Circulating Protein Biomarkers Associated with Heart Failure with Preserved Ejection Fraction

Introduction The prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing. This disease has posed diagnostic and therapeutic challenges; mortality and morbidity remain unacceptably high. Unbiased molecular studies are necessary to identify better diagnostic biomarkers. Hypothesis Large-scale discovery proteomics with a multiplex immunoassay platform will identify novel molecular mechanisms that differentiate HFpEF from patients without heart failure (HF). Methods We performed proteomic analyses (Olink) of 552 proteins on 88 HFpEF cases and 88 no HF controls from individuals referred for cardiac catheterization at Duke University. HFpEF was defined as history of HF, ejection fraction >45% and diastolic dysfunction class ≥1; no-HF controls had no diastolic dysfunction. Univariate logistic regression was used to identify proteins associated with HFpEF; associated proteins at a false discovery rate Results As expected, HFpEF cases were older and had higher BMI, SBP, creatinine and prevalence of DM (p Conclusions Biomarkers of angiogenesis, fibrosis, fatty acid metabolism and inflammation are associated with HFpEF and improve discriminative capabilities on top of clinical factors and NT-proBNP. These findings highlight the importance of these pathways in HFpEF and identify potential novel circulating diagnostic biomarkers.