Researchers have discovered that patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis have considerably poorer outcomes than patients with idiopathic PAH, according to a study published in Chest.
PAH is driven by high pulmonary arterial pressures and extensive pulmonary vascular resistance. Two of the most common subtypes are idiopathic PAH and PAH associated with systemic sclerosis. Studies have shown that patients with PAH associated with systemic sclerosis have a 3-fold higher risk of death than patients with idiopathic PAH.
“Systemic sclerosis is a complex, immunological disease, characterized by autoimmunity, fibrosis of the skin and internal organs, and small vessel vasculopathy,” the authors of the study wrote.
In addition to systemic sclerosis being a severe diagnosis in its own right, patients with both PAH and this disease have been shown to demonstrate impaired responses to traditional therapies, inevitably worsening the overall clinical picture. Scientists have suggested that factors such as increased inflammation, autoimmunity, and abnormal vasculopathy are partly to blame.
Read more about PAH etiology
The authors of this study hence decided to further investigate whether patients with PAH associated with systemic sclerosis demonstrated unfavorable bioactive metabolomic derangements that underscore how it drives pathology more severely than idiopathic PAH. They collected patient information in a prespecified discovery cohort. The research team performed metabolite profiling and statistical analysis on the data obtained.
The results of the study demonstrated that significant bioactive lipid alterations existed between the 2 subtypes of PAH. This strengthens the hypothesis that PAH is a highly heterogeneous disease. The researchers also discovered that biochemical differences between the 2 subtypes of PAH led to patients with PAH associated with systemic sclerosis having considerably poorer outcomes than patients with idiopathic PAH.
“Our findings shed light on possible molecular mechanisms of how [systemic sclerosis] disease contributes to accelerated vascular remodeling and impaired cardiac function and could potentially have therapeutic implications,” the authors of the study concluded.
Alotaibi M, Shao J, Pauciulo MW, et al. Metabolomic profiles differentiate scleroderma-PAH from idiopathic PAH and correspond with worsened functional capacity. Chest. Published online September 7, 2022. doi:10.1016/j.chest.2022.08.2230