title: Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited.
  
  
  OBJECTIVE
  We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design.
  
  
  METHODS
  Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial.
  
  
  RESULTS
  The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01].
  
  
  CONCLUSIONS
  Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.
authors.affiliation: Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. kshea@wakehealth.edu
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.forename: Michael E
authors.initials: ME
authors.lastname: Miller
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Burke
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy*; D002118:Calcium / Q000097:blood*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D019587:Dietary Supplements; D018450:Disease Progression; D004311:Double-Blind Method; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D061205:Vascular Calcification / Q000188:drug therapy; D010837:Vitamin K 1 / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D010837:Vitamin K 1; D002118:Calcium