Background: Dietary vitamin K (K ₁ and K ₂ ) 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 K ₁ and vitamin K ₂ 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 K ₁ 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 K ₂ , the risk of an ASCVD‐related hospitalization for participants with the highest intakes was 14% lower than participants with the lowest vitamin K ₂ intake (hazard ratio, 0.86; 95% CI, 0.81–0.91). Conclusions: Risk of ASCVD was inversely associated with diets high in vitamin K ₁ or K ₂ . The similar inverse associations with both vitamin K ₁ and K ₂ , despite very different dietary sources, highlight the potential importance of vitamin K for ASCVD prevention.

Reported associations between vitamin K₁ and both all-cause and cause-specific mortality are conflicting. The 56,048 participants from the Danish Diet, Cancer, and Health prospective cohort study, with a median [IQR] age of 56 [52–60] years at entry and of whom 47.6% male, were followed for 23 years, with 14,083 reported deaths. Of these, 5015 deaths were CVD-related, and 6342 deaths were cancer-related. Intake of vitamin K₁ (phylloquinone) was estimated from a food-frequency questionnaire (FFQ), and its relationship with mortality outcomes was investigated using Cox proportional hazards models. A moderate to high (87–192 µg/d) intake of vitamin K₁ was associated with a lower risk of all-cause [HR (95%CI) for quintile 5 vs quintile 1: 0.76 (0.72, 0.79)], cardiovascular disease (CVD)-related [quintile 5 vs quintile 1: 0.72 (0.66, 0.79)], and cancer-related mortality [quintile 5 vs quintile 1: 0.80 (0.75, 0.86)], after adjusting for demographic and lifestyle confounders. The association between vitamin K₁ intake and cardiovascular disease-related mortality was present in all subpopulations (categorised according to sex, smoking status, diabetes status, and hypertension status), while the association with cancer-related mortality was only present in current/former smokers (p for interaction = 0.002). These findings suggest that promoting adequate intakes of foods rich in vitamin K₁ may help to reduce all-cause, CVD-related, and cancer-related mortality at the population level.

Coronary and aortic artery calcifications are generally slow to develop, and their burden predicts cardiovascular disease events. In patients with diabetes mellitus, arterial calcification is accelerated and calcification activity can be detected using 18F-sodium fluoride positron emission tomography (18F-NaF PET). We aimed to determine whether vitamin K₁ supplementation inhibits arterial calcification activity in individuals with diabetes mellitus. This was a post hoc analysis of the ViKCoVaC (effect of Vitamin-K₁ and Colchicine on Vascular Calcification activity in subjects with Diabetes Mellitus) double-blind randomized controlled trial conducted in Perth, Western Australia. Individuals with diabetes mellitus and established coronary calcification (coronary calcium score > 10), but without clinical coronary artery disease, underwent baseline 18F-NaF PET imaging, followed by oral vitamin K₁ supplementation (10 mg/d) or placebo for 3 mo, after which 18F-NaF PET imaging was repeated. We tested whether individuals randomly assigned to vitamin K₁ supplementation had reduced development of new 18F-NaF PET positive lesions within the coronary arteries and aorta. In total, 149 individuals completed baseline and follow-up imaging studies. Vitamin K₁ supplementation independently decreased the odds of developing new 18F-NaF PET positive lesions in the coronary arteries (OR: 0.35; 95% CI: 0.16, 0.78; P = 0.010), aorta (OR: 0.27; 95% CI: 0.08, 0.94; P = 0.040), and in both aortic and coronary arteries (OR: 0.28; 95% CI: 0.13, 0.63; P = 0.002). In individuals with diabetes mellitus, supplementation with 10 mg vitamin K₁/d may prevent the development of newly calcifying lesions within the aorta and the coronary arteries as detected using 18F-NaF PET. Further long-term studies are needed to test this hypothesis. This trial was registered at anzctr.org.au as ACTRN12616000024448.

BACKGROUND: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K ₁ are associated with a lower incidence of aortic stenosis. METHODS: In the Danish Diet, Cancer and Health study, participants aged 50 to 64 years completed a 192-item food frequency questionnaire at baseline, from which habitual intakes of vitamin K ₁ were estimated. Participants were prospectively followed using linkage to nationwide registers to determine incident aortic valve stenosis (primary outcome) and aortic stenosis with subsequent complications (aortic valve replacement, heart failure, or cardiovascular disease–related mortality; secondary outcome). RESULTS: In 55 545 participants who were followed for a maximum of 21.5 years, 1085 were diagnosed with aortic stenosis and 615 were identified as having subsequent complications. Participants in the highest quintile of vitamin K ₁ intake had a 23% lower risk of aortic stenosis (hazard ratio, 0.77 [95% CI, 0.63–0.94]) and a 27% lower risk of aortic stenosis with subsequent complications (hazard ratio, 0.73 [95% CI, 0.56–0.95]), compared with participants in the lowest quintile after adjusting for demographics and cardiovascular risk factors. CONCLUSIONS: In this study, a high intake of vitamin K ₁ –rich foods was associated with a lower incidence of aortic stenosis and a lower risk of aortic stenosis with subsequent complications.