Neutrophil-to-Lymphocyte Ratio Identifies a Pulmonary Vascular High-Risk Phenotype in Heart Failure with Preserved Ejection Fraction
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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.
Clinical Perspective
What Is New?
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In patients with HFpEF and invasively confirmed postcapillary pulmonary hypertension, higher neutrophil-to-lymphocyte ratio (NLR) was associated with progressively greater pulmonary vascular resistance without a corresponding significant increase in left-sided filling pressure.
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Higher NLR was associated with greater odds of combined post- and precapillary pulmonary hypertension and with increased risk of cardiovascular death or first heart failure hospitalization, with the prognostic association persisting after adjustment for clinical and invasive hemodynamic variables.
What Are the Clinical Implications?
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NLR, a readily available blood-count-derived marker, may complement invasive hemodynamic phenotyping by identifying patients with HFpEF-associated pulmonary hypertension who have greater pulmonary vascular burden and higher cardiovascular risk, although prospective validation is required before its use for clinical decision-making.
