matosus, livedo reticularis, recurrent fetal loss, valvular heart disease) or laboratory features (prolonged activated partial thromboplastin time, thrombocytopenia ...
© Springer-Verlag 2003
Neurol Sci (2003) 24:S11–S12
R. Abbate • F. Sofi • D. Brogi • R. Marcucci
Emerging risk factors for ischemic stroke
Abstract The strongest evidence of a relationship between homocysteine (Hcy) and risk of cerebrovascular disease has been provided by six prospective studies. The vascular risk was shown to be dose dependent for both fasting and postmethionine Hcy levels and statistically independent of traditional cardiovascular risk factors, although there was a multiple effect in the presence of smoking and hypertension. Recently, it was demonstrated that not only hyperHcy but also MTHFR polymorphism is an independent risk factor for dissection. Finally, preliminary data suggest that hyperHcy is a risk factor for the occurrence of cerebrovascular events (transient ischemic attack/stroke) in patients with atrial fibrillation. On the basis of these results, several intervention trials are ongoing to determine whether lowering Hcy levels with vitamin supplementation will reduce the recurrence of stroke.
R. Abbate () • F. Sofi • D. Brogi • R. Marcucci Dipartimento Area Critica Medico-Chirurgica Università di Firenze Centro Trombosi, AO Careggi, Italy
A mild hyperhomocysteinemia is present in between 12% and 47% of patients with coronary artery disease, ischemic stroke, or peripheral artery disease. In a meta-analysis of nine studies, the odds ratio (OR) for ischemic stroke was 2.5 [95% confidence interval (CI) 2.0–3.0]. The strongest evidence of a relationship between homocysteine (Hcy) and risk of cerebrovascular disease has been provided by six prospective studies with a follow-up of 1.4–12.8 years of 830 cases and 1,872 controls. The vascular risk was dose-dependent for both fasting and post-methionine Hcy levels and statistically independent of traditional cardiovascular risk factors, although there was a multiple effect in the presence of smoking and hypertension. In a subgroup of patients from the ARIC study, intima media thickness was associated with high levels of Hcy. Moreover, analysis of the Framingham study showed that the severity of carotid stenosis was inversely associated with the dietary intake of folic acid and vitamin B6. Several studies, both case-control and prospective, have demonstrated elevated Hcy levels in patients with a history of transient ischemic attack (TIA) and/or stroke. In the Caerphilly study, a prospective study of 2,254 males (aged 50–64 years), Hcy levels within the 5th quintile were associated with a significant risk (OR=2.5, CI 1.0–6.2) in the subgroup of subjects with stroke below 65 years of age. In addition to these results, a recent study indicated that mild hyperHcy is the only variable able to identify patients with juvenile ischemic stroke. Elevated levels of Hcy seem to significantly affect the extent of aortic ateroma, evaluated with a transesophageous echo, in patients with previous ischemic stroke. One of the major causes of premature ischemic stroke is artery dissection. Recently, it was demonstrated that not only hyperHcy but also MTHFR polymorphism is an independent risk factor for dissection. Finally, preliminary data suggest that hyperHcy is a risk factor for the occurrence of cerebrovascular events (TIA/stroke) in patients with atrial fibrillation. On the basis of these results, several intervention trials are ongoing attempting to determine whether lowering Hcy levels with vitamin supplementation will reduce the recurrence of stroke. Several data demonstrate that inflammation plays an important role in the pathophysiology of ischemic stroke.
S12
Elevated blood levels of inflammatory and hemostatic markers are associated with increased cardiovascular risk in healthy subjects and in patients with coronary artery disease and ischemic stroke. Recently, it has been demonstrated that elevated C-reactive protein (CRP) levels independently predict the risk of future stroke and TIA. From a pathophysiological perspective, these data support the hypothesis that patients who respond to stroke with marked activation of the inflammatory system may be at risk for more-intense activation of coronary triggering events. Moreover, these results can improve the prediction of vascular risk in patients with ischemic stroke and may lead to a better clinical identification of patients who might benefit from aggressive secondary prevention and for whom the cost-to-benefit ratio for long-term use of new antiplatelet agents would be improved. Furthermore, it was demonstrated that the CRP level measured within 12 h of onset of symptoms of an acute ischemic stroke is not independently related to long-term prognosis. In contrast, a CRP increase between 12 and 24 h after onset of symptoms predicts an unfavourable outcome and is associated with an increase incidence of cerebrovascular and cardiovascular events.
R. Abbate et al.: Emerging risk factors for ischemic stroke
TIA and strokes are the most-common types of arterial thrombosis reported in antiphospholipid antibody syndrome. The association of antiphospholipid antibodies (aPL) with stroke is most clearly shown in studies of young stroke patients (below 50 years). Studies of all stroke patients have reported conflicting results, with some case-control studies showing a strong association (34% vs. 11%) with aPL. In a prospective nested case-control study, anti-b2-glycoprotein-I predicted later stroke risk at 15 years (with less of an association at 20 years). It is not reasonable to suggest that all patients with a first ischemic stroke be screened for aPL. Currently available information allows us to suggest screening for aPL in selected subgroups of patients. Stroke patients younger than 40 years should have aPL determinations as part of the evaluation for stroke etiology. Patients of any age with unexplained stroke should likewise be screened for aPL. Any stroke patient with first or recurrent stroke who has some other clinical (systemic lupus erythematosus, livedo reticularis, recurrent fetal loss, valvular heart disease) or laboratory features (prolonged activated partial thromboplastin time, thrombocytopenia, hemolytic anemia, Coombs’ test positive) should also be screened for aPL.
