What is the clinical evidence from this study?

Study design: Cohort. Population: Idiopathic Pulmonary Arterial Hypertension (IPAH) (n=263). Intervention: Baseline plasma extracellular superoxide dismutase (Ec-SOD) activity ≤ 83 U/L vs. Ec-SOD activity > 83 U/L. Primary outcome: All-cause mortality (p=<0.001).

November 17, 2020Open Access

Alteration of Extracellular Superoxide Dismutase in Idiopathic Pulmonary Arterial Hypertension

Q: What are the key findings of this study?

In patients with idiopathic pulmonary arterial hypertension, lower baseline plasma extracellular superoxide dismutase activity (≤83 U/L) was associated with significantly higher mortality (41% vs 15%, p<0.001) compared to those with higher levels.

RZRui ZhangDartmouth–Hitchcock Medical Center LWLan WangBeijing Chuiyangliu Hospital QZQin‐Hua ZhaoTongji University

Key Result

In patients with idiopathic pulmonary arterial hypertension, lower baseline plasma extracellular superoxide dismutase activity (≤83 U/L) was associated with significantly higher mortality (41% vs 15%, p<0.001) compared to those with higher levels.

Study Design

Type

Cohort (n=263)

Multicenter

Structured PICO

Does plasma extracellular superoxide dismutase (Ec-SOD) activity predict mortality and correlate with hemodynamics in adult patients with idiopathic pulmonary arterial hypertension?

Population

133 adult patients with idiopathic pulmonary arterial hypertension and 130 healthy controls, followed prospectively for a mean of 26 months to assess the prognostic value of plasma superoxide dismutase levels.

Comparator

Healthy control subjects (n=130) and internal comparison between BMPR2 mutation carriers (n=28) and wild-type (n=105)

Outcome

All-cause mortalityhard clinical

Reduced plasma extracellular superoxide dismutase (Ec-SOD) activity is associated with BMPR2 mutations, worse hemodynamics, and increased mortality in patients with idiopathic pulmonary arterial hypertension.

Main Result

Absolute Event Rate: 41% vs 15%

p-value: p=<0.001

Limitations

Plasma SOD levels were only measured at baseline, making it difficult to evaluate variability and prognosis of level changes over time or the impact of different therapies.
Blood samples were collected after an overnight fast; the best time to collect samples for prediction remains unclear.
Lack of racial diversity, as findings may only be applicable to the Chinese Han population.
Sensitivity analyses were not performed to assess the validity and robustness of the analyses based on the cutoff value.

Abstract

Background: Superoxide dismutases (SODs) are an important family of antioxidant enzymes that modulate reactive oxidative species levels. It is largely unknown which SOD isoform(s) change in vivo in idiopathic pulmonary arterial hypertension (IPAH) patients. Methods: A total 133 consecutive adult IPAH patients who underwent bone morphogenetic protein receptor type 2 (BMPR2) genetic counseling were enrolled in this prospective study. Three subtypes of SODs Copper-Zinc (Cu/Zn-SOD), Manganese (Mn-SOD) and extracellular SOD (Ec-SOD) plasma activities were examined. Results: The activities of SODs were significantly lower in IPAH patients than in healthy subjects. However, only Ec-SOD activity with BMPR2 mutation patients were significantly decreased compared to those without mutation. Reduced Ec-SOD activity was markedly associated with mean pulmonary arterial pressure, pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD). Reduction of Mn-SOD activity was only associated with 6MWD, there was not association between Cu/Zn-SOD and hemodynamics. Patients with a lower Ec-SOD level had a worse survival compared to those with higher baseline. The reduced Ec-SOD activity and raised PVR remained an increased mortality risk. Conclusions: Ec-SOD was correlated with BMPR2 mutation, hemodynamic dysfunction and poor outcomes. Circulating Ec-SOD could be potentially vital antioxidant enzymes in pathogenesis of IPAH.

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