Vitamin K status, cardiovascular disease and all-cause mortality: a participant-level meta-analysis of 3 US cohorts

Authors: SHEA, M. KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CUSHMAN, MARY - University Of Vermont; BENJAMIN, EMELIA - Boston University; KRITCHEVSKY, STEPHEN - Wake Forest University; WEINER, DANIEL - Tufts Medical Center

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/31/2020
Publication Date: 5/2/2020
Citation: Shea, M., Barger, K., Booth, S.L., Matuszek, G., Cushman, M., Benjamin, E.J., Kritchevsky, S.B., Weiner, D.E. 2020. Vitamin K status, cardiovascular disease and all-cause mortality: a participant-level meta-analysis of 3 US cohorts. American Journal of Clinical Nutrition. 111(6):1170-1177. https://doi.org/10.1093/ajcn/nqaa082.
DOI: https://doi.org/10.1093/ajcn/nqaa082

Interpretive Summary: We investigated the association of vitamin K nutritional status with cardiovascular disease and all-cause mortality by combining data from three separate US cohorts. In each cohort, the vitamin K concentrations were measured in blood, as an indicator of vitamin K nutritional status. On average, participants were 65 years old and were followed for 13 years. We found participants with low circulating vitamin K had a 19% higher risk for death from all causes compared to those with high circulating vitamin K. However, the risk of developing cardiovascular disease did not differ according to circulating vitamin K concentrations. Additional studies are needed to clarify why circulating vitamin K was associated with risk for death but not cardiovascular disease.

Technical Abstract: Background: Vitamin K-dependent proteins in vascular tissue affect vascular stiffness and calcification, which is associated with cardiovascular disease (CVD) and all-cause mortality. Objective: To determine the association between circulating vitamin K concentrations with CVD and all-cause mortality by conducting a participant-level meta-analysis. Design: We obtained individual participant-level data from the Health, Aging, and Body Composition Study, the Multi-Ethnic Study of Atherosclerosis, and the Framingham Offspring Study, known cohorts with available measures of fasting circulating phylloquinone (vitamin K1) and confirmed CVD events and mortality. Circulating phylloquinone was measured in a central laboratory from fasting blood samples and categorized as 0.5 to 1.0 nmol/L and >1.0 nmol/L. Multivariable Cox proportional hazard regression with multiple imputations was used to evaluate the association of circulating phylloquinone with incident CVD and all-cause mortality risk. Results: Among 3891 participants (mean (SD) age 65 (11) years; 55% women and 35% non-white), there were 858 incident CVD events and 1209 deaths over a median of 13.0 years. The risk for CVD did not significantly differ according to circulating phylloquinone [fully adjusted hazard ratio and 95% confidence interval (HR(95%CI)) relative to >1.0 nmol/L: 0.5-1.0 nmol/L [fully-adjusted HR(95%CI) 1.19 (1.03, 1.38)]. Mortality risk was similar in participants with >0.5-1.0 nmol/L compared to >1.0 nmol/L [HR(95%CI) fully-adjusted = 1.04 (0.92, 1.17)]. Conclusion: Low circulating phylloquinone concentrations were associated with an increased risk for all-cause mortality, but not for CVD. Additional studies are needed to clarify the mechanism underlying this association and evaluate the impact of increased phylloquinone intake on cardiovascular and other health outcomes in individuals with low vitamin K status.