Mechanisms of Lipoprotein(a) Pathogenicity

Abstract

High quality, large prospective population-based studies are like well-tended orchards: they take many years to bear fruit, but when they do, they yield a bounty. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , fruit is on offer from 2 important Danish population-based studies, the Copenhagen City Heart Study and the Copenhagen General Population Study, which previously provided key evidence that genetically based levels of C-reactive protein were not related to vascular disease,1 and from 3 case-control studies conducted in Copenhagen. In the present study,2 Kamstrup et al3 use a Mendelian randomization study similar to that described in 2009 to probe the relationship between plasma-derived and genetically determined levels of lipoprotein(a) (Lp[a]), and the development of venous thromboembolism (VTE; thrombotic events), vascular stenosis (atherosclerotic events), and myocardial infarction (which they called combined atherosclerotic and thrombotic events). See accompanying article on page 1732 The ultimate goal of the study was to further our understanding of the mechanism of Lp(a) action in vascular disease, which has been controversial. Results over the years from both in vitro and in vivo studies have reflected the duality of Lp(a) structure: in this regard, both proatherosclerotic (low-density lipoprotein–like) and prothrombotic (plasminogen-like) functions have been reported (Figure).4 By comparing the contribution of genetically elevated Lp(a) to arterial stenosis, thrombotic events secondary to atherosclerosis, and pure thrombotic events in …