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Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

ABSTRACT: Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes.Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed (1) endothelial function as flow-mediated dilation of the brachial artery, (2) arterial stiffness and central augmentation index using applanation tonometry, (3) vascular function as fingertip reactive hyperemia index, (4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, (5) oxidative stress by measuring plasma aminothiols, and (6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period.Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells.Our findings suggest a solitary antiplatelet effect of clopidogrel therapy in patients with stable coronary artery disease, with no effect on other subclinical markers of cardiovascular disease risk.

SUBMITTER: Ramadan R

PROVIDER: S-EPMC4046585 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

Ramadan Ronnie R Dhawan Saurabh S SS Syed Hamid H Pohlel F Khan FK Binongo Jose N G JN Ghazzal Ziyad B ZB Quyyumi Arshed A AA

Journal of cardiovascular pharmacology 20140401 4

<h4>Background</h4>Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes.<h4>Methods</h4>Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopido ...[more]

PMID: 24336012

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Project description:BackgroundRemote ischaemic preconditioning (RIPC) is a cardioprotective intervention invoking intermittent periods of ischaemia in a tissue or organ remote from the heart. The mechanisms of this effect are incompletely understood. We hypothesised that RIPC might enhance coronary vasodilatation by an endothelium-dependent mechanism.MethodsWe performed a prospective, randomised, sham-controlled, blinded clinical trial. Patients with stable coronary artery disease (CAD) undergoing elective invasive management were prospectively enrolled, and randomised to RIPC or sham (1:1) prior to angiography. Endothelial-dependent vasodilator function was assessed in a non-target coronary artery with intracoronary infusion of incremental acetylcholine doses (10-6, 10-5, 10-4mol/l). Venous blood was sampled pre- and post-RIPC or sham, and analysed for circulating markers of endothelial function. Coronary luminal diameter was assessed by quantitative coronary angiography. The primary outcome was the between-group difference in the mean percentage change in coronary luminal diameter following the maximal acetylcholine dose (Clinicaltrials.gov identifier: NCT02666235).Results75 patients were enrolled. Following angiography, 60 patients (mean±SD age 57.5±8.5years; 80% male) were eligible and completed the protocol (n=30 RIPC, n=30 sham). The mean percentage change in coronary luminal diameter was -13.3±22.3% and -2.0±17.2% in the sham and RIPC groups respectively (difference 11.32%, 95%CI: 1.2- 21.4, p=0.032). This remained significant when age and sex were included as covariates (difference 11.01%, 95%CI: 1.01- 21.0, p=0.035). There were no between-group differences in endothelial-independent vasodilation, ECG parameters or circulating markers of endothelial function.ConclusionsRIPC attenuates the extent of vasoconstriction induced by intracoronary acetylcholine infusion. This endothelium-dependent mechanism may contribute to the cardioprotective effects of RIPC.

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Dataset Information

Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

Publications

Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

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