title: 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).
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.
authors.affiliation: USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA; kyla.shea@tufts.edu.
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.affiliation: USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.affiliation: Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weiner
authors.affiliation: Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Tina E
authors.initials: TE
authors.lastname: Brinkley
authors.affiliation: University of California-San Francisco, San Francisco, CA.
authors.forename: Alka M
authors.initials: AM
authors.lastname: Kanaya
authors.affiliation: School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Murphy
authors.affiliation: National Institute on Aging/NIH, Baltimore, MD.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Simonsick
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; and.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Wassel
authors.affiliation: VitaK, University of Maastricht, Maastricht, Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
mesh_terms: D000368:Aged; D000375:Aging; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001361:Avitaminosis / Q000097:blood / Q000150:complications*; D001823:Body Composition; D002114:Calcinosis / Q000209:etiology; D002135:Calcium-Binding Proteins / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology; D017202:Myocardial Ischemia / Q000209:etiology; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000209:etiology; D010837:Vitamin K 1 / Q000097:blood*; D000097568:Matrix Gla Protein
chemical_list: D000959:Antihypertensive Agents; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D010837:Vitamin K 1; D000097568:Matrix Gla Protein
keywords: cardiovascular disease; hypertension; matrix Gla protein; phylloquinone; vitamin K