Ngo Doan T M, Sverdlov Aaron L, Willoughby Scott R, Nightingale Angus K, Chirkov Yuliy Y, McNeil John J, Horowitz John D
University of Adelaide, South Australia, Australia.
JACC Cardiovasc Imaging. 2009 Aug;2(8):919-27. doi: 10.1016/j.jcmg.2009.03.016.
We sought to identify clinical, physiological, and biochemical correlates, including markers of endothelial dysfunction and of tissue nitric oxide (NO) responsiveness, of the presence of aortic sclerosis (ASc) in an aging population.
Aortic sclerosis has been regarded predominantly as a precursor of hemodynamically significant aortic stenosis. However, ASc also represents an independent correlate of increased risk of cardiovascular morbidity and mortality; the basis of this association is incompletely understood. The assumption that the pathogenesis of aortic valve disease is similar to that of atherosclerosis has not been supported by recent studies; rather there has been increasing evidence of a pathogenetic role of inflammation and endothelial dysfunction. Furthermore, we have recently developed methodology for echocardiographic quantitation of early aortic valve disease.
Randomly selected subjects (n = 253) ages 51 to 77 years underwent transthoracic echocardiography; aortic valve ultrasonic backscatter score (AV(BS)) was used to quantitate echogenicity of the aortic valve. Conventional coronary risk factors were identified. Integrity of NO generation/response was assessed via: 1) plasma asymmetric dimethylarginine concentrations, as a marker of endothelial dysfunction; 2) inhibition of platelet aggregation by the NO donor sodium nitroprusside, as a measure of tissue NO responsiveness and also a coronary prognostic marker; and 3) aortic augmentation index, as a measure of arterial stiffness/wave reflection. All putative correlations with AV(BS) were examined by univariate and multiple linear regression analyses.
On the basis of AV(BS) scores, ASc was present in 19.4% of subjects. The AV(BS) directly correlated with patients' age but inversely correlated with high-sensitivity C-reactive protein, creatinine clearance, and platelet NO responsiveness. On multiple linear regression, ASc was associated with impaired platelet NO responsiveness (beta = -0.16, p = 0.02), advancing age (beta = 0.21, p = 0.003), and low body mass index (beta = -0.23, p = 0.001).
Aortic sclerosis is associated with platelet NO resistance rather than conventional coronary risk factors: this might explain the increased thrombotic risk in ASc.
我们试图确定老年人群中主动脉硬化（ASc）存在的临床、生理和生化相关因素，包括内皮功能障碍和组织一氧化氮（NO）反应性的标志物。
主动脉硬化主要被视为血流动力学上显著的主动脉狭窄的先兆。然而，ASc也代表心血管发病和死亡风险增加的一个独立相关因素；这种关联的基础尚未完全明确。主动脉瓣疾病的发病机制与动脉粥样硬化相似这一假设未得到近期研究的支持；相反，越来越多的证据表明炎症和内皮功能障碍在发病机制中起作用。此外，我们最近开发了超声心动图定量早期主动脉瓣疾病的方法。
随机选取年龄在51至77岁的受试者（n = 253）进行经胸超声心动图检查；主动脉瓣超声背向散射评分（AV(BS)）用于定量主动脉瓣的回声性。确定传统的冠状动脉危险因素。通过以下方式评估NO生成/反应的完整性：1）血浆不对称二甲基精氨酸浓度，作为内皮功能障碍的标志物；2）NO供体硝普钠对血小板聚集的抑制作用，作为组织NO反应性的指标以及冠状动脉预后标志物；3）主动脉增强指数，作为动脉僵硬度/波反射的指标。通过单变量和多元线性回归分析检查所有与AV(BS)的假定相关性。
根据AV(BS)评分，19.4%的受试者存在ASc。AV(BS)与患者年龄直接相关，但与高敏C反应蛋白、肌酐清除率和血小板NO反应性呈负相关。在多元线性回归中，ASc与血小板NO反应性受损（β = -0.16，p = 0.02）、年龄增长（β = 0.21，p = 0.003）和低体重指数（β = -0.23，p = 0.001）相关。
主动脉硬化与血小板NO抵抗相关，而非传统的冠状动脉危险因素：这可能解释了ASc中血栓形成风险增加的原因。
