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The relationship between vitamin K and peripheral arterial disease

      Highlights

      • High menaquinone intake is associated with lower risk of peripheral arterial disease.
      • This association is stronger in hypertensive participants.
      • Phylloquinone intake is not associated with peripheral arterial disease.

      Abstract

      Background and aims

      A high dietary intake of vitamin K1 (phylloquinone) and vitamin K2 (menaquinones) is thought to decrease cardiovascular disease risk by reducing vascular calcification. The objective of this study is to explore if there is a relationship between phylloquinone and menaquinones intake and risk of PAD.

      Methods

      We investigated the association between intake of phylloquinone and menaquinones with PAD in a prospective cohort with 36,629 participants. Occurrence of PAD was obtained by linkage to national registries. Baseline intake of phylloquinone and menaquinones was estimated using a validated food-frequency questionnaire. Multivariate Cox regression was used to estimate adjusted hazard ratio's for the association.

      Results

      During 12.1 years (standard deviation 2.1 years) of follow-up, 489 incident cases of PAD were documented. Menaquinones intake was associated with a reduced risk of PAD with a hazard ratio (HR) of 0.71, 95% CI; 0.53–0.95 for the highest versus lowest quartile. A stronger association was observed (p interaction 0.0001) in participants with hypertension (HRQ4 versus Q1 0.59; 95% CI 0.39–0.87) or diabetes (HRQ4 versus Q1 0.56; 95% CI 0.18–1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk.

      Conclusions

      High intake of menaquinones was associated with a reduced risk of PAD, at least in hypertensive participants. High intake of phylloquinone was not associated with a reduced risk of PAD.

      Keywords

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      References

        • Bolton-Smith C.
        • Price R.J.
        • Fenton S.T.
        • Harrington D.J.
        • Shearer M.J.
        Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods.
        Br. J. Nutr. 2000; 83: 389-399
        • Schurgers L.J.
        • Vermeer C.
        Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations.
        Haemostasis. 2000; 30: 298-307
        • Cranenburg E.C.
        • Schurgers L.J.
        • Vermeer C.
        Vitamin K: the coagulation vitamin that became omnipotent.
        Thromb. Haemost. 2007; 98: 120-125
        • Theuwissen E.
        • Smit E.
        • Vermeer C.
        The role of vitamin K in soft-tissue calcification.
        Adv. Nutr. 2012; 3: 166-173
        • Booth S.L.
        • Martini L.
        • Peterson J.W.
        • Saltzman E.
        • Dallal G.E.
        • Wood R.J.
        Dietary phylloquinone depletion and repletion in older women.
        J. Nutr. 2003; 133: 2565-2569
        • McCann J.C.
        • Ames B.N.
        Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?.
        Am. J. Clin. Nutr. 2009; 90: 889-907
        • Luo G.
        • Ducy P.
        • McKee M.D.
        • et al.
        Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein.
        Nature. 1997; 386: 78-81
        • Schurgers L.J.
        • Teunissen K.J.
        • Knapen M.H.
        • et al.
        Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification.
        Arterioscler. Thromb. Vasc. Biol. 2005; 25: 1629-1633
        • Vermeer C.
        • Schurgers L.J.
        A comprehensive review of vitamin K and vitamin K antagonists.
        Hematol. Oncol. Clin. North Am. 2000; 14: 339-353
        • Schurgers L.J.
        • Spronk H.M.
        • Soute B.A.
        • Schiffers P.M.
        • DeMey J.G.
        • Vermeer C.
        Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats.
        Blood. 2007; 109: 2823-2831
        • Tantisattamo E.
        • Han K.H.
        • O'Neill W.C.
        Increased vascular calcification in patients receiving warfarin.
        Arterioscler. Thromb. Vasc. Biol. 2015; 35: 237-242
        • Beulens J.W.
        • Bots M.L.
        • Atsma F.
        • et al.
        High dietary menaquinone intake is associated with reduced coronary calcification.
        Atherosclerosis. 2009; 203: 489-493
        • Geleijnse J.M.
        • Vermeer C.
        • Grobbee D.E.
        • et al.
        Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.
        J. Nutr. 2004; 134: 3100-3105
        • Gast G.C.
        • de Roos N.M.
        • Sluijs I.
        • et al.
        A high menaquinone intake reduces the incidence of coronary heart disease.
        Nutr. Metab. Cardiovasc Dis. 2009; 19: 504-510
        • Erkkila A.T.
        • Booth S.L.
        • Hu F.B.
        • et al.
        Phylloquinone intake as a marker for coronary heart disease risk but not stroke in women.
        Eur. J. Clin. Nutr. 2005; 59: 196-204
        • Erkkila A.T.
        • Booth S.L.
        • Hu F.B.
        • Jacques P.F.
        • Lichtenstein A.H.
        Phylloquinone intake and risk of cardiovascular diseases in men.
        Nutr. Metab. Cardiovasc Dis. 2007; 17: 58-62
        • Vissers L.E.
        • Dalmeijer G.W.
        • Boer J.M.
        • Monique Verschuren W.M.
        • van der Schouw Y.T.
        • Beulens J.W.
        Intake of dietary phylloquinone and menaquinones and risk of stroke.
        J. Am. Heart Assoc. 2013; 2: e000455
        • Dalmeijer G.W.
        • van der Schouw Y.T.
        • Magdeleyns E.J.
        • et al.
        Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients.
        Diabetes Care. 2013; 36: 3766-3771
        • Beulens J.W.
        • Monninkhof E.M.
        • Verschuren W.M.
        • et al.
        Cohort profile: the EPIC-NL study.
        Int. J. Epidemiol. 2010; 39: 1170-1178
        • Haftenberger M.
        • Schuit A.J.
        • Tormo M.J.
        • et al.
        Physical activity of subjects aged 50-64 years involved in the European prospective investigation into cancer and nutrition (EPIC).
        Public Health Nutr. 2002; 5: 1163-1176
        • Wareham N.J.
        • Jakes R.W.
        • Rennie K.L.
        • et al.
        Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European prospective investigation into cancer and nutrition (EPIC) study.
        Public Health Nutr. 2003; 6: 407-413
        • Van der Heijden L.J.M.
        • Hulshof K.F.A.M.
        • Langius J.A.E.
        • Oosten H.M.V.
        • Pruissen-Boskaljon J.C.
        NEVO tabel: Nederlands voedingsstoffenbestand, Den Haag: Voorlichtingsbureau voor de voeding; 2012.
        1996
        • Booth S.L.
        • Sadowski J.A.
        • Weihrauch J.L.
        • Ferland G.
        Vitamin K1 (Phylloquinone) content of common foods; A provisional table.
        J. Food Comp. 1993; 6: 109-120
        • Shearer M.J.
        • Bach A.
        • Kohlmeier M.
        Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health.
        J. Nutr. 1996; 126: 1181S-1186S
        • Suttie J.W.
        Vitamin K and human nutrition.
        J. Am. Diet. Assoc. 1992; 92: 585-590
        • Booth S.L.
        • Madabushi H.T.
        • Davidson K.W.
        • Sadowski J.A.
        Tea and coffee brews are not dietary sources of vitamin K-1 (phylloquinone).
        J. Am. Diet. Assoc. 1995; 95: 82-83
        • Ferland G.
        • MacDonald D.L.
        • Sadowski J.A.
        Development of a diet low in vitamin K-1 (phylloquinone).
        J. Am. Diet. Assoc. 1992; 92: 593-597
        • Ocke M.C.
        • Bueno-de-Mesquita H.B.
        • Goddijn H.E.
        • et al.
        The Dutch EPIC food frequency questionnaire. I. Description of the questionnaire, and relative validity and reproducibility for food groups.
        Int. J. Epidemiol. 1997; 26: S37-S48
        • Herings R.M.
        • Bakker A.
        • Stricker B.H.
        • Nap G.
        Pharmaco-morbidity linkage: a feasibility study comparing morbidity in two pharmacy based exposure cohorts.
        J. Epidemiol. Community Health. 1992; 46: 136-140
        • Boomsma L.J.
        • Bartelink M.L.
        • Stoffers H.E.
        • Wiersma T.
        • Assendelft W.J.
        Nederlands huisartsen genootschap. Summary of the practice guideline 'peripheral vascular disease' (first revision) from the Dutch college of general practitioners.
        Ned. Tijdschr. Geneeskd. 2004; 148: 1490-1494
        • Nagel G.
        • Zoller D.
        • Ruf T.
        • Rohrmann S.
        • Linseisen J.
        Long-term reproducibility of a food-frequency questionnaire and dietary changes in the European prospective investigation into cancer and nutrition (EPIC)-Heidelberg cohort.
        Br. J. Nutr. 2007; 98: 194-200
        • Schurgers L.J.
        • Vermeer C.
        Differential lipoprotein transport pathways of K-vitamins in healthy subjects.
        Biochim. Biophys. Acta. 2002; 1570: 27-32
        • Will B.H.
        • Suttie J.W.
        Comparative metabolism of phylloquinone and menaquinone-9 in rat liver.
        J. Nutr. 1992; 122: 953-958
        • Theuwissen E.
        • Cranenburg E.C.
        • Knapen M.H.
        • et al.
        Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects.
        Br. J. Nutr. 2012; 108: 1652-1657
        • Shea M.K.
        • O'Donnell C.J.
        • Hoffmann U.
        • et al.
        Vitamin K supplementation and progression of coronary artery calcium in older men and women.
        Am. J. Clin. Nutr. 2009; 89: 1799-1807