McNulty Marie, Mahmud Azra, Feely John
Department of Pharmacology and Therapeutics, Trinity College, Dublin, Ireland.
Am J Hypertens. 2007 Mar;20(3):242-7. doi: 10.1016/j.amjhyper.2006.08.009.
The formation of advanced glycation end-products is associated with arterial stiffness in experimental models and alagebrium (formerly known as ALT-711), an advanced glycation end-product cross-link breaker, has been shown to reduce arterial stiffness in elderly subjects.
We related plasma concentrations of advanced glycation end-products (AGEs), measured using a noncompetitive immunoassay, and markers of aortic stiffness-pulse wave velocity (PWV) and augmentation index (AIx), a measure of aortic wave reflection-in 46 subjects, aged 47 +/- 2 years, comprising 30 untreated hypertensive and 16 normotensive subjects. Results were analyzed using univariate and multiple logistic regression analysis.
Plasma AGEs were significantly higher in hypertensive than in normotensive subjects (7.8 +/- 1 v 3 +/- 1 mug/ml; P < .0001). There was a significant relationship between plasma AGEs and aortic PWV (r = 0.49, P < .01), but not with AIx. In a stepwise regression model age, plasma AGE levels, smoking status, and total cholesterol explained 67% of the variability in PWV. For AIx, the only variables that entered the model were age, gender, and heart rate (R(2) = 0.53, P < .0001) with no contribution from plasma AGEs.
Concentration of plasma AGEs is significantly higher in hypertensive than in normotensive subjects and related to aortic stiffness independent of age and blood pressure, with no relationship with aortic wave reflection. Plasma AGEs may play a blood pressure-independent role in large but not small vessel remodeling in essential hypertension.
在实验模型中,晚期糖基化终产物的形成与动脉僵硬度相关,而阿伐吉林(曾称为ALT - 711),一种晚期糖基化终产物交联断裂剂,已被证明可降低老年受试者的动脉僵硬度。
我们测定了46名年龄为47±2岁的受试者(包括30名未经治疗的高血压患者和16名血压正常者)血浆中晚期糖基化终产物(AGEs)的浓度(采用非竞争性免疫测定法)以及主动脉僵硬度标志物——脉搏波速度(PWV)和增强指数(AIx,一种主动脉波反射的测量指标)。结果采用单因素和多因素逻辑回归分析。
高血压患者的血浆AGEs显著高于血压正常者(7.8±1对3±1μg/ml;P <.0001)。血浆AGEs与主动脉PWV之间存在显著相关性(r = 0.49,P <.01),但与AIx无关。在逐步回归模型中,年龄、血浆AGE水平、吸烟状况和总胆固醇解释了PWV变异性的67%。对于AIx,进入模型的唯一变量是年龄、性别和心率(R² = 0.53,P <.0001),血浆AGEs无贡献。
高血压患者血浆AGEs浓度显著高于血压正常者,且与主动脉僵硬度相关,独立于年龄和血压,与主动脉波反射无关。血浆AGEs可能在原发性高血压的大血管而非小血管重塑中发挥独立于血压的作用。