Measuring cardiorespiratory fitness in a blood sample. Higher NT-pro-BNP and HS-CRP levels correlate with reduced VO2-peak but not 6-minute walk distance

Abstract
Background
The CopenHeart trials investigated the effects of cardiac rehabilitation in patients treated for atrial fibrillation with ablation (RFA), patients after infective endocarditis (IE), and after heart valve surgery (VR).

Cardiorespiratory fitness (CRF) is a key measurement for evaluating cardiac patients, with higher CRF linked to lower mortality. Maximum oxygen uptake (VO2-peak), measured during exercise, is a prognostic parameter of CRF but has limitations. Therefore, biomarkers that offer quantitative and objective knowledge of CFR are warranted. Brain natriuretic peptide (BNP) is produced by the ventricles in response to damage, myocardial stretch, or ischemia. N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is the biologically inactive peptide that is cleaved off the pro-hormone, proBNP. Higher levels of both peptides have been associated with poorer cardiac outcomes in patients with cardiac conditions.

The aim of this study was to investigate whether NT-pro-BNP and HS-CRP (high sensitive CRP) can be used as biomarkers of CFR (VO2-peak and 6 minutes walk distance (6MWD)) and their change over time in patients with RFA, VR or IE.

Study Design and Methods
We used data from 342 participants included in the CopenHeart trials with complete data on NT-pro-BNP, HS-CRP, 6MWD and VO2-peak at baseline.

Results
Of the 342 participant, 242 completed follow-up at 4 months and 222 at 12 months.

Multivariate models, adjusting for age group, sex and cardiac complications showed that higher baseline NT-pro-BNP and HS-CRP was associated with lower VO2-peak (p=0.002 and p=0.006). Addition of NT-pro-BNP and HS-CRP in the same model showed similar results (see figure 1 and 2). VO2-peak was higher among individuals with RFA compared to IE, and VO2-peak decreased significantly by higher age group compared to age <50 years. However, higher baseline NT-pro-BNP and HS-CRP was not associated with poorer/shorter 6MWD. Compared to participants after IE, participants in the RFA and VR groups had better 6MWD, and 6MWD decreased significantly by higher age group compared to age <50 years.

Neither NT-pro-BNP nor HS-CRP at baseline was associated with changes in VO2-peak or 6MWD from baseline until 4th months.

Conclusion
Higher baseline NT-pro-BNP and HS-CRP was associated with lower VO2-peak, but not 6MWT. Since VO2 peak is considered the most valid CRF test, the results could indicate that higher NT-pro-BNP and HS-CRP is associated with lower CRF in patients with RFA, IE and VR similarly to patients with other cardiovascular diseases.