The association between uncarboxylated matrix Gla protein and lipoprotein-associated phospholipase A2

Abstract

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) is independently associated with cardiovascular risk, probably via inflammatory activity in sclerotic plaque. We speculated whether Lp-PLA2 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-PLA2 and MGP in terms of mortality. Materials and MethodsWe 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) ResultsLp-PLA2 activity was independently positively associated with desphospho-uncarboxylated MGP (dp-ucMGP) [β coeff=0.098, p=0.006]. 1SD of Lp-PLA2 activity was associated with 37% increased risk (p=0.001) of elevated dp-ucMGP (≥977pmol/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 (<2660nmol/L) had higher risk of all-cause mortality [HRR 2.79 (95% CI 1.97–3.94) and HRR 1.69 (95% CI 1.18–2.42), respectively]. We observed no effect of high Lp-PLA2 activity (≥195nmol/min/mL) on total mortality. ConclusionsWe assume that Lp-PLA2 is involved in vascular calcification and that dp-ucMGP is a more appropriate biomarker of residual risk than Lp-PLA2 itself.