Circulating CD31+ leukocyte frequency is associated with cardiovascular risk factors

Objectives: CD31 identifies a heterogeneous population of cells in the blood, consisting of mature leukocytes and platelets, as well as smaller numbers of endothelial and progenitor cells. Because unfractionated CD31+ blood cells have demonstrated angiogenic properties invivo, we hypothesized that circulating CD31+ cells would be related to the presence of cardiovascular risk factors in humans. Methods and results: We studied 1487 participants, free of cardiovascular disease, from the Framingham Offspring Study. Using anti-human CD31 and CD45 antibodies, distinct CD31+/CD45+ leukocyte populations were enumerated in blood samples by FACS analysis. We used linear regression analyses to investigate the relation of each cell phenotype with cardiovascular risk factors. We identified 3 distinct leukocyte populations: CD31-, CD31 dim, and CD31 bright cells. Using forward/side scatter analyses, CD31- and CD31 dim cells mapped to lymphoid gates while CD31 bright cells were monocytoid. In multivariable analyses, higher frequency of CD31 bright cells was associated with older age, male sex, HDL cholesterol, and CRP (all P<0.01). In contrast, CD31 dim was inversely associated with age, male sex, CRP, and smoking (all P<0.01). Framingham Risk Score was positively associated with CD31 bright frequency (P=0.002), and negatively associated with CD31 dim frequency (P=0.020). Conclusions: CD31+ staining identifies 2 major leukocyte populations, CD31 bright and CD31 dim, which demonstrated significant and opposite associations with cardiovascular risk in humans. Further research is needed to define the biological and potential therapeutic roles of CD31+ subpopulations in vascular disease.