Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts
M Kyla Shea, The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1170–1177,
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 of circulating vitamin K concentrations with CVD and all-cause mortality by conducting a participant-level meta-analysis.
Methods
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 K-1) and confirmed CVD events and mortality. Circulating phylloquinone was measured in a central laboratory from fasting blood samples and categorized as ≤0.5 nmol/L, >0.5–1.0 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 age 65 ± 11 y; 55% women; 35% nonwhite), there were 858 incident CVD events and 1209 deaths over a median of 13.0 y. The risk of CVD did not significantly differ according to circulating phylloquinone [fully adjusted HR (95% CI) relative to >1.0 nmol/L: ≤0.5 nmol/L, 1.12 (0.94, 1.33); >0.5–1.0 nmol/L, 1.02 (0.86, 1.20)]. Participants with ≤0.5 nmol/L circulating phylloquinone had an adjusted 19% higher risk of all-cause mortality compared with those with >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 with >1.0 nmol/L [fully adjusted HR (95% CI): 1.04 (0.92, 1.17)].
Conclusions
Low circulating phylloquinone concentrations were associated with an increased risk of all-cause mortality, but not of 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.