The effect of docosahexaenoic acid on predicting the survival of patients with idiopathic pulmonary arterial hypertension

Ann Transl Med. 2021 Jun;9(12):995. doi: 10.21037/atm-21-2479.

Abstract

Background: Abnormal lipid metabolism has been reported in patients with idiopathic pulmonary arterial hypertension (IPAH); however, the prognostic value of plasma free fatty acids (FFAs) for these patients is unclear. The present study aimed to determine whether FFA can play a role in predicting the survival of patients with IPAH.

Methods: A total of 69 blood samples from patients with IPAH were subjected to liquid chromatography-mass spectrometry (LC-MS). According to the classification criteria for pulmonary hypertension in the European Society of Cardiology (ESC) guidelines, patients were divided into low-risk, intermediate-risk, and high-risk groups. The FFA expression levels of patients in the three groups were compared, and the indicators with significant differences were selected. Cox regression analysis was performed to examine the associations between survival and different factors. Receiver operator characteristic (ROC) curves were used to assess the predictive effect of plasma lipids in assessing patients' risk of morbidity, including area under the curve (AUC), sensitivity, specificity and the best cutoff value. Kaplan-Meier curves were used to predict survival.

Results: A total of 24 FFA molecules were detected in the patients with IPAH. Among them, FFA (20:4), FFA (20:5), FFA (22:5), FFA (22:6), FFA (24:0) and FFA (30:4) showed significant differences between the low-risk and the intermediate-risk or high-risk patients with IPAH. These six FFAs were significantly correlated with hemodynamic parameters. FFA (22:6), named docosahexaenoic acid (DHA), displayed significant negative correlations with World Health Organization functional classification (WHO FC), mean right atrial pressure (mRAP), and pulmonary vascular resistance (PVR), and significant positive correlations with 6-minute walking distance (6MWD) and cardiac index (CI). Cox regression analyses demonstrated that total bilirubin (TBIL) and DHA were independent risk factors for survival of IPAH. Receiver operating characteristic curve analysis revealed that DHA had a cut-off value of 77.55, which had a sensitivity of 96.7% and a specificity of 62.5% for predicting survival. Kaplan-Meier curve analysis showed that a lower level of DHA predicted a poor outcome in patients with IPAH.

Conclusions: Our study suggested that FFA levels were correlated with disease severity. Lower levels of DHA predict poor survival in patients with IPAH.

Keywords: Idiopathic pulmonary arterial hypertension (IPAH); biomarker; docosahexaenoic acid (DHA); free fatty acids (FFAs); prognosis.