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.

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

doi:10.3389/fcvm.2018.00178

Abstract

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 established.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 [106–1,464] 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.

Highlights

Heart failure (HF) is a syndrome that presents clinically with dyspnea, fatigue, and/or edema caused by structural or functional cardiac defects that lead to reduced cardiac output and/or increased cardiac pressure at rest or during stress
The objective of this study was to investigate whether C-reactive protein (CRP) and/or NT-proBNP can independently predict cardiorespiratory fitness (CRF) impairment, defined as reduced peak Peak Oxygen Consumption (VO2) in patients with heart failure (HF) across a wide range of ejection fraction
We retrospectively queried a database of de-identified data that was prospectively collected data from patients with symptomatic HF who completed one or more cardiopulmonary exercise tests (CPX) using a symptom-limited ramp protocol on a treadmill and had paired measurements of serum high-sensitivity CRP and NT-proBNP on the same day

Summary

Introduction

Heart failure (HF) is a syndrome that presents clinically with dyspnea, fatigue, and/or edema caused by structural or functional cardiac defects that lead to reduced cardiac output and/or increased cardiac pressure at rest or during stress. C-reactive protein (CRP), a marker for systemic inflammation, is produced by the hepatocytes upon inflammation, infection, or tissue injury [4]. Patients with HF show signs of chronic systemic inflammation, as shown by elevated serum levels of CRP [5]. Higher CRP levels are associated with worse cardiopulmonary exercise performance in patients with ischemic heart disease and systolic HF [8, 9]. 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 predict the degree of CRF impairment in HF patients across a wide range of ejection fraction is not yet established

Objectives

Methods

Results