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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #416105
Research Project: Nutrient Metabolism and Musculoskeletal Health in Older Adults

Location: Jean Mayer Human Nutrition Research Center On Aging

Title: Inactive matrix Gla Protein and cardiovascular outcomes: the multi-ethnic study of atherosclerosis

Author
item BERLOT, ASHLEY - Albert Einstein College Of Medicine
item FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TRACY, RUSSELL - University Of Vermont
item BUDOFF, MATTHEW - Ucla Medical Center
item KIM, RYUNG - Albert Einstein College Of Medicine
item NAVEED, MAHIM - San Francisco Veteran Affairs Medical Center
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item KIZER, JORGE - University Of California San Francisco (UCSF)
item BORTNICK, ANNA - Albert Einstein College Of Medicine

Submitted to: Journal of American Hospital Association
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2024
Publication Date: 3/4/2025
Citation: Berlot, A.A., Fu, X., Shea, K., Tracy, R., Budoff, M., Kim, R.S., Naveed, M., Booth, S.L., Kizer, J.R., Bortnick, A.E. 2025. Inactive matrix Gla Protein and cardiovascular outcomes: the multi-ethnic study of atherosclerosis. Journal of American Hospital Association. Volume 14, Number 5. https://doi.org/10.1161/JAHA.124.036459.
DOI: https://doi.org/10.1161/JAHA.124.036459

Interpretive Summary: Low amounts of vitamin K have been implicated in an increased risk of cardiovascular disease in older adults; however, this has not been studied in a diverse population with an extended follow-up. To address this gap, a vitamin K biomarker was measured in 2663 older adults participating in the Multi-Ethnic Study of Atherosclerosis who were followed for 10 years. Higher vitamin K status was associated with less progression of heart disease. These data provide justification for future clinical studies focused on vitamin K intake and heart disease risk.

Technical Abstract: Background Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, in its dephosphorylated-uncarboxylated (dp-uc) form, is positively associated with vascular calcification, possibly portending adverse cardiovascular events. The objective of this study was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods MESA is a prospective cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Age-stratified Cox proportional hazard models were used to assess dp-ucMGP with risk of all (CVD) (mean follow up 16 + 4 years), hard CVD (17 + 3 years), hard CHD (17 + 3 years), and all-cause mortality (18 + 2 years). Results The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. Conclusions Younger individuals 45-53 years old with elevated dp-ucMGP levels (>520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality. No association was seen in older adults. Additional studies are needed to better delineate the relationship of inactive MGP with incident CVD, CHD, and all-cause mortality.