Desphospho-uncarboxylated matrix Gla-protein is associated with mortality risk in patients with chronic stable vascular disease.
BACKGROUND
Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease.


METHODS
We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK).


RESULTS
During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥ 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32-2.72) and 1.88 (95% CI, 1.22-2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18-2.61) and 1.79 (95% CI, 1.12-2.57).


CONCLUSIONS
In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk.
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic. Electronic address: mayero@fnplzen.cz.
Otto
O
Mayer
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic.
Jitka
J
Seidlerová
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic.
Jan
J
Bruthans
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic; Biomedical Center, Medical Faculty of Charles University, Pilsen, Czech Republic.
Jan
J
Filipovský
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic.
Katarina
K
Timoracká
2nd Department of Internal Medicine, Medical Faculty of Charles University and University Hospital, Pilsen, Czech Republic.
Jiří
J
Vaněk
Department of Neurology, University Hospital, Pilsen, Czech Republic.
Lenka
L
Cerná
Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Czech Republic.
Peter
P
Wohlfahrt
Centre for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital, Prague, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital Brno, Czech Republic.
Renata
R
Cífková
VitaK, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Elke
E
Theuwissen
VitaK, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Cees
C
Vermeer
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood* / Q000737:chemistry; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000737:chemistry; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality; D017202:Myocardial Ischemia / Q000097:blood / Q000401:mortality; D009204:Myocardial Revascularization / Q000401:mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012044:Regression Analysis; D020521:Stroke / Q000097:blood* / Q000401:mortality; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000097:blood* / Q000401:mortality*; D014812:Vitamin K / Q000378:metabolism; D000097568:Matrix Gla Protein
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014812:Vitamin K; D000097568:Matrix Gla Protein
Coronary heart disease; Dp-cMGP; Dp-ucMGP; EUROASPIRE; Matrix Gla-protein; Mortality; Secondary prevention; Stroke