(Circulation. 1999;100:1154-1160.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Role of Lipoprotein(a) and Apolipoprotein(a) Phenotype in Atherogenesis
Prospective Results From the Bruneck Study
From the Institute of Medical Biology and Human Genetics, University of Innsbruck (F.K., E.T., G.U.), and Innsbruck University Hospital, Department of Neurology (M.F.K., S.K., J.W.), Austria, and Bruneck Hospital, Department of Internal Medicine, Italy (P.S., F.O., G.E.).
Correspondence to Dr Florian Kronenberg, Institute of Medical Biology and Human Genetics, Schöpfstraße 41, A-6020 Innsbruck. E-mail florian.kronenberg{at}uibk.ac.at
Background—Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a) [Lp(a)], depending on Lp(a) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a) [apo(a)] isoforms. Epidemiological studies may contribute to assessment of the relevance of these findings in the general population.
Methods and Results—This study prospectively investigated the association between Lp(a) plasma concentrations, apo(a) phenotypes, and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a random sample population of 826 individuals. We differentiated early atherogenesis (incident nonstenotic atherosclerosis) from advanced (stenotic) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms. Lp(a) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion, with this association being confined to subjects with LDL cholesterol levels above the population median (3.3 mmol/L). Apo(a) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis. In contrast, apo(a) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis, especially when associated with high Lp(a) plasma 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 predicted the risk of early atherogenesis synergistically with high LDL cholesterol. Low-molecular-weight apo(a) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis.
Key Words: atherosclerosis • apolipoproteins • lipoproteins • genetics • carotid arteries
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