Ferreira João Pedro, Packer Milton, Sattar Naveed, Butler Javed, González Maldonado Sandra, Panova-Noeva Marina, Sumin Mikhail, Masson Serge, Pocock Stuart J, Anker Stefan D, Zannad Faiez, Januzzi James L
Centre d'Investigations Cliniques Plurithématique 1433, INSERM, Université de Lorraine, Nancy, France; F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), INSERM U1116, Centre Hospitalier Régional Universitaire de Nancy, Nancy, France.
UnIC@RISE, Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal.
Eur J Heart Fail. 2024 Apr;26(4):806-816. doi: 10.1002/ejhf.3227. Epub 2024 Apr 8.
Insulin-like growth factor binding protein-7 (IGFBP7) is a biomarker of tissue senescence with a role in cardio-renal pathophysiology. The role of IGFBP7 as a prognostic biomarker across the full ejection fraction (EF) spectrum of heart failure (HF) remains less well understood. We examined associations between IGFBP7 and risk of cardio-renal outcomes regardless of EF and the effect of empagliflozin treatment on IGFBP7 concentrations among individuals with HF.
IGFBP7 was measured in 1125 study participants from the EMPEROR-Reduced and EMPEROR-Preserved trials. Cox regression was used to study associations with outcomes. Study participants with IGFBP7 levels in the highest tertile had a higher-risk clinical profile. In Cox proportional hazards models adjusted for clinical variables, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T, baseline IGFBP7 values in the highest tertile predicted an increased risk of HF hospitalization or cardiovascular death (hazard ratio [HR] 2.00, 95% confidence interval [CI] 1.28-3.10, p = 0.002, p for trend <0.001) and higher risk of the renal composite endpoint (HR 4.66, 95% CI 1.61-13.53, p = 0.005, p for trend = 0.001), regardless of EF. Empagliflozin reduced risk for cardiovascular death/HF hospitalization irrespective of baseline IGFBP7 (p for trend across IGFBP7 tertiles = 0.26). Empagliflozin treatment was not associated with meaningful change in IGFBP7 at 12 or 52 weeks.
Across the entire left ventricular EF spectrum in the EMPEROR Programme, concentrations of the senescence-associated biomarker IGFBP7 were associated with higher risk clinical status and predicted adverse cardio-renal outcomes even in models adjusted for conventional biomarkers. Empagliflozin did not significantly affect IGFBP7 levels over time.
胰岛素样生长因子结合蛋白7（IGFBP7）是一种组织衰老生物标志物，在心脏-肾脏病理生理学中发挥作用。IGFBP7作为心力衰竭（HF）全射血分数（EF）范围内的预后生物标志物的作用仍不太清楚。我们研究了无论EF如何，IGFBP7与心脏-肾脏结局风险之间的关联，以及恩格列净治疗对HF患者IGFBP7浓度的影响。
在EMPEROR-Reduced和EMPEROR-Preserved试验的1125名研究参与者中测量了IGFBP7。使用Cox回归研究与结局的关联。IGFBP7水平处于最高三分位数的研究参与者具有更高风险的临床特征。在针对临床变量、N末端前B型利钠肽和高敏心肌肌钙蛋白T进行调整的Cox比例风险模型中，最高三分位数的基线IGFBP7值预测HF住院或心血管死亡风险增加（风险比[HR]2.00，95%置信区间[CI]1.28-3.10，p = 0.002，趋势p<0.001）以及肾脏复合终点风险更高（HR 4.66，95%CI 1.61-13.53，p = 0.005，趋势p = 0.001），无论EF如何。无论基线IGFBP7如何，恩格列净均可降低心血管死亡/HF住院风险（IGFBP7三分位数间的趋势p = 0.26）。恩格列净治疗在12周或52周时与IGFBP7的有意义变化无关。
在EMPEROR计划的整个左心室EF范围内，衰老相关生物标志物IGFBP7的浓度与更高风险的临床状态相关，并且即使在针对传统生物标志物进行调整的模型中也能预测不良心脏-肾脏结局。随着时间的推移，恩格列净对IGFBP7水平没有显著影响。
