Background:Increased activity of IGFBP7 (insulin-like growth factor–binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people.Methods and Results:In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks. Patient characteristics and echocardiographic measures including left atrial (LA) size and volume, ratio of early mitral inflow velocity/annular diastolic velocity, and ratio of early diastole/peak late diastolic velocity were assessed as a function of IGFBP7 concentration. Effect of sacubitril/valsartan on IGFBP7 concentrations was analyzed. With increasing baseline IGFBP7 quartiles, LA size and LA volume index (LAVi) were higher (both P<0.001); modest association between IGFBP7 and higher early mitral inflow velocity/annular diastolic velocity (P=0.03) and early diastole/peak late diastolic velocity ratio (P=0.04) was also seen. IGFBP7 concentrations were higher in those with LAVi ≥34 mL/m² compared with lower LAVi at all time points (all P<0.01). IGFBP7 independently predicted LAVi at baseline even in the presence of NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentrations; highest LAVi was seen in those with elevation in both biomarkers. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations over 36 weeks compared with valsartan (adjusted treatment effect, −7%; P<0.001).Conclusions:Among patients with heart failure with preserved ejection fraction, concentrations of the cellular senescence biomarker IGFBP7 were associated with abnormalities in diastolic filling and LA dilation. Treatment with sacubitril/valsartan resulted in lower IGFBP7 concentrations compared with valsartan.Clinical Trial Registration:URL: https://www.clinicaltrials.gov. Unique identifier: NCT00887588.

中文翻译：

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心力衰竭患者的IGFBP7（胰岛素样生长因子结合蛋白7）和中性溶酶抑制作用

背景：IGFBP7（胰岛素样生长因子结合蛋白-7）活性增加与细胞衰老，组织衰老和肥胖有关。IGFBP7可能与射血分数保留的心力衰竭有关，这是一种老年肥胖症。方法和结果：在一部分患有射血分数保留的心力衰竭患者（N = 228）中，随机分配接受沙比特比/缬沙坦与缬沙坦的比较，IGFBP7在基线，12周和36周时测量浓度。根据IGFBP7浓度评估患者的特征和超声心动图测量指标，包括左心房（LA）的大小和体积，早期二尖瓣流入速度/环舒张速度的比率以及早期舒张/峰值舒张末速度的比率。分析了沙必特/缬沙坦对IGFBP7浓度的影响。P <0.001）；还观察到IGFBP7与较高的早期二尖瓣流入速度/瓣环舒张速度（P = 0.03）和早期舒张/峰值舒张末期速度比（P = 0.04）之间的适度关联。在所有时间点，LAVi≥34mL / m ^2的人的IGFBP7浓度均高于较低的LAVi（所有P <0.01）。即使在NT-proBNP（N-末端pro-B型利钠肽）浓度存在的情况下，IGFBP7仍可独立预测基线时的LAVi。在两个生物标记均升高的患者中观察到最高的LAVi。与缬沙坦相比，用沙比特比/缬沙坦治疗可降低36周内的IGFBP7浓度（调整后的治疗效果为-7％；P<0.001）。结论：在射血分数保持不变的心力衰竭患者中，细胞衰老生物标志物IGFBP7的浓度与舒张期充盈和LA扩张异常有关。与缬沙坦相比，沙库比特/缬沙坦治疗可降低IGFBP7浓度。临床试验注册：URL：https://www.clinicaltrials.gov。唯一标识符：NCT00887588。