Calprotectin and Platelet Aggregation in Patients with Stable Coronary Artery Disease

Background Recent 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. Objectives We 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. Methods We 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 B-2, both measured by ELISA. Results Calprotectin 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 B-2 (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 B-2 levels in all patients (median [25%; 75%]: 1.07 [0.52; 1.87]ng/mL). Conclusion Calprotectin levels correlated positively, though weakly, with platelet aggregation and activation as well as serum thromboxane B-2 in high-risk, stable CAD patients treated with aspirin.