Neutrophil to Lymphocyte Ratio and Outcomes in Patients with New-Onset or Worsening Heart Failure with Reduced and Preserved Ejection Fraction

Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients. Methods We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population. Results 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11–1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (<40%: HR 2.75; 95% CI 1.84–4.09, P < 0.001; LVEF ≥ 40%: HR 1.51; 95% CI 1.05–2.16, P = 0.026). When NLR was added to the BIOSTAT-CHF risk score, there were improvements in integrated discrimination index (IDI) and net reclassification index (NRI) for occurrence of the primary outcome (IDI + 0.009; 95% CI 0.00–0.019, P = 0.030; continuous NRI + 0.112, 95% CI 0.012–0.176, P = 0.040). Elevated NLR was similarly associated with adverse outcome in the validation cohort. Decrease in NLR at 6 months was associated with reduced incidence of the primary outcome (HR 0.75; 95% CI 0.57–0.98, P = 0.036). Conclusions Elevated NLR is significantly associated with elevated markers of inflammation in HF patients and is associated with worse outcome. Elevated NLR might potentially be useful in identifying high-risk HF patients and may represent a treatment target

Association between up‐titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum

Background: The role of neurohormonal inhibition in chronic heart failure is well established. There is limited data on the effect of up-titration of renin angiotensin inhibition (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening heart failure (HF) across the left ventricular ejection fraction (LVEF) spectrum. Methods and results: We analyzed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF&lt;40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50%–99%, 1%–49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BBs dose and all-cause and HF hospitalizations. In the 21-months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose-levels compared to no treatment [HR (95%CI): ≥100%: 0.60(0.49–0.74), p &lt; 0.001; 50%–99%: 0.56(0.46–0.68), p &lt; 0.001; 1%–49%: 0.71(0.59–0.86), p &lt; 0.001]. This association was consistent up to an LVEF of 49% (p &lt; 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was &lt;40% (overall p &lt; 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%. Conclusion: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%