A systematic review and meta-analysis of the effect of statin treatment on sVCAM-1 and sICAM-1

Background and aims: Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on soluble vascular (sVCAM-1) and intercellular (sICAM-1) adhesion molecule 1. Methods: A systematic 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 for analytical studies and GRADE, respectively. Results: Statins significantly reduced both sVCAM-1 (standard mean difference, SMD=-0.28, 95% CI -0.44 to -0.12, p=0.001; 46 treatment arms; low certainty of evidence) and sICAM-1 (SMD=-0.75, 95% CI -1.00 to -0.50, p<0.001; 61 treatment arms; moderate certainty of evidence) concentrations. In sensitivity analysis, the SMD values were not modified when individual studies were sequentially removed. There were significant associations between SMD and publication year and, for sICAM-1, statin-induced changes in HDL-cholesterol. In subgroup analysis, the lowering effect was significant with liphophilic, but not hydrophilic, statins, and similar, for sICAM-1, in participants with or without clinically overt atherosclerosis. Conclusions: Statins significantly lower sVCAM-1/sICAM-1. Prospective studies are required to determine whether this mediates their atheroprotective effects (PROSPERO registration number: CRD42021276825).