Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis

Background MGP (matrix Gla protein) 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 ass...

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Main Authors: Ashley A. Berlot, Xueyan Fu, M. Kyla Shea, Russell Tracy, Matthew Budoff, Ryung S. Kim, Mahim Naveed, Sarah L. Booth, Jorge R. Kizer, Anna E. Bortnick
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.036459
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author Ashley A. Berlot
Xueyan Fu
M. Kyla Shea
Russell Tracy
Matthew Budoff
Ryung S. Kim
Mahim Naveed
Sarah L. Booth
Jorge R. Kizer
Anna E. Bortnick
author_facet Ashley A. Berlot
Xueyan Fu
M. Kyla Shea
Russell Tracy
Matthew Budoff
Ryung S. Kim
Mahim Naveed
Sarah L. Booth
Jorge R. Kizer
Anna E. Bortnick
author_sort Ashley A. Berlot
collection DOAJ
description Background MGP (matrix Gla protein) 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 MESA (Multi‐Ethnic Study of Atherosclerosis). Methods MESA is a prospective cohort study of 45‐ to 84‐year‐old individuals enrolled between 2000 and 2002 with adjudicated outcomes through 2019. Dp‐ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000–2002) and 5 (2010–2012). 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 coronary heart disease (17±3 years), and all‐cause mortality (18±2 years). Results The youngest age quartile (45‐ to 53‐years‐old) with higher dp‐ucMGP levels (520–2934 pmol/L) had an increased risk of all CVD (hazard ratio [HR], 3.05 [95% CI, 1.58–5.90], P=0.001), hard CVD (HR, 2.85 [95% CI, 1.30–6.23], P=0.009), hard coronary heart disease (HR, 3.79 [95% CI, 1.31–10.95], P=0.014), and all‐cause mortality (HR, 2.73 [95% CI, 1.19–6.30], P=0.018) compared with those with dp‐ucMGP levels between 150 and 519 pmol/L in maximally adjusted models. Conclusions Younger individuals 45 to 53 years old with elevated dp‐ucMGP levels (≥520 pmol/L) had an increased risk of incident CVD, coronary heart disease, 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, coronary heart disease, and all‐cause mortality.
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spelling doaj-art-847619a68e714f3d9d41921f596e4b1a2025-08-20T02:24:59ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-03-0114510.1161/JAHA.124.036459Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of AtherosclerosisAshley A. Berlot0Xueyan Fu1M. Kyla Shea2Russell Tracy3Matthew Budoff4Ryung S. Kim5Mahim Naveed6Sarah L. Booth7Jorge R. Kizer8Anna E. Bortnick9Albert Einstein College of Medicine Bronx NY USAJean Mayer USDA Human Nutrition Research Center on Aging at Tufts University Boston MA USAJean Mayer USDA Human Nutrition Research Center on Aging at Tufts University Boston MA USAUniversity of Vermont Larner College of Medicine Burlington VA USADivision of Cardiology The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center Torrance CA USADepartment of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USADepartment of Medicine, Division of Cardiology San Francisco VA Health Care System San Francisco CA USAJean Mayer USDA Human Nutrition Research Center on Aging at Tufts University Boston MA USADepartment of Medicine, Division of Cardiology San Francisco VA Health Care System San Francisco CA USADepartment of Medicine, Division of Cardiology Montefiore Medical Center and Albert Einstein College of Medicine Bronx NY USABackground MGP (matrix Gla protein) 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 MESA (Multi‐Ethnic Study of Atherosclerosis). Methods MESA is a prospective cohort study of 45‐ to 84‐year‐old individuals enrolled between 2000 and 2002 with adjudicated outcomes through 2019. Dp‐ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000–2002) and 5 (2010–2012). 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 coronary heart disease (17±3 years), and all‐cause mortality (18±2 years). Results The youngest age quartile (45‐ to 53‐years‐old) with higher dp‐ucMGP levels (520–2934 pmol/L) had an increased risk of all CVD (hazard ratio [HR], 3.05 [95% CI, 1.58–5.90], P=0.001), hard CVD (HR, 2.85 [95% CI, 1.30–6.23], P=0.009), hard coronary heart disease (HR, 3.79 [95% CI, 1.31–10.95], P=0.014), and all‐cause mortality (HR, 2.73 [95% CI, 1.19–6.30], P=0.018) compared with those with dp‐ucMGP levels between 150 and 519 pmol/L in maximally adjusted models. Conclusions Younger individuals 45 to 53 years old with elevated dp‐ucMGP levels (≥520 pmol/L) had an increased risk of incident CVD, coronary heart disease, 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, coronary heart disease, and all‐cause mortality.https://www.ahajournals.org/doi/10.1161/JAHA.124.036459cardiovascular diseaseeventsmatrix Gla
spellingShingle Ashley A. Berlot
Xueyan Fu
M. Kyla Shea
Russell Tracy
Matthew Budoff
Ryung S. Kim
Mahim Naveed
Sarah L. Booth
Jorge R. Kizer
Anna E. Bortnick
Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiovascular disease
events
matrix Gla
title Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
title_full Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
title_fullStr Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
title_full_unstemmed Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
title_short Inactive Matrix Gla Protein and Cardiovascular Outcomes: The Multi‐Ethnic Study of Atherosclerosis
title_sort inactive matrix gla protein and cardiovascular outcomes the multi ethnic study of atherosclerosis
topic cardiovascular disease
events
matrix Gla
url https://www.ahajournals.org/doi/10.1161/JAHA.124.036459
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