Cahill Leah E, Warren Rachel A, Lavallée Samantha K, Levy Andrew P, Carew Allie S, Sapp John, Samuel Michelle, Selvin Elizabeth, Poulter Neil, Marre Michel, Harrap Stephen, Mancia Giuseppe, Harris Katie, Chalmers John, Woodward Mark, Rimm Eric
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Nova Scotia Health, QEII Health Sciences Centre, Halifax, Nova Scotia, Canada.
BMJ Open Diabetes Res Care. 2025 May 6;13(3):e004713. doi: 10.1136/bmjdrc-2024-004713.
This study sought to determine whether the association between attaining specific glycated hemoglobin (HbA) targets (<7.0% (<53 mmol/mol) and ≥8.0% (≥64 mmol/mol) compared with 7.0%-7.9%) over time and risk of incident coronary artery disease (CAD) was dependent on haptoglobin (Hp) phenotype in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.
Prospectively collected HbA data from the ADVANCE biomarker case-cohort study, updated at 6 months and every 12 months thereafter over a median of 5.0 (IQR 4.5-5.3) years, were analyzed in relation to incident CAD in the Hp2-2 (n=1323) and non-Hp2-2 (n=2069) phenotypes separately using weighted multivariable-adjusted Cox regression models. Additional a priori stratifications by sex, race, previous cardiovascular disease (CVD), and type 2 diabetes duration were performed.
Mean HbA was similar in each phenotype group throughout the study. Compared with HbA of 7.0%-7.9%, HbA <7.0% was not associated with CAD risk for any phenotype group or subgroup. HbA ≥8.0% compared with 7.0%-7.9% over time was associated with higher CAD risk for the Hp2-2 phenotype only (HR 1.53, 95% CI 1.01 to 2.32; no significant association in the non-Hp2-2 type: 1.26, 0.89 to 1.77, p-interaction=0.71); this was pronounced when those with previous CVD at baseline were excluded (Hp2-2: 2.80, 1.41 to 5.53, p-interaction=0.03). Compared with HbA of <8.0%, having HbA ≥8.0% was associated with a 59% higher CAD risk among participants with the Hp2-2 phenotype (1.59, 1.12 to 2.26) and a 39% higher CAD risk among participants without the Hp2-2 phenotype (1.39, 1.03 to 1.88, p-interaction=0.97).
The present ADVANCE analysis suggests that not having HbA ≥8.0%, rather than achieving HbA <7.0%, was found to be particularly important for CAD prevention among people with type 2 diabetes and the common Hp2-2 phenotype. While the subgroup analyses were likely underpowered, their inclusion is hypothesis generating and can be used in future meta-analyses to improve power and generalizability.
在糖尿病和血管疾病行动：培哚普利和达美康缓释片对照评估（ADVANCE）研究中，本研究旨在确定随着时间推移达到特定糖化血红蛋白（HbA）目标（<7.0%（<53 mmol/mol）和≥8.0%（≥64 mmol/mol），与7.0%-7.9%相比）与冠心病（CAD）发病风险之间的关联是否取决于触珠蛋白（Hp）表型。
前瞻性收集ADVANCE生物标志物病例队列研究中的HbA数据，此后每6个月更新一次，每12个月更新一次，中位数为5.0（四分位间距4.5 - 5.3）年，分别使用加权多变量调整Cox回归模型分析Hp2 - 2（n = 1323）和非Hp2 - 2（n = 2069）表型中与CAD发病的关系。还按性别、种族、既往心血管疾病（CVD）和2型糖尿病病程进行了额外的先验分层。
在整个研究过程中，各表型组的平均HbA相似。与7.0%-7.9%的HbA相比，HbA <7.0%与任何表型组或亚组的CAD风险均无关联。随着时间推移，与7.0%-7.9%相比，HbA≥8.0%仅与Hp2 - 2表型的CAD风险较高相关（风险比[HR] 1.53，95%置信区间[CI] 1.01至2.32；非Hp2 - 2型无显著关联：1.26，0.89至1.77，交互作用p值 = 0.71）；当排除基线时有既往CVD的患者时，这种关联更为明显（Hp2 - 2：2.80，1.41至5.53，交互作用p值 = 0.03）。与<8.0%的HbA相比，HbA≥8.0%使Hp2 - 2表型参与者的CAD风险升高59%（1.59，1.12至2.26），使无Hp2 - 2表型参与者的CAD风险升高39%（1.39，1.03至1.88，交互作用p值 = 0.97）。
目前的ADVANCE分析表明，对于2型糖尿病患者和常见的Hp2 - 2表型，未达到HbA≥8.0%而非达到HbA <7.0%对预防CAD尤为重要。虽然亚组分析的效力可能不足，但纳入这些分析可产生假设，并可用于未来的荟萃分析以提高效力和普遍性。
