Iveljic Ivana, Young Megan, Corhodzic Elvira, Cullen Fenn, Prag Hiran A, Murphy Michael P, Aksentijevic Dunja
Faculty of Medicine, University of Tuzla, Tuzla, Bosnia and Herzegovina.
University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina.
Cardiovasc Diabetol. 2025 Jun 7;24(1):243. doi: 10.1186/s12933-025-02771-z.
Heart failure with preserved ejection fraction (HFpEF) poses a significant global health challenge, disproportionately affecting women. Diabetic women with HFpEF represent a high-risk subgroup, particularly after experiencing ST-segment elevation myocardial infarction (STEMI), exhibiting increased mortality compared to men. While prolonged door-to-balloon (DTB) times, reflecting delayed reperfusion, are a critical factor in STEMI outcomes, they alone do not fully capture the observed outcome variability in diabetic women. Using an integrated clinical and pre-clinical approach this study aimed to investigate the relative contributions of metabolic dysfunction and coronary artery disease (CAD) in type 2 diabetes (T2D) to STEMI outcomes in women, beyond the impact of DTB time.
A retrospective case-control study analysed female STEMI patients undergoing primary percutaneous coronary intervention (pPCI, n = 40 T2D, n = 40 non-diabetic controls), comparing clinical characteristics, treatment strategies, and early outcomes. A preclinical model (female db/db mice) assessed cardiac function via echocardiography, Langendorff perfusions, and ischemia-reperfusion protocols. Metabolome of heart, liver, and skeletal muscle was assessed by H NMR spectroscopy.
Our study reveals significantly higher mortality, impaired left ventricular function post-pPCI, and increased implantable cardioverter-defibrillator (ICD) implantation rates in diabetic STEMI patients, irrespective of DTB time, when compared to non-diabetic controls. Elevated inflammatory markers, acute hyperglycaemia and evidence of cardio-hepatic damage were identified in T2D patients. db/db mice exhibited analogous T2D-associated pathophysiology, including increased ischemia-reperfusion injury exacerbated by metabolic disturbances in the myocardium, liver, and skeletal muscle versus non-diabetic controls.
In diabetic women, multiple factors beyond reperfusion delays exacerbate acute myocardial injury. This necessitates the development of sex-specific strategies to manage the cardiovascular complications of diabetic HFpEF. The db/db mouse model provides a relevant preclinical tool for future research as it mimics human T2D-associated HFpEF and STEMI outcome.
射血分数保留的心力衰竭（HFpEF）对全球健康构成重大挑战，对女性的影响尤为严重。患有HFpEF的糖尿病女性是一个高危亚组，尤其是在经历ST段抬高型心肌梗死（STEMI）后，其死亡率高于男性。虽然反映再灌注延迟的延长门球时间（DTB）是STEMI预后的关键因素，但仅凭这一点并不能完全解释糖尿病女性中观察到的预后差异。本研究采用综合临床和临床前方法，旨在探讨2型糖尿病（T2D）中的代谢功能障碍和冠状动脉疾病（CAD）对女性STEMI预后的相对贡献，超越DTB时间的影响。
一项回顾性病例对照研究分析了接受直接经皮冠状动脉介入治疗（pPCI，n = 40例T2D患者，n = 40例非糖尿病对照）的女性STEMI患者，比较了临床特征、治疗策略和早期预后。一个临床前模型（雌性db/db小鼠）通过超声心动图、Langendorff灌注和缺血再灌注方案评估心脏功能。通过核磁共振波谱法评估心脏、肝脏和骨骼肌的代谢组。
我们的研究表明，与非糖尿病对照相比，糖尿病STEMI患者无论DTB时间如何，死亡率显著更高，pPCI后左心室功能受损，植入式心脏复律除颤器（ICD）植入率增加。在T2D患者中发现炎症标志物升高、急性高血糖以及心肝损伤的证据。与非糖尿病对照相比，db/db小鼠表现出类似的T2D相关病理生理学，包括缺血再灌注损伤增加，心肌、肝脏和骨骼肌中的代谢紊乱使其恶化。
在糖尿病女性中，除再灌注延迟外的多种因素会加重急性心肌损伤。这就需要制定针对性别的策略来管理糖尿病HFpEF的心血管并发症。db/db小鼠模型为未来研究提供了一个相关的临床前工具，因为它模拟了人类T2D相关的HFpEF和STEMI结局。
