Pulmonary hypertension (PH) is a rare disease that still carries a poor prognosis in spite of recent advances in management and the availability of new therapies. With current best practice, survival at one and five years is 90% and 65%, respectively.1

Risk stratification plays a central role in disease management, guiding treatment strategies. At present it relies on a panel of indicators derived from clinical, exercise and hemodynamic evaluation.2 Although this assessment is of recognized value, it is complex and sometimes subjective and inaccurate.

The development of new biomarkers has the potential to improve risk stratification. In order to be clinically useful, biomarkers must be reliable surrogates of meaningful clinical endpoints like mortality and must fully capture the net effect of treatment on clinical outcomes. Moreover, a valuable biomarker must be easy to measure and interpret, inexpensive, and provide independent information on prognosis.

In order to address this problem, various compounds have been studied in recent years and there is intense investigation of novel biomarkers.3,4

Potential biomarkers for PH can generally be categorized based on their association with cardiac dysfunction, vascular and endothelial dysfunction, collagen metabolism, systemic inflammation and oxidative stress, and non-cardiopulmonary organ dysfunction.

At present only two biomarkers, brain natriuretic peptide (BNP) and its N-terminal prohormone fragment (NT-proBNP), are recommended in clinical guidelines for risk stratification and follow-up in PH.2,5

In this issue of the Journal, Plácido et al.6 analyze the role of novel biomarkers in PH and compare them to conventional NT-proBNP measurement and echocardiographic parameters. Based on their findings they propose a score that combines several biomarkers and has greater prognostic value than any of them separately.

This prospective observational study has the merit of analyzing several biomarkers in this population that have been more extensively studied in left heart failure.

Interestingly, the authors identify different temporal relationships between the biomarkers and the endpoints of mortality and death or hospitalization, suggesting that different pathogenic processes might play different roles according to disease states.

The findings of this study are in line with increasing evidence that a multiple biomarker approach could be superior to using only one biomarker.

Although promising, the proposed multi-biomarker score needs further investigation and prospective validation in larger populations before it can be used in routine practice.

The development of valid new biomarkers will increase our knowledge of the basic pathologic mechanisms behind vascular pulmonary disease, as well as contributing to early diagnosis and differentiation of PH from other diseases and improving risk assessment before and during treatment. In the best scenario they might even help in individualizing prevention and treatment.