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

•Lipoprotein-associated phospholipase A2 activity (aLp-PLA2) was associated with desphospho-uncarboxylated matrix Gla protein (dp-ucMGP).•The patients in the top quartile of dp-ucMGP had three-fold increase of all-cause mortality, but no effect of high Lp-PLA2 activity was found.•No interaction of dp-ucMGP and aLp-PLA2 in terms of mortality risk was found.•We may speculate, that pathophysiology of aLp-PLA2 involves also vascular calcification.•Increased dp-ucMGP should be more appropriate biomarker of residual mortality risk than increased Lp-PLA2 activity.

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 (≥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 (<2660 nmol/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 (≥195 nmol/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.