Kozlova Dariya, Gimblet Colin, Wendt Linder, Akbari Sadaf, Taiwo Adeyinka, Dayal Sanjana, Ten Eyck Patrick, Stanhewicz Anna, Trinity Joel, Jalal Diana
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Institute for Clinical and Translational Science, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2025 Jun 5;20(6):e0324945. doi: 10.1371/journal.pone.0324945. eCollection 2025.
Prediabetes is a growing public health concern that increases the risk of major adverse cardiovascular events (MACE). Vascular dysfunction worsens with hyperglycemia and is associated with MACE in several high-risk populations. However, it is unknown whether vascular dysfunction contributes to MACE in prediabetes. We hypothesized that vascular dysfunction is associated with elevated risk of MACE in prediabetes.
We conducted an observational study of 5742 adults (age 54.9 ± 11.5 years, 54% female) in the Framingham Offspring and Generation III cohorts. Prediabetes was defined using the ADA criteria. Endothelial function was determined via brachial artery flow-mediated dilation (BA-FMD), aortic stiffness via carotid-femoral pulse wave velocity (cfPWV), and coronary artery calcium (CAC) score via computed tomography. Stepwise selection models evaluated BA-FMD, cfPWV, and CAC score by prediabetes status. The association of BA-FMD, cfPWV, and CAC score with time to MACE was assessed via Cox proportional hazards regression.
Individuals with prediabetes had lower BA-FMD and higher cfPWV and CAC score (p < 0.001). In stepwise selection models, age, sex, smoking history, systolic blood pressure, triglycerides, high-density lipoprotein, low-density lipoprotein, and fasting glucose related to vascular dysfunction. After adjusting for traditional cardiovascular risk factors, BA-FMD (HR [95% CI], 0.93 [0.90,0.97]; p < 0.001) and CAC score >100 [HR [95% CI], 4.15 [2.24, 7.70]; p < 0.001)] were associated with MACE in prediabetes while cfPWV was not (p = 0.051).
Vascular dysfunction measured by BA-FMD independently associates with MACE in prediabetes. Therapies that target vascular dysfunction may reduce CVD risk in prediabetes.
糖尿病前期是一个日益受到关注的公共卫生问题，它会增加主要不良心血管事件（MACE）的风险。血管功能障碍会随着血糖升高而恶化，并在几个高危人群中与MACE相关。然而，尚不清楚血管功能障碍是否会导致糖尿病前期患者发生MACE。我们假设血管功能障碍与糖尿病前期患者发生MACE的风险升高有关。
我们对弗雷明汉后代队列和第三代队列中的5742名成年人（年龄54.9±11.5岁，54%为女性）进行了一项观察性研究。糖尿病前期采用美国糖尿病协会（ADA）标准定义。通过肱动脉血流介导的血管舒张功能（BA-FMD）测定内皮功能，通过颈股脉搏波速度（cfPWV）测定主动脉僵硬度，通过计算机断层扫描测定冠状动脉钙化（CAC）评分。逐步选择模型根据糖尿病前期状态评估BA-FMD、cfPWV和CAC评分。通过Cox比例风险回归评估BA-FMD、cfPWV和CAC评分与发生MACE时间的关联。
糖尿病前期个体的BA-FMD较低，cfPWV和CAC评分较高（p<0.001）。在逐步选择模型中，年龄、性别、吸烟史、收缩压、甘油三酯、高密度脂蛋白、低密度脂蛋白和空腹血糖与血管功能障碍有关。在调整传统心血管危险因素后，BA-FMD（HR[95%CI]，0.93[0.90，0.97]；p<0.001）和CAC评分>100[HR[95%CI]，4.15[2.24，7.70]；p<0.001]与糖尿病前期患者发生MACE相关，而cfPWV则无此关联（p=0.051）。
通过BA-FMD测量的血管功能障碍与糖尿病前期患者发生MACE独立相关。针对血管功能障碍的治疗可能会降低糖尿病前期患者的心血管疾病风险。
