Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5
Prognostic value of desphospho-uncarboxylated matrix Gla-protein as a biomarker of vascular vitamin K status for risk of adverse events in a cohort of patients with stable coronary heart disease
U. Mons1, B. Schöttker2, H. Brenner2
1Klinik III für Innere Medizin, Universitätsklinikum Köln, Köln; 2Deutsches Krebsforschungszentrum (DKFZ), Heidelberg;
Background: Desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) needs vitamin K-dependent carboxylation for activity and thus serves as a biomarker of vitamin K status. Since the protein is known to be a potent inhibitor of arterial calcification, circulating dp-ucMGP has also been proposed as a biomarker for cardiovascular calcification detection. Indeed, single studies suggested associations of dp-ucMGP with mortality risk in patients with chronic stable vascular disease, but further studies are required to clarify the usefulness of dp-ucMGP as a biomarker of prognosis in patients with stable coronary heart disease (CHD). We thus sought to study the prognostic value of dp-ucMGP for risk of adverse events in a cohort of CHD patients.

Methods: Data were drawn from a prospective cohort of 1153 subjects with stable CHD in which concentrations of dp-ucMGP were measured in baseline plasma samples using enzyme-linked immunosorbent assay methods (VitaK; Maastricht University, The Netherlands). Kaplan-Meier curves displaying time to event were estimated for quartiles of dp-ucMGP. Multiple Cox proportional regression models were used to assess the association of dp-ucMGP concentration with different outcomes of prognosis (major cardiovascular events, cardiovascular mortality, all-cause mortality), with different sets of adjustments for potential confounders.

Results: Mean (±SD) concentrations of dp-ucMGP in pmol/L per quartile (Q) were: Q1: 299 (±82), Q2: 492 (±51), Q3: 674 (±65), Q4: 1397 (±696). Over a follow-up period of about 13 years, 270 major cardiovascular events, 141 cardiovascular deaths and 260 deaths of any cause were recorded. Kaplan-Meier curves indicated poorer survival for the highest quartile of dp-ucMGP (see figure). In Cox models adjusted for demographic, lifestyle and vascular risk factors and comorbidities, higher levels of dp-ucMGP were consistently associated with higher rates of major cardiovascular events (HR per increase in dp-ucMGP levels by one SD: 1.15; 95%-CI: 1.04-1.28), higher cardiovascular mortality (1.24; 1.09-1.41) and higher all-cause mortality (1.22; 1.10-1.35). When comparing quartiles, the hazards of adverse outcomes were roughly twofold in the highest quartile compared to the lowest quartile (HR and 95%CI for Q4 vs. Q1; major cardiovascular events: 1.73; 1.15-2.62; cardiovascular mortality: 2.40, 1.33-4.34; all-cause mortality: 1.92; 1.29-2.88).

Conclusions: In this cohort of patients with stable coronary heart disease, increased dp-ucMGP, reflecting poor vascular vitamin K status, was found to be associated with adverse cardiovascular events and all-cause mortality.


 

Figure: Kaplan-Meier curves displaying the time to first major cardiovascular event for quartiles of dp-ucMGP
https://dgk.org/kongress_programme/jt2022/aP2025.html