Abstract

BackgroundThe phosphodiesterase inhibitor cilostazol has beneficial effects on atherosclerosis by virtue of vasodilatory and antiplatelet effects. However, less is known about the effect of cilostazol on arterial stiffness and biochemical markers related to vascular inflammation and endothelial dysfunction in type 2 diabetic patients with metabolic syndrome.MethodsIn this randomized, double-blind, crossover trial, 45 diabetic patients with metabolic syndrome were randomly assigned to either the cilostazol group (50 mg for 2 weeks, 100 mg for 6 weeks) or placebo group for an 8-week treatment phase, and then crossed over. Brachial-ankle pulse wave velocity (baPWV) and serum levels of inflammatory cytokines and vascular cellular adhesion molecules were measured before and after each treatment phase.ResultsCompared with the placebo group, the mean baPWV did not improve in the cilostazol group (mean difference 31.42 cm/sec, 95% CI −55.67 to 118.5). Cilostazol treatment significantly reduced soluble vascular cellular adhesion molecule-1 (sVCAM-1) level (from 1288.7 ± 285.6 to 1168.2 ± 252.3 ng/dL, P = 0.0003), and there was also significant mean difference between groups (mean difference 105.18 ng/dL, 95% CI 10.65 to 199.71). However, other biochemical markers including lipid profiles, high sensitivity C-reactive protein, adiponectin, interleukin-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1, and soluble intercellular adhesion molecule-1 did not improve with cilostazol treatment.ConclusionCilostazol treatment significantly reduced serum sVCAM-1 level, but this short term treatment was not associated with beneficial effect on arterial stiffness and other inflammatory markers.Trial registration(Clinical trial reg. no. NCT00573950, clinicaltrials.gov.)

Highlights

  • Cardiovascular disease (CVD) is the major cause of mortality in patients with diabetes and metabolic syndrome

  • We evaluated the effect of cilostazol on proinflammatory cytokines and inflammatory markers related to vascular inflammation and endothelial dysfunction

  • To the best of our knowledge, this is the first randomized controlled trial comparing the effect of cilostazol and placebo on arterial stiffness and biochemical markers related to vascular inflammation including vascular cellular adhesion molecules in diabetic patients without established CVD

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Summary

Introduction

Cardiovascular disease (CVD) is the major cause of mortality in patients with diabetes and metabolic syndrome. Chronic inflammation and endothelial dysfunction appear to be major components contributing to the development of atherosclerosis in a background of insulin resistance in diabetic patients [1,2] Biochemical markers such as proinflammatory cytokines and vascular cellular adhesion molecules are related to the progression of atherosclerosis and CVD [3,4] and are helpful for the screening of subclinical atherosclerosis [5,6]. Various noninvasive measures of these changes, such as carotid intima-media thickness (IMT), pulse wave velocity (PWV), and coronary artery calcification have been developed and commonly used [7] Of these methods, PWV is the most commonly used measure of arterial stiffness, and predicts the development of CVD and mortality in type 2 diabetes [8]. Less is known about the effect of cilostazol on arterial stiffness and biochemical markers related to vascular inflammation and endothelial dysfunction in type 2 diabetic patients with metabolic syndrome

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