The Residual Risks Associated with Atherothrombosis of RecurrentIschemic Stroke (IS) After Non-cardiogenic IS

Abstract: Recurrent ischemic stroke (IS) is one of the leading causes of disability and death worldwide. Patients with recurrent IS, in comparison with survivors of the initial non-cardiogenic IS, have more serious neurological deficit and longer hospital stay with heavier family and socio-economic burden. Therefore, recurrent IS is a major challenge that we urgently need to address. The recurrence rate of non-cardiogenic IS is not zero and even shows an increasing trend over a long period of time, despite receiving evidence-based management in accordance with guideline, indicating that patients suffering from non-cardiogenic IS and who are receiving optimal management remain at considerable residual risks (RRs) responsible for the recurrence of cerebrovascular events. In addition to low-density lipoprotein cholesterol (LDL-C) and platelets, some new non-traditional parameters such as high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], peripheral circulating platelet-derived microvesicles, white blood cells-platelet complexes, NODlike receptor protein 3 (NLRP3) inflammasome, monomeric C-reactive protein, neutrophils and their products (neutrophil extracellular traps, NETs), may also be potential sources of RRs for recurrent IS. On the basis of the three pillars of secondary stroke prevention, namely, blood pressure reduction, lipid-lowering and antiplatelet therapy, the reduction in RRs may provide additional protection against recurrent IS. With this background, the identification and quantification of RRs associated with disease heterogeneity and individualized treatment strategies based on risk stratification are favorable in the mitigation of the huge stroke burden people unceasingly face.