Evaluating the Genetic Component of Ischemic Stroke Subtypes A Family History Study

• Published in: Stroke (1970) Vol. 34; no. 6; pp. 1364 - 1369
• Main Authors: Jerrard-Dunne, Paula, Cloud, Geoffrey, Hassan, Ahamad, Markus, Hugh S.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.06.2003
• Subjects: Aged; Biological and medical sciences; Brain Ischemia - classification; Brain Ischemia - epidemiology; Brain Ischemia - genetics; Case-Control Studies; European Continental Ancestry Group - genetics; Family; Female; Gene Frequency; Humans; Ischemic Attack, Transient - epidemiology; Ischemic Attack, Transient - genetics; London - epidemiology; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neurology; Odds Ratio; Risk; Risk Factors; Sample Size; Stroke - classification; Stroke - epidemiology; Stroke - genetics; Vascular Diseases - epidemiology; Vascular Diseases - genetics; Vascular diseases and vascular malformations of the nervous system; London; Human; stroke classification; Nervous system diseases; risk factors; Family study; Cardiovascular disease; Case control study; Epidemiology; Cerebral disorder; Vascular disease; Phenotype; genetics; Ischemia; cerebral infarction; Central nervous system disease; Classification; Risk factor; Cerebrovascular disease; Brain (vertebrata)
• DOI: 10.1161/01.STR.0000069723.17984.FD
• ISSN: 0039-2499; 1524-4628

Background and Purpose— Twin and family history studies support a role for genetic factors in stroke risk. Because the etiology of ischemic stroke is heterogeneous, genetic factors may vary by etiologic subtype. We determined the familial aggregation of stroke risk in different stroke phenotypes and used the results to model estimated sample size requirements for case-control studies. Methods— One thousand consecutive white subjects with ischemic stroke and 800 white controls matched for age and sex were recruited. A first-degree family history of stroke and myocardial infarction was obtained by structured interview. Stroke subtype was determined with the use of modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results— A family history of stroke at ≤65 years was a significant risk factor for large-vessel disease (odds ratio [OR], 2.24; 95% CI, 1.49 to 3.36; P <0.001) and for small-vessel disease (OR, 1.93; 95% CI, 1.25 to 2.97; P =0.003). When only cases aged ≤65 years were considered, these ORs increased to 2.93 (95% CI, 1.68 to 5.13) ( P <0.001) and 3.15 (95% CI, 1.81 to 5.50) ( P <0.001), respectively. No significant associations were seen for cardioembolic stroke or stroke of undetermined etiology. Conclusions— A family history of vascular disease is an independent risk factor for both large-vessel atherosclerosis and small-vessel disease, especially in cases presenting before age 65 years. The estimated sample sizes for case-control studies illustrate how candidate gene studies for ischemic stroke might be made more effective by focusing on these specific phenotypes, in which the genetic component of the disease appears to be strongest.