Low ADAMTS13 activity is associated with an increased risk of ischemic stroke.
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) has antithrombotic properties because it cleaves von Willebrand factor (VWF) in smaller, less active multimers. The aim of our study was to investigate prospectively the association between ADAMTS13 activity and ischemic stroke. We included 5941 individuals ≥55 years without a history of stroke or transient ischemic attack (TIA) of the Rotterdam Study, a population-based cohort study. ADAMTS13 activity was measured at inclusion with the FRETS-VWF73 assay and VWF antigen (VWF:Ag) levels by enzyme-linked immunosorbent assay. We assessed the association among ADAMTS13 activity, VWF:Ag levels, and ischemic stroke by Cox proportional hazard analysis. The added value of ADAMTS13 activity above the traditional risk factors for ischemic stroke risk prediction was examined by the C-statistic and the net reclassification improvement index (NRI). All individuals were followed for incident stroke or TIA. Over a median follow-up time of 10.7 years (56,403 total person-years), 461 participants had a stroke, 306 of which were ischemic. After adjustment for cardiovascular risk factors, individuals with ADAMTS13 activity in the lowest quartile had a higher risk of ischemic stroke (absolute risk, 7.3%) than did those in the reference highest quartile (absolute risk, 3.8%; hazard ratio, 1.65; 95% confidence interval [CI], 1.16-2.32). Adding ADAMTS13 to the model in prediction of ischemic stroke, increased the C-statistic by 0.013 (P = .003) and provided 0.058 (95% CI, -0.002 to 0.119) NRI. Low ADAMTS13 activity is associated with the risk of ischemic stroke and improves the accuracy of risk predictions for ischemic stroke beyond traditional risk factors.
Department of Hematology, Department of Neurology, and.
Michelle A H
MA
Sonneveld
Department of Hematology.
Moniek P M
http://orcid.org/0000-0001-7749-334X
MP
de Maat
Department of Neurology, and Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Marileen L P
ML
Portegies
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Maryam
M
Kavousi
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands;
Albert
A
Hofman
Baxter Innovations GmbH, Vienna, Austria; and.
Peter L
PL
Turecek
Baxter Innovations GmbH, Vienna, Austria; and.
Hanspeter
H
Rottensteiner
Baxter Innovations GmbH, Vienna, Austria; and.
Fritz
F
Scheiflinger
Department of Neurology, and.
Peter J
PJ
Koudstaal
Department of Neurology, and Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
M Arfan
MA
Ikram
Department of Hematology.
Frank W G
FW
Leebeek
D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000368:Aged; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000097:blood*
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human