糖尿病对射血分数保留的心力衰竭患者血清生物标志物的影响：TOPCAT试验的见解
Impact of diabetes on serum biomarkers in heart failure with preserved ejection fraction: insights from the TOPCAT trial.
作者信息
De Marco Corrado, Claggett Brian L, de Denus Simon, Zile Michael R, Huynh Thao, Desai Akshay S, Sirois Martin G, Solomon Scott D, Pitt Bertram, Rouleau Jean L, Pfeffer Marc A, O'Meara Eileen
机构信息
Division of Cardiology, Montreal Heart Institute and Université de Montréal, 5000 rue Bélanger, Montreal, QC, H1T 1C8, Canada.
Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.
出版信息
ESC Heart Fail. 2021 Apr;8(2):1130-1138. doi: 10.1002/ehf2.13153. Epub 2021 Jan 12.
AIMS
Diabetes mellitus (DM) is common in heart failure with preserved ejection fraction (HFpEF). Patients with DM and heart failure with reduced ejection fraction have higher levels of cardiac, profibrotic, and proinflammatory biomarkers relative to non-diabetics. Limited data are available regarding the biomarker profiles of HFpEF patients with diabetes (DM) vs. no diabetes (non-DM) and the impact of spironolactone on these biomarkers. This study aims to address such gaps in the literature.
METHODS AND RESULTS
Biomarkers were measured at randomization and at 12 months in 248 patients enrolled in Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist's North American cohort. At baseline, DM patients had significantly lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein, pro-collagen type III amino-terminal peptide, tissue inhibitor of metalloproteinase 1 (TIMP-1), and galectin-3 levels than those without diabetes. There was a significantly larger 12 month increase in levels of high-sensitivity troponin T (hs-TnT), a marker of myocyte death, in DM patients. Elevated pro-collagen type III amino-terminal peptide and galectin-3 levels were associated with an increased risk of the primary outcome (cardiovascular mortality, aborted cardiac arrest, or heart failure hospitalization) in DM patients, but not in those without diabetes. A statistically significant interaction between spironolactone and diabetes status was observed for hs-TnT and for TIMP-1, with greater biomarker reductions among those with diabetes treated with spironolactone.
CONCLUSIONS
The presence of diabetes is associated with higher levels of cardiac, profibrotic, and proinflammatory biomarkers in HFpEF. Spironolactone appears to alter the determinants of extracellular matrix remodelling in an anti-fibrotic fashion in patients with diabetes, reflected by changes in hs-TnT and TIMP-1 levels over time.
目的
糖尿病（DM）在射血分数保留的心力衰竭（HFpEF）中很常见。与非糖尿病患者相比，糖尿病合并射血分数降低的心力衰竭患者的心脏、促纤维化和促炎生物标志物水平更高。关于糖尿病（DM）与非糖尿病（非DM）的HFpEF患者的生物标志物谱以及螺内酯对这些生物标志物的影响，现有数据有限。本研究旨在填补文献中的此类空白。
方法和结果
在醛固酮拮抗剂治疗保留心功能心力衰竭的北美队列研究中，对248例患者在随机分组时和12个月时测量了生物标志物。基线时，糖尿病患者的估计肾小球滤过率显著低于非糖尿病患者，而高敏C反应蛋白、III型前胶原氨基末端肽、金属蛋白酶组织抑制剂1（TIMP-1）和半乳糖凝集素-3水平则显著高于非糖尿病患者。糖尿病患者中，作为心肌细胞死亡标志物的高敏肌钙蛋白T（hs-TnT）水平在12个月时的升高幅度显著更大。III型前胶原氨基末端肽和半乳糖凝集素-3水平升高与糖尿病患者发生主要结局（心血管死亡、心脏骤停未遂或心力衰竭住院）的风险增加相关，但在非糖尿病患者中并非如此。观察到螺内酯与糖尿病状态在hs-TnT和TIMP-1方面存在统计学显著的相互作用，接受螺内酯治疗的糖尿病患者的生物标志物降低幅度更大。
结论
糖尿病的存在与HFpEF患者中更高水平的心脏、促纤维化和促炎生物标志物相关。螺内酯似乎以抗纤维化的方式改变糖尿病患者细胞外基质重塑的决定因素，这通过hs-TnT和TIMP-1水平随时间的变化得以体现。
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