Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study

Abstract

Background Dietary vitamin K (K₁ and K₂) may reduce atherosclerotic cardiovascular disease (ASCVD) risk via several mechanisms. However, studies linking vitamin K intake with incident ASCVD are limited. We aimed to determine the relationship between dietary vitamin K intake and ASCVD hospitalizations. Methods and Results In this prospective cohort study, participants from the Danish Diet, Cancer, and Health Study, with no prior ASCVD, completed a food-frequency questionnaire at baseline and were followed up for hospital admissions of ASCVD; ischemic heart disease, ischemic stroke, or peripheral artery disease. Intakes of vitamin K₁ and vitamin K₂ were estimated from the food-frequency questionnaire, and their relationship with ASCVD hospitalizations was determined using Cox proportional hazards models. Among 53 372 Danish citizens with a median (interquartile range) age of 56 (52-60) years, 8726 individuals were hospitalized for any ASCVD during 21 (17-22) years of follow-up. Compared with participants with the lowest vitamin K₁ intakes, participants with the highest intakes had a 21% lower risk of an ASCVD-related hospitalization (hazard ratio, 0.79; 95% CI: 0.74-0.84), after multivariable adjustments for relevant demographic covariates. Likewise for vitamin K₂, the risk of an ASCVD-related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K₂ intake (hazard ratio, 0.86; 95% CI, 0.81-0.91). Conclusions Risk of ASCVD was inversely associated with diets high in vitamin K₁ or K₂. The similar inverse associations with both vitamin K₁ and K₂, despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Keywords: atherosclerotic cardiovascular disease; dietary vitamin K; menaquinone; phylloquinone; primary prevention; prospective cohort study.

Figure 1. Consolidated Standards of Reporting Trials flow diagram.

ASCVD indicates atherosclerotic cardiovascular disease; FFQ, food‐frequency questionnaire; and VKA, vitamin K antagonist.

Figure 2. Hazard ratios from Cox proportional hazards model with restricted cubic spline curves describing the association between vitamin K₁ intake (µg/d) and both total atherosclerotic cardiovascular disease (ASCVD) hospitalizations and subtypes of ASCVD hospitalizations (ischemic heart disease, peripheral artery disease, and ischemic stroke).

Hazard ratios are based on models adjusted for age, sex, body mass index, smoking status, social economic status (income), physical activity, alcohol intake, and education (model 1b), and are comparing the specific level of vitamin K₁ intake (horizontal axis) to the median intake for participants in the lowest‐intake quintile (57 µg/d).

Figure 3. Hazard ratios from Cox proportional hazards model with restricted cubic spline curves describing the association between vitamin K₂ intake (µg/d) and both total atherosclerotic cardiovascular disease (ASCVD) hospitalizations and subtypes of ASCVD hospitalizations (ischemic heart disease, peripheral artery disease, and ischemic stroke).

Hazard ratios are based on models adjusted for age, sex, body mass index, smoking status, social economic status (income), physical activity, alcohol intake, and education (model 1b), and are comparing the specific level of vitamin K₂ intake (horizontal axis) to the median intake for participants in the lowest‐intake quintile (23 µg/d).