The coincidence of low vitamin K status and high expression of growth differentiation factor 15 may indicate increased mortality risk in stable coronary heart disease patients.
Aged
Biomarkers
/ blood
Calcium-Binding Proteins
/ blood
Chronic Disease
Coronary Disease
/ blood
Cross-Sectional Studies
Czech Republic
/ epidemiology
Extracellular Matrix Proteins
/ blood
Female
Growth Differentiation Factor 15
/ blood
Humans
Incidence
Male
Middle Aged
Prognosis
Prospective Studies
Risk Assessment
Risk Factors
Time Factors
Up-Regulation
Vitamin D Deficiency
/ blood
Matrix Gla Protein
All-cause death
Cardiovascular death
EUROASPIRE
Heart failure
Matrix γ-carboxyglutamate protein (MGP)
Non-fatal cardiovascular events
dp-ucMGP
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
08 02 2021
08 02 2021
Historique:
received:
24
04
2020
revised:
11
09
2020
accepted:
15
09
2020
pubmed:
2
12
2020
medline:
18
3
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD). 894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF. The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.
Sections du résumé
BACKGROUND AND AIMS
Matrix Gla protein (MGP) is a natural inhibitor of vascular calcification critically dependent on circulating vitamin K status. Growth differentiation factor 15 (GDF-15) is a regulatory cytokine mainly of the inflammatory and angiogenesis pathways, but potentially also involved in bone mineralization. We sought to determine whether these two circulating biomarkers jointly influenced morbidity and mortality risk in patients with chronic coronary heart disease (CHD).
METHODS AND RESULTS
894 patients ≥6 months after myocardial infarction and/or coronary revascularization at baseline were followed in a prospective study. All-cause and cardiovascular mortality, non-fatal cardiovascular events (myocardial infarction, stroke, any revascularization), and hospitalization for heart failure (HF) were followed as outcomes. Desphospho-uncarboxylated MGP (dp-ucMGP) was used as a biomarker of vitamin K status. Both, increased concentrations of dp-ucMGP (≥884 pmol/L) and GDF-15 (≥1339 pg/mL) were identified as independent predictors of 5-year all-cause or cardiovascular mortality. However, their coincidence further increased mortality risk. The highest risk was observed in patients with high dp-ucMGP plus high GDF-15, not only when compared with those with "normal" concentrations of both biomarkers [HR 5.51 (95% CI 2.91-10.44), p < 0.0001 and 6.79 (95% CI 3.06-15.08), p < 0.0001 for all-cause and cardiovascular mortality, respectively], but even when compared with patients with only one factor increased. This pattern was less convincing with non-fatal cardiovascular events or hospitalization for HF.
CONCLUSIONS
The individual coincidence of low vitamin K status (high dp-ucMGP) and high GDF-15 expression predicts poor survival of stable CHD patients.
Identifiants
pubmed: 33257192
pii: S0939-4753(20)30402-6
doi: 10.1016/j.numecd.2020.09.015
pii:
doi:
Substances chimiques
Biomarkers
0
Calcium-Binding Proteins
0
Extracellular Matrix Proteins
0
GDF15 protein, human
0
Growth Differentiation Factor 15
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
540-551Informations de copyright
Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest None.