Division of Cardiology, Massachusetts General Hospital, Boston (J.L.J.).
Cardiometabolic Trials, Baim Institute for Clinical Research, Boston, MA (J.L.J.).
Circ Heart Fail. 2018 Oct;11(10):e005133. doi: 10.1161/CIRCHEARTFAILURE.118.005133.
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.
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/m 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).
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.
URL: https://www.clinicaltrials.gov . Unique identifier: NCT00887588.
IGFBP7（胰岛素样生长因子结合蛋白 7）活性增加与细胞衰老、组织老化和肥胖有关。IGFBP7 可能与射血分数保留的心力衰竭有关，这是一种老年肥胖人群的疾病。
在接受 sacubitril/valsartan 或 valsartan 治疗的射血分数保留的心力衰竭患者亚组（N=228）中，测量基线、12 周和 36 周时的 IGFBP7 浓度。评估患者特征和超声心动图测量值，包括左心房（LA）大小和容量、早期二尖瓣流入速度/环状舒张速度比以及早期舒张/峰值晚期舒张速度比，作为 IGFBP7 浓度的函数。分析 sacubitril/valsartan 对 IGFBP7 浓度的影响。随着基线 IGFBP7 四分位数的增加，LA 大小和 LA 容量指数（LAVi）更高（均 P<0.001）；IGFBP7 与较高的早期二尖瓣流入速度/环状舒张速度比（P=0.03）和早期舒张/峰值晚期舒张速度比（P=0.04）也有适度的关联。在所有时间点，LAVi≥34mL/m 的患者的 IGFBP7 浓度均高于 LAVi 较低的患者（均 P<0.01）。即使在存在 N 端脑钠肽前体（N-terminal pro-B-type natriuretic peptide，NT-proBNP）浓度的情况下，IGFBP7 在基线时也能独立预测 LAVi；在两种生物标志物均升高的患者中，LAVi 最高。与 valsartan 相比，在 36 周时 sacubitril/valsartan 治疗导致 IGFBP7 浓度降低（调整后的治疗效果，-7%；P<0.001）。
在射血分数保留的心力衰竭患者中，细胞衰老生物标志物 IGFBP7 的浓度与舒张充盈和 LA 扩张的异常有关。与 valsartan 相比，使用 sacubitril/valsartan 治疗导致 IGFBP7 浓度降低。
