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Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

Wu F, Wang HY, Cai F, Wang LJ, Zhang FR, Chen XN, Yang Q, Jiang MH, Wang XF, Shen WF - Chin. Med. J. (2015)

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China.

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.

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Flowchart of patient enrollment.
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Figure 1: Flowchart of patient enrollment.

Mentions: Two hundred and thirty-six consecutive elderly (>60 years in age) patients with hypertension who were admitted to the Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between April 2011 and August 2013 were screened. Hypertension was diagnosed as systolic blood pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg before recruitment.[15] For the purpose of research, patients with acute or chronic infection, hepatic or at least moderate renal insufficiency (estimated glomerular filtration rate [eGFR] <60 ml·min-1·1.73 m-2) (n = 17), trauma or surgery within 2 months (n = 2), and other blood diseases (e.g. hemophilia, and leukemia, aplastic anemia) (n = 5) were excluded. We also excluded patients with resistant hypertension (n = 2).[16] The remaining 210 eligible elderly hypertensive patients (191 men and 19 women, mean age 79.2 ± 1.0 years) were randomized to valsartan (Beijing Novartis Pharma Ltd., China) (AT1R group; n = 140) or amlodipine (Beijing Novartis Pharma Ltd.) (non-AT1R group; n = 70) in a 2:1 ratio [Figure 1] by random group design. For each group, the initial dose of valsartan (80 mg, once daily) or amlordipine (5 mg, once daily) was titrated to achieve target blood pressure (<140/90 mmHg for patients under 80 years and < 150/90 mmHg for those older than 80 years). A small dose of diuretics like hydrochlorothiazide (Shanghai Xinyi Pharma Ltd., China) (12.5–25 mg, once daily) may be added if maximum daily dose of valsartan (160 mg) or amlodipine (10 mg) was insufficient for optimal blood pressure control. Other medications including β-blockers, anti-platelet agents, and statins were prescribed at the discretion of the physicians.


Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

Wu F, Wang HY, Cai F, Wang LJ, Zhang FR, Chen XN, Yang Q, Jiang MH, Wang XF, Shen WF - Chin. Med. J. (2015)

Flowchart of patient enrollment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837831&req=5

Figure 1: Flowchart of patient enrollment.
Mentions: Two hundred and thirty-six consecutive elderly (>60 years in age) patients with hypertension who were admitted to the Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine between April 2011 and August 2013 were screened. Hypertension was diagnosed as systolic blood pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg before recruitment.[15] For the purpose of research, patients with acute or chronic infection, hepatic or at least moderate renal insufficiency (estimated glomerular filtration rate [eGFR] <60 ml·min-1·1.73 m-2) (n = 17), trauma or surgery within 2 months (n = 2), and other blood diseases (e.g. hemophilia, and leukemia, aplastic anemia) (n = 5) were excluded. We also excluded patients with resistant hypertension (n = 2).[16] The remaining 210 eligible elderly hypertensive patients (191 men and 19 women, mean age 79.2 ± 1.0 years) were randomized to valsartan (Beijing Novartis Pharma Ltd., China) (AT1R group; n = 140) or amlodipine (Beijing Novartis Pharma Ltd.) (non-AT1R group; n = 70) in a 2:1 ratio [Figure 1] by random group design. For each group, the initial dose of valsartan (80 mg, once daily) or amlordipine (5 mg, once daily) was titrated to achieve target blood pressure (<140/90 mmHg for patients under 80 years and < 150/90 mmHg for those older than 80 years). A small dose of diuretics like hydrochlorothiazide (Shanghai Xinyi Pharma Ltd., China) (12.5–25 mg, once daily) may be added if maximum daily dose of valsartan (160 mg) or amlodipine (10 mg) was insufficient for optimal blood pressure control. Other medications including β-blockers, anti-platelet agents, and statins were prescribed at the discretion of the physicians.

Bottom Line: 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).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai 200025, China.

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.

Show MeSH
Related in: MedlinePlus