Koh Kwang Kon, Quon Michael J, Han Seung Hwan, Chung Wook-Jin, Ahn Jeong Yeal, Seo Yiel-Hea, Kang Moon Ho, Ahn Tae Hoon, Choi In Suck, Shin Eak Kyun
Cardiology, Vascular Medicine and Atherosclerosis Unit,Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, Korea.
Circulation. 2004 Dec 14;110(24):3687-92. doi: 10.1161/01.CIR.0000143085.86697.13. Epub 2004 Nov 29.
Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in hypercholesterolemic, hypertensive patients.
This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2-month treatment period. Losartan alone or combined therapy significantly reduced blood pressure compared with simvastatin alone. Compared with losartan alone, simvastatin alone or combined therapy significantly changed lipoproteins. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and decreased plasma malondialdehyde and monocyte chemoattractant protein-1 levels relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy compared with simvastatin or losartan alone (both P<0.001 and P=0.030 for monocyte chemoattractant protein-1 by ANOVA). Combined therapy or losartan alone significantly increased plasma adiponectin levels and insulin sensitivity (determined by QUICKI) relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.001 for adiponectin, P=0.029 for QUICKI by ANOVA).
Simvastatin combined with losartan improves endothelial function and reduces inflammatory markers to a greater extent than monotherapy with either drug in hypercholesterolemic, hypertensive patients.
他汀类药物和血管紧张素II 1型受体阻滞剂治疗的生物学机制不同。因此，我们比较了这些治疗方法单独使用或联合使用时，对高胆固醇血症、高血压患者的血管和代谢反应。
这是一项随机、双盲、安慰剂对照的交叉试验，有3个治疗组（每组2个月）和2个洗脱期（每个2个月）。47例高血压、高胆固醇血症患者在每个2个月的治疗期内，每天给予辛伐他汀20mg和安慰剂、辛伐他汀20mg和氯沙坦100mg或氯沙坦100mg和安慰剂。与单独使用辛伐他汀相比，单独使用氯沙坦或联合治疗可显著降低血压。与单独使用氯沙坦相比，单独使用辛伐他汀或联合治疗可显著改变脂蛋白。相对于基线测量值，所有3个治疗组均显著改善了血流介导的血管扩张反应，并降低了血浆丙二醛和单核细胞趋化蛋白-1水平。然而，与单独使用辛伐他汀或氯沙坦相比，联合治疗对这些参数的改变更大（通过方差分析，单核细胞趋化蛋白-1的P均<0.001和P = 0.030）。相对于基线测量值，联合治疗或单独使用氯沙坦可显著提高血浆脂联素水平和胰岛素敏感性（通过QUICKI测定）。这些变化显著大于单独使用辛伐他汀治疗的组（脂联素P<0.001，QUICKI通过方差分析P = 0.029）。
在高胆固醇血症、高血压患者中，辛伐他汀与氯沙坦联合使用比单独使用任何一种药物能更大程度地改善内皮功能并降低炎症标志物。
