and colleagues measured blood levels of sST2 in patients with different types of PH attained during right heart catheterization — a standard diagnostic procedure for PH that measures the pressure in the arteries of the lungs, and assesses the heart’s capacity to pump blood.

Between May 2012 and October 2016, the prospective cohort study enrolled more than 100 adults with PH (median age of 59): 53 with PAH, 21 with chronic thromboembolic pulmonary hypertension (CTEPH), 16 with mixed PH, and 15 with PH due to lung disease.

The study’s main goal was to determine if there was a correlation between the levels of sST2 and poor clinical outcomes in PH, including the need for a lung transplant, signs of heart failure, or death.

Results showed that high sST2 levels were associated with severe right heart dysfunction, higher PAP values, and a worse exercise capacity. But only a moderate positive correlation was found between the levels of sST2 and N‐terminal pro‐brain natriuretic peptide (NT-proBNP), a validated and widely accepted prognostic marker of PH.

After a median follow-up of about three years, 33 (31.7%) of these patients had either died or required a lung transplant (primary composite endpoint), while 43 (41.3%) had either died, received a lung transplant, or been hospitalized due to heart failure (composite secondary endpoint).

Correlation analyses found that sST2 levels were associated with both composite endpoints. However, once researchers normalized the data for the levels of NT-proBNP in each patient, both correlations were no longer statistically significant.

Overall, data showed that “higher sST2 is associated with a worse exercise capacity, higher pulmonary and cardiac pressures, and with more severe right ventricular [heart] dysfunction. Moreover, sST2 is significantly associated with the risk of death or lung transplantation,” the researchers wrote.

“Nevertheless, as sST2 yielded no independent prognostic value besides the conventional biomarker NT-proBNP, the usefulness of sST2 as prognostic biomarker in adults with pulmonary hypertension seems to be limited,” they added.

A Conversation With Rare Disease Advocates