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NEUROLOGY 2007;68:427-431
© 2007 American Academy of Neurology

Lack of aggregation of ischemic stroke subtypes within affected sibling pairs

P. G. Wiklund, MD, W. M. Brown, MA, T. G. Brott, MD, B. Stegmayr, MD, R. D. Brown, Jr, MD, S. Nilsson-Ardnor, MD, J. A. Hardy, PhD, B. M. Kissela, MD, A. Singleton, PhD, D. Holmberg, PhD, S. S. Rich, PhD and J. F. Meschia, MD

From the Departments of Medicine (P.G.W., B.S.) and Medical Biosciences (S.N.-A., D.H.), Umeå University, Umeå, Sweden; the Department of Biostatistics (W.M.B., S.S.R.), Wake Forest University School of Medicine, Winston-Salem, NC; Department of Neurology (T.G.B., J.F.M.), Mayo Clinic, Jacksonville, FL; the Department of Neurology (R.D.B.), Mayo Clinic, Rochester, MN; the National Institute on Aging (J.A.H., A.S.), Bethesda, MD; and the Department of Neurology (B.M.K.), University of Cincinnati, Cincinnati, OH.

Address correspondence and reprint requests to Dr. James F. Meschia, Department of Neurology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; e-mail: meschia.james{at}mayo.edu

Objective: To establish whether subtypes of ischemic stroke aggregate within ischemic stroke–affected sibling pairs more than expected by chance alone.

Methods: This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umeå, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.

Results: Agreement for subtype diagnoses within families was poor (mean ± asymptotic SE {kappa} = 0.17 ± 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same-sex sibling pairs ({kappa} = 0.22 ± 0.05) to sibling pairs in which the proband’s stroke occurred before the age of 65 years ({kappa} = 0.16 ± 0.05) or to pairs in which the proband’s stroke occurred at or after the age of 65 years ({kappa} = 0.19 ± 0.05).

Conclusions: The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the February 6 issue to find the title link for this article.

SWISS is supported by a grant from the National Institute of Neurological Disorders and Stroke (R01 NS39987, J.F. Meschia, Principal Investigator). The Umeå Stroke Research Group is supported by grants from the Swedish Medical Research Council (project 825-2005-1126), Våsterbotten and Norbotten County Councils, and other funds supporting the Northern Sweden MONICA project.

Disclosure: The authors report no conflicts of interest.

Received August 3, 2006. Accepted in final form October 18, 2006.


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Neurology 2007 68: 397. [Full Text]  



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