Gui H, She R, Luzum J, Li J, Bryson TD, Pinto Y, Sabbah HN, Williams LK, and Lanfear DE. Plasma Proteomic Profile Predicts Survival in Heart Failure with Reduced Ejection Fraction. Circ Genom Precis Med 2021.
Circ Genom Precis Med
BACKGROUND: It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS).
Methods: Patients meeting Framingham criteria for HF with EF<50% were enrolled (n=1017) and plasma underwent SOMAscan® profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and N-Terminal pro-B-Type Natriuretic Peptide (NTproBNP), then was tested in the validation cohort. Risk stratification improvement was evaluated by C-statistic, integrated discrimination index (IDI), continuous net reclassification index (NRI), and median improvement in risk score (MIRS) for 1-year and 3-year mortality.
Results: Participants' mean age was 68 years, 48% identified as African American, 35% were female and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio (HR) =2.27 [95% Confidence interval (95%CI) 1.84-2.82], p=6.3x10(-14)), Kaplan-Meier curves differed significantly between HFrEF-PRS quartiles (p=2.2x10(-6)), and it remained significant after adjustment for clinical score and NTproBNP (HR=1.37, 95%CI 1.05-1.79, p=0.021). The HFrEF-PRS improved metrics of risk stratification (C-statistic change=0.009, p=0.612; IDI=0.041, p=0.010; NRI=0.391, p=0.078; MIRS=0.039, p=0.016) and associated with cardiovascular death and HF phenotypes (e.g. 6-minute walk distance, EF change). Most HFrEF-PRS proteins had little known connection to HFrEF.
Conclusions: A plasma multi-protein score improved risk stratification in HFrEF patients and identified novel candidates.
ePub ahead of print