Gandhi Parul U, Gaggin Hanna K, Redfield Margaret M, Chen Horng H, Stevens Susanna R, Anstrom Kevin J, Semigran Marc J, Liu Peter, Januzzi James L
VA CT Healthcare System, West Haven, Connecticut; Yale University School of Medicine New Haven, Connecticut.
Massachusetts General Hospital, Boston, Massachusetts.
JACC Heart Fail. 2016 Nov;4(11):860-869. doi: 10.1016/j.jchf.2016.08.002. Epub 2016 Oct 12.
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.
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.
At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo.
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' (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', and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo (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).
In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.
本研究旨在调查胰岛素样生长因子结合蛋白7(IGFBP7)与射血分数保留的心力衰竭(HFpEF)患者舒张功能参数或功能能力之间的关系,这些患者被随机分配接受西地那非或安慰剂治疗。
先前发现IGFBP7与射血分数降低的心力衰竭患者的舒张功能有关,但尚不清楚这些关联在HFpEF中是否存在。
在基线和24周时,对160例随机接受西地那非或安慰剂治疗的HFpEF患者进行IGFBP7、影像学检查和峰值耗氧量(Vo)的测定并比较。
基线IGFBP7浓度高于中位数的患者年龄较大,有体循环淤血体征且肾功能较差,并且包括氨基末端B型利钠肽原在内的心力衰竭预后生物标志物浓度较高(p<0.05)。较高的基线IGFBP7与较差的舒张功能适度相关:较高的E波速度(斯皮尔曼相关性[ρ]=0.40)、E/E'比值(ρ=0.40)、左心房容积指数(ρ=0.39)和估计的右心室收缩压(ρ=0.41;均p<0.001),与二尖瓣E/A比值弱相关(ρ=0.26;p=0.006)。值得注意的是,IGFBP7的变化与E波、E/A比值、E/E'比值和右心室收缩压的变化显著相关。基线IGFBP7升高与较低的基线Vo相关(13.2对11.1 ml/min/kg;p<0.001),IGFBP7的变化与Vo的变化呈弱负相关(ρ=-0.19;p=0.01)。与接受安慰剂治疗的患者相比,接受西地那非治疗的受试者在24周内IGFBP7有所下降(IGFBP7的中位数变化为-1.5对+13.6 ng/ml;p<0.001)。
在HFpEF患者中,IGFBP可能是舒张功能和运动能力的一种新型生物标志物。