Medical Research Institute, University of Dundee, Dundee, U.K.
Diabetes. 2011 Sep;60(9):2379-85. doi: 10.2337/db11-0291. Epub 2011 Jul 19.
Circulating levels of soluble receptor for advanced glycation end products (sRAGE) likely comprise both a secreted isoform (esRAGE) and wild-type RAGE cleaved from the cell membrane. Both sRAGE and esRAGE have been proposed as biomarkers of cardiovascular disease (CVD), but prospective data are limited. We examined the relationship of sRAGE and esRAGE to incident coronary heart disease (CHD) and stroke in type 2 diabetic patients followed for 3.9 years in a trial of atorvastatin: the Collaborative Atorvastatin Diabetes Study (CARDS).
We used a nested case-control design sampling all incident cases of CVD with available plasma and randomly selecting three control subjects, who were free of CVD throughout follow-up, per case. Analysis was by Cox regression with adjustment for treatment allocation and relevant covariates.
sRAGE and esRAGE were strongly correlated (ρ = 0.88) and were both higher in those with lower BMI (P < 0.001), higher adiponectin (P < 0.001), lower estimated glomerular filtration rate (P = 0.009), and white ethnicity (P < 0.001). Both sRAGE and esRAGE were associated with incident CHD events, independently of treatment allocation and the above factors; hazard ratio (HR) = 1.74 (95% CI 1.25-2.41; P = 0.002) for a doubling of the sRAGE level; HR = 1.45 (1.11-1.89; P = 0.006) for a doubling of the esRAGE level. There was no significant association with stroke; HR for sRAGE = 0.66 (0.38-1.14). Atorvastatin, 10 mg daily, did not alter sRAGE.
Higher levels of sRAGE and esRAGE are associated with incident CHD but not stroke in type 2 diabetes.
循环可溶性晚期糖基化终产物受体（sRAGE）水平可能包括分泌型异构体（esRAGE）和从细胞膜上切割下来的野生型 RAGE。sRAGE 和 esRAGE 都被提出作为心血管疾病（CVD）的生物标志物，但前瞻性数据有限。我们在阿托伐他汀的临床试验中（协作阿托伐他汀糖尿病研究（CARDS）），对 2 型糖尿病患者进行了 3.9 年的随访，研究了 sRAGE 和 esRAGE 与新发冠心病（CHD）和卒中的关系。
我们采用嵌套病例对照设计，对所有 CVD 事件的病例进行抽样，对每个病例，都随机选择 3 名无 CVD 随访的对照者。分析采用 Cox 回归，调整治疗分配和相关协变量。
sRAGE 和 esRAGE 呈强相关性（ρ=0.88），且在 BMI 较低（P<0.001）、脂联素水平较高（P<0.001）、估算肾小球滤过率较低（P=0.009）和白人种族（P<0.001）者中水平更高。sRAGE 和 esRAGE 均与 CHD 事件的发生相关，独立于治疗分配和上述因素；sRAGE 水平加倍的危险比（HR）为 1.74（95%CI 1.25-2.41；P=0.002）；esRAGE 水平加倍的 HR 为 1.45（1.11-1.89；P=0.006）。sRAGE 与卒中无显著相关性；HR 为 0.66（0.38-1.14）。阿托伐他汀 10mg 每日治疗并未改变 sRAGE。
在 2 型糖尿病患者中，sRAGE 和 esRAGE 水平升高与 CHD 发生相关，但与卒中无关。
