Dietary intake of vitamin K and risk of incident and fatal myocardial infarction in the EPIC-Heidelberg cohort study

Background: The vitamin K-dependent Matrix-Gla-protein (MGP) has been shown to inhibit vascular calcification. Few prospective studies have been conducted relating habitual dietary vitamin K intake to the risk of coronary events. We investigated the association between phylloquinone (vitamin K1) and menaquinones (vitamin K2) intake and the risk incident and fatal myocardial infarction (MI) in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: The study was conducted in 23,464 EPIC-Heidelberg participants aged 35–64 years and free of prevalent coronary heart disease at enrolment 1994–1998. Dietary vitamin K intake was estimated from food frequency questionnaires completed at baseline using HPLC-based food composition data. Hazard ratios (HR) and 95% confidence intervals (CI) adjusted for lifestyle (smoking, body mass index, waist circumference, hypercholesterolemia, high blood pressure, aspirin use, physical activity, and education) and dietary (energy, fat, alcohol, calcium, and folate intake) factors associated with coronary heart disease were estimated using Cox proportional hazards models. Results: Between recruitment and March 2009, 420 incident events of MI occurred, of which 98 were fatal. Dietary intake of phylloquinone was not associated with incident MI (HR comparing highest versus lowest quartile was 0.87, 95% CI 0.64–1.18, p-trend=0.44), but inversely associated with fatal MI (HR 0.49, 95% CI 0.25–0.94, p-trend=0.03). The inverse association with fatal MI persisted after additional adjustment for vegetable intake. Dietary intake of menaquinones was not associated with incident (HR 1.21, 95% CI 0.81–1.80, p-trend=0.31) or fatal (HR 1.09, 95% CI 0.46–2.62, p-trend=0.97) MI. Conclusion: This study does not confirm an inverse association between menaquinones intake and coronary heart disease as shown in two Dutch cohorts. The here observed inverse association for phylloquinone intake should be interpreted with caution since it was significant only for fatal MI (and thus based on small numbers).