RESUMEN
BACKGROUND AND PURPOSE: Elevated von Willebrand factor (vWF) concentrations are associated with an increased risk of ischemic heart disease. Several factors influence vWF antigen levels and activity, including blood group, genetic variability, acute-phase response, and proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13), a determinant of proteolytic cleavage of vWF. We assessed how these factors affect the relation between vWF and the occurrence of stroke to understand the underlying mechanism. METHODS: In a case-control study of 124 first-ever ischemic stroke patients and 125 age- and sex-matched controls, we studied vWF antigen (vWF:Ag), vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the -1793C/G polymorphism in the vWF gene, and C-reactive protein. RESULTS: vWF antigen and activity levels were significantly higher in cases than in controls. The relative risk of ischemic stroke was highest in individuals in the upper quartile of vWF:Ag (odds ratio, 3.2; 95% CI, 1.4 to 7.5) and vWF:RCo (odds ratio, 2.1; 95% CI, 0.9 to 4.8) compared with individuals in the lowest quartiles. In individuals with ADAMTS13 in the lowest quartile, the relative risk of stroke was 1.7 (95% CI, 0.7 to 3.9) compared with the highest quartile. C-reactive protein, ADAMTS13, and genetic variation did not affect the association between vWF and the relative risk of stroke, whereas blood group did affect the association. CONCLUSIONS: vWF antigen and activity are associated with the occurrence of acute ischemic stroke. This relation is unaffected by the severity of the acute-phase response or by genetic variation or degradation.
Asunto(s)
Proteínas ADAM/genética , Isquemia Encefálica/genética , Variación Genética/genética , Accidente Cerebrovascular/genética , Regulación hacia Arriba/fisiología , Factor de von Willebrand/biosíntesis , Factor de von Willebrand/genética , Proteínas ADAM/sangre , Proteína ADAMTS13 , Adulto , Anciano , Isquemia Encefálica/sangre , Isquemia Encefálica/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Inflamación/sangre , Inflamación/epidemiología , Inflamación/genética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/epidemiología , Factor de von Willebrand/metabolismoRESUMEN
OBJECTIVES: Young patients with an ischaemic stroke or transient ischaemic attack (TIA) often have no vascular risk factors. Hyper-homocysteinaemia is an established risk factor for stroke in elderly patients but it is uncertain whether it is also important for the prognosis of young ischaemic stroke and TIA patients. We examined the possible effect of the plasma homocysteine level on the risk of recurrent vascular events in patients between 18 and 45 years of age. METHODS: The study population consisted of 161 consecutive patients with a recent cerebral infarction or TIA. Data on the primary event and the homocysteine level were collected retrospectively from hospital records. General practitioners and patients were contacted by telephone to record vascular events and the type of medication used during the follow-up period. Vascular events included cerebral infarction, TIA, pulmonary embolism, venous thrombosis, myocardial infarction and peripheral arterial disease. RESULTS: A Kaplan- Meier curve showed a dose effect relationship between event-free survival time and tertiles of the homocysteine level (Log rank statistic 5.91; p=0.05). The Cox hazard ratio, after adjustment for homocysteine lowering treatment, was 1.7 (95 % CI, 1.1 to 2.8) for any vascular outcome event, 1.9 (95% CI, 1.1 to 3.0) for arterial outcome events and 1.8 (95 % CI, 1.1 to 2.9) for cerebral outcome events. CONCLUSIONS: In spite of our small number of outcome events we found a significant association at the 95% confidence level between homocysteine level and the risk of recurrent vascular events in young patients with an ischaemic stroke or TIA. The association is of the same magnitude as in elderly people.
Asunto(s)
Homocistina/sangre , Ataque Isquémico Transitorio/sangre , Accidente Cerebrovascular/sangre , Enfermedades Vasculares/sangre , Adolescente , Adulto , Infarto Cerebral/sangre , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/fisiopatología , Ataque Isquémico Transitorio/terapia , Masculino , Recurrencia , Estudios Retrospectivos , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Enfermedades Vasculares/terapiaRESUMEN
BACKGROUND: The relationship between the PIA2 allele of the Leu(33)Pro polymorphism of glycoprotein IIb/IIIa receptor (GPIIb/IIIa) and ischemic stroke is uncertain. The purpose of this study was to investigate a possible association between the GPIIb/IIIa PIA1/A2 polymorphism and the occurrence of cryptogenic stroke in young patients. METHODS: From a consecutive series of 80 patients aged 45 or less with a recent ischemic stroke or TIA, we selected 45 patients with stroke due to small vessel occlusion or stroke of undetermined etiology (according to the TOAST criteria). Controls were 60 healthy blood donors with a similar age distribution. All patients underwent CT of the brain and were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. The frequency of the PIA2 allele was determined by PCR and Msp1 restriction analysis. RESULTS: Eight patients (16%) and 16 controls (27%) were heterozygous for PIA2 allele. Two patients (4%) were homozygous for PIA2. The relative risk of ischemic stroke associated with PIA2 allele was estimated at 0.8 (95% CI: 0.3-1.9). CONCLUSION: This study does not support the association between the PIA1/A2 polymorphism and cryptogenic stroke or TIA in patients aged 45 or less.