Lower levels of ADAMTS13 are associated with cardiovascular disease in young patients.
ADAMTS13 may play a role in arterial thrombosis by cleaving the highly active and thrombogenic ultralarge Von Willebrand Factor (VWF) multimers into less active VWF multimers. The aim was to investigate the relationship between plasma levels of ADAMTS13, VWF and genetic variation in the ADAMTS13 gene with cardiovascular disease. We performed a case-control study in 374 patients with a first-ever arterial thrombosis before the age of 45 years in males and 55 years in women. We included 218 patients with coronary heart disease (CHD), 109 patients with ischemic stroke (IS) and 47 patients with peripheral arterial disease (PAD) and 332 healthy population-based controls. ADAMTS13 and VWF levels were measured 1-3 months after the event. ADAMTS13 levels were associated with cardiovascular disease (OR antigen 5.1 (95% CI 3.1-8.5, p<0.001) and OR activity 4.4 (95% CI 2.5-7.5, p<0.001), in the lowest quartiles). VWF levels were associated with cardiovascular disease (OR antigen 2.1 (95% CI 1.3-3.3, p=0.001) and OR activity 2.0 (95% CI 1.3-3.1, p=0.003), in the highest quartile). Patients with combined low ADAMTS13 levels and high VWF levels had an odds ratio of 7.7 (95% CI 3.3-17.7) (p for trend <0.0001). No association was found between genetic variation in the ADAMTS13 gene with levels of ADAMTS13 or with risk of cardiovascular disease. In conclusion, levels of ADAMTS13 and VWF are strongly associated with the risk of cardiovascular disease.
Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
T N
TN
Bongers
E L E
EL
de Bruijne
D W J
DW
Dippel
A J
AJ
de Jong
J W
JW
Deckers
D
D
Poldermans
M P M
MP
de Maat
F W G
FW
Leebeek
D051722:ADAM Proteins / Q000097:blood* / Q000235:genetics; D000071120:ADAMTS13 Protein; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics; D016022:Case-Control Studies; D003327:Coronary Disease / Q000201:enzymology; D015536:Down-Regulation; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016491:Peripheral Vascular Diseases / Q000201:enzymology; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology; D013927:Thrombosis / Q000201:enzymology; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human