Elevated Neutrophil-Lymphocyte Ratio is Associated with a Poorer Cardiopulmonary Exercise Test Performance in Patients with Heart Failure

Abstract

Background The neutrophil-lymphocyte ratio (NLR) is an easily-obtained biomarker of systemic inflammation. An elevated NLR represents greater inflammatory activation and has been associated with higher mortality in patients with heart failure (HF), including after left ventricular assist device implantation. We sought to determine whether NLR is associated with the metabolic response to exercise in patients undergoing cardiopulmonary exercise testing (CPET) for diagnostic or prognostic indications. Methods We retrospectively reviewed CPETs performed between 4/2017 and 11/2018 at a single tertiary center. We included only the first CPET for unique patients, performed for an indication of cardiomyopathy or HF (systolic or diastolic). Patients referred for congenital or valvular heart disease were excluded. Baseline demographics and key CPET parameters were recorded and NLR noted if performed within 100 days of CPET. Pearson correlation coefficients were calculated between NLR and key CPET parameters. Two linear regression models were constructed, to determine the relationship between the NLR and peak oxygen consumption (pkVO2) or minute ventilation/carbon dioxide production slope (VE/VCO2), respectively. Each model was adjusted for age, sex and body mass index (BMI). Results There were 142 CPETs during the study period, of which 121 met inclusion criteria and 94 had an NLR value. The cohort (n=94) was 30% female, with primary cardiac conditions identified as non-ischemic cardiomyopathy in 42%, ischemic cardiomyopathy in 38%, hypertrophic cardiomyopathy in 13% and HF with preserved ejection fraction in 7%. Median age was 60 years, BMI 29.2 kg/m2 and NLR 2.58 (quartile range 1.76-4.00). The median CPET parameters achieved were exercise time 9.0 min, metabolic equivalents (METS) 5.3, respiratory exchange ratio (RER) 1.10, pkVO2 1.18 L/min, pkVO2 adjusted for weight 14.2 mL/kg/min, VE/VCO2 35. There was a negative correlation between NLR and pkVO2 (r=-0.24, p=0.020) or weight-adjusted pkVO2 (r=-0.22, p=0.033, Fig 1A) and a positive correlation between NLR and VE/VCO2 (r=0.31, p= 0.003, Fig 1B). On multivariable regression, the NLR remained significantly associated with both the pkVO2 (p=0.048) and the VE/VCO2 (p=0.013) after adjustment for age, sex and BMI. Conclusion Greater systemic inflammation, represented by a higher NLR, is associated with poorer CPET performance in patients with HF, as characterized by a lower pkVO2 and higher VE/VCO2. Systemic inflammation is an important correlate of functional limitations for patients with HF and warrants further investigation as a therapeutic target.