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

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

Keywords

• coronary artery bypass grafting
• asymmetric dimethylarginine
• oxidative stress
• 8-iso-prostaglandin F_2α
• long-term cardiovascular death