The following is the summary of “Association of Protein Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction” published in the December 2022 issue of Circulation Heart Failure by Takvorian, et al.

Heart failure with maintained ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are separate clinical entities, although there is minimal evidence indicating connections of proteomic profiles with the future development of HFpEF versus HFrEF. Using multivariable Cox models, researchers examined the relationship of 71 protein biomarkers with incident HFpEF versus HFrEF (left ventricular ejection fraction ≥ versus <50%) among Framingham Heart Study patients. 

Among 7,038 participants (mean age 49 years; 54% women), 5 biomarkers were associated with increased risk of incident HFpEF (false discovery rate q<0.05): NT-proBNP (N-terminal pro-B-type natriuretic peptide; hazard ratio [HR]‚ 2.13; 95% CI‚ 1.52–2.99; P<0.001), growth differentiation factor-15 (HR‚ 1.67; 95% CI‚ 1.32–2.12; P<0.001), adrenomedullin (HR‚ 1.58; 95% CI‚ 1.23–2.04; P<0.001), uncarboxylated matrix Gla protein (HR‚ 1.55; 95% CI 1.23–1.95; P<0.001), and C-reactive protein (HR‚ 1.46; 95% CI‚ 1.17–1.83; P=0.001). In addition, about 14 biomarkers were related to the incidence of HFrEF (multivariable P<0.001, q<0.05 for all). Of these, 3 biomarkers were associated with HF subtypes (NT-proBNP, growth differentiation factor-15, and C-reactive protein) (NT-proBNP, growth differentiation factor-15, and C-reactive protein). 

When examined directly, myeloperoxidase, resistin, and paraoxonase-1 were more strongly related to HFrEF than HFpEF. Investigators discovered 5 protein biomarkers of new-onset HFpEF representing pathways of inflammation, cardiac stress, and vascular stiffness, which partly overlapped with HFrEF. They observed 14 biomarkers related to new-onset HFrEF, with some specific relationships including myeloperoxidase, resistin, and paraoxonase-1. These data provide insights into parallels and differences in the development of HF subtypes.