Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case-control study.

BACKGROUND AND PURPOSE Apolipoprotein E polymorphism may influence the early development of coronary artery disease. We investigated the putative role of apolipoprotein E phenotypes in cerebral infarction. METHODS The apolipoprotein E phenotypes of 69 patients (mean +/- SD age, 72 +/- 11 years) who had suffered completed stroke or a transient ischemic attack and 68 sex- and age-matched control subjects free of cerebrovascular disease were determined by isoelectric focusing. The relative frequency of the apolipoprotein E phenotypes in the general population was estimated in 498 healthy blood donors (mean age, 37 years). RESULTS The prevalences of hypertension, diabetes mellitus, obesity, and intermittent claudication were significantly higher in patients than in control subjects. Serum lipid and apolipoprotein B concentrations and the composition of very low density lipoproteins were not significantly different between patients and control subjects. Apolipoprotein A-I and E levels were significantly lower in patients. Cholesterol levels were higher in male patients than in male control subjects (5.10 +/- 1.46 versus 4.41 +/- 0.80 mmol/L; p = 0.036), and the ratio of apolipoprotein A-I to B was lower (0.77 +/- 0.29 versus 1.03 +/- 0.37; p < 0.001). The E3/E3 phenotype was more frequent in control subjects (85%) than in patients (72.5%; p < 0.05) and healthy blood donors (64%; p < 0.02). The E3/E2 phenotype was more frequent in patients (10.1%) than in control subjects (1.4%; p < 0.05). A stepwise logistic regression showed that the presence of stroke was significantly related to high blood pressure (p < 0.0001), low apo E levels (p < 0.008), obesity (p < 0.041), the apo E phenotype (p < 0.05), and diabetes mellitus (p < 0.05). CONCLUSIONS The E3/E3 phenotype may protect against early vascular morbidity, and the epsilon 2 gene may be a risk factor for cerebrovascular morbidity, possibly related to diabetes, hypertension, and/or obesity.