title: Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.
abstract: BACKGROUND
  Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R 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 B 2 (TXB 2 ) 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 (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 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 TXB 2 with concordant phosphorylation of p38MAPK 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
  AT 1 R antagonist valsartan decreases platelet activity by attenuating COX-2/TXA 2 expression through p38MAPK and NF-kB pathways and reduces the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension.
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Cai
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Wang
authors.forename: Feng-Ru
authors.initials: FR
authors.lastname: Zhang
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.forename: Meng-Hui
authors.initials: MH
authors.lastname: Jiang
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Shen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D013777:Tetrazoles / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D013929:Thromboxane B2 / Q000097:blood; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D013777:Tetrazoles; D013929:Thromboxane B2; D000068756:Valsartan; D051546:Cyclooxygenase 2; D014633:Valine