Elevated alpha1-antitrypsin is a risk factor for arterial ischemic stroke in childhood

Abstract

Alpha1-antitrypsin (alpha1-AT) is a physiological inhibitor of activated protein C (APC) and therefore decreased APC activity. APC itself causes an anticoagulant effect by inactivating factors Va and VIIIa. The present case-control study was performed to evaluate the role of the elevated alpha1-AT concentration in pediatric patients with ischemic stroke (IS). alpha1-AT concentrations were measured along with established prothrombotic risk factors 6-12 months after the acute thrombotic onset in 81 Caucasian children with IS aged 1 month to 18 years. The cutoff values defined as age-dependent 90th percentiles were obtained from 229 healthy controls. Median (range) values of alpha1-AT were significantly higher in patients compared with control subjects [122.0 mg/dl (61.4-224.0) vs. 114.0 mg/dl (66.8-156.0); p = 0.016]. In addition, 14 of the 81 patients (17.3%) compared with 10 of the 162 controls (6.2%) had alpha1-AT concentrations above the 90th age-dependent percentiles (p = 0.012). Multivariate analysis performed in a 1:2 matched case-control setting adjusted for the presence of established prothrombotic risk factors showed a significantly increased odds ratio (OR) and 95% confidence interval (CI) for patients with elevated alpha1-AT >90th percentiles and IS (OR/CI: 4.0/1.64-9.92; p = 0.0024). Data shown here give evidence that total alpha1-AT concentrations above the 90th age-dependent percentiles independently increase the risk of IS 4.0-fold in Caucasian children.