Sauer Andrew J, Chang Joycie, Fu Zhuxuan, Valenzuela Ripoll Carla, Cho Yoonje, Guo Zhen, Jones Philip, Selvaraj Senthil, Windsor Sheryl L, Husain Mansoor, Inzucchi Silvio E, McGuire Darren K, Pitt Bertram, Scirica Benjamin M, Austin Bethany A, Umpierrez Guillermo, Tran Sinh, Dahlbäck Björn, Javaheri Ali, Kosiborod Mikhail N
Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA; University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.
JACC Adv. 2025 Jun;4(6 Pt 2):101800. doi: 10.1016/j.jacadv.2025.101800.
Apolipoprotein M (ApoM) is associated with lower mortality in heart failure (HF) patients and protects against cardiac and kidney injury in mice.
The authors investigated dapagliflozin's cardiorenal effects by studying its association with ApoM in patients with HF with reduced ejection fraction.
We performed a secondary analysis of DEFINE-HF (Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients with HF with Reduced Ejection Fraction) to assess dapagliflozin's effects on ApoM, N-terminal pro B-type natriuretic peptide (NT-proBNP), and urine albumin-creatinine ratio (UACR) changes from baseline to 12 weeks.
Of 263 randomized patients, 236 had ApoM values at baseline (mean 0.641 ± 0.181 μM) and 12 weeks. Dapagliflozin did not significantly affect ApoM vs placebo. However, each 0.1 μM increase in ApoM was associated with a significant decrease in log-transformed NT-proBNP overall (β = -0.11, P = 0.006), particularly in dapagliflozin-treated patients (β = -0.19, P < 0.001; P interaction = 0.025). The inverse relationship between ApoM and NT-proBNP varied by changes in UACR. Dapagliflozin-treated patients with reduced UACR at 12 weeks (n = 53, 22%) experienced a mean NT-proBNP reduction of -0.28 per 0.1 μM increase in ApoM (P < 0.001), compared to a smaller reduction in those without UACR change (-0.07, P = 0.47). Placebo-treated patients with reduced UACR over 12 weeks did not show significant NT-proBNP changes (β = -0.17, P = 0.11).
Dapagliflozin did not significantly alter ApoM overall; however, an inverse association between ApoM and NT-proBNP was observed in dapagliflozin-treated patients with albuminuria. While some NT-proBNP reductions were seen in the placebo group, the significant interaction with treatment allocation suggests a potential dapagliflozin-mediated effect.
载脂蛋白M（ApoM）与心力衰竭（HF）患者较低的死亡率相关，并能保护小鼠免受心脏和肾脏损伤。
作者通过研究达格列净与射血分数降低的HF患者中ApoM的关联，调查其对心肾的影响。
我们对DEFINE-HF（达格列净对射血分数降低的HF患者生物标志物、症状和功能状态的影响）进行了二次分析，以评估达格列净从基线到12周对ApoM、N末端B型利钠肽原（NT-proBNP）和尿白蛋白肌酐比值（UACR）变化的影响。
在263例随机分组的患者中，236例在基线（平均0.641±0.181μM）和12周时有ApoM值。与安慰剂相比，达格列净对ApoM无显著影响。然而，ApoM每增加0.1μM，总体上log转换后的NT-proBNP显著降低（β=-0.11，P=0.006），特别是在接受达格列净治疗的患者中（β=-0.19，P<0.001；P交互作用=0.025）。ApoM与NT-proBNP之间的负相关关系因UACR的变化而异。12周时UACR降低的达格列净治疗患者（n=53，22%），ApoM每增加0.1μM，NT-proBNP平均降低-0.28（P<0.001），而UACR无变化的患者降低幅度较小（-0.07，P=0.47）。12周内UACR降低的安慰剂治疗患者未显示NT-proBNP有显著变化（β=-0.17，P=0.11）。
达格列净总体上未显著改变ApoM；然而，在接受达格列净治疗的蛋白尿患者中观察到ApoM与NT-proBNP之间存在负相关。虽然安慰剂组的NT-proBNP有一些降低，但与治疗分配的显著交互作用表明达格列净可能有介导作用。
