|Shea, Kyla - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Booth, Sarah - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|Weiner, Daniel - Tufts University|
|Brinkley, Tina - Wake Forest University|
|Kanaya, Alka - University Of California|
|Murphy, Rachel - University Of British Columbia|
|Simonsick, Eleanor - National Institute On Aging (NIA, NIH)|
|Wassel, Christina - University Of Pittsburgh|
|Vermeer, Cees - Maastricht University|
|Kritchevsky, Stephen - Wake Forest University|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2017
Publication Date: 3/29/2017
Citation: Shea, K., Booth, S.L., Weiner, D.E., Brinkley, T.E., Kanaya, A.A., Murphy, R.A., Simonsick, E.M., Wassel, C.L., Vermeer, C., Kritchevsky, S.B. 2017. Circulating vitamin K is inversely associated with incident cardiovascular disease risk among those treated for hypertension in the Health, Aging, and Body Composition Study (Health ABC). Journal of Nutrition. 32(2):243-249. doi: 10.3945/jn.117.249375.
Interpretive Summary: We investigated whether vitamin K nutritional status was associated with incident cardiovascular disease (CVD) in older men and women. Vitamin K status was measured in blood samples using two biomarkers: phylloquinone (vitamin K1) and uncarboxylated matrix gla protein. Concentrations of uncarboxylated matrix gla protein (the non-functional form of the protein) increase when vitamin K status is low. In a previous study, we found low plasma phylloquinone was associated with a higher risk for CVD only in adults treated for hypertension, so we also evaluated whether the relationship between vitamin K nutritional status and clinical CVD was different in older adults treated for hypertension compared to older adults not treated for hypertension. We found older adults treated for hypertension with very low circulating phylloquinone concentrations were more likely to develop clinical CVD over 12 years of follow-up. Circulating phylloquinone was not associated with CVD in older adults not treated for hypertension. The concentration of uncarboxylated matrix gla protein in blood was not associated with CVD overall, and this finding was not different in those treated for hypertension. Additional studies are needed to clarify the importance of vitamin K to CVD in persons treated for hypertension.
Technical Abstract: Background: A role for vitamin K in coronary artery calcification (CAC), a subclinical manifestation of cardiovascular disease (CVD), has been proposed because vitamin K-dependent proteins, including the calcification inhibitor matrix Gla protein (MGP), are present in vascular tissue. Observational studies found that low circulating phylloquinone (vitamin K-1) was associated with increased CAC progression, especially in persons treated for hypertension. It is unknown whether hypertension treatment modifies this putative role of vitamin K in clinical CVD risk. Objective: We determined the association between vitamin K status and incident clinical CVD in older adults in the Health ABC (Health, Aging, and Body Composition Study) and whether the association differed by hypertension treatment status. Methods: Plasma phylloquinone was measured in 1061 participants free of CVD (70-79 y of age, 58% women, 39% black). Plasma uncarboxylated MGP [(dp)ucMGP] was measured in a subset of 635 participants. Multivariate Cox models estimated the HR for incident CVD over 12.1 follow-up years. Effect modification by hypertension was tested with the use of interaction terms. Results: Neither low plasma phylloquinone (<0.2 nmol/L) nor elevated (dp)ucMGP (=574 pmol/L) was significantly associated with incident CVD [respective HRs (95% CIs): 1.27 (0.75, 2.13) and 1.02 (0.72, 1.45)]. In participants treated for hypertension (n = 489; 135 events), low plasma phylloquinone was associated with higher CVD risk overall (HR: 2.94; 95% CI: 1.41, 6.13). In those with untreated hypertension (n = 153; 48 events) and without hypertension (n = 418; 92 events), low plasma phylloquinone was not associated with incident CVD. The association between high (dp)ucMGP did not differ by hypertension treatment status (P-interaction = 0.72). Conclusions: Vitamin K status was not significantly associated with CVD risk overall, but low plasma phylloquinone was associated with a higher CVD risk in older adults treated for hypertension. Additional evidence from larger clinical studies is needed to clarify the importance of vitamin K to CVD in persons treated for hypertension, a segment of the population at high risk of clinical CVD events.