Exercise Stress Testing Enhances Plasma Protein Carbonyl Levels in Patients With Asymptomatic Moderate-to-Severe Aortic Stenosis.

Abstract

Background: Exercise stress test-induced hypofibrinolysis and changes in circulating levels of several interleukins have been observed in aortic stenosis (AS). However, it is unknown whether the pattern of exercise-induced changes in oxidative stress differs between AS patients and controls and if the differences are associated with changes in fibrinolysis and inflammation. Methods: We studied 32 asymptomatic patients with moderate-to-severe AS and 32 controls of similar age, sex, and body mass index. We assessed plasma protein carbonyl (PC) concentrations, a marker of oxidative stress, in relation to interleukin (IL)-10 and -6 levels and fibrinolysis capacity, expressed as plasma clot lysis time (CLT) at four time points: at baseline, at peak exercise, 1 and 24 h after a symptom-limited exercise test. Results: AS patients had 12.8% and 27% higher PC concentrations 1 and 24 h after exercise than controls (both p  < 0.05), with no differences at baseline and peak exercise. In AS patients, PC concentration was 8.3% higher at peak exercise compared to baseline followed by further PC increase (+12.8% at 1 h and +20.5% at 24 h) compared to peak exercise (all p  < 0.05). In controls, PC concentrations increased during exercise, reaching the highest values 1 h after exercise (+21.9%). In the AS group, PC concentrations at baseline correlated with AS severity measured as peak transvalvular velocity (V _max: r = 0.49, p  < 0.05), mean (PG_mean: r = 0.42, p  < 0.05), and maximal transvalvular pressure gradients (PG_max: r = 0.41, p  < 0.05). PC concentrations correlated with IL-10 levels 1 h (r = 0.37, p  < 0.05) and 24 h (r = 0.38, p  < 0.05) post exercise in AS patients, whereas in controls only at baseline (r = 0.42, p  < 0.05). No associations between PC levels and IL-6 or CLT were observed at any time point. Conclusions: Our findings show that AS patients respond differently to exercise in terms of PC compared to controls, which suggests a novel effect of hemodynamic abnormalities in this disease on intensity of oxidative stress.