Introduction It is increasingly recognised that inflammation plays an important role in the pathogenesis and progression of heart failure (HF) and may have important therapeutic and diagnostic implications. Research has shown that raised inflammatory cytokines are associated with adverse outcomes, however these are not routinely assessed in clinical practice. The aim of this study was to evaluate the association of neutrophil to lymphocyte ratio (NLR), a simple, routinely-measured parameter of inflammatory status, with prognostic outcomes in a cohort of HF patients.
Methods Patients who had survived to 30 days or discharge following an initial HF hospitalisation from the Genetics of Diabetes and Audit Research Tayside Scotland (GoDARTS) study were included. Baseline clinical and demographic data were obtained from electronic health records. Patients with available echocardiography were used to perform a stratified analysis (HFrEF – ejection fraction <50%, HFpEF ≥50%). NLR was calculated from baseline blood results taken nearest the time of initial HF diagnosis (within 90 days). The primary outcome was combined all-cause mortality or HF hospitalisation.
Results In total 1,157 patients with HF were included (mean age 73 years, 61.7% male, 740 HFrEF, 417 HFpEF), 847 reached primary outcome (713 deaths and 471 HF admissions). Median follow-up was 769 days. In multivariable analysis (adjusting for blood-pressure, cholesterol, age, gender, diabetes and smoking status) higher NLR at the time of HF diagnosis was significantly associated with the primary outcome (HR 1.04; 95% CI 1.02–1.05, p<0.001) and the individual endpoints (all-cause mortality HR 1.03; 95% CI 1.02–1.05, p<0.001; HF hospitalisation HR 1.03; 95% CI 1.01–1.05, p=0.002). When stratified by ejection fraction higher NLR at the time of admission was significantly associated with the primary outcome in both HFrEF (HR 1.04; 95% CI 1.03–1.06, p <0.001) and HFpEF (HR 1.04; 95% CI 1.01–1.06, p=0.002) and all-cause mortality (HFrEF HR 1.03; 95% CI 1.02–1.05, p<0.001, HFpEF HR 1.04; 95% CI 1.02–1.07, p=0.01). NLR was only associated with HF hospitalisation alone in HFrEF HR 1.04; 95% CI 1.02–1.06, p<0.001; HFpEF HR 1.01; 95% CI 0.96–1.05, p=0.9). Interaction testing showed no significant difference in the association of NLR and the primary outcome (p-value 0.65), or individual end-points (all-cause mortality p=0.47, HF hospitalisation p=0.22) based on ejection fraction. Results of Kaplan-Meier (KM) analysis highlighting the association between NLR Tertiles and the primary outcome in HFpEF and HFrEF can be seen in Figure 1. and Figure 2, respectively.
Conclusion We found that NLR, a simple measure of inflammation was significantly associated with prognosis in HFrEF and HFpEF. These results support the growing consensus that inflammation plays a key role in HF. Future research should focus on comparing the NLR with established markers in HF, and the potential use of anti-inflammatory interventions targeting NLR in the treatment of HF.
Kaplan-Meier curves of the association between NLR Tertiles and the primary outcome in HFpEF and HFrEF:
Conflict of Interest No
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