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Front. Cardiovasc. Med. | doi: 10.3389/fcvm.2018.00178

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

 Jessie v. Wezenbeek1, Justin M. Canada1,  Krishna Ravindra1,  Salvatore Carbone1, Cory R. Trankle1,  Dinesh Kadariya1, Leo Buckley1,  Marco D. Buono1, Hayley Billingsley1,  Michele Viscusi1, George Wohlford1, Ross Arena2, Benjamin V. Tassell1 and  Antonio Abbate1*
  • 1Virginia Commonwealth University, United States
  • 2University of Illinois at Chicago, United States

Background. 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
Methods. 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 (log10) and NT-proBNP (logN).
Results. 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 [106-1464] pg/ml, respectively. Mean peak oxygen consumption (peak VO2) was 16±4 mlO2•kg-1•min-1. CRP levels significantly correlated with peakVO2 in all patients (R=-0.350, p <0.001) and also separately in the subgroup of patients with reduced left ventricular ejection fraction (LVEF)(HFrEF, N=109)(R=-0.282, p<0.001) and in those with preserved EF (HFpEF, N=57)(R=-0.459, p<0.001). NT-proBNP levels also
significantly correlated with peak VO2 in all patients (R=-0.330, p<0.001) and separately in
patients with HFrEF (R=-0.342, p<0.001) and HFpEF (R=-0.275, p=0.032). CRP and NT-
proBNP did not correlate with each other (R=0.05, p=0.426), but independently predicted
peak VO2 (R=0.421, p<0.001 and p<0.001, respectively).
Conclusions. Biomarkers of inflammation and myocardial strain independently predict peak VO2 in HF patients. Anti-inflammatory therapies and therapies alleviating myocardial strain may independently improve CRF in HF patients across a large spectrum of LVEF.

Keywords: CRP - C-reactive protein, bnp, Inflammation, Heart Failure, exercise capacity

Received: 12 Sep 2018; Accepted: 30 Nov 2018.

Edited by:

Pietro Enea Lazzerini, Università degli Studi di Siena, Italy

Reviewed by:

Gaetano Ruocco, Università degli Studi di Siena, Italy
Carl Lavie, Ochsner Medical Center, United States  

Copyright: © 2018 Wezenbeek, Canada, Ravindra, Carbone, Trankle, Kadariya, Buckley, Buono, Billingsley, Viscusi, Wohlford, Arena, Tassell and Abbate. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Antonio Abbate, Virginia Commonwealth University, Richmond, United States,