厄贝沙坦与老年高血压患者血栓事件的相关性研究

Study on correlation between irbesartan and thromboembolic events in elderly patients with hypertension

目的 :探讨血管紧张素1型受体(AT_1R)拮抗剂厄贝沙坦对老年高血压患者心脑血栓事件发生的影响及相关机制。方法:入选170例年龄大于60岁的高血压患者,根据用药情况分为厄贝沙坦组(n=100)和氨氯地平组(n=70),比较随访过程中发生血栓事件如脑梗死、心肌梗死发生率的差异;分别测定各组血小板聚集率(PAR)、血管紧张素Ⅱ(AngⅡ)、环氧化酶-2(COX-2)、凝血噁恶烷B2(TXB2)水平。检测经体外培养人主动脉内皮细胞(HAEC)中,由AngⅡ诱导产生的COX-2 m RNA及蛋白表达量、TXB2水平。结果 :厄贝沙坦组患者中PAR(%)明显低于氨氯地平组患者(11.52±0.70比18.71±2.47,P<0.001),其血浆COX-2水平[(76.01±7.09)U/L比(116.40±15.89)U/L,P<0.001]和TXB2[(1 687.00±59.14)ng/L比(2 207.00±180.20)ng/L,P<0.001]也明显降低,且血浆COX-2和TXB2水平降低同PAR降低存在相关性(r=0.109,P<0.001)。中位随访时间18个月,血栓事件的发生率在服用厄贝沙坦的患者中明显降低(15.0%比32.8%,P=0.002)。厄贝沙坦预处理后HAEC后可明显抑制AngⅡ(100 nmol/L)诱导细胞产生的COX-2、TXB2水平。结论 :AT_1R拮抗剂厄贝沙坦抑制COX-2/TXB2表达,能有效抑制老年高血压患者的血小板活性,从而抑制老年高血压患者心脑血栓事件发生风险。

Objective To investigate the effect of angiotensin type 1 receptor （AT1R） antagonist irbesartan on platelet aggregation and occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Methods A total of 200 hypertensive patients over the age of 60 were enrolled and according to the drug used divided into irbesartan （n=100） or amlodipine （n=70） groups on admission. The secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Platelet aggregation rate （PAR） and plasma levels of angiotension Ⅱ （Ang I ）, cyclooxygenase-2 （COX-2） and thromboxane B2 （TXB2） were determined. Human aortic endothelial cells （HAECs） were stimulated by Ang I with or without the treatment of irbesartan, and the relative expression of COX-2 and TXB2 was assessed. Results PAR（%） was lower in irbesartan group （11.52±0.70 vs 18.71±2.47, P〈0.001）, associated with reduced plasma levels of COX-2 [（76.01±7.09） U/L vs （116.40±15.89） U/L, P〈0.001] and TXB2 [（1 687.00±59.14） ng/L vs （2 207.00±180.20） ng/L, P〈0.001]. Plasma COX-2 and TXB2 levels were correlated with PAR in both groups （r=0.109, P〈 0.001）. During follow-up （median, 18 months）, there was a significantly lower thrombotic event rate in patients treated with irbesartan （15% vs 32.8%, P=0.002）. Ang Ⅱ induced expression of COX-2 and secretion of TXB2 were inhibited in HAECs when pretreated with irbesartan. Conclusions AT1R antagonist irbesartan may effectively decrease platelet activity in elderly hypertensive patients by attenuating the expression of COX-2/TXB2, and reduces the occurrence of cardio- cerebral thrombotic events in elderly patients with hypertension.