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Purpose There is evidence of complex interaction between vitamin B 12 (vB 12 ) level, hyperhomocysteinemia (HyCy), and natriuretic peptide secretion. Exercise training could also modulate such interaction. In this secondary analysis of a Randomized Clinical Trial performed in a chronic obstructive pulmonary disease (COPD) rehabilitation setting, our primary objective was to investigate the interaction between vB 12 supplementation, exercise training, and changes in NT-proBNP levels after 8 weeks of intervention. Secondary objectives were to explore the correlations between acute changes in NT-proBNP levels with (i) acute exercise and (ii) oxygen uptake ( V ’O 2 ) kinetics during rest-to-exercise transition. Methods Thirty-two subjects with COPD were randomized into four groups: Rehabilitation+vB 12 ( n = 8), Rehabilitation ( n = 8), vB 12 ( n = 8), or Maltodextrin( n = 8). They were evaluated at baseline and after 8 weeks, during resting and immediately after maximal exercise constant work-rate tests (CWTs, T lim), for NT-proBNP plasmatic levels. Results After interaction analysis, the supplementation with vB 12 significantly changed the time course of NT-proBNP responses during treatment ( p = 0.048). However, the final analysis could not support a significant change in NT-proBNP levels owing to high-intensity constant work-rate exercise ( p -value > 0.05). There was a statistically significant correlation between V ’O 2 time constant and ΔNT-proBNP values ( T lim – rest) at baseline ( p = 0.049) and 2 months later ( p = 0.015), considering all subjects ( n = 32). Conclusion We conclude that vB 12 supplementation could modulate NT-proBNP secretion. Moreover, possibly, the slower the initial V ’O 2 adjustments toward a steady-state during rest-to-exercise transitions, the more severe the ventricular chamber volume/pressure stress recruitment, expressed through higher NT-proBNP secretion in subjects with larger V ’O 2 time constants, despite unchanged final acute exercise-induced neurohormone secretion.

Non-anemic iron deficiency (NAID) is common in COPD, and could induce functional/structural changes in the pulmonary vascular bed. Thus, we aimed to study, during resting and ambient oxygen conditions, the systolic pulmonary arterial pressure (sPAP) changes during dobutamine stress echocardiography (DSE) for NAID+ compared to NAID-subjects with COPD. Patients and Methods: We analyzed 24 patients with COPD and evaluated their clinical parameters, including lung function and serum iron profile, followed by the changes in the sPAP under DSE. Results: Ten subjects with NAID+ were compared with fourteen NAID-subjects for sPAP measurement. At baseline, only left atrial volume was significantly different between groups (30±4 vs 23±5 mL * m 2 ), respectively (p-value=0.002). For the right side, tricuspid annular plane systolic excursion (TAPSE) was similar between-groups (22±2 vs 20±4, p-value >0.05), at baseline. The sPAP (mmHg) changes were also not significantly different between groups (pre 32±14 vs peak 48±14 for NAID+ and pre 29±7 vs peak 43±10 for NAID-, Group p-value=0.400, Time p-value <0.0001, and Interaction p-value=0.606). Conclusion: COPD subjects with NAID do not show increased sPAP responses during DSE, compared with iron-replete subjects.

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