Purpose: To evaluate the effects of cardiovascular rehabilitation on the endothelial function, assessed through changes of circulating blood markers of endothelial function: the stable end product of Nitric oxide (NOx), Xanthine Oxidase (XO) and Advanced Oxidation Protein Products (AOPP), and its association with hypertensive response to exercise in patients (pts) with stable coronary artery disease (CAD).
Design and methods: 88 subjects; 70pts with stable CAD (CAD group, 55.98±8.12 years, 55 men) and 18 healthy controls (H group; 55.1±8.0 years, 11 men) were studied. At baseline in all pts and controls, values of NOx, XO and AOPP were determined and exercise test was performed. After the initial study, all patients underwent a supervised 3 weeks exercise training at residential center, and after that period values of NOx, XOD and AOPP as well as exercise tolerance were determined again.
Results: After 3 weeks NOx increased in CAD group (from 41.19±14.09 to 50.16±16.27 μmol/L, P<0.001); XO decreased (from 317.42±35.71 to 209.83±29.33 μmol/L, P<0.001) and AOPP also decreased (from 217.71±115.77 to 192.91±114.63 μmol/L, P<0.001). Exercise capacity increased from 6.03±1.54 to 7.34±2.21 METs in CAD group, and SBP per minute changes during the first exercise test were 5.12±4.28 mmHg/min; value of SBP per minute changes during the second exercise test in CAD group, at the level on which the first exercise test was ended were 3.25±1.58 mmHg/min, P<0.001. Baseline values of NOx was significantly lower in CAD than in H group (73.29±30.37 μmol/L, P<0.001), also second measurements (P<0.001). Second measurements of XO and AOPP in CAD group also observed a trend of approaching to H group values (XO, 100.19±29.88 μmol/L, P<0.001) and (AOPP, 80.83±33.9 μmol/L, P<0.001). Exercise capacity (METs) at baseline were significantly lower in CAD than in H group (P<0.001), and it significantly increase in CAD group after exercise period (P<0.001). A positive correlation in difference achieved during exercise period was found between SBP per minute decrease and NOx level increase (r=0.664, P<0.001); SBP per minute decrease and XO decrease (r=0.757, P<0.001); SBP per minute decrease and AOPP level decrease (r=0.817, P<0.001). Also, positive correlation in difference achieved during exercise period was found between increase in NOx and decrease in XO (r=0.754, p<0.001), between decrease in XO and decrease in AOPP (r=0.764, p<0.001).
Conclusion: Regular physical exercise leads to an improvement in endothelial function in patients with stable CAD. Results show coherence between SBP per minute changes during exercise test and biomarkers of endothelial function. Improvement in endothelial function is associated with significant improvement in exercise capacity, also beneficial changes in NOx, XO and AOPP may induce favorable changes in vascular tone, and hence they might contribute to better SBP regulation during exercise.