Possible Enzymatic Downregulation of the Natriuretic Peptide System in Patients with Reduced Systolic Function and Heart Failure: A Pilot Study

收缩功能减退和心力衰竭患者中可能存在利钠肽系统的酶促下调:一项初步研究

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作者:Syed S Zaidi, Ryan D Ward, Kodangudi Ramanathan, Xinhua Yu, Inna P Gladysheva, Guy L Reed

Background

In patients with reduced systolic function, the natriuretic peptide system affects heart failure (HF) progression, but the expression of key activating (corin) and degrading enzymes (neprilysin) is not well understood.

Conclusions

Levels of neprilysin, ANP, BNP, and cGMP increased in patients with reduced systolic function and were the highest in dHF patients. Conversely, corin levels were low in patients with reduced EF with or without dHF. This pattern suggests possible enzymatic downregulation of natriuretic peptide activity in patients with reduced EF, which may have diagnostic and prognostic implications.

Results

This pilot study (n=48) compared plasma levels of corin, neprilysin, ANP, BNP, and cGMP in control patients with normal ejection fractions (mean EF 63 ± 3%) versus patients with systolic dysfunction, with (EF 24 ± 8%) and without (EF 27 ± 7%) decompensated HF (dHF), as defined by Framingham and BNP criteria. Mean ages, use of beta blockers, and ACE-inhibitors-angiotensin receptor blockers were similar between the groups. Corin levels were depressed in systolic dysfunction patients (797 ± 346 pg/ml) versus controls (1188 ± 549, p<0.02), but levels were not affected by dHF (p=0.77). In contrast, levels of neprilysin (p<0.01), cGMP (p<0.001), and ANP (p<0.001) were higher in systolic dysfunction patients than controls and were the highest in patients with dHF. Conclusions: Levels of neprilysin, ANP, BNP, and cGMP increased in patients with reduced systolic function and were the highest in dHF patients. Conversely, corin levels were low in patients with reduced EF with or without dHF. This pattern suggests possible enzymatic downregulation of natriuretic peptide activity in patients with reduced EF, which may have diagnostic and prognostic implications.

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