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Title: Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

Author
item SHEA, M KYLA - Wake Forest School Of Medicine
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MILLER, MICHAEL - Wake Forest School Of Medicine
item BURKE, GREGORY - Wake Forest School Of Medicine
item CHEN, HAIYING - Wake Forest School Of Medicine
item CUSHMAN, MARY - University Of Vermont
item TRACY, RUSSELL - University Of Vermont
item KRITCHEVSKY, STEPHEN - Wake Forest School Of Medicine

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/2/2013
Publication Date: 7/1/2013
Citation: Shea, M., Booth, S.L., Miller, M., Burke, G., Chen, H., Cushman, M., Tracy, R., Kritchevsky, S. 2013. Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis. American Journal of Clinical Nutrition. 98(1):197-208.

Interpretive Summary: Some studies have reported that vitamin K protects against, which is a characteristic of heart disease. We measured vitamin K concentrations in blood samples from community-dwelling older men and women (meaning those who are not in assisted living or nursing homes) and determined its association with coronary calcium progression. While the overall findings suggest those with low vitamin K were more likely to have coronary calcium progression, the results were not statistically significant. However, among participants who were taking blood pressure medication, those with low vitamin K were more likely to have coronary calcium progression, which was statistically significant. These findings need to be explored more thoroughly in larger studies before conclusions about vitamin K’s association with cardiovascular disease can be made.

Technical Abstract: While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without, all with baseline and follow-up CAC measures (mean follow-up=2.5 yrs), and was considered low if less than 1.0nmol/L (the distribution median). The Odds Ratio (OR) (95% Confidence Interval {CI}) for extreme CAC progression comparing those with low serum phylloquinone to those without was 1.34(0.94-1.90), adjusted for demographics and confounders. A significant interaction between low phylloquinone and anti-hypertension medication use was detected (p=0.016). Medication users with low serum phylloquinone were more likely to have extreme CAC progression compared to medication users without [OR(95%CI)=2.37(1.38-4.09)]. In replication using a post-hoc per-protocol analyses of a phylloquinone supplementation trial, baseline anti-hypertensive medication users in the supplementation group had less CAC progression than those in the control group [adjusted mean+/-SEM 3-year CAC change: phylloquinone supplementation (n=40),+5+/-20 Agatston units; control (n=49);+44+/- 13 Agatston units, p less than 0.01)]. Although the overall results suggest participants with low serum phylloquinone are more likely to have extreme CAC progression, the role of chance could not be excluded. Low serum phylloquinone was associated with CAC progression in anti-hypertension medication users, a novel finding conditionally replicated using an independent sample. Intervention trials are needed to determine whether improving serum phylloquinone reduces CAC progression, especially among persons treated for hypertension.