Leukocyte Indices as Markers of Inflammation and Predictors of Outcome in Heart Failure with Preserved Ejection Fraction

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil-lymphocyte ratio (NLR), the monocyte-lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22-78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11-70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38-2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14-1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30-2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22-2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06-2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10-2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF.