Does statin therapy reduce plasma VEGF levels in humans? A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: The effect of statins on plasma concentrations of vascular endothelial growth factor (VEGF), the main angiogenic growth factor with pro-inflammatory and atherogenic properties, is controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to obtain a conclusive result in humans. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched to identify RCTs investigating the impact of statins on plasma VEGF concentrations. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Meta-regression, sensitivity analysis and publication bias assessments were performed using standard methods. RESULTS: Eight RCTs examining the effects of statins on plasma VEGF concentrations were included. Meta-analysis suggested a significant reduction of plasma VEGF levels following statin therapy (weighed mean difference: -19.88pg/mL, 95% CI: -35.87, -3.89, p=0.015). VEGF reductions were observed in the subsets of trials with treatment durations ≥4weeks (-19.54, -37.78, -1.30, p=0.036), LDL-C reductions ≥50mg/dL (-28.59, -43.68, -13.50, p<0.001), lipophilic statins (-22.31, -40.65, -3.98, p=0.017), and diseased populations (-21.08, -39.97, -2.18, p=0.029), but not in the opposite subsets. Meta-regression also suggested a significant association between changes in plasma VEGF levels and LDL-C changes, treatment duration, but not molar dose of statins. CONCLUSIONS: These results suggest a significant reduction in plasma VEGF concentrations following statin therapy. This effect depends on duration of treatment, LDL-lowering activity, lipophilicity of statins, and health status of studied individuals. Further RCTs are needed to explore if the VEGF reduction is implicated in the statin benefits on cardiovascular outcomes.