Abstract

Background: Matrix Gla protein (MGP) is a vitamin K dependent protein and a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP) is a marker for vitamin K status with high dp-ucMGP concentration reflecting a low vitamin K status. High dp-ucMGP concentrations are thought to be associated with an increased risk of cardiovascular disease, but this has never been investigated in the general population. Objective: This study aimed to investigate the association of dp-ucMGP with incident coronary heart disease (CHD) or stroke in the general population. Design and Methods: A prospective case-cohort study with a representative baseline sample of 1406 participants and 1154 and 380 incident cases of CHD and stroke, respectively, was nested within the EPIC-NL study. Dp-ucMGP concentrations were measured by ELISA technique in baseline plasma samples. The incidence of fatal and non-fatal CHD and stroke was obtained by linkage to national registers. Cox proportional hazard models adapted for the case-cohort design were used to calculate hazard ratios (HRs) per standard deviation (SD) and per quartile of circulating dp-ucMGP levels, adjusted for cardiovascular risk factors. Results: This case-cohort study had an average follow-up of 11.5 years. Circulating dp-ucMGP levels were not associated with CHD risk with a HR per SD of 1.00 (95% CI: 0.93-1.07) and a HR Q4 vs Q1 of 0.94 (95% CI: 0.79-1.13) after multivariate adjustment. Circulating dp-ucMGP was not associated with stroke risk with a HR per SD of 0.98 (95% CI: 0.90-1.08) and a HR Q4 vs Q1 of 1.09 (95% CI: 0.78-1.51). Conclusion: This study does not support the hypothesis that high dp-ucMGP levels, reflecting a poor vitamin K status, are associated with increased CHD or stroke risk.

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