Aernoud Fiolet

281 Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels atherosclerosis. 28 Its inhibition by colchicine may contribute to the risk reduction of cardiovascular events as observed in the COLCOT and LoDoCo2 trials. 4,5 However, the relation between EV NLRP3 protein levels and clinical outcomes is not clear and colchicine affects a broad spectrum of inflammatory proteins. 50 How NLRP3 inflammasome inhibition contributes to the atheroprotective effects of colchicine therefore remains a topic for further investigation. Study limitations The EV isolations and measurements of NLRP3 were performed in a research setting since, at this stage, no standardized clinical assays exist. The limited sample size and follow-up of one year did not allow us to investigate the relation between EVNLRP3 protein levels and clinical outcomes. Although the significant reduction of EV NLRP3 strongly suggests an effect of colchicine on the NLRP3-mediated signaling pathway, the absolute difference seems small. It is, however, in line with other studies that showed similar effects of colchicine treatment on circulating IL-6 and other inflammatory proteins involved in the NLRP3 inflammasome pathway. 50 The larger absolute effect on hs-CRP (-40%) suggests that colchicine is not only inhibiting the NLRP3 inflammasome but also other inflammatory pathways and confirms previous findings. 49-50 Unfortunately, in 5% of patients we were unable to obtain blood samples, although this was equal in both treatment groups. CONCLUSION Colchicine leads to a reduction of EVNLRP3 protein levels. Whether this explains the reduction in cardiovascular events in patients with chronic coronary disease remains to be determined.