Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: a multicenter and multiethnic study.
OBJECTIVE
Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI).


RESULTS
We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8-2.9), total VWF was 1.8 (1.4-2.3), ADAMTS13 was 0.6 (05-0.8), OPG was 1.6 (1.2-2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2-2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant.


CONCLUSIONS
We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.
Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, The Netherlands.
B
B
Rutten
Heart Care Foundation, Florence, Italy.
A
A
Maseri
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
D
D
Cianflone
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
A
A
Laricchia
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
N A
NA
Cristell
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
A
A
Durante
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
M
M
Spartera
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
F
F
Ancona
Clinical Cardiovascular Biology Centre, Universita Vita-Salute San Raffaele, Italy.
L
L
Limite
The Heart Center, People's Hospital of Peking University, China.
D
D
Hu
The Heart Center, People's Hospital of Peking University, China.
H
H
Li
Department of Cardiology, Royal Infirmary of Edinburgh, UK.
N G
NG
Uren
Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, The Netherlands.
P G
PG
de Groot
A Bianchi Bonomi Hemophilia and Thrombosis Center, Ospedale Maggiore Policlinico, Italy.
P M
PM
Mannucci
Laboratory of Clinical Chemistry and Haematology, University Medical Center Utrecht, The Netherlands M.Roest@umcutrecht.nl.
M
M
Roest
D051722:ADAM Proteins / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D005260:Female; D006801:Humans; D007558:Italy / Q000208:ethnology; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis* / Q000208:ethnology; D053244:Osteoprotegerin / Q000378:metabolism; D012044:Regression Analysis; D012307:Risk Factors; D012606:Scotland / Q000208:ethnology; D014841:von Willebrand Factor / Q000378:metabolism*
D015415:Biomarkers; D053244:Osteoprotegerin; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
ADAMTS13; Active von Willebrand factor; ST-segment elevation myocardial infarction; osteoprotegerin; risk factors; von Willebrand factor