Ghiadoni Lorenzo, Bruno Rosa Maria, Cartoni Giulia, Stea Francesco, Magagna Armando, Virdis Agostino, Grassi Davide, Ferri Claudio, Taddei Stefano
Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Institute of Clinical Physiology - CNR, Pisa, Italy.
Vascul Pharmacol. 2017 May;92:16-21. doi: 10.1016/j.vph.2015.06.004. Epub 2015 Jun 10.
Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, p<0.05; ENA/HCT from 8.5±1.2 to 8.2±1.0m/s, p<0.05). Finally, both combinations reduced AIx, but its reduction was significantly greater (p<0.05) in ENA/LER (from 26.8±10.9 to 20.6±9.1%) than in ENA/HCT arm (from 28.2±9.0 to 24.7±8.7%). In conclusion, the combination with LER caused a similar PWV reduction as compared to HCT, but a greater reduction in AIx in hypertensive patients with metabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection.
动脉僵硬度和血压（BP）升高是心血管事件的独立预测因素。在一项随机、开放、平行组研究中，我们比较了血管紧张素转换酶抑制剂（ACE）与钙通道阻滞剂或噻嗪类利尿剂联合治疗对76例单药使用ACE抑制剂无法控制的代谢综合征高血压患者这些参数的影响。在使用依那普利（ENA，20mg）进行4周导入期治疗后，患者被随机分为接受乐卡地平（LER，10 - 20mg）或氢氯噻嗪（HCT，12.5 - 25mg）联合治疗24周。采用压平式眼压计测量主动脉僵硬度（颈动脉至股动脉脉搏波速度，PWV）、中心血压值和血压升高（血压升高指数，AIx）。导入期后两组的诊室血压和中心血压相似。24周后，诊室血压（ENA/LER：从149.1±4.9/94.5±1.5降至131.7±8.1/82.2±5.3；ENA/HCT：从150.3±4.7/94.7±2.1降至133.1±7.1/82.8±5.3mmHg）和中心血压（ENA/LER从127.4±17.1/85.2±12.1降至120.5±13.5/80.0±9.5mmHg；ENA/HCT为121.6±13.4/79.3±9.5mmHg）均有相似程度的降低。导入期后PWV相当，两种治疗降低PWV的程度无差异（ENA/LER从8.6±1.5降至8.1±1.3m/s，p<0.05；ENA/HCT从8.5±1.2降至8.2±1.0m/s，p<0.05）。最后，两种联合治疗均降低了AIx，但ENA/LER组AIx的降低幅度（从26.8±10.9降至20.6±9.1%）显著大于ENA/HCT组（从28.2±9.0降至24.7±8.7%，p<0.05）。总之，与HCT相比，LER联合治疗使PWV降低程度相似，但在单药使用ENA无法控制的代谢综合征高血压患者中，LER联合治疗使AIx降低幅度更大。这些结果表明ENA/LER联合治疗对中心血压升高有积极作用，提示其在心血管保护方面可能具有相加作用。
