Valsartan Decreases Platelet Activity and Arterial Thrombotic Events in Elderly Patients with Hypertension

摘要

Background:Angiotensin type 1 receptor (AT1R) antagonists are extensively used for blood pressure control in elderly patients with hypertension.This study aimed to investigate the inhibitory effects of AT1R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.Methods:Two-hundred and ten patients with hypertension and aged ＞ 60 years were randomized to valsartan (n =140) or amlodipine (n =70) on admission.The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge,and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up.Human aortic endothelial cells (HAECs) were stimulated by angiotensin Ⅱ (Ang Ⅱ,100 nmol/L) with or without pretreatment of valsartan (100 nmol/L),and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B2 (TXB2) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed.Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software,Inc.,California,USA).Results:PAR was lower after treatment with valsartan (1 1.49 ± 0.69％ vs.18.71 ± 2.47％,P ＜ 0.001),associated with more reduced plasmalevels of COX-2 (76.94 ± 7.07 U/L vs.116.4 ± 15.89 U/L,P ＜ 0.001) and TXB2 (1667 ± 56.50 pg/ml vs.2207 ± 180.20 pg/ml) (all P ＜ 0.001).Plasma COX-2 and TXB2 levels correlated significantly with PAR in overall patients (r =0.109,P ＜ 0.001).During follow-up (median,18 months),there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3％ vs.32.8％,P =0.002).Relative expression of COX-2 and secretion of TXB2 with concordant phosphorylation ofp38MAPK and NF-kB were increased in HAECs when stimulated by Ang Ⅱ (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L).Conclusions:AT1R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.