Longitudinal proteomic changes following hospitalization for acute heart failure
A Dieden, H Holm, A Yaghoubi, M A Ohlsson, Z Nezami, A Zaghi, H Zilic, J Molvin, A Jujic, M MagnussonAbstract
Background
Acute heart failure (HF) triggers biological disturbances, reflected in circulating protein levels. While proteomic studies have improved understanding of HF pathophysiology, most are cross-sectional and do not capture temporal changes. How the circulating proteome changes from acute phase to recovery remains poorly defined. We aimed to characterize longitudinal proteomic changes between hospitalization for acute HF and 6-month follow-up.
Methods
Using a proximity extension assay in a Swedish HF cohort, a total of 136 individuals underwent proteomic analysis of 92 proteins at baseline (hospitalized for acute HF) and 6 months later. Differential protein expression between follow-up and baseline was assessed using the Linear Models for Microarray Data analysis (Limma). Multiple testing was addressed using the Benjamini-Hochberg false discovery rate (FDR). Proteins were considered significantly changed at FDR <0.05, with an additional effect size threshold of |log2FC| ≥0.2 (~15% change) to highlight biologically meaningful changes.
Results
One-hundred-thirty-six individuals (29 % women; mean age 74.2 ±10.9) had complete baseline and follow-up data. After FDR adjustment, the differential protein expression in follow-up phase vs acute phase yielded 20 proteins. After applying the |log2FC| ≥0.2 threshold 4 proteins were upregulated (higher in the follow-up phase) while 5 proteins were downregulated (lower in the follow-up phase) (figure 1). The most upregulated protein was Epithelial Cell Adhesion Molecule (EpCAM) (log2FC 0.38, ~30% higher, FDR <0.001) while NT-proBNP (log2FC –0.48, ~ 39% lower, FDR 0.003) showed the greatest decrease 6 months later. Most proteins (83/92) remained unchanged (FDR≥0.05 and |log2FC| <0.2) over 6 months (figure 2).
Conclusion
In this longitudinal proteomic study of patients hospitalized for acute HF, only a small subset of circulating proteins changed meaningfully between the acute phase and 6-month follow-up, while most proteins remained stable. These findings suggest that recovery from acute HF is characterized by selective, rather than global, remodelling of the circulating proteome. Proteins with the largest temporal shifts—most notably NT-proBNP and EpCAM—may reflect biological processes linked to acute decompensation and recovery and warrant further mechanistic and prognostic investigation.BarplotVolcanoplot