Abstract

BackgroundRecent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD). However, the impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated.ObjectivesWe investigated the association between calprotectin levels and platelet aggregation in stable, high-risk CAD patients receiving aspirin as mono antiplatelet therapy. Furthermore, we aimed to investigate independent clinical and laboratory determinants of calprotectin levels.MethodsWe performed a cross-sectional study including 581 stable, high-risk CAD patients. All patients received 75 mg aspirin daily as mono antiplatelet therapy. Platelet aggregation was assessed by 1) impedance aggregometry (Multiplate Analyzer) using arachidonic acid (AA) and collagen as agonists and by 2) the VerifyNow Aspirin Assay. Low-grade inflammation was evaluated by calprotectin, high-sensitive C-reactive-protein (hs-CRP) and interleukin-6. Platelet activation was assessed by soluble P-selectin, and cyclooxygenase-1 inhibition was evaluated by serum thromboxane B2, both measured by ELISA.ResultsCalprotectin levels correlated positively with platelet aggregation according to Multiplate Analyzer (r=0.12, p=0.01). Additionally, calprotectin was positively associated with leukocytes (r=0.33, p<0.0001), hs-CRP (r=0.31, p<0.0001), interleukin-6 (r=0.28, p<0.0001), soluble P-selectin (r=0.10, p=0.02) and serum thromboxane B2 (r=0.10, p=0.02). Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004), and trends were seen for body mass index (p=0.06) and smoking (p=0.07). Compliance with aspirin was confirmed by low serum thromboxane B2 levels in all patients (median [25%;75%]: 1.07 [0.52;1.87] ng/mL).ConclusionCalprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B2 in high-risk, stable CAD patients treated with aspirin.

Highlights

  • Inflammation plays an important role in the pathogenesis of atherosclerosis [1]

  • We investigated the association between calprotectin levels and platelet aggregation in stable, high-risk coronary artery disease (CAD) patients receiving aspirin as mono antiplatelet therapy

  • Type 2 diabetes mellitus was an independent predictor of increased calprotectin levels (p=0.004), and trends were seen for body mass index (p=0.06) and smoking (p=0.07)

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Summary

Introduction

Inflammation plays an important role in the pathogenesis of atherosclerosis [1]. Coronary atherosclerosis is the underlying substrate of most coronary events, and rupture of an atherosclerotic plaque with exposure of the thrombogenic lipid-core promotes platelet adhesion followed by platelet activation and aggregation [2]. Platelet inhibition with aspirin continues to be the antiplatelet backbone in prevention and treatment of coronary artery disease (CAD) [3]. Calprotectin plasma levels have primarily been investigated as a marker of inflammatory conditions such as inflammatory bowel disease and rheumatoid arthritis [9,10], but recent studies suggest that calprotectin may be implicated in the pathogenesis of CAD [11,12,13,14,15]. Recent studies suggest that the inflammation-associated protein calprotectin may be implicated in the pathogenesis of coronary artery disease (CAD). The impact of calprotectin levels on platelet aggregation in CAD patients has never been investigated

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