Circulating neutrophils as a marker of systemic inflammation in heart failure with preserved ejection fraction

Aim. To assess the count and phenotype of circulating neutrophils in patients with varying severity of heart failure with preserved ejection fraction (HFpEF).

Material and methods. The study included 42 patients with HFpEF (men, 43%; median age, 73 years); 15 asymptomatic patients (men, 67%; median age, 60 years) formed the control group. Total neutrophil (CD11b+CD66b+) and activated degranulating neutrophil counts (CD11bhighCD66bhigh) were determined in peri­pheral blood samples using direct immunofluorescence and flow cytometry. Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and plasma C-reactive protein (CRP) concentrations were measured using commercial enzyme-linked immunosorbent assay kits.

Results. Patients with HFpEF were older and had worse functional status compared to controls. Fifteen patients with HFpEF had early-stage disease (increased left ventricular (LV) filling pressure (FP) only during exercise), while 27 had advanced di­sease (increased LVFP at rest). In the HFpEF group, the absolute neutrophil count in the blood was higher compared to the control (4,0 (3,2; 5,3) vs, 3,0 (2,8; 4,3) thousand/μl, p=0,027), mainly due to activated neutrophils (0,74 (0,38; 1,27) vs 0,37 (0,29; 0,72) thousand/μl, p=0,038). The total neutrophil count and the number of activated cells were significantly higher in severe HFpEF compared to the initial disease stage, and in HFpEF patients with NT-proBNP levels above the median (≥318 pg/ml). The predictive value of the absolute neutrophil count and the number of activated cells for HFpEF detection exceeded the CRP value (according to ROC analysis, AUC 0,69 (95% confidence interval (CI) 0,54-0,84), p=0,025 and 0,69 (95% CI 0,54-0,83), p=0,021, respectively, versus 0,64 (95% CI 0,48-0,79), p=0,078). With a combination of an increased blood count of neutrophil granulocytes and an increased CRP level, the odds of HFpEF tended to increase (odds ratio=5,3 at 95% CI 0,85-32,4, p=0,074).

Conclusion. The absolute count of circulating neutrophils, including activated cells, characterizes the severity of HFpEF. The obtained results confirm the contribution of innate immunity to disease development.

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