Jumar Agnes, Ott Christian, Kistner Iris, Friedrich Stefanie, Schmidt Stephanie, Harazny Joanna M, Schmieder Roland E
aDepartment of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany bDepartment of Pathophysiology, University of Warmia and Mazury, Olsztyn, Poland.
J Hypertens. 2015 Dec;33(12):2491-9. doi: 10.1097/HJH.0000000000000735.
In hypertension, changes in small arterial structure are characterized by an increased wall-to-lumen ratio (WLR). These adaptive processes are modulated by the rennin-angiotensin system. It is unclear whether direct renin inhibitors exert protective effects on small arteries in hypertensive patients.
In this double-blind, randomized, placebo-controlled study (http://www.clinicaltrials.gov: NCT01318395), 114 patients with primary hypertension were randomized to additional therapy with either placebo or aliskiren 300 mg for 8 weeks after 4 weeks of standardized open-label treatment with valsartan 320 mg (run-in phase). Parameter of arteriolar remodelling was WLR of retinal arterioles (80 - 140 μm) assessed noninvasively and in vivo by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). In addition, pulse wave analysis (SphygmoCor, AtCor Medical, Australia) and pulse pressure (PP) amplification were determined.
In the whole study population, no clear effect of additional therapy with aliskiren on vascular parameters was documented. When analyses were restricted to patients with vascular remodelling, defined by a median of WLR more than 0.3326 (n = 57), WLR was reduced after 8 weeks by the treatment with aliskiren compared with placebo (-0.044 ± 0.07 versus 0.0043 ± 0.07, P = 0.015). Consistently, after 8 weeks of on-top treatment with aliskiren, there was an improvement of PP amplification compared with placebo (0.025 ± 0.07 versus -0.034 ± 0.08, P = 0.013), indicative of less stiff arteries in the peripheral circulation.
Thus, our data indicate that treatment with aliskiren, given on top of valsartan therapy, improves altered vascular remodelling in hypertensive patients.
在高血压患者中,小动脉结构改变的特征是壁腔比(WLR)增加。这些适应性过程受肾素 - 血管紧张素系统调节。目前尚不清楚直接肾素抑制剂对高血压患者的小动脉是否具有保护作用。
在这项双盲、随机、安慰剂对照研究(http://www.clinicaltrials.gov: NCT01318395)中,114例原发性高血压患者在接受4周缬沙坦320mg标准化开放标签治疗(导入期)后,随机分为两组,分别接受安慰剂或阿利吉仑300mg的额外治疗,为期8周。通过扫描激光多普勒血流仪(德国海德堡工程公司)对视网膜小动脉(80 - 140μm)的WLR进行无创和体内评估,以此作为小动脉重塑的参数。此外,还测定了脉搏波分析(澳大利亚AtCor Medical公司的SphygmoCor)和脉压(PP)放大情况。
在整个研究人群中,未发现阿利吉仑额外治疗对血管参数有明显影响。当分析仅限于血管重塑患者(定义为WLR中位数大于0.3326,n = 57)时,与安慰剂相比,阿利吉仑治疗8周后WLR降低(-0.044 ± 0.07对0.0043 ± 0.07,P = 0.015)。同样,在接受阿利吉仑强化治疗8周后,与安慰剂相比,PP放大情况有所改善(0.025 ± 0.07对-0.034 ± 0.08,P = 0.013),这表明外周循环中动脉僵硬度降低。
因此,我们的数据表明,在缬沙坦治疗基础上加用阿利吉仑可改善高血压患者改变的血管重塑。