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: M Kyla Shea, Sarah L Booth, Daniel E Weiner, Tina E Brinkley, Alka M Kanaya, Rachel A Murphy, Eleanor M Simonsick, Christina L Wassel, Cees Vermeer, Stephen B Kritchevsky, Health ABC Study
• Journal: The Journal of nutrition (J Nutr) Vol. 147 Issue 5 Pg. 888-895 (05 2017) ISSN: 1541-6100 [Electronic] United States
• PMID: 28356433 (Publication Type: Journal Article, 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)
• Copyright: © 2017 American Society for Nutrition.

Chemical References

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

Topics

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