The association between uncarboxylated matrix Gla protein and lipoprotein-associated phospholipase A(2)

Background: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is independently associated with cardiovascular risk, probably via inflammatory activity in sclerotic plaque. We speculated whether Lp-PLA(2) has a role in the aetiology of vascular calcifications, estimated from circulating uncarboxylated matrix Gla protein (MGP) species and whether we could find a potential interaction of Lp-PLA(2) and MGP in terms of mortality. Materials and Methods: We examined 798 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays, developed by VitaK (Maastricht, The Netherland) Results: Lp-PLA(2) activity was independently positively associated with desphospho-uncarboxylated MGP (dp-ucMGP) [beta coeff = 0.098, p = 0.006]. 1SD of Lp-PLA(2) activity was associated with 37% increased risk (p = 0.001) of elevated dp-ucMGP (>= 977 pmol/L, top quartile). In the Cox proportional hazard model adjusted for conventional risk factors, the patients in the highest quartile of dp-ucMGP or lowest quintile of total-uncarboxylated ucMGP (= 195 nmol/min/mL) on total mortality. Conclusions: We assume that Lp-PLA(2) is involved in vascular calcification and that dp-ucMGP is a more appropriate biomarker of residual risk than Lp-PLA(2) itself.