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Abstract

Clinically evident atherosclerotic cardiovascular disease (ASCVD) is a pro-inflammatory state associated with increased platelet aggregability (PAGG) and activation of the renin angiotensin system.

We hypothesize that: a) in hypertensive patients a selective angiotensin II AT1 receptor antagonist Irbesartan (IRB) in addition to its hypotensive effect may also contribute to reduction of PAGG and of plasma markers of inflammation; b) these effects of IRB are different in patients with and without ASCVD.

This randomized, double-blind, placebo-controlled crossover study was performed in 18 non-smokers with Stage I hypertension (10 pts w/o ASCVD [Group A; 60% males; 50% whites]; 8 pts w/ASCVD [Group B; 63% males; 50% white]). Nine pts had hyperlipidemia (8 treated with statins). Patients received IRB or placebo for 6 weeks each (the IRB dose was uptitrated from 150 mg to 300 mg after 3 wks), with a 4-wk wash-out. No antiplatelet, or antidepressant agents, or NSAID were permitted. PAGG was tested with thrombin-receptor agonist (TRA) and adenosin-diphosphate (ADP). Plasma concentration of CRP, IL-6, P-and E-selectins were obtained at baseline and at the end of each treatment period.

IRB treatment decreased SBP (mean ± SD mm Hg; from 146.4 ± 12.4 to 140.7 ± 10.3; p<0.05). There was a greater impact of IRB on reduction of ADP-induced PAGG in Group A vs Group B pts (mean relative impact −1.57 ± 0.63 μ mol/L; p=0.02). This decrease in PAGG was independent of IRB dose and BP control. In contrast, Group B pts treated with IRB tended to have greater reduction in E-selectin (−7.72 ± 4.10 ng/dl; p=0.08); no differential effect on the changes in other inflammatory marker concentrations was noted. There was a greater reduction in TRA-induced PAGG with IRB 300 mg in hyperlipidemic pts (−0.67 ± 0.31; p=0.05).

Our findings suggest a possible impact of ASCVD and hyperlipidemia on the effects of IRB therapy on platelet aggregability and markers of inflammation in hypertensive patients. IRB therapy was associated with greater reduction of PAGG in patients without ASCVD, and of E-selectin concentration in patients with ASCVD. Greater reduction of PAGG in patients with hyperlipidemia may suggest a synergistic effect of IRB and statin therapies.

Am J Hypertens (2004) 17, 115A–116A; doi: 10.1016/j.amjhyper.2004.03.302

Cardiovascular Disease, Angiotensin-Receptor Blocker, Platelet Aggregation
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© American Journal of Hypertension, Ltd. 2004
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