Reference Intervals for the Neutrophil to Lymphocyte Ratio (NLR) in the Elderly: Results from the Prospective Seniorlab Study

Abstract

Introduction: The neutrophil to lymphocyte ratio (NLR) has increasingly gained interest as an independent and easy to obtain prognostic factor of morbidity and mortality in malignant, immunologic, infectious, and cardiovascular disease. Whereas reference intervals in non-geriatric patients have already been described, such decision aids are so far lacking in the elderly. Thus, reference intervals for the NLR were evaluated in seniors, where diseases with NLR-associated prognosis are frequently encountered. Methods: Within the framework of the SENIORLAB study, subjectively healthy Swiss individuals aged 60 years and older were prospectively included and followed for morbidity and mortality. Participants who had circumstances known to affect the NLR were excluded (i.e., smoking, cancer, steroids, inflammation with CRP>5mg/L, known underlying hematological disease) as were participants, who did not survive during a prespecified follow-up period. Automated blood cell differential was measured with a Sysmex XE-5000 hematology analyzer (Sysmex, Horgen, Switzerland). Double sided 95%-reference intervals (RI) together with their 90% confidence intervals (CI) were calculated according to the Clinical and Laboratory Standards Institute (CLSI) guideline EP28-A3c by means of the robust method. Outliers were eliminated according to Tukey. Results: A total of 976 individuals (441 male/535 female) aged 60 to 99 years and a mean follow-up period of 3.7+/- 0.7 years were included into the study. NLR increased significantly with age (Spearman rank rho= 0.22; p<0.001) and males had a significantly higher median NLR (1.91, interquartile range, IQR [1.5,2.47]) than females (1.73, IQR [1,34,2.25]) (p<0.001). Thus, RI were stratified according to age and gender. In males, RI were 0.98 to 3.22 (90%CI [0.92,1.06] and [3.06,3.39]) at age 60-69 years, 0.95 to 4.28 (90%CI [0.88,1.02] and [3.90,4.69]) at age 70 to 79 years, and 1.01 to 6.43 (90%CI [0.90,1.14] and [5.36,7.66] at age 80 years and older. In females the respective RI's were: 0.83 to 3.38 (90% CI [0.79,0.88] and [3.12,3.66]) at age 60-69 years, 0.84 to 3.58 (90% CI [0.77,0.91] and [3.36,3.82]) at age 70-79 years, as well as 1.09 to 4.76 (90%CI [1.01,1-18] and [4.14,5.48]) at age 80 years and older. Conclusions: In the elderly, age, and sex specific differences in the NLR can be observed. Male sex and older age is associated with higher reference limits. An age and gender specific use of reference intervals for NLR is thus suggested in the elderly.