Key result
Circulating plasma proteins showed significant interactions between E/e' and heart failure subtype for 43% (n=1822) of 4210 measured proteins, with weaker associations in HFpEF compared to HFrEF.
Why the study?
This study investigates the interplay between the circulating plasma proteome and echocardiographic parameters in patients across the spectrum of HF, ranging from at risk of or with HFpEF to HFrEF.
Cohort (n=750)
Yes
Proteomic profiling reveals that biological processes and pathways have weaker associations with diastolic function (E/e') in HFpEF compared to HFrEF, and identifies specific proteins associated with worsening diastolic dysfunction.
Weaker proteomic links to diastolic function in HFpEF warrant caution extrapolating from HFrEF; leaves open distinct pathways for targeted study.
INTRODUCTION: This study investigates the interplay between the circulating plasma proteome and echocardiographic parameters in patients across the spectrum of heart failure (HF) (ranging from patients at risk of/with preserved (HFpEF) to reduced (HFrEF) ejection fraction). METHODS: Data from two cohort studies, HELPFul and Bio-SHiFT, were analyzed. We measured 4210 circulating plasma proteins in a total of 750 patients using SomaScan® proteomics. Echocardiographic parameters in both studies included left ventricular ejection fraction (LVEF) and the ratio of the peak early left ventricular (LV) filling velocity and early diastolic mitral annular velocity (E/e'). In further analyses, we classified patients in left ventricular diastolic dysfunction (LVDD) groups according to the prevailing guidelines. RESULTS: Out of the 4210 plasma proteins, 21 proteins were significantly associated with E/e' in patients at risk of/with HFpEF, whereas 9 proteins were associated with LVEF. Approximately 43 % (n = 1822) of the proteins showed significant interactions between E/e' and HF subtype. All of these proteins showed weaker associations with E/e' in patients at risk of/with HFpEF compared to the ones with HFrEF. These proteins were related to the extracellular matrix, cellular processes, insulin-like growth factor (IGF) transport, metabolic and catabolic processes. Furthermore, comparisons between LVDD groups and those with normal diastolic function identified 40 proteins associated with grade 2 (top 5: Cystatin C, TMEDA, NT-proBNP, GDF-15 and PXDN) and 198 with grade 3 LVDD (top 5: NT-proBNP, Cystatin C, PXDN, RNasa1, and Factor D). CONCLUSION: In patients at risk of/with HFpEF, biological processes and pathways showed weaker associations with E/e' compared to patients with HFrEF. Varying pathways identified through proteomics were associated with deterioration of LVDD across the ejection fraction spectrum. Our results are in line with the mechanistic frameworks currently thought to underlie the various types of HF.
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Kamar et al. (2025) conducted a cohort in Heart failure (n=750). Circulating plasma proteins was evaluated on Association of plasma proteins with echocardiographic parameters (E/e' and LVEF) and left ventricular diastolic dysfunction (LVDD) grades. Circulating plasma proteins showed significant interactions between E/e' and heart failure subtype for 43% (n=1822) of 4210 measured proteins, with weaker associations in HFpEF compared to HFrEF.
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