The Effects of Statin Therapy on Oxidized LDL and Its Antibodies: A Systematic Review and Meta-Analysis

BACKGROUND: Elevated serum low-density lipoproteins (LDL), the substrate for the formation of atherogenic oxidized LDLs (oxLDL), are a causal factor for atherosclerotic cardiovascular disease (ASCVD). Statins are well known to decrease LDL particle concentration and reduce ASCVD morbidity and mortality. OBJECTIVE: To perform a meta-analysis of the effects of statins (i.e., type, dose, and duration of treatment) on serum levels of oxLDL and on immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels against oxLDL. METHODS: PubMed, Scopus, Embase, and Web of Science were searched up to February 5th, 2021, for randomized controlled trials (RCT) evaluating the effect of statins on oxLDL and anti-oxLDL antibody levels. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. To evaluate the influence of each study on the overall effect size, a sensitivity analysis was performed using the leave-one-out method. Evaluation of the funnel plot, Begg's rank correlation, and Egger's weighted regression tests was used to assess the presence of publication bias in the meta-analysis. RESULTS: A total of 28 RCTs including 4019 subjects were finally included in the meta-analysis. The results indicated a significant decrease in circulating concentrations of oxLDL after treatment with statins (SMD: -2.150, 95% CI: -2.640, -1.697, p < 0.001). Subgroup analysis found no significant effect of the intensity of statin treatment or statin lipophilicity on the reduction of circulating concentrations of oxLDL. An additional meta-analysis of 3 trials showed that statins did not change the serum levels of IgM and IgG antibodies to oxLDL. CONCLUSION: Statin therapy decreases serum oxLDL concentrations but does not affect circulating levels of anti-oxLDL antibodies.