贝尼地平与阿托伐他汀联合治疗对老年单纯收缩期高血压患者的抗炎症和改善血管内皮功能的作用

Effect of Benidipine-atorvastatin Combination Therapy on Inflammatory Markers and Flow-mediated Dilatation in Elderly Patients with Isolated Systolic Hypertension

目的探讨贝尼地平和阿托伐他汀联合治疗老年单纯收缩期高血压（ISH）患者的疗效。方法ISH患者90例分为对照组（n=15）、贝尼地平组（4～8mg／d，n=25）、阿托伐他汀组（20mg／d，n=25）和联合治疗组（贝尼地平4～8mg／d＋阿托伐他汀20mg／d，n=25），分别治疗5月。用药前后分别测血清白介素6（IL-6）、白介素8（IL-8）、高敏C反应蛋白（hscRP）浓度，肱动脉内皮舒张功能（FMD），尿微量白蛋白（MAU），左室质量指数（LV—MI），颈动脉内膜厚度（CIMT），血压及血脂含量。结果所有患者治疗前后MAu、LVMI均无统计学差异。联合用药组明显升高FMDF联合用药组（5．5±4．4）％比贝尼地平组（2．4±2．7）％比阿托伐他汀组（2．9±3．7）％，P〈0．05]，和单药治疗组相比，联合用药组明显降低血清IL-6浓度[IL-6下降值，联合用药组（6.5±6．3）ng／L，比贝尼地平组：（3．1±3.2）ng／L比阿托伐他汀组：（3．3±2．3）ng／L，P〈0．05]。联合治疗组IL-8下降幅度亦显著高于贝尼地平、阿托伐他汀组[IL-8下降值，联合用药组（69．4±46．4）ng／L比贝尼地平组（30．4±21．0）ng／L比阿托伐他汀组（29．1±24．9）ng／L，P〈0．053。阿托伐他汀组和联合治疗组用药后hsCRP、CIMT显著下降（P值均〈0．01），贝尼地平组无显著变化。校正年龄和脉压差变化之后，治疗组FMD升高与IL-6下降呈微弱负相关（r=-0．322，P=0．003）。结论贝尼地平和阿托伐他汀联合应用治疗老年ISH加强了抗炎、保护血管内皮功能，联合治疗的内皮保护作用可能与降低炎性因子有关。

Objective The effect of combined treatment of statins and calcium channel blockers（CCB） in elderly patients with isolated systolic hypertensionlISH） are not well understood. The purpose of the present study was to assess the additive effect of benidipine-atorvastatin combination therapy in old patients with ISH. Methods Ninety patients with ISH were randomized to receive： placebo （n= 15）, benidipine treatment （4-8 mg/d, n= 25）, atorvastatin （20 mg/d, n= 25 ） and benidipine plus atorvastatin treatment （4 - 8 mg/d ＋ 20 mg/d, n = 25 ） for 5 months. Serum concentrations of IL-6, IL-8, hsCRP, flow-mediated dilatation of the brachial artery, urine microalbumin, left ventricular mass index （LVMI）, carotid intima-media thickness（CIMT）, BP and plasma lipids profiles were examined before and after treatment. Results After 5-months of treatment, the combination treatment significantly reduced IL-6 （IL-6 reduction magnitude, combination group： 6.5＋6.3 ng/L vs benidipine group： 3.1 ±3.2 ng/L vs atorvastatin group： 3.3±2.3 ng/L, P〈0.05） , and IL-8 （IL-8 reduction magnitude, combination group： 69.4±46.4 ng/L vs benidipine group： 30.4 ± 21.0 ng/L vs atorvastatin group： 29.1 ± 24.9 ng/L, P〈 0.05）. The increase of FMD were significantly enhanced by combination therapy （FMD increase %, combination group： 5.5±4.4% vs benidipine group： 2.4±2.7% vs atorvastatin group： 2.9±3.7%, P〈0.05 ）. No significant changes of MAU and LVMI after treatment in all patients was found. Serum concentration of hsCRP and carotid CIMT were reduced significantly in atorvastatin group and combination group, while little changes were found by benidipine and placebo（P〈 0.05 ）. Changes of FMD correlated inversely with changes of IL-6 （ r = -0. 322, P=0. 003 ）, which remained significant after adjustment as age and pulse pressure. Conclusion Greater beneficial effect of benidipine-atorvastatin combination on inflammation markers（IL-6, IL-8） and flow-mediated dilatation was found than monotherapy in patients with isolated systolic hypertension.