Among 169 adults with HFpEF and invasively confirmed postcapillary pulmonary hypertension, higher neutrophil-to-lymphocyte ratio (NLR) tracked closely with pulmonary vascular resistance (PVR) across tertiles — rising from 1.8 to 2.6 Wood units — while pulmonary artery wedge pressure showed no parallel trend. The highest NLR tertile carried a 2.47-fold adjusted odds of combined post- and precapillary pulmonary hypertension (CpcPH) and a 2.37-fold adjusted hazard of cardiovascular death or heart failure hospitalization versus the lowest tertile.
HFpEF remains notoriously difficult to phenotype and treat, partly because its pulmonary vascular complications — particularly CpcPH — demand costly right heart catheterization to diagnose. If NLR, a routine CBC-derived index reflecting systemic neutrophilic inflammation, can stratify patients before invasive workup, it could meaningfully triage who needs urgent hemodynamic evaluation. The mechanism is biologically plausible: neutrophil-driven vascular inflammation contributes to pulmonary arterial remodeling independently of passive congestion, consistent with the finding that wedge pressure did not trend with NLR while PVR did.
Limitations are substantial: the retrospective single-center design, modest cohort of 169, and selection bias toward catheterized patients all constrain generalizability. NLR is also nonspecific, elevated by infections, steroids, and malignancy. Critically, this is a preprint posted on medRxiv and has not yet undergone peer review — findings and effect sizes could change. Prospective multicenter validation is essential before NLR enters routine HFpEF risk stratification. Incremental rather than paradigm-shifting, but clinically actionable if confirmed.
