Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide, 28 Woodville Road, Woodville, South Australia 5011, Australia.
Eur Heart J. 2012 Oct;33(19):2419-25. doi: 10.1093/eurheartj/ehs171. Epub 2012 Jul 6.
Aortic valve stenosis (AS) and its precursor, aortic valve sclerosis (ASc), occur frequently in Western populations. Investigations to retard the progression of AS using statins have been unsuccessful. Development of ASc in humans is associated with increased aortic valve backscatter (AVBS) and poor tissue nitric oxide (NO) responsiveness. In an animal model, ramipril retarded AS/ASc development. We have now set out to identify factors associated with the progression of ASc in humans.
At baseline and after 4 years, 204 randomly selected subjects (age 63 ± 6 years at study entry) underwent echocardiography with the determination of AVBS values, measurements of platelet NO responsiveness, plasma asymmetric dimethylarginine concentrations, lipid profile, high-sensitivity-C-reactive protein, routine biochemistry, and 25-hydroxy-vitamin D levels. During the study period, 68% of subjects had detectable AVBS progression. On multivariate analysis, higher calcium concentrations (β = 0.22; P = 0.004), poor platelet NO responsiveness (β = 0.18; P = 0.018), and increased arterial stiffness (β = 0.15; P = 0.044) were independent predictors of disease progression. The use of angiotensin-converting enzyme-inhibitors/angiotensin II receptor blockers (ACE-I/ARB) predicted the lack of disease progression (assessed categorically) in the overall cohort and in those without ASc at baseline (n = 159) (β = 0.8; P = 0.025 and β = 1.3; P = 0.001, respectively). No conventional coronary risk factors were associated with disease progression.
This study of early aortic valve disease (i) demonstrates that disease progression occurs in the majority of the normal ageing population over a 4-year period; (ii) provides evidence of the importance of the NO signalling cascade in disease development and progression; and (iii) provides additional data linking ACE-I/ARB use with the retardation of ASc.
主动脉瓣狭窄（AS）及其前体主动脉瓣钙化（ASc）在西方人群中较为常见。使用他汀类药物延缓 AS 进展的研究并未成功。人类 ASc 的发展与主动脉瓣背向散射（AVBS）增加和组织中一氧化氮（NO）反应性差有关。在动物模型中，雷米普利可延缓 AS/ASc 的发展。我们现在着手确定与人类 ASc 进展相关的因素。
在基线和 4 年后，随机选择 204 名研究对象（研究开始时年龄为 63±6 岁）进行超声心动图检查，以确定 AVBS 值、血小板 NO 反应性、血浆非对称二甲基精氨酸浓度、血脂谱、高敏 C 反应蛋白、常规生化和 25-羟维生素 D 水平。在研究期间，68%的研究对象的 AVBS 出现可检测到的进展。多变量分析表明，较高的钙浓度（β=0.22；P=0.004）、血小板 NO 反应性差（β=0.18；P=0.018）和动脉僵硬度增加（β=0.15；P=0.044）是疾病进展的独立预测因子。血管紧张素转换酶抑制剂/血管紧张素 II 受体阻滞剂（ACE-I/ARB）的使用预测了整个队列以及基线时无 ASc 的研究对象（n=159）中疾病的无进展（分类评估）（β=0.8；P=0.025 和β=1.3；P=0.001）。没有常规的冠心病危险因素与疾病进展相关。
这项对早期主动脉瓣疾病的研究（i）表明，在 4 年内，大多数正常衰老人群的疾病会出现进展；（ii）提供了证据表明，NO 信号级联在疾病的发展和进展中很重要；（iii）提供了额外的数据，将 ACE-I/ARB 的使用与 ASc 的延缓联系起来。
