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

作者：Sahebkar Amirhossein; Ponziani Maria Chantal; Goitre Ilaria; Bo Simona

来源：Metabolism-Clinical and Experimental, 2015, 64(11): 1466-1476.

DOI：10.1016/j.metabol.2015.08.002

• Angiogenesis
• Atherosclerosis
• Cholesterol
• Pleiotropic effect
• Statins

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.

• 出版日期2015-11