8-Isoprostanes and Asymmetric Dimethylarginine as Predictors of Mortality in Patients Following Coronary Bypass Surgery: A Long-Term Follow-Up Study.

Aleksandra Gołąb,Anetta Undas,Bogusław Gawęda,Anna Rzucidło-Hymczak,Bogusław Kapelak,Dariusz Plicner,Lidia Tomkiewicz-Pająk

doi:10.3390/jcm11010246

Abstract

Background: We previously demonstrated that enhanced oxidative stress and reduced nitric oxide bioavailability are associated with unfavorable outcomes early after coronary artery bypass grafting. It is not known whether these processes may impact long-term results. We sought to assess whether during long-term follow-up, markers of oxidative stress and nitric oxide bioavailability may predict cardiovascular mortality following bypass surgery. Methods: We studied 152 consecutive patients (118 men, age 65.2 ± 8.3 years) who underwent elective, primary, isolated on-pump bypass surgery. We measured plasma 8-iso-prostaglandin F2α and asymmetric dimethylarginine before surgery and twice after surgery (18–36 h and 5–7 days). We assessed all-cause and cardiovascular death in relation to these two biomarkers during a mean follow-up time of 11.7 years. Results: The overall mortality was 44.7% (4.7 per 100 patient-years) and cardiovascular mortality was 21.0% (2.2 per 100 patient-years). Baseline 8-iso-prostaglandin F2α was associated with cardiovascular mortality (HR 1 pg/mL 1.010, 95% CI 1.001–1.021, p = 0.036) with the optimal cut-off ≤ 364 pg/mL for higher survival rate (HR 0.460, 95% CI 0.224–0.942, p = 0.030). Asymmetric dimethylarginine > 1.01 μmol/L measured 18–36 h after surgery also predicted cardiovascular death (HR 2.467, 95% CI 1.140–5.340, p = 0.020). Additionally, elevated 8-iso-prostaglandin F2α measured at the same time point associated with all-cause mortality (HR 1 pg/mL 1.007, 95% CI 1.000–1.014, p = 0.048). Conclusions: Our findings indicate that in advanced coronary disease, increased oxidative stress, reflected by 8-iso-prostaglandin F2α before bypass surgery and enhanced asymmetric dimethylarginine accumulation just after the surgery are associated with cardiovascular death during long-term follow-up

Highlights

The disproportion between the production of reactive oxygen species (ROS) and antioxidant clearance, termed as oxidative stress, has been involved in the pathogenesis of several disorders [1,2,3]
We have shown that a significant increase of Asymmetric dimethylarginine (ADMA) and oxidative stress, reflected by
All coronary artery bypass grafting (CABG) procedures were performed between January and March 2008 and each patient received both an internal mammary artery and a saphenous vein grafts

Summary

Introduction

The disproportion between the production of reactive oxygen species (ROS) and antioxidant clearance, termed as oxidative stress, has been involved in the pathogenesis of several disorders [1,2,3]. Numerous reports have demonstrated that enhanced oxidative stress is associated with coronary artery disease [4]. Asymmetric dimethylarginine (ADMA), a natural inhibitor of nitric oxide synthase, has been shown to accumulate in oxidative stress reducing the nitric oxide bioavailability which, among others, results in the inhibition of ROS inactivation [7]. We previously demonstrated that enhanced oxidative stress and reduced nitric oxide bioavailability are associated with unfavorable outcomes early after coronary artery bypass grafting. It is not known whether these processes may impact long-term results. We sought to assess whether during long-term follow-up, markers of oxidative stress and nitric oxide bioavailability may predict cardiovascular mortality following bypass surgery. Results: The overall mortality was 44.7% (4.7 per 100 patient-years) and cardiovascular mortality was 21.0%

Methods

Results

Discussion

Conclusion