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Background  Atherosclerosis is an inflammatory lipid disorder and the main underlying pathology of acute ischemic events. Despite a vast amount of data from murine atherosclerosis models, evidence of B‐cell involvement in human atherosclerotic disease is limited. We therefore investigated the association of circulating B‐cell subtypes with the occurrence of secondary cardiovascular events in advanced atherosclerotic disease.    Methods and Results  This cohort study consists of 168 patients who were included in the Athero‐Express biobank between 2009 and 2011. Before surgery, peripheral blood mononuclear cells were isolated and stored in liquid nitrogen. After gentle thawing of the peripheral blood mononuclear cells, different B‐cell subtypes including naïve, (un)switched memory, and  CD 27 +  CD 43 +  B1‐like B cells, were analyzed by flow cytometry. Univariable and multivariable Cox proportional hazard models were used to analyze associations between B‐cell subtypes, circulating antibodies and secondary cardiovascular manifestations during the 3‐year follow‐up period. Mean age was 70.1±9.6 years, males represented 62.8% of the population, and 54 patients had secondary manifestations during follow‐up. High numbers of unswitched memory cells were protective against secondary outcome (hazard ratio, 0.30 [95%  CI , 0.13–0.69];  P <0.01). Similar results were obtained for the switched memory cells that also showed to be protective against secondary outcome (hazard ratio, 0.33 [95%  CI , 0.14–0.77];  P =0.01).    Conclusions  A high number of (un)switched memory B cells is associated with better outcome following carotid artery endarterectomy. These findings suggest a potential role for B‐cell subsets in prediction and prevention of secondary cardiovascular events in patients with atherosclerosis.

High Levels of (Un)Switched Memory B Cells Are Associated With Better Outcome in Patients With Advanced Atherosclerotic Disease