Dykun Iryna, Bayturan Ozgur, Carlo Julie, Nissen Steven E, Kapadia Samir R, Tuzcu E Murat, Nicholls Stephen J, Puri Rishi
C5Research, Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH.
Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, Essen, Germany.
Am J Prev Cardiol. 2022 Jan 18;9:100317. doi: 10.1016/j.ajpc.2022.100317. eCollection 2022 Mar.
We tested the hypothesis that on-treatment HbA1c levels independently associate with coronary atheroma progression and major adverse cardiovascular events (MACE: death, myocardial infarction, cerebrovascular accident, coronary revascularization, or hospitalization for unstable angina) rates.
We performed a pooled analysis of data from seven prospective, randomized trials involving serial coronary intravascular ultrasonography (IVUS). The percent atheroma volume (PAV) was calculated as the proportion of the entire vessel wall occupied by atherosclerotic plaque. Using multivariable mixed modeling, we determined the association of on-treatment HbA1c with annualized change in PAV. Cox proportional hazard models were used to assess the association of HbA1c with incidence of MACE.
Among 3,312 patients (mean age 58.6±9years, 28.4%women) average on-treatment HbA1c was 6.2±1.1%. Overall, there was no net significant annualized change in PAV (0.12±0.19%, = 0.52). In a fully adjusted multivariable analysis (following adjustment of age, sex, body mass index, systolic blood pressure, smoking, low- and high-density lipoprotein cholesterol, triglyceride levels, peripheral vascular disease, trial, region, and baseline PAV), higher on-treatment HbA1c levels were independently associated with annualized changes in PAV [beta-estimate (95% confidence interval): 0.13(0.08, 0.19), < 0.001]. On-treatment HbA1c levels were independently associated with MACE [hazard ratio (95% confidence interval): 1.13(1.04, 1.23), 0.005].
Independent of achieved cardiovascular risk factor control, greater HbA1c levels significantly associate with coronary atheroma progression rates and clinical outcomes. These results support the notion of a direct, specific effect of glycemic control upon coronary atheroma and atherosclerotic events, supporting the rationale of therapies designed to directly modulate it.
我们检验了如下假设，即治疗期间的糖化血红蛋白（HbA1c）水平与冠状动脉粥样硬化进展及主要不良心血管事件（MACE：死亡、心肌梗死、脑血管意外、冠状动脉血运重建或因不稳定型心绞痛住院）发生率独立相关。
我们对七项涉及系列冠状动脉血管内超声检查（IVUS）的前瞻性随机试验数据进行了汇总分析。粥样硬化体积百分比（PAV）计算为动脉粥样硬化斑块占据的整个血管壁的比例。使用多变量混合模型，我们确定了治疗期间HbA1c与PAV年化变化之间的关联。采用Cox比例风险模型评估HbA1c与MACE发生率之间的关联。
在3312例患者（平均年龄58.6±9岁，女性占28.4%）中，治疗期间平均HbA1c为6.2±1.1%。总体而言，PAV没有显著的年化净变化（0.12±0.19%，P = 0.52）。在一项完全调整的多变量分析中（调整年龄、性别、体重指数、收缩压、吸烟、低密度和高密度脂蛋白胆固醇、甘油三酯水平、外周血管疾病、试验、地区和基线PAV后），较高的治疗期间HbA1c水平与PAV的年化变化独立相关[β估计值（95%置信区间）：0.13(0.08, 0.19)，P < 0.001]。治疗期间HbA1c水平与MACE独立相关[风险比（95%置信区间）：1.13(1.04, 1.23)，P = 0.005]。
独立于已实现的心血管危险因素控制，更高的HbA1c水平与冠状动脉粥样硬化进展率和临床结局显著相关。这些结果支持血糖控制对冠状动脉粥样硬化和动脉粥样硬化事件有直接、特定作用的观点，支持旨在直接调节血糖的治疗原理。
