Abstract P051: Matrix Gla Protein Species and Risk of Cardiovascular Diseases in Type 2 Diabetes Patients
Background: Observational studies showed that high vitamin K intake is associated with reduced coronary artery calcification (CAC) and risk of cardiovascular disease (CVD). These effects are thought to be mediated by increased activation of the vitamin K-dependent protein matrix Gla protein (MGP). Circulating MGP occurs as various species with different conformations depending on carboxylation and phosphorylation. In high risk populations, high levels of total uncarboxylated MGP (t-ucMGP) were associated with decreased vascular calcification, while high levels of dephospho-uncarboxylated MGP (dp-ucMGP) were associated with low vitamin K status and increased vascular calcification. So far, there are no studies that investigated the association between circulating MGP species and CVD risk in type 2 diabetes patients.
Objective: This study aimed to investigate the relationship between MGP species (dp-ucMGP, t-ucMGP and dephospho carboxylated MGP, dp-cMGP) with incident CVD and coronary heart disease (CHD) in type 2 diabetes patients.
Methods: EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997) 605 participants were known with type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and non-fatal CVD and CHD was obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs). We adjusted for sex, waist hip ratio, physical activity and history of CVD or CHD.
Results: During 10 years of follow-up, 160 cases of CVD and 99 cases of CHD were documented. Higher circulating dp-ucMGP levels were significantly associated with higher risk of CVD HR per SD 1.21 (95%CI: 1.06-1.38) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 (95%CI: 0.94-1.34).
Circulating dp-cMGP levels were not associated with CVD risk (HRSD: 0.96; 95%CI: 0.81-1.14) or with CHD risk (HRSD: 0.77; 95%CI: 0.58-1.03). Circulating t-ucMGP levels were not associated with CVD risk with a HRSD 0.99 (95%CI: 0.85-1.16) or CHD risk (HRSD: 0.94; 95%-CI:0.76-1.15).
Conclusion: High circulating dp-ucMGP levels, reflecting poor vitamin K status, were associated with increased CVD risk. Circulating dp-cMGP and t-ucMGP levels were not related to CVD.
- © 2013 by American Heart Association, Inc.