Neutrophil-to-Lymphocyte Ratio Identifies a Pulmonary Vascular High-Risk Phenotype in Heart Failure with Preserved Ejection Fraction

Background: Pulmonary vascular disease identifies an important phenotype of heart failure with preserved ejection fraction (HFpEF), but the relationship between systemic leukocyte activation and invasively measured pulmonary vascular hemodynamics is incompletely understood. We investigated whether the neutrophil-to-lymphocyte ratio (NLR) is associated with combined post- and precapillary pulmonary hypertension (CpcPH), pulmonary vascular burden, and subsequent cardiovascular events in HFpEF. Methods: We retrospectively studied 169 adults with HFpEF and invasively confirmed postcapillary pulmonary hypertension undergoing clinically indicated right heart catheterization. CpcPH was defined as pulmonary vascular resistance (PVR) >2 Wood units. Associations between NLR and CpcPH were evaluated using multivariable logistic regression. Fine-Gray competing-risk models assessed the composite of cardiovascular death or first heart failure hospitalization. Results: Overall, 80 patients had isolated postcapillary pulmonary hypertension and 89 had CpcPH. PVR increased across ascending NLR tertiles (1.8 [1.4-2.5], 2.2 [1.6-3.1], and 2.6 [1.7-3.8] Wood units; P for trend=0.002), whereas pulmonary artery wedge pressure showed no significant trend. Compared with the lowest NLR tertile, the highest tertile was associated with greater odds of CpcPH after adjustment for clinical covariates and filling pressure (adjusted odds ratio, 2.47 [95% CI, 1.01-6.01]; P=0.047). Higher NLR tertiles were also associated with a graded increase in cardiovascular events (Gray's P<0.001). The highest NLR tertile remained associated with outcome after adjustment for clinical and hemodynamic variables (adjusted subdistribution hazard ratio [sHR], 2.37 [95% CI, 1.12-5.03]; P=0.024). Conclusions: Among patients with HFpEF and postcapillary pulmonary hypertension, higher NLR was associated with greater pulmonary vascular hemodynamic burden, CpcPH, and subsequent cardiovascular risk. NLR may provide a readily available marker of a high-risk HFpEF phenotype warranting prospective validation.