Biomarkers Emerging to Track Pulmonary Hypertension, But Picture Remains Complex

Although a number of biomarkers can be used to track features of pulmonary hypertension, no single biomarker is sufficient, according to a new review.

Biomarkers have the potential to help physicians better understand cases of pulmonary hypertension (PH) and other cardiovascular diseases, but a new review article makes clear that the connections are complex, and investigators have not yet reached a point of being able to synthesize multiple biomarker signals into concrete individualized treatment plans.

The new review appears in the Journal of Clinical Medicine. It was authored by Marta Banaszkiewicz, MD, of the European Health Center Otwock in Poland, and colleagues.

The investigators began by noting that the disease—characterized by increased pulmonary vascular resistance—is both progressive and heterogenous, meaning one patient’s case could look very different from the next patient’s case, and a single patient’s disease will evolve and change over time. There are 5 subcategories of the disease, and a patient’s prognosis can vary widely based on the specifics of his or her case.

Such heterogeneity means that the identification of meaningful biomarkers could lead to substantial gains in therapy.

“[B]iomarkers may specifically indicate the disease and provide information about the disease stage and treatment response in a relatively easily accessible and noninvasive way,” Banaszkiewicz and colleagues wrote.

The process of finding novel biomarkers is still a work in progress, the authors said, but the potential exists to find biomarkers that might be able to indicate and differentiate a number of pathophysiological courses of the disease.

The investigators next laid out some of the biomarkers that have already been found. For instance, natriuretic peptides, cardiac troponins, soluble ST2, and heart-type fatty acid-binding protein have been associated with heart failure, myocardial injury, and myocardial remodeling.

At the same time, biomarkers like C-reactive protein and red blood cell distribution width could have implications for the study of PH, the investigators said, given that inflammation is increasingly seen as a potential pathophysiological factor related to the disease.

Banaszkiewicz and colleagues also discussed excessive pulmonary arterial smooth muscle cell proliferation and endothelial dysfunction, noting that pulmonary arterial microcirculation has been associated with 2 types of PH.

They said several biomarkers have been found for both pulmonary arterial smooth muscle cell proliferation and endothelial cells as they relate to PH.

Finally, they said, markers of hypoxia and tissue damage, as well as the concentration of extracellular vesicles may be meaningful biomarkers to investigate, among others.

In their conclusion, the investigators sound a note of caution. While much progress has been made, they wrote that the current knowledge around PH biomarkers represents something akin to puzzle pieces, rather than a complete picture.

“Although a wide range of biomarkers have been explored, none of them are specific enough to be used alone in the diagnostic process and prognosis assessment,” they wrote. “Moreover, the majority of biomarkers mentioned in this review have been evaluated in retrospective studies with a small number of patients and/or controls, divergent studied populations, and with potential selection bias.”

They said bigger trials will be needed to better understand and validate these biomarkers, but also to understand the interplay between them.

“Furthermore, given the complexity of the disease, it remains unlikely that a single biomarker can be used successfully in patients with precapillary PH,” they said.


Banaszkiewicz M, Gąsecka A, Darocha S, et al. Circulating blood-based biomarkers in pulmonary hypertension. J Clin Med. Published online January 13, 2022. doi:10.3390/jcm11020383

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