Associations between biomarkers of vitamin K and cardiovascular disease risk factors: the role of lipids

PURPOSE: Emerging evidence indicates that vitamin K is important not only for its role in blood coagulation activation, but also for cardiovascular health. However, the results are equivocal, and due to the lipophilic nature of vitamin K, adjustment for triglycerides may be important. We investigated the associations between levels of circulating vitamin K vitamers, phylloquinone (PK) and total menaquinones (MK), and dephospho-undercarboxylated matrix Gla protein (dp-ucMGP, a biomarker of functional vitamin K status), with multiple cardiovascular disease risk factors and adjusted for triglycerides. METHODS: From the population-based Inter99 cohort, 2,195 participants had available fasting blood samples from which dp-ucMGP, PK, and MK-4 to MK-10 were analysed (mean age, ± SD: 68, ± 7 years, 48% female). Cross-sectional associations with cardiovascular disease risk factors were examined per doubling of vitamin K biomarkers using multivariable regression models. RESULTS: Both PK and total MK were positively associated with hypertriglyceridemia: OR (95%CI) 1.91, (1.69, 2.18) and 13.1, (7.55, 23.4), respectively, but not measures of adiposity and diabetes. However, after triglyceride adjustment, higher PK and total MK were inversely associated with central obesity: 0.86, (0.79, 0.95) and 0.61, (0.37, 0.98), respectively, and diabetes: 0.81, (0.69, 0.95) and 0.33, (0.13, 0.81), respectively. Higher dp-ucMGP was associated with hypertriglyceridemia: 1.50, (1.08, 2.09). After adjustment for triglycerides, higher dp-ucMGP remained associated with central obesity: 2.81, (2.16, 3.70) and obesity: 3.31, (2.50, 4.42). CONCLUSION: After accounting for triglycerides, both PK and total MK were inversely associated with measures of adiposity and diabetes, suggesting that blood triglyceride levels need to be accounted for when considering circulating vitamin K levels. Higher dp-ucMGP, reflecting reduced vitamin K-dependent MGP carboxylation, was associated with adiposity markers independent of triglycerides.