Systematic Review and Meta-Analysis of the Effect of Statins on Circulating E-Selectin, L-Selectin, and P-Selectin

The pleiotropic effects of statins might involve preventing inflammatory cell adhesion to the endothelium, which is a critical step in the pathogenesis of atherosclerosis. We conducted a systematic review and meta-analysis of the effects of statins on the circulating cell adhesion molecules E-Selectin, L-Selectin, and P-Selectin. A literature search was conducted in PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. In 61 studies, statins significantly reduced P-selectin (standard mean difference, SMD = -0.39, 95% CI -0.55 to -0.22, p < 0.001; moderate certainty of evidence), L-selectin (SMD = -0.49, 95% CI -0.89 to -0.10, p = 0.014; very low certainty of evidence), and E-Selectin (SMD = -0.73, 95% CI -1.02 to -0.43, p < 0.001; moderate certainty of evidence), independently of baseline lipid profile and other study and patient characteristics. The corresponding pooled SMD values in sensitivity analysis were not substantially altered when individual studies were sequentially removed. Simvastatin had a significant lowering effect on both P-selectin and E-selectin. Therefore, statins significantly reduce circulating selectins. Further studies are required to investigate whether selectin lowering mediates cardiovascular risk reduction with these agents. (PROSPERO registration number: CRD42021282778).