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

Abstract

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: -19.88 pg/mL, 95% CI: -35.87, -3.89, p=0.015). VEGF reductions were observed in the subsets of trials with treatment durations ≥4 weeks (-19.54, -37.78, -1.30, p=0.036), LDL-C reductions ≥50 mg/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.

Keywords: Angiogenesis; Atherosclerosis; Cholesterol; Pleiotropic effect; Statins.