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Abstract：
OBJECTIVE: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation.
METHODS: We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.
RESULTS: Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months.
CONCLUSIONS: Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin.
BACKGROUND: Clinicaltrials.gov NCT02956811 (06/11/2016).
METHODS: We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.
RESULTS: Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months.
CONCLUSIONS: Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin.
BACKGROUND: Clinicaltrials.gov NCT02956811 (06/11/2016).
摘要：
目的：钠葡萄糖协同转运蛋白2（SGLT2）抑制剂在心力衰竭（HF）中具有有益作用，包括反向重塑，但这些获益的机制尚不清楚.炎症与心力衰竭（HF）的病理生理学有关，并且有一些临床前数据表明SGLT2抑制剂可以减轻炎症。然而，缺乏临床数据。我们研究的目的是调查达格列净在2型糖尿病（T2D）和左心室肥厚（LVH）患者中引起的心脏重塑改善是否与其对炎症的影响有关。
方法：我们测量了C反应蛋白（CRP），肿瘤坏死因子α（TNF-α），白细胞介素-1β（IL-1β），白细胞介素6（IL-6），来自DAPA-LVH试验的60例患有T2D和左心室肥厚(LVH)但没有症状性HF的患者的血浆样本中的白细胞介素10(IL-10)和中性粒细胞与淋巴细胞比率(NLR),在该试验中,参与者随机接受达格列净每日10mg或安慰剂治疗12个月,并在基线和治疗结束时接受心脏磁共振成像(CMR).主要分析是研究达格列净对炎症的影响，并评估炎症标志物变化与左心室质量和整体纵向应变（GLS）之间的关系，以及达格列净对左心室质量和GLS的影响是否受基线水平的调节炎症。
结果：治疗12个月后，与安慰剂相比，达格列净显著降低CRP（平均差异-1.96；95%CI-3.68至-0.24，p=0.026）。其他炎性标记物没有显著的统计学改变。GLS的改善和炎症的减少之间存在适度的相关性(NLR(r=0.311)，IL-1β（r=0.246），12个月时TNF-α（r=0.230）。
结论：与安慰剂相比，达格列净导致CRP显著降低。包括IL-1β在内的炎症标志物的减少与整体纵向应变的改善（但不减少LV质量）之间存在相关性。全身炎症的减少可能在达格列净的心血管益处中起作用。
背景：Clinicaltrials.govNCT02956811（2016年6月11日）。
方法：我们测量了C反应蛋白（CRP），肿瘤坏死因子α（TNF-α），白细胞介素-1β（IL-1β），白细胞介素6（IL-6），来自DAPA-LVH试验的60例患有T2D和左心室肥厚(LVH)但没有症状性HF的患者的血浆样本中的白细胞介素10(IL-10)和中性粒细胞与淋巴细胞比率(NLR),在该试验中,参与者随机接受达格列净每日10mg或安慰剂治疗12个月,并在基线和治疗结束时接受心脏磁共振成像(CMR).主要分析是研究达格列净对炎症的影响，并评估炎症标志物变化与左心室质量和整体纵向应变（GLS）之间的关系，以及达格列净对左心室质量和GLS的影响是否受基线水平的调节炎症。
结果：治疗12个月后，与安慰剂相比，达格列净显著降低CRP（平均差异-1.96；95%CI-3.68至-0.24，p=0.026）。其他炎性标记物没有显著的统计学改变。GLS的改善和炎症的减少之间存在适度的相关性(NLR(r=0.311)，IL-1β（r=0.246），12个月时TNF-α（r=0.230）。
结论：与安慰剂相比，达格列净导致CRP显著降低。包括IL-1β在内的炎症标志物的减少与整体纵向应变的改善（但不减少LV质量）之间存在相关性。全身炎症的减少可能在达格列净的心血管益处中起作用。
背景：Clinicaltrials.govNCT02956811（2016年6月11日）。
