CD142+/CD61+, CD146+ and CD45+ microparticles predict cardiovascular events in high risk patients following a Mediterranean diet supplemented with nuts

Abstract

Circulating microparticles (cMPs) are small phospholipid-rich microvesicles shed by activated cells that play a pivotal role in cell signalling related to the pathogenesis of atherothrombosis. We aimed to investigate the prognostic value of cMPs released from different vascular cells for cardiovascular event (CVE) presentation in asymptomatic patients at high cardiovascular risk factors under nutritional and pharmacologic treatment. This is a nested case-control study of 50 patients from the five-year follow-up prospective PREDIMED trial enrolled in the nuts arm of the Mediterranean diet (MedDiet-nuts). We randomly selected 25 patients who had suffered a CVE during follow-up and pair-matched them for sex, age, and classical CV risk factors to 25 patients who remained asymptomatic (no-CVE). Total Annexin V-(AV)+ cMPs and cMPs from cells of the vascular compartment were quantified by flow cytometry at baseline and after one year follow-up. MedDiet-nuts and pharmacological treatment neither modified levels nor source of MP shedding in CVE patients. However, no-CVE patients showed 40-86 % decreased total AV+, PAC-1+/AV+, CD61+/AV+, CD142+/CD61+/AV+, CD62P+/AV+, CD146+/AV+, CD63+/AV+ and CD11a+/AV+ cMPs at one year follow-up (p≤0.046, all). CD142+/CD61+/AV+, CD146+/AV+ and CD45+/AV+ cMPs were decreased in no-CVE patients compared to CVE patients. A ROC-curve clustered model for CD142+/CD61+/AV+, CD45+/AV+ and CD146+/AV+ cMPs predicted a future CVE [p<0.0001, AUC=0.805 (0.672 to 0.938)]. In patients at high CV risk profile treated with a controlled MedDiet supplemented with nuts and receiving up-to-date CV drug treatment, reduced cMPs derived from activated platelets, leukocytes and endothelial cells are predictive of protection against CVE within the next four years. ; GC-B is a Sara Borrell Postdoctoral Fellow (CD13/00023) from Instituto de Salud Carlos III. This work has been possible thanks to funding received from the Spanish Ministry of Economy and Competitiveness (Plan Estatal de I+D+I 2013-2016, SAF2013-42962-R, to LB), from the Cardiovascular Research Network of Instituto de Salud Carlos III (RIC, RD12/0042/0027 to LB; SAF2012-40208 to GV) and from CIBER CB06/03 Fisiopatología de la Obesidad y la Nutrición of Instituto de Salud Carlos III, (CIBERobn, RD06/0045 to RE). All grants were co-financed by European Union Funds, Fondo Europeo de Desarrollo Regional (FEDER) "Una manera de hacer Europa."