High WIF-1 Blood Levels May Suggest Poorer PH-LHD Outcomes

Protein's levels may be prognostic marker for PH with left-sided heart disease

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

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Levels of the Wnt inhibitory factor 1 (WIF-1) protein were elevated in the blood of people with pulmonary hypertension (PH) associated with left-sided heart failure, according to a new study.

WIF-1 was linked with higher levels of NT-proBNP — a marker of heart failure — as well as several other parameters of heart function. Higher WIF-1 levels also associated with poorer rates of survival in patients without a heart transplant, and its levels decreased in those who underwent a transplant, the researchers reported.

Despite findings suggesting that Wnt-1 could be a prognostic blood biomarker, meaning a noninvasive marker of a person’s likely disease outcomes, more studies are needed to validate its potential.

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The study, “Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension,” was published in the journal ESC Heart Failure.

Left heart disease due to left heart failure is the most common cause of PH, the study noted. How PH arises as a result of heart failure is still unknown, but dysfunction of the left ventricle — the chamber responsible for pumping oxygen-rich blood throughout the body — is considered to play a role.

Specific blood markers of likely PH-LHD prognosis needed

Brain natriuretic peptide (BNP) and NT-proBNP are highly sensitive and widely used markers of heart failure. Yet, given the complexity of heart failure, researchers argue that more specific biomarkers with better prognostic potential should be developed.

A research team in Sweden sought to assess the levels of 33 proteins involved in multiple biological processes and health conditions in the blood of PH patients associated with left-sided heart failure — termed LHF-PH — and determine which could be useful as potential biomarkers.

Blood samples were collected from 67 LHF-PH patients (42% women) and 20 healthy controls (50% women) between October 2011 and February 2017. Patients’ median age was 63 and that of the controls was 41. Median follow-up was 6.2 years.

Among people with LHF-PH, 20 had undergone a heart transplant, but one patient whose PH continued after the procedure was excluded from analyses of this group. Across the LHF-PH group, 17 patients died without a transplant.

Lab tests showed that the levels of 11 proteins, among the 33 studied, were significantly different between the LHF-PH and control groups. After a transplant, levels of these specific proteins were significantly lower compared with before.

High levels of four of the 11 proteins — growth hormone, PD-L2, TFPI-2, and WIF-1 — were associated with lower transplant-free survival rates among LFH-PH patients, statistical analysis showed.

However, after adjusting for age, sex, and NT-proBNP, only WIF-1 could predict transplant-free survival in the LHF-PH group. WIF-1 inhibits Wnt signaling, a pathway that is implicated in several cellular processes, such as cell proliferation, differentiation, and migration.

“Although Wnt signalling is largely inactive in the healthy adult heart, recent studies have found that Wnt signalling can be reactivated in the adult heart in certain pathological [disease] states,” the scientists wrote.

Next, the team used right heart catheterization to evaluate several parameters of heart function. In LHF-PH patients, high WIF-1 levels were significantly associated with mean right atrial pressure (the blood pressure in the upper-right chamber of the heart), stroke volume index — how much blood the heart pumps with each beat divided by the body surface area — cardiac index, (cardiac output corrected for the body surface area), left ventricular stroke work index, and NT-proBNP.

“Our results suggest that WIF-1 levels are associated with LHF-PH and may aid in determining its prognosis. Taken together, our study demonstrates that WIF-1 may be an interesting future prognostic biomarker candidate,” the investigators wrote.

“Additional studies are needed, with a mechanistic emphasis to define the role of WIF-1 in [PH] and in larger cohorts to better evaluate its prognostic ability,” they added.

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