Prognostic Value of Oxidative Stress Markers in Patients with Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertension

Abstract

Oxidative stress is regarded to play a crucial role in the pathophysiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This study evaluated the prognostic value of serum oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), catalase activity (CAT), and superoxide activity (SOD)) in patients with PAH and CTEPH (n=45). During 13 months of follow-up (median 9 months), clinical deterioration occurred in 14 patients (including 2 deaths). On the Cox regression analysis, MDA, TAC, and CAT were associated with clinical deterioration (p=0.0068,HR=1.42, 95% CI: 1.10-1.82;p=0.0038,HR=0.033, 95% CI: 0.0032-0.33; andp=0.046,HR=0.20, 95% CI: 0.04-0.98, respectively). There was no significant difference in SOD (p=0.53,HR=0.97, 95% CI: 0.87-1.08). The cut-off value derived from ROC curve analysis was 3.79 μM (p=0.0048,AUC=0.76, 95% CI: 0.62-0.91) for MDA, 0.49 mM (p=0.027,AUC=0.71, 95% CI: 0.18-0.47) for TAC, and 1.34 U/L (p=0.029,AUC=0.71, 95% CI: 0.55-0.86) for CAT. MDA in the group with deterioration was higher (p=0.0041), while TAC as well as CAT were lower (p=0.027andp=0.028, respectively) when compared to stable patients. Survival without clinical deterioration was significantly longer in patients with lower MDA (p=0.037,HR=0.37, 95% CI: 0.12-1.14, log-rank), higher TAC (p=0.0018,HR=0.19, 95% CI: 0.06-0.60, log-rank), and higher CAT (p=0.044,HR=0.3195% CI: 0.11-0.88, log-rank). Markers of oxidative stress such as MDA, TAC, and CAT were associated with adverse clinical outcomes in patients with PAH and inoperable or residual CTEPH.