AUTHOR=van Wezenbeek Jessie , Canada Justin M. , Ravindra Krishna , Carbone Salvatore , Trankle Cory R. , Kadariya Dinesh , Buckley Leo F. , Del Buono Marco , Billingsley Hayley , Viscusi Michele , Wohlford George F. , Arena Ross , Van Tassell Benjamin , Abbate Antonio 

TITLE=C-Reactive Protein and N-Terminal Pro-brain Natriuretic Peptide Levels Correlate With Impaired Cardiorespiratory Fitness in Patients With Heart Failure Across a Wide Range of Ejection Fraction

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=5

YEAR=2018

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2018.00178

DOI=10.3389/fcvm.2018.00178

ISSN=2297-055X

ABSTRACT=<p><bold>Background:</bold> Impaired cardiorespiratory fitness (CRF) is a hallmark of heart failure (HF). Serum levels of C-reactive protein (CRP), a systemic inflammatory marker, and of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker of myocardial strain, independently predict adverse outcomes in HF patients. Whether CRP and/or NT-proBNP also predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established.</p><p><bold>Methods:</bold> Using retrospective analysis, 200 patients with symptomatic HF who completed one or more treadmill cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day were evaluated. Univariate and multivariate correlations were evaluated with linear regression after logarithmic transformation of CRP (log<sub>10</sub>) and NT-proBNP (log<sub>N</sub>).</p><p><bold>Results:</bold> Mean age of patients was 57 ± 10 years and 55% were male. Median CRP levels were 3.7 [1.5–9.0] mg/L, and NT-proBNP levels were 377 [106–1,464] pg/ml, respectively. Mean peak oxygen consumption (peak VO<sub>2</sub>) was 16 ± 4 mlO<sub>2</sub>•kg<sup>−1</sup>•min<sup>−1</sup>. CRP levels significantly correlated with peakVO<sub>2</sub> in all patients (<italic>R</italic> = −0.350, <italic>p</italic> &lt; 0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF) (HFrEF, <italic>N</italic> = 109) (<italic>R</italic> = −0.282, <italic>p</italic> &lt; 0.001) and in those with preserved EF (HFpEF, <italic>N</italic> = 57) (<italic>R</italic> = −0.459, <italic>p</italic> &lt; 0.001). NT-proBNP levels also significantly correlated with peak VO<sub>2</sub> in all patients (<italic>R</italic> = −0.330, <italic>p</italic> &lt; 0.001) and separately in patients with HFrEF (<italic>R</italic> = −0.342, <italic>p</italic> &lt; 0.001) and HFpEF (<italic>R</italic> = −0.275, <italic>p</italic> = 0.032). CRP and NT-proBNP did not correlate with each other (<italic>R</italic> = 0.05, <italic>p</italic> = 0.426), but independently predicted peak VO<sub>2</sub> (<italic>R</italic> = 0.421, <italic>p</italic> &lt; 0.001 and <italic>p</italic> &lt; 0.001, respectively).</p><p><bold>Conclusions:</bold> Biomarkers of inflammation and myocardial strain independently predict peak VO<sub>2</sub> in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.</p>