Neutrophil to high-density lipoprotein cholesterol ratio as a potential inflammatory marker for predicting all-cause mortality in out-of-hospital cardiac arrest survivors

Abstract

Out-of-hospital cardiac arrest (OHCA) survivors have more than one-third mortality rate. Numerous inflammatory indicators are available, and it should be feasible to identify a fast and accurate way to aid medical decisions. This retrospective cohort study included 247 patients with OHCA, hospitalized between January 2015 and August 2024. The study was conducted in the intensive care unit of China Medical University Hospital, Taichung, Taiwan. A variety of inflammatory markers, including interleukin-6, neutrophil to high-density lipoprotein cholesterol ratio (NHR), and C-reactive protein, were screened at 24 h after OHCA. The primary endpoint was the 90-day all-cause mortality. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves of NHR were analyzed. Possible risk factors for all-cause mortality were estimated by Cox regression modeling. NHR and interleukin-6 were similarly predictive of all-cause mortality in inflammatory response, and both were superior to C-reactive protein at 24 h after OHCA (p < 0.001). The area under the ROC curve of NHR was 0.74 (95% confidence interval [CI]: 0.66-0.81, p < 0.001), sensitivity: 0.68, and specificity: 0.68, and NHR = 16.1. The 90-day all-cause mortality rate for NHR > 16.1 compared to those with NHR ≤ 16.1 was 0.51 and 0.21, respectively, according to Kaplan-Meier curves analysis. The hazard ratio for NHR > 16.1 was 2.54 (95% CI: 1.68-3.82, p < 0.001). An NHR > 16.1 at 24 h after OHCA is a potential inflammatory marker for predicting all-cause mortality.

Keywords: Cardiac arrest; High-density lipoprotein cholesterol; Neurological outcomes; Neutrophils; Systemic inflammatory response.

Fig. 1

STROBE flow chart of OHCA survivors.

Fig. 2

Sub-analysis of cholesterol and NHR according to CPC. (A) Sub-analysis of cholesterol according to CPC. CPC 1–4 vs. CPC 5 data of cholesterol as below: RC: 22.7 ± 13.2 vs. 23.0 ± 13.4 mg/dL, p = 0.85; HDL-C: 35.7 ± 10.3 vs. 26.4 ± 11.2 mg/dL, p < 0.001; LDL-C: 96.3 ± 45.5 vs. 65.8 ± 26.8 mg/dL, p < 0.001. (B) Sub-analysis of NHR according to CPC. CPC 1–4 vs. CPC 5 data of NHR as below: 12.8 ± 6.4 vs. 19.2 ± 10.3, p < 0.001. NHR neutrophil to high-density lipoprotein-cholesterol ratio, CPC cerebral performance categories, RC remnant-cholesterol, HDL-C high-density lipoprotein-cholesterol, LDL-C low-density lipoprotein-cholesterol.

Fig. 3

ROC curves of inflammatory markers and Kaplan–Meier survival curves of NHR. (A) Area under the ROC curve of NHR = 0.74 (95% CI: 0.66–0.81, p < 0.001), similar as that of IL-6 = 0.69 (95% CI: 0.62–0.76, p < 0.001). The AUC of NHR or IL-6 all were better than that for CRP = 0.58 (95% CI: 0.51–0.63, p = 0.18). NHR = 16.1 with maximal Youden index, sensitivity = 0.68, and specificity = 0.68. (B) The 90-day survival rate for NHR ≤ 16.1 compared with that for NHR > 16.1 was 0.79 and 0.49, respectively, according to Kaplan-Meier curves analysis. ROC receiver operating characteristic curve, NHR neutrophil to high-density lipoprotein cholesterol ratio, CI confidence interval, IL-6 interleukin-6, AUC the area under the ROC curve, CRP C-reactive protein.

Fig. 4

Ninety-day mortality rate-adjusted covariables of OHCA survivors using the Cox regression model.

Fig. 5

The difference between chronic and acute inflammation-related immune and metabolic markers.