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THE ASSOCIATION BETWEEN DEPHOSPHO-UNCARBOXYLATED MATRIX GLA-PROTEIN AND INCIDENT CARDIOVASCULAR DISEASE AND MORTALITY IN THE PROSPECTIVE POPULATION-BASED BRUNECK STUDY
Abstract
Background and Aims
Vascular calcification is assumed to contribute to cardiovascular disease and mortality. Matrix Gla protein, a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. This study aims to investigate whether circulating desphospho-uncarboxylated MGP (dp-ucMGP) reflecting insufficient vitamin K status is associated with incident cardiovascular disease and mortality in the general population.
Methods
Plasma dp-ucMGP was measured in samples taken in 2000 from 685 participants of the prospective population-based Bruneck Study (age, mean±SD, 66.1±10.2; 51.8% female). Cox proportional hazard models were employed to assess the association between dp-ucMGP and incident CVD and all-cause mortality, and to determine potential interactions with predicted 10-year CVD risk according to the Framingham Risk Score.
Results
During a 10-year follow-up, 118 participants experienced a CVD event (17.3%) and 153 (22.4%) participants died. In fully adjusted models, circulating dp-ucMGP levels were significantly associated with higher CVD risk, with an HR per SD of 1.34 (95%CI: 1.08-1.65; p=0.008), and all-cause mortality (HR per 1-SD of 1.54; 95% CI: 1.27–1.86; p<0.001). The effect of dp-ucMGP on CVD was stronger in individuals with low predicted cardiovascular risk as compared to those with high predicted cardiovascular risk (p value for interaction =0.004). For the outcome all-cause mortality, a formal interaction test was nonsignificant (p value for interaction =0.192).
Conclusions
Plasma level of dp-ucMGP is associated with incident CVD and all-cause mortality in the general community. Future studies should determine the impact of vitamin K supplementation on dp-uc-MGP levels and CVD risk.