This study sought to determine the relationship between serum lipoprotein (a) levels and angiographically visible coronary collateral circulation and to evaluate whether lipoprotein (a) exerts any effect on vascular endothelial cell growth factor. The study population included 60 patients (39 men, mean age 59 +/- 13 years) with angiographically documented total occlusion in one of the major coronary arteries. Development of collaterals was classified by Rentrop's method. Patients were defined as having poorly developed collaterals for grades 0 and 1 (group 1), or well-developed collaterals for grades 2 and 3 (group 2). Serum lipoprotein (a) and vascular endothelial cell growth factor levels were determined by enzyme-linked immunosorbent assay. In group 1, lipoprotein (a) levels were significantly higher and vascular endothelial cell growth factor levels were significantly lower than in group 2 (34 +/- 19 vs. 20 +/- 12 mg/dl, P < 0.001, and 25 +/- 0.7 vs. 3.4 +/- 0.8 mg/dl, P < 0.001, respectively). Poorly developed collaterals were significantly more frequent in patients with lipoprotein (a) levels >= 30 mg/dl than in patients with levels < 30 mg/dl (72 vs. 37%, P = 0.008). A strong negative correlation was observed between lipoprotein (a) and vascular endothelial cell growth, factor (r = -0.708, P < 0.0001). Multivariate analysis revealed that a high level of lipoprotein (a) negatively affected the development of collaterals, whereas the duration of angina had a positive effect. This study demonstrated for the first time that the high level of lipoprotein (a) negatively affects the formation of coronary collateral vessels in human beings. Reduced production or bioactivity of vascular endothelial cell growth factor caused by high levels of lipoprotein (a) may be the possible responsible mechanism of hyperlipoprotein (a)-related poor collateral formation.