Plasma Levels of Apolipoprotein E and Risk of Stroke in Old Age PETER VAN VLIET, a SIMON P. MOOIJAART, a ANTON J. M. DE CRAEN, a PATRICK C. N. RENSEN, b,c DIANA VAN HEEMST, a AND RUDI G. J. WESTENDORP a a Department of Gerontology and Geriatrics, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands b Department of General Internal Medicine, Endocrinology, and Metabolic Diseases, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands c Netherlands Organisation for Applied Scientific Research-Quality of Life, Gaubius Laboratory, 2300 RC, Leiden, The Netherlands ABSTRACT: Recently, high plasma apoE levels have been shown to be re- lated to increased cardiovascular mortality, independent of APOE geno- type. Here we studied the association of plasma apoE levels with risk of stroke. Within the Leiden 85-plus Study, a prospective population-based study of 561 subjects aged 85 years, we measured plasma apoE level and determined APOE genotype at base line. The presence of stroke in the medical history and the incidence of stroke during a 5-year follow-up pe- riod were assessed by interviewing treating physicians. At base line, an increase of one standard deviation (SD) of plasma apoE level associated with a 1.47-fold higher risk of a history of stroke (P = 0.025). During follow-up, an increase of one SD of plasma apoE level associated with an increased risk of stroke (risk of stroke: 1.58, P = 0.010). This association was also observed in 33- (1.95, P = 0.002) and 34 carriers (3.01, P = 0.008), but not in 23 carriers (0.62, P = 0.440). In conclusion, in old age, except for 2-allele carriers, high plasma apoE levels are associated with a higher risk of stroke, independent of APOE genotype, plasma levels of lipids, and other cardiovascular risk factors. KEYWORDS: plasma apolipoprotein E levels; stroke; atherosclerosis; elderly INTRODUCTION Genetic variation in the apolipoprotein E gene (APOE), encoding for the three functionally different isoforms apoE2, apoE3, and apoE4, has been shown to be associated with cardiovascular disease. 1–3 Compared to ε 3ε 3 carriers, Address for correspondence: Peter van Vliet, Department of Gerontology and Geriatrics (C2-R), Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. Voice: +31-71- 526-6640; fax: +31-71-524-8159. p.van vliet@lumc.nl Ann. N.Y. Acad. Sci. 1100: 140–147 (2007). C  2007 New York Academy of Sciences. doi: 10.1196/annals.1395.012 140