Study IDs 2 blood biomarkers as key to accurate PH diagnosis
2 biomarkers shown best out of 5 at distinguishing adults with condition
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Two blood-based biomarkers — GDF-15 and NT-proBNP — most accurately distinguished adults with pulmonary hypertension (PH) from healthy individuals in a study that compared five biomarkers.
The retrospective study, conducted at Beijing Anzhen Hospital in China, evaluated traditional and newer biomarkers across the four main clinical subtypes of PH, but found that their ability to distinguish those subtypes was limited.
“These biomarkers may provide complementary laboratory information for PH assessment but should not be used as stand-alone tools for PH subtype classification,” the researchers wrote in the study, “Comparative evaluation of traditional and novel biomarkers for pulmonary hypertension across clinical subtypes,” published in Clinica Chimica Acta.
PH is a group of conditions characterized by increased blood pressure in the pulmonary arteries (those that pass through the lungs), putting strain on the right side of the heart. The condition carries a high risk of death, particularly in advanced stages when the right side of the heart begins to fail.
Diagnosing PHÂ relies on a combination of symptom assessment, blood tests, and cardiac imaging and ultrasound. Right heart catheterization is the gold-standard test for PH. It involves inserting a thin, flexible tube into a blood vessel and guiding it to the right side of the heart and pulmonary artery, where it measures pressure directly.
New, old blood biomarkers
Blood biomarkers are attractive as supporting tools because they are minimally invasive, can be repeated over time, and fit into routine laboratory workflows.
Two well-established biomarkers used to detect strain on the heart muscle are BNP and NT-proBNP, but their levels can also be influenced by age, kidney function, and fluid status.
Newer blood biomarkers representing different biological pathways may provide additional information beyond heart strain.
The researchers compared the diagnostic performances of BNP and NT-proBNP to three newer biomarkers: GDF-15, NT-IGFBP-4, and ST2.
GDF-15 is a protein linked to inflammation, low oxygen injury, and oxidative stress, a type of tissue damage. NT-IGFBP-4 may reflect changes in blood vessel structure, cardiopulmonary stress, and disease severity. ST2 is a protein associated with heart muscle strain, fibrosis (scarring), and inflammatory signaling.
The researchers measured biomarker levels in blood samples from 228 adults (57.5% women) with PH and 213 sex-matched healthy individuals who served as controls. The patients were grouped by subtype: 101 had pulmonary arterial hypertension (PAH), 53 had PH due to left heart disease, 33 had PH due to lung disease/hypoxia, and 41 had PH due to blood clots in the lungs.
Results showed that PH patients had significantly higher median blood levels of all five biomarkers than in controls: NT-proBNP (701 vs. 31 picograms/mL), BNP (112 vs. 15 picograms/mL), GDF-15 (2570.1 vs. 608.1 picograms/mL), NT-IGFBP-4 (150 vs. 98.9 nanograns/mL), and ST2 (29 vs. 14.57 nanograns/mL).
Regarding PH subtype, those with PH due to left heart disease had the highest levels of NT-proBNP and BNP, “consistent with the greater contribution of cardiac dysfunction and volume or pressure load,” the team noted.
While GDF-15 and NT-IGFBP-4 were elevated across all PH subtypes, with higher levels also observed in PH due to left heart disease, ST2 showed less variation across subtypes.
In distinguishing PH from controls, GDF-15 had the highest individual accuracy, with an area under the curve (AUC) of 0.96. An AUC of 1 represents a perfect distinction. This was followed by NT-proBNP, with an AUC of 0.95. When NT-proBNP and GDF-15 were combined into a single model, performance improved further, reaching an AUC of 0.99.
BNP and NT-IGFBP-4 showed moderate-to-good performance, with AUCs of 0.88 and 0.86, respectively, while ST2 had the lowest performance, with an AUC of 0.81.
When each subtype was gauged separately against controls, NT-proBNP performed well for PAH, PH due to left heart disease, and PH due to lung disease/hypoxia, with AUCs higher than 0.95. GDF-15 also showed consistently strong results across subtypes, including AUCs of 0.99 for PH due to left heart disease and PH due to lung disease/hypoxia and 0.97 for PH due to blood clots in the lungs.
However, when the subtypes were compared directly rather than against controls, NT-proBNP and BNP showed only moderate ability to distinguish PH due to left heart disease from the other subtypes, with AUCs of 0.80 and 0.81, respectively. No biomarker reliably distinguished the other types from each other.
The researchers noted that adjusting for age did not meaningfully alter the performance of NT-proBNP or GDF-15, whereas BNP and ST2 showed significant shifts after this adjustment.
“GDF-15 and NT-proBNP showed strong auxiliary discriminatory performance for PH versus healthy controls, whereas their ability to distinguish PH subtypes was limited,” the team wrote. “Subtype-oriented biomarker interpretation therefore remains exploratory and requires further validation.”
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