Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck Study

Karin Willeit, Peter Santer, Lena Tschiderer, Raimund Pechlaner, Cees Vermeer, Johann Willeit, Stefan Kiechl*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND AND AIMS: Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated with dp-ucMGP also applies to the general, and especially, the elderly population has not yet been fully elucidated.

METHODS AND RESULTS: Plasma dp-ucMGP was measured in 684 individuals aged 50-89 years of the prospective population-based Bruneck Study (baseline evaluation in 2000). Baseline median dp-ucMGP was 478.4 (IQR 335.0-635.2) pmol/L. Over a median follow-up of 15.5 years, 163 CVD events occurred and 235 participants died. Age-/sex-adjusted hazard ratios (HRs) per 1-SD higher level of loge transformed dp-ucMGP were 1.30 (95%CI: 1.09-1.55; p=0.004) for incident CVD and 1.36 (95%CI: 1.17-1.57; p<0.001) for all-cause mortality. After multivariable adjustment, the associations remained significant with HRs of 1.23 (95%CI: 1.02-1.47, p=0.029) for CVD and 1.40 (95%CI: 1.20-1.64; p<0.001) for all-cause mortality. The associations remained virtually unchanged after additional adjustment for dietary quality as measured with the Alternative Healthy Eating Index. We found no association of dp-ucMGP with myocardial infarction and sudden cardiac deaths, but a strong association with other vascular deaths and non-vascular/non-cancer deaths.

CONCLUSIONS: This study shows a significant association of plasma dp-ucMGP with incident CVD and a significant and even stronger association with all-cause mortality. Clinical trials are needed to investigate whether vitamin K substitution results in improved health outcomes.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalAtherosclerosis
Volume353
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Calcium-Binding Proteins
  • Cardiovascular Diseases/epidemiology
  • Extracellular Matrix Proteins
  • Humans
  • Middle Aged
  • Prospective Studies
  • Vitamin K
  • DIAGNOSIS
  • MARKER
  • Mortality
  • VITAMIN-K STATUS
  • Cardiovascular disease
  • Matrix gla protein
  • Prospective studies
  • MESSENGER-RNA
  • RISK-FACTOR
  • RECEPTOR ACTIVATOR
  • OUTCOMES
  • HEALTH
  • CORONARY-HEART-DISEASE
  • EXPRESSION

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