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

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.