The neutrophil-lymphocyte ratio as a risk factor for all-cause and cardiovascular mortality among individuals with diabetes: evidence from the NHANES 2003-2016

Abstract

Background: Evidence regarding the neutrophil-lymphocyte ratio (NLR) and mortality risk in diabetes patients is scarce. This study investigated the relationship of the NLR with all-cause and cardiovascular mortality risk in diabetes patients.

Methods: Diabetes patients (n = 3251) from seven National Health and Nutrition Examination Survey (NHANES) cycles (2003-2016) were included in this study. The cause of death and mortality status of the participants were obtained from National Death Index records. Restricted cubic spline (RCS) was used to visualize the association of the NLR with mortality risk. The maximally selected rank statistics method (MSRSM) was used to determine the optimal NLR cutoff value corresponding to the most significant association with survival outcomes. Weighted multivariable Cox regression models and subgroup analyses were adopted to assess the association of the NLR with all-cause and cardiovascular mortality. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to evaluate the accuracy of the NLR in predicting survival outcomes.

Results: During a median follow-up of 91 months (interquartile range, 55-131 months), 896 (27.5%) of the 3251 diabetes patients died, including 261 (8.0%) with cardiovascular deaths and 635 (19.5%) with noncardiovascular deaths. The RCS regression analysis showed a positive linear association between the NLR and all-cause and cardiovascular mortality (both p > 0.05 for nonlinearity) in diabetes patients. Participants were divided into higher (> 3.48) and lower (≤ 3.48) NLR groups according to the MSRSM. In the multivariable-adjusted model, compared with participants with a lower NLR, those with a higher NLR had a significantly higher risk of both all-cause (HR 2.03, 95% confidence interval (CI) 1.64-2.51, p < 0.0001) and cardiovascular mortality (HR 2.76, 95% CI 1.84-4.14, p < 0.0001). The association was consistent in subgroup analyses based on age, sex, smoking status, drinking status, and hypertension, with no significant interaction between the aforementioned characteristics and the NLR (p interaction > 0.05). The time-dependent ROC curve showed that the areas under the curve of the 1-, 3-, 5-, and 10-year survival rates were 0.72, 0.66, 0.64, and 0.64 for all-cause mortality and 0.69, 0.71, 0.69 and 0.65, respectively, for cardiovascular mortality.

Conclusion: An elevated NLR is independently associated with increased all-cause and cardiovascular mortality in diabetes patients.

Keywords: All-cause mortality; Cardiovascular mortality; Diabetes; Neutrophil lymphocyte ratio.

Fig. 1

The flow chart of participants inclusion and exclusion in current study

Fig. 2

The cutoff point was calculated using the maximally selected rank statistics based on the ‘maxstat’ package. SLRS indicates Standardized Log-Rank Statistic

Fig. 3

The association of NLR with all-cause (A) and cardiovascular mortality (B) among diabetes visualized by restricted cubic spline (NLR breakpoint: 3.48). Hazard ratios were adjusted for age, sex, race, BMI, smoking status, drinking status, hypertension, HDL, LDL, TG, TC, HbA1c, education level, the family income-to-poverty ratio and the eGFR. Both p value for nonlinearity > 0.05

Fig. 4

Kaplan–Meier curves of the survival rate and the number (%) of at-risk diabetes patients with higher (> 3.48) and lower (≤ 3.48) NLR values. A All-cause mortality. B cardiovascular mortality

Fig. 5

Time-dependent ROC curves and time-dependent AUC values (with 95% confidence band) of the NLR for predicting all-cause mortality (A, B) and cardiovascular mortality (C, D)