The most reliable way to assess the clinical impact of a therapeutic intervention in pulmonary arterial hypertension (PAH) is through its effect on well-defined clinical end-points, such as mortality. However, this standard is often impractical because of the long period and large number of patients required to reach these clinical end-points, and substitutes, such as the 6-min walking distance, are often used. Biomarkers may also be reliable substitutes for clinical end-points, and are called surrogate end-points when they meet such requirements. According to the US National Institutes of Health Biomarkers Definitions Working Group, a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [1]. However, while this definition is used for drug discovery, another narrower definition is still commonly used: “disease-associated molecular changes in body tissue and fluids”, i.e. a biological marker [2]. Among the estimated 150,000 papers documenting thousands of biological markers, less than 100 biomarkers are routinely used in the clinic [2]. In the field of PAH, which is a rare disease, most biomarker studies examined less than 100 patients, and therefore lacked the statistical power needed to demonstrate a strong association between any biomarker and death. Registries such as the Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) [3] have the advantage of enabling the study of larger populations and, therefore, have much better statistical power. However, in most cases, registries are not designed to evaluate new biomarkers, as they do not reach the necessary quality of biological sampling with storage of samples in a biobank, and are often a mix of incident and prevalent patients. In addition, many studies have focused on just one biomarker, while there is increasing …