Insulin-Like Growth Factor-Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction: Results From the RELAX Trial

详细信息    查看全文

• 作者：Parul U. Gandhi ; MD^a ; ^b ; Hanna K. Gaggin ; MD ; MPH^c ; Margaret M. Redfield ; MD^d ; Horng H. Chen ; MD^d ; Susanna R. Stevens ; MS^e ; Kevin J. Anstrom ; PhD^e ; Marc J. Semigran ; MD^c ; Peter Liu ; MD^f ; James L. Januzzi Jr. ; MD^c ; ^{jjanuzzi@partners.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：biomarkers ; diastolic function ; heart failure with preserved ejection fraction ; insulin-like growth factor&ndash ; binding protein 7
• 刊名：JACC: Heart Failure
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：4
• 期：11
• 页码：860-869
• 全文大小：631 K

文摘

This study sought to investigate relationships between insulin-like growth factor–binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo.

Background

ra0015">IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF.

Methods

ra0020">At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo_2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo.

Results

ra0025">Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E&prime; (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E&prime;, and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo_2max (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo_2max (ρ = −0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 −1.5 vs. +13.6 ng/ml; p < 0.001).

Conclusions

ra0030">In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.