In most medical pamphlets that are handed out to patients during a consultation, there is usually a section on “risk factors.” Although certain medical conditions have very specific risk factors, a number of risk factors that are often cited are rather generic: smoking, obesity, excessive alcohol consumption, and so on. 

However, there is a movement to stratify risk factors in a manner that is clinically meaningful. The question that physicians and researchers are rightfully asking is: how do we create a comprehensive risk assessment tool so that proclivity to certain outcomes can be meaningfully identified and preemptive steps can be taken? 

The ability to identify the possibility of one developing severe forms of a disease down the road would be a powerful tool, especially in the face of rare and crippling illnesses that do not have an outright cure. In this article, we will be looking at various attempts by researchers to stratify the risk of patients developing pulmonary arterial hypertension (PAH). 

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Reducing the Burden of PAH 

Galiè and colleagues presented a compelling reason that risk stratification of PAH remains of interest to the medical community, writing that PAH “remains a severe clinical condition despite the publication of 41 randomized clinical trials (RCTs) in the past 25 years and the regulatory approval of multiple drugs active by four routes of administration.” In other words, despite enormous sums invested into research and the development of a number of different therapies, PAH remains a condition that inflicts a significant disease burden onto patients. 

Read more about PAH epidemiology 

In view of this, it is quite pragmatic to think of ways to prevent PAH, or at the very least identify key risk factors that predispose one to severe morbidity when diagnosed with PAH. The European Society of Cardiology/European Respiratory Society reported in 2015 that PAH treatment guidelines are closely linked to the baseline severity of newly diagnosed PAH cases. Treatment regimens differ between patients who are considered to have low, intermediate, or high risk for 1-year mortality. 

“Risk assessment is essential for the management of patients with pulmonary arterial hypertension (PAH),“ Vraka and colleagues wrote. “Risk stratification scores provide prediction of mortality risk and allow clinicians to determine [a] patient’s prognosis and treatment approach, and optimize lung transplantation timing.”

Choosing the Best Tool

Vraka and colleagues hence sought to investigate the comparative value of three existing PAH scores: the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score, the Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) score, and the score developed by the French Pulmonary Hypertension Network (FPHN) Registry. The research team wanted to evaluate the ability of the 3 scoring methods to predict transplant-free survival at 3 years and 5 years after diagnosis.

They carried out a retrospective observational study at a hospital in Switzerland with PAH patients. The participants were split into 2 groups: the first consisted of transplant-free survivors while the second consisted of the deceased and transplant recipients. All the participants had been started on a specific treatment regime upon diagnosis.

Read more about PAH patient education 

The researchers categorized the risk of each patient as low, intermediate, or high using the 3 risk stratification scoring methods. The results demonstrated that the 3-year prediction for transplant-free survival was roughly the same when using any of the 3 scoring methods. However, the 5-year prediction for transplant-free survival was inferior for REVEAL 2.0 compared to both COMPERA and FPHN computed at baseline. 

The main limitation in the study conducted by Vraka et al is that the patients studied were diagnosed more than 15 years earlier, meaning that monotherapy was the default treatment, even in patients considered high risk. They added, “Furthermore, none of the 3 scores nor practice guidelines were established, so the decision of the treatment strategy was based on clinical evaluation and medical experience.”

Limitations of Existing Assessments 

Galiè and colleagues also looked at the value of the main risk stratification scoring methods for PAH, including all 3 methods studied by Vraka et al, as well as an additional Swedish PAH Register (SPAHR). They found that even though the objective of the PAH risk stratification scoring methods remained the same, they differed significantly in terms of strategy.

For example, the SPAHR and COMPERA scores evaluated risk at baseline and at the first follow-up by assigning a score to each criterion. However, in the FPHN registry, risk assessment was evaluated in incident idiopathic PAH according to 4 low-risk criteria: the 6-minute walk distance, right atrial pressure, cardiac index ≥2.5 L·min−1·m−2, and WHO/New York Heart Association Functional Class I or II. 

In addition, certain limitations were identified in all the risk stratification methods studied. Among them were: 

  • The retrospective nature of the scoring systems
  • The lack of a standardized data collection method across published registries
  • The significant amount of missing data and the number of patients lost to follow-up
  • Important prognostic variables, such as echocardiogram, cardiac MRI, and cardiopulmonary exercise test data were not factored into consideration
  • Life-threatening complications, such as arrhythmias and hemoptysis, were not included in the scoring systems. 

We can conclude based on the studies above that PAH risk stratification scoring methods do indeed provide physicians with a better understanding of the potential disease course and the prognosis of the patients under their care. Future research should focus on refining existing risk stratification scoring methods to better factor in the missing elements in order to further improve PAH management. 


Vraka A, Yerly P, Aubert JD. Comparison of risk stratification scores in pulmonary arterial hypertension: a monocentric retrospective study at Lausanne University HospitalRespiration. 2022;1-12. doi:10.1159/000520886

Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertensionEur Respir J. 2019;53(1):1801889. Published January 24, 2019. doi:10.1183/13993003.01889-2018