Zanchetti Alberto, Bond M Gene, Hennig Michael, Neiss Albrecht, Mancia Giuseppe, Dal Palù Cesare, Hansson Lennart, Magnani Bruno, Rahn Karl-Heinz, Reid John L, Rodicio Josè, Safar Michel, Eckes Lothar, Rizzini Paolo
University of Milan, Ospedale Maggiore, Istituto Auxologico Italiano, Milan, Italy.
Circulation. 2002 Nov 5;106(19):2422-7. doi: 10.1161/01.cir.0000039288.86470.dd.
Most cardiovascular events associated with hypertension are complications of atherosclerosis. Some antihypertensive agents influence experimental models of atherosclerosis through mechanisms independent of blood pressure lowering.
The European Lacidipine Study on Atherosclerosis (ELSA) was a randomized, double-blind trial in 2334 patients with hypertension that compared the effects of a 4-year treatment based on either lacidipine or atenolol on an index of carotid atherosclerosis, the mean of the maximum intima-media thicknesses (IMT) in far walls of common carotids and bifurcations (CBM(max)). This index has been shown by epidemiological studies to be predictive of cardiovascular events. A significant (P<0.0001) effect of lacidipine was found compared with atenolol, with a treatment difference in 4-year CBM(max) progression of -0.0227 mm (intention-to-treat population) and -0.0281 mm (completers). The yearly IMT progression rate was 0.0145 mm/y in atenolol-treated and 0.0087 mm/y in lacidipine-treated patients (completers, 40% reduction; P=0.0073). Patients with plaque progression were significantly less common, and patients with plaque regression were significantly more common in the lacidipine group. Clinic blood pressure reductions were identical with both treatments, but 24-hour ambulatory systolic/diastolic blood pressure changes were greater with atenolol (-10/-9 mm Hg) than with lacidipine (-7/-5 mm Hg). No significant difference between treatments was found in any cardiovascular events, although the relative risk for stroke, major cardiovascular events, and mortality showed a trend favoring lacidipine.
The greater efficacy of lacidipine on carotid IMT progression and number of plaques per patient, despite a smaller ambulatory blood pressure reduction, indicates an antiatherosclerotic action of lacidipine independent of its antihypertensive action.
大多数与高血压相关的心血管事件是动脉粥样硬化的并发症。一些抗高血压药物通过独立于降低血压的机制影响动脉粥样硬化的实验模型。
欧洲拉西地平动脉粥样硬化研究（ELSA）是一项针对2334例高血压患者的随机双盲试验，比较了基于拉西地平或阿替洛尔的4年治疗对颈动脉粥样硬化指标（颈总动脉远壁和分叉处最大内膜中层厚度（IMT）的平均值（CBM(max)））的影响。流行病学研究表明该指标可预测心血管事件。与阿替洛尔相比，拉西地平有显著（P<0.0001）效果，4年CBM(max)进展的治疗差异为-0.0227mm（意向性治疗人群）和-0.0281mm（完成治疗者）。阿替洛尔治疗患者的每年IMT进展率为0.0145mm/年，拉西地平治疗患者为0.0087mm/年（完成治疗者，降低40%；P=0.0073）。拉西地平组斑块进展的患者明显较少，斑块消退的患者明显较多。两种治疗的诊室血压降低相同，但阿替洛尔的24小时动态收缩压/舒张压变化（-10/-9mmHg）大于拉西地平（-7/-5mmHg）。在任何心血管事件中，治疗之间均未发现显著差异，尽管中风、主要心血管事件和死亡率的相对风险显示出有利于拉西地平的趋势。
尽管动态血压降低幅度较小，但拉西地平对颈动脉IMT进展和每位患者斑块数量的疗效更佳，表明拉西地平具有独立于其抗高血压作用的抗动脉粥样硬化作用。
