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)

J Nutr. 2017 May;147(5):888-895. doi: 10.3945/jn.117.249375. Epub 2017 Mar 29.


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.

Keywords: cardiovascular disease; hypertension; matrix Gla protein; phylloquinone; vitamin K.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aging
  • Antihypertensive Agents / therapeutic use
  • Avitaminosis / blood
  • Avitaminosis / complications*
  • Body Composition
  • Calcinosis / etiology
  • Calcium-Binding Proteins / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Extracellular Matrix Proteins / blood
  • Female
  • Humans
  • Hypertension / blood
  • Hypertension / complications*
  • Hypertension / drug therapy
  • Male
  • Myocardial Infarction / etiology
  • Myocardial Ischemia / etiology
  • Proportional Hazards Models
  • Risk Factors
  • Stroke / etiology
  • Vitamin K 1 / blood*


  • Antihypertensive Agents
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • Vitamin K 1