Wang Xinkang, Keith James C, Struthers Allan D, Feuerstein Giora Z
Discovery Translational Medicine, Wyeth Research, Collegeville, PA 19426, USA.
Cardiovasc Ther. 2008 Fall;26(3):214-23. doi: 10.1111/j.1755-5922.2008.00051.x.
Stiffening of the large arteries is a common feature of aging and is exacerbated by a number of disorders such as hypertension, diabetes, and renal disease. Arterial stiffening is recognized as an important and independent risk factor for cardiovascular events. This article will provide a comprehensive review of the recent advance on assessment of arterial stiffness as a translational medicine biomarker for cardiovascular risk.
The key topics related to the mechanisms of arterial stiffness, the methodologies commonly used to measure arterial stiffness, and the potential therapeutic strategies are discussed. A number of factors are associated with arterial stiffness and may even contribute to it, including endothelial dysfunction, altered vascular smooth muscle cell (SMC) function, vascular inflammation, and genetic determinants, which overlap in a large degree with atherosclerosis. Arterial stiffness is represented by biomarkers that can be measured noninvasively in large populations. The most commonly used methodologies include pulse wave velocity (PWV), relating change in vessel diameter (or area) to distending pressure, arterial pulse waveform analysis, and ambulatory arterial stiffness index (AASI). The advantages and limitations of these key methodologies for monitoring arterial stiffness are reviewed in this article. In addition, the potential utility of arterial stiffness as a translational medicine surrogate biomarker for evaluation of new potentially vascular protective drugs is evaluated.
Assessment of arterial stiffness is a sensitive and useful biomarker of cardiovascular risk because of its underlying pathophysiological mechanisms. PWV is an emerging biomarker useful for reflecting risk stratification of patients and for assessing pharmacodynamic effects and efficacy in clinical studies.
大动脉僵硬度增加是衰老的常见特征,且在高血压、糖尿病和肾脏疾病等多种病症中会加剧。动脉僵硬度增加被认为是心血管事件的一个重要且独立的危险因素。本文将全面综述动脉僵硬度评估作为心血管风险转化医学生物标志物的最新进展。
讨论了与动脉僵硬度机制、测量动脉僵硬度常用方法以及潜在治疗策略相关的关键主题。许多因素与动脉僵硬度相关,甚至可能导致动脉僵硬度增加,包括内皮功能障碍、血管平滑肌细胞(SMC)功能改变、血管炎症和遗传决定因素,这些因素在很大程度上与动脉粥样硬化重叠。动脉僵硬度由可在大量人群中进行无创测量的生物标志物表示。最常用的方法包括脉搏波速度(PWV)、将血管直径(或面积)变化与扩张压力相关联、动脉脉搏波形分析以及动态动脉僵硬度指数(AASI)。本文综述了这些监测动脉僵硬度关键方法的优缺点。此外,还评估了动脉僵硬度作为转化医学替代生物标志物在评估新的潜在血管保护药物方面的潜在效用。
由于其潜在的病理生理机制,动脉僵硬度评估是心血管风险的一个敏感且有用的生物标志物。PWV是一种新兴的生物标志物,可用于反映患者的风险分层以及评估临床研究中的药效学效应和疗效。