Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of Fluvastatin or Fenofibrate

Increased vascular endothelial cell growth factor (VEGF) may be important i n cardiovascular pathophysiology (perhaps relating to angiogenesis and coll ateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VE GF and Flt-1 in patients with atherosclerosis and others with hyperlipidemi a compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosc lerosis, and 40 matched controls were studied. Plasma VEGF was higher in pa tient groups than in healthy controls (p <0.01), but Flt-1 was not signific antly altered. After lipid-lowering therapy, patients with uncomplicated hy perlipidemia had significantly reduced total cholesterol and VEGF (all p <0 .05) but no significant change in Flt-1. Lack of a significant correlation between the van Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncompl icated hyperlipidemia free of major underlying atherosclerosis and in patie nts with hyperlipidemia plus established atherosclerosis is reduced by succ essful lipid-lowering treatment. These findings may have implications for t he pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by whi ch lipid-lowering therapy may reduce cardiovascular events beyond lipid red uction alone. (C)2001 by Excerpta Medica, Inc.