Altered platelet reactivity, coagulation, endothelial and inflammatory markers early after smoking cessation verified with cotinine plasma concentration

Abstract

Abstract Background/Introduction Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD) including patients after percutaneous coronary interventions (PCI). Cigarette smoking is associated with major changes in platelet, endothelial, inflammatory, and coagulation responses. The early period after PCI witnesses the highest risk of thrombotic events. However, data regarding alterations of prothrombotic state and platelet reactivity early after smoking cessation are scarce. Purpose We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial and neutrophil activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation. Methods Patients aged 18 years or older, who smoked at least 10 cigarettes per day, at least 30 days after successful PCI with stent placement, and those treated with 75 mg clopidogrel and 75 mg acetylsalicylic acid (ASA) once daily, were included in the study and were encouraged to quit the habit. Platelet reactivity was measured with VerifyNow system and the concentrations of cotinine, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit), were assessed in blood samples at baseline and at the 30-day follow-up visit. Smoking cessation was defined as cotinine concentrations of <50 ng/ml. Results Among 117 patients, being current smokers, who attended the baseline visit, 84 patients completed a 30-day follow-up. The median [interquartile range] age of patients was 50 [55–65] years, median body mass index was 27.55 [25.2–30.9] kg/m2, and a median load of smoking was 40 [30–47] pack-years. At the follow-up visit, 30 patients stopped smoking as confirmed by cotinine concentrations (study group) and 54 patients continued smoking (control group). Baseline characteristics were similar in both groups. In the study group as compared to the control group, at day 30 a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs −6 [−32, 37], p=0.018), along with a change in P-selectin concentration (−11.82 [−23.62, 1.34] vs 7.19 [−14.24, 17.19] ng/ml), p=0.005). The change in the concentrations of thrombomodulin, CXCL4/PF4, and citH3 did not differ significantly between groups. Conclusion In the early period after smoking cessation in coronary artery disease patients following PCI treated with clopidogrel and ASA, an increase in platelet reactivity with a decrease in P-selectin levels was observed. No significant changes in other markers were noticed. It might be speculated that the risk of thrombotic complications might be paradoxically enhanced among such patients after smoking cessation despite dual antiplatelet therapy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education