Munich Diabetes Research Group e.V. at Helmholtz Centre, Neuherberg, Germany
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
Diabetes Care. 2020 Mar;43(3):643-652. doi: 10.2337/dc19-1079. Epub 2019 Dec 27.
We sought to confirm a bidirectional association between severe hypoglycemic events (SHEs) and cardiovascular (CV) event risk and to characterize individuals at dual risk.
In a post hoc analysis of 14,752 Exenatide Study of Cardiovascular Event Lowering (EXSCEL) participants, we examined time-dependent associations between SHEs and subsequent major adverse cardiac events (CV death, nonfatal myocardial infarction [MI] or stroke), fatal/nonfatal MI, fatal/nonfatal stroke, hospitalization for acute coronary syndrome (hACS), hospitalization for heart failure (hHF), and all-cause mortality (ACM), as well as time-dependent associations between nonfatal CV events and subsequent SHEs.
SHEs were uncommon and not associated with once-weekly exenatide therapy (hazard ratio 1.13 [95% CI 0.94-1.36], = 0.179). In fully adjusted models, SHEs were associated with an increased risk of subsequent ACM (1.83 [1.38-2.42], < 0.001), CV death (1.60 [1.11-2.30], = 0.012), and hHF (2.09 [1.37-3.17], = 0.001), while nonfatal MI (2.02 [1.35-3.01], = 0.001), nonfatal stroke (2.30 [1.25-4.23], = 0.007), hACS (2.00 [1.39-2.90], < 0.001), and hHF (3.24 [1.98-5.30], < 0.001) were all associated with a subsequent increased risk of SHEs. The elevated bidirectional time-dependent hazards linking SHEs and a composite of all CV events were approximately constant over time, with those individuals at dual risk showing higher comorbidity scores compared with those without.
These findings, showing greater risk of SHEs after CV events as well as greater risk of CV events after SHEs, validate a bidirectional relationship between CV events and SHEs in patients with high comorbidity scores.
我们旨在确认严重低血糖事件 (SHEs) 与心血管 (CV) 事件风险之间存在双向关联，并确定双重风险个体的特征。
在 Exenatide 研究心血管事件降低（EXSCEL）的 14752 名参与者的事后分析中，我们检查了 SHEs 与随后的主要不良心脏事件（CV 死亡、非致命性心肌梗死 [MI] 或中风）、致命/非致命性 MI、致命/非致命性中风、急性冠状动脉综合征（hACS）住院、心力衰竭（hHF）住院和全因死亡率（ACM）之间的时间依赖性关联，以及非致命性 CV 事件与随后 SHEs 之间的时间依赖性关联。
SHEs 较为罕见，与每周一次的 exenatide 治疗无关（风险比 1.13 [95%CI 0.94-1.36]，=0.179）。在完全调整的模型中，SHEs 与随后的 ACM 风险增加相关（1.83 [1.38-2.42]，<0.001）、CV 死亡（1.60 [1.11-2.30]，=0.012）和 hHF（2.09 [1.37-3.17]，=0.001），而非致命性 MI（2.02 [1.35-3.01]，=0.001）、非致命性中风（2.30 [1.25-4.23]，=0.007）、hACS（2.00 [1.39-2.90]，<0.001）和 hHF（3.24 [1.98-5.30]，<0.001）均与 SHEs 的后续风险增加相关。SHEs 和所有 CV 事件综合的双向时间依赖性危害增加，与那些具有双重风险的个体相比，那些具有更高合并症评分的个体风险更高。
这些发现表明，CV 事件后 SHEs 的风险增加，以及 SHEs 后 CV 事件的风险增加，验证了高合并症评分患者中 CV 事件和 SHEs 之间存在双向关系。
