Published Online
on July 7, 2005

A more recent version of this article appeared on August 1, 2005

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Submitted on February 22, 2005
Revised on April 20, 2005
Accepted on May 20, 2005

Serum Ferritin Is a Risk Factor for Stroke in Postmenopausal Women

Daphne L. van der A PhD; Diederick E. Grobbee MD, PhD; Mark Roest PhD; Joannes J.M. Marx MD, PhD; Hieronymus A. Voorbij MD, PhD; and Yvonne T. van der Schouw PhD^*

From the Julius Center for Health Sciences and Primary Care (D.L.v.d.A, D.E.G, Y.T.v.d.S), the Research Laboratory of the Department of Clinical Chemistry (M.R, H.A.V), and the Eijkman Winkler Institute for Microbiology, Infectious Diseases and Inflammation (J.J.M.M), University Medical Center Utrecht, The Netherlands.

^* To whom correspondence should be addressed. E-mail: y.t.vanderschouw{at}umcutrecht.nl.

Background and Purpose--Iron is an essential element for the human body. It has, however, been suggested that excessive iron stores may increase the risk of vascular disease. So far, epidemiologic studies on stroke are sparse.

Methods--We studied the association between iron status and stroke risk in a population-based cohort of 11 471 Dutch postmenopausal women between 49 and 70 years of age. Women were included between 1993 and 1997 and followed up until January 1, 2000, for cerebrovascular events. We conducted a case-cohort study by using all stroke cases (n=63) and a random sample of the baseline cohort (n=1134). Serum ferritin, serum iron, and transferrin saturation were measured as markers of iron status. A weighted Cox proportional-hazards model was used to estimate crude and multivariate-adjusted hazard ratios for tertiles of different iron parameters in relation to stroke.

Results--In a multivariate model, the highest tertile of serum ferritin concentration was associated with an increased risk of stroke (hazard ratio [HR], 1.45; 95% confidence interval [CI], 0.87 to 2.42) compared with the lowest tertile. For ischemic stroke, the increase was more pronounced (HR, 2.23; 95% CI, 1.05 to 4.73) and reached statistical significance.

Conclusions--Neither serum iron nor transferrin saturation was associated with an increased stroke risk. However, higher serum ferritin concentrations in postmenopausal women are associated with an increased risk of ischemic stroke.

Key words: iron • stroke, ischemic • menopause • prospective studies

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