Diabetes and Vascular Medicine, University of Exeter Medical School, National Institute for Health Research Exeter Clinical Research Facility, Exeter, U.K.
Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, U.K.
Diabetes Care. 2018 Oct;41(10):2212-2219. doi: 10.2337/dc18-0185. Epub 2018 Jul 30.
Cardiovascular disease (CVD) risk prediction represents an increasing clinical challenge in the treatment of diabetes. We used a panel of vascular imaging, functional assessments, and biomarkers reflecting different disease mechanisms to identify clinically useful markers of risk for cardiovascular (CV) events in subjects with type 2 diabetes (T2D) with or without manifest CVD.
The study cohort consisted of 936 subjects with T2D recruited at four European centers. Carotid intima-media thickness and plaque area, ankle-brachial pressure index, arterial stiffness, endothelial function, and circulating biomarkers were analyzed at baseline, and CV events were monitored during a 3-year follow-up period.
The CV event rate in subjects with T2D was higher in those with ( = 440) than in those without ( = 496) manifest CVD at baseline (5.53 vs. 2.15/100 life-years, < 0.0001). New CV events in subjects with T2D with manifest CVD were associated with higher baseline levels of inflammatory biomarkers (interleukin 6, chemokine ligand 3, pentraxin 3, and hs-CRP) and endothelial mitogens (hepatocyte growth factor and vascular endothelial growth factor A), whereas CV events in subjects with T2D without manifest CVD were associated with more severe baseline atherosclerosis (median carotid plaque area 30.4 mm [16.1-92.2] vs. 19.5 mm [9.5-40.5], = 0.01). Conventional risk factors, as well as measurements of arterial stiffness and endothelial reactivity, were not associated with CV events.
Our observations demonstrate that markers of inflammation and endothelial stress reflect CV risk in subjects with T2D with manifest CVD, whereas the risk for CV events in subjects with T2D without manifest CVD is primarily related to the severity of atherosclerosis.
心血管疾病（CVD）风险预测在糖尿病治疗中是一个日益严峻的临床挑战。我们使用了一组血管成像、功能评估和生物标志物，这些标志物反映了不同的疾病机制，旨在确定 2 型糖尿病（T2D）患者（无论是否有显性 CVD）心血管（CV）事件风险的临床有用标志物。
该研究队列由 936 名在欧洲四个中心招募的 T2D 患者组成。在基线时分析颈动脉内膜中层厚度和斑块面积、踝臂血压指数、动脉僵硬度、内皮功能和循环生物标志物，并在 3 年随访期间监测 CV 事件。
在基线时，T2D 患者中（=440 人）的 CV 事件发生率高于无显性 CVD 的患者（=496 人）（5.53比 2.15/100 人年，<0.0001）。T2D 合并显性 CVD 的患者中，新发 CV 事件与炎症生物标志物（白细胞介素 6、趋化因子配体 3、五聚素 3 和高敏 C 反应蛋白）和内皮有丝分裂原（肝细胞生长因子和血管内皮生长因子 A）的基线水平较高相关，而 T2D 无显性 CVD 的患者的 CV 事件与更严重的基线动脉粥样硬化（颈动脉斑块面积中位数为 30.4mm[16.1-92.2]比 19.5mm[9.5-40.5]，=0.01）相关。传统危险因素，以及动脉僵硬和内皮反应性的测量，与 CV 事件无关。
我们的观察结果表明，炎症和内皮应激标志物反映了有显性 CVD 的 T2D 患者的 CV 风险，而无显性 CVD 的 T2D 患者的 CV 事件风险主要与动脉粥样硬化的严重程度有关。
