Fogari Roberto, Preti Paola, Zoppi Annalisa, Lazzari Pierangelo, Corradi Luca, Fogari Elena, Ciccarelli Leonardina, Derosa Giuseppe
Department of Internal Medicine and Therapeutics, Clinica Medica II, IRCCS Policlinico S.Matteo, University of Pavia, Piazzale Golgi 19, 27100, Pavia, Italy.
Eur J Clin Pharmacol. 2006 Oct;62(10):817-22. doi: 10.1007/s00228-006-0176-1. Epub 2006 Aug 2.
The objective of this study was to assess the effect of amlodipine-atorvastatin combination on plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and insulin sensitivity in normocholesterolemic obese hypertensive patients.
After a 4-week placebo wash-out period, 50 normocholesterolemic [total cholesterol (TC) <5.2 mmol/L], obese (BMI >/=30 kg/m(2)) hypertensive patients (DBP >90 and <105 mm Hg and SBP >140 and <180 mm Hg) were randomly treated with amlodipine (10 mg) or with amlodipine (10 mg) plus atorvastatin (20 mg) according to a cross-over design; each treatment had a 12-week duration. At the end of the placebo and of each treatment period, blood pressure (BP), TNF-alpha, IL-6, insulin resistance (IR) by homeostasis model assessment of IR index (HOMA-IR) and TC were evaluated.
Amlodipine monotherapy decreased both SBP (-17.1 mm Hg, p=0.008 vs. placebo) and DBP (-14.3 mm Hg, p=0.008) as well as TNF-alpha (from 3.66+/-1.6 to 3.09+/-1.1 pg/ml, p=0.045) and HOMA-IR (from 4.58+/-0.7 to 3.88+/-0.6, p=0.007). The amlodipine-atorvastatin combination produced a decrease in SBP (-22.5 mm Hg, p=0.0007 vs. placebo, p=0.039 vs. amlodipine), DBP (-17.7 mm Hg, p=0.0007 vs. placebo; p=0.04 vs. amlodipine), TNF-alpha (2.59+/-0.9 pg/mL, p=0.007 vs. placebo and p=0.038 vs. amlodipine) and HOMA-IR (2.86+/-0.4, p=0.0008 vs. placebo and p=0.007 vs. amlodipine). The combination reduced IL-6 (from 7.93+/-1.9 to 5.59+/-1.2 pg/mL, p=0.008 vs. placebo and p=0.007 vs. amlodipine) and TC (from 4.3+/-0.5 to 3.6+/-0.4 mmol/L, p=0.008 vs. placebo and vs. amlodipine). HOMA-IR changes significantly correlated with TNF-alpha changes (r=0.38, p<0.05) during combination but not during amlodipine monotherapy. In normocholesterolemic, obese hypertensive patients, the amlodipine-atorvastatin combination decreased inflammatory markers and IR more than amlodipine monotherapy and produced a greater SBP and DBP reduction.
本研究旨在评估氨氯地平 - 阿托伐他汀联合用药对血脂正常的肥胖高血压患者血浆白细胞介素 -6（IL -6）、肿瘤坏死因子 -α（TNF -α）及胰岛素敏感性的影响。
经过4周的安慰剂洗脱期后，50名血脂正常[总胆固醇（TC）<5.2 mmol/L]、肥胖（BMI≥30 kg/m²）的高血压患者（舒张压>90且<105 mmHg，收缩压>140且<180 mmHg）按照交叉设计随机接受氨氯地平（10 mg）治疗或氨氯地平（10 mg）加阿托伐他汀（20 mg）治疗；每种治疗为期12周。在安慰剂期及每个治疗期结束时，评估血压（BP）、TNF -α、IL -6、通过稳态模型评估胰岛素抵抗指数（HOMA -IR）得出的胰岛素抵抗（IR）以及TC。
氨氯地平单药治疗可降低收缩压（-17.1 mmHg，与安慰剂相比p = 0.008）和舒张压（-14.3 mmHg，p = 0.008），以及TNF -α（从3.66±1.6降至3.09±1.1 pg/ml，p = 0.045）和HOMA -IR（从4.58±0.7降至3.88±0.6，p = 0.007）。氨氯地平 - 阿托伐他汀联合用药可使收缩压降低（-22.5 mmHg，与安慰剂相比p = 0.0007，与氨氯地平相比p = 0.039），舒张压降低（-17.7 mmHg，与安慰剂相比p = 0.0007；与氨氯地平相比p = 0.04），TNF -α降低（2.59±0.9 pg/mL，与安慰剂相比p = 0.007，与氨氯地平相比p = 0.038）以及HOMA -IR降低（2.86±0.4，与安慰剂相比p = 0.0008，与氨氯地平相比p = 0.007）。联合用药可降低IL -6（从7.93±1.9降至5.59±1.2 pg/mL，与安慰剂相比p = 0.008，与氨氯地平相比p = 0.007）和TC（从4.3±0.5降至3.6±0.4 mmol/L，与安慰剂相比p = 0.008以及与氨氯地平相比）。联合用药期间HOMA -IR变化与TNF -α变化显著相关（r = 0.38，p<0.05），但氨氯地平单药治疗期间无此相关性。在血脂正常的肥胖高血压患者中，氨氯地平 - 阿托伐他汀联合用药比氨氯地平单药治疗更能降低炎症标志物和IR，并能更大程度地降低收缩压和舒张压。
