Verdonschot Job A J, Ferreira JoÃo Pedro, Pizard Anne, Pellicori Pierpaolo, Brunner La Rocca Hans-Peter, Clark Andrew L, Cosmi Franco, Cuthbert Joe, Girerd Nicolas, Waring Olivia J, Henkens Michiel H T M, Mariottoni Beatrice, Petutschnigg Johannes, Rossignol Patrick, Hazebroek Mark R, Cleland John G F, Zannad Faiez, Heymans Stephane R B
Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands.
Universite de Lorraine, Inserm, Centre d'Investigation Clinique Plurithe´matique 1433, CHRU de Nancy, F-CRIN INI-CRCT, Nancy, France.
J Card Fail. 2022 May;28(5):778-786. doi: 10.1016/j.cardfail.2021.12.005. Epub 2021 Dec 18.
Adipose tissue influences the expression and degradation of circulating biomarkers. We aimed to identify the biomarker profile and biological meaning of biomarkers associated with obesity to assess the effect of spironolactone on the circulating biomarkers and to explore whether obesity might modify the effect of spironolactone.
Protein biomarkers (n = 276) from the Olink Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline, 1 month and 9 months from the HOMAGE randomized controlled trial participants. Of the 510 participants, 299 had obesity defined as an increased waist circumference (≥102 cm in men and ≥88 cm in women). Biomarkers at baseline reflected adipogenesis, increased vascularization, decreased fibrinolysis, and glucose intolerance in patients with obesity at baseline. Treatment with spironolactone had only minor effects on this proteomic profile. Obesity modified the effect of spironolactone on systolic blood pressure (P = 0.001), showing a stronger decrease of blood pressure in obese patients (-14.8 mm Hg 95% confidence interval -18.45 to -11.12) compared with nonobese patients (-3.6 mm Hg 95% confidence interval -7.82 to 0.66).
Among patients at risk for heart failure, those with obesity have a characteristic proteomic profile reflecting adipogenesis and glucose intolerance. Spironolactone had only minor effects on this obesity-related proteomic profile, but obesity significantly modified the effect of spironolactone on systolic blood pressure.
脂肪组织会影响循环生物标志物的表达和降解。我们旨在确定与肥胖相关的生物标志物谱及其生物学意义，以评估螺内酯对循环生物标志物的影响，并探讨肥胖是否可能改变螺内酯的作用效果。
在HOMAGE随机对照试验参与者基线、1个月和9个月时采集的血浆中，检测了Olink Proseek-Multiplex心血管和炎症检测板中的276种蛋白质生物标志物。在510名参与者中，299人患有肥胖症，定义为腰围增加（男性≥102厘米，女性≥88厘米）。基线时的生物标志物反映了肥胖患者在基线时的脂肪生成增加、血管生成增加、纤维蛋白溶解减少和葡萄糖不耐受。螺内酯治疗对该蛋白质组学谱的影响较小。肥胖改变了螺内酯对收缩压的作用效果（P = 0.001），与非肥胖患者相比，肥胖患者的血压下降幅度更大（-14.8毫米汞柱，95%置信区间-18.45至-11.12），而非肥胖患者为（-3.6毫米汞柱，95%置信区间-7.82至0.66）。
在有心力衰竭风险的患者中，肥胖患者具有反映脂肪生成和葡萄糖不耐受的特征性蛋白质组学谱。螺内酯对这种与肥胖相关的蛋白质组学谱影响较小，但肥胖显著改变了螺内酯对收缩压的作用效果。
