Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis - Prospective results from the Bruneck study

Background-Experimental studies have suggested both atherogenic and thrombo genic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma conce ntrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a )] isoforms. Epidemiological studies may contribute to assessment of the re levance of these findings in the general population. Methods and Results-This study prospectively investigated the association b etween Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progr ession of carotid atherosclerosis assessed by high-resolution duplex ultras ound in a random sample population of 826 individuals. We differentiated ea rly atherogenesis (incident nonstenotic atherosclerosis) from advanced (ste notic) stages in atherosclerosis that originate mainly from atherothromboti c mechanisms. Lp(a) plasma concentrations predicted the risk of early ather ogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mm ol/L). po(a) phenotypes were distributed similarly in subjects with and wit hout early carotid atherosclerosis. In contrast, apo(a) phenotypes of low m olecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasm a concentrations (odds ratio, 6.4; 95% CI, 2.8 to 14.9) Conclusions-Lp(a) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis, Lp(a) plasma concentrations pre dicted the risk of early atherogenesis synergistically with high LDL choles terol. Low-molecular-weight apo(a) phenotypes with a putatively high antifi brinolytic capacity in turn emerged as one of the leading risk conditions o f advanced stenotic stages of atherosclerosis.