Prevalence of Double Pre-Beta Lipoproteinemia in Hyperlipidemic Patients Is Influenced by Gender, Menopausal Status, and ApoE Phenotype

Abstract

Abstract Double pre-beta lipoproteinemia (DPBL) is a plasma lipoprotein phenotype characterized by the presence of two agarose gel electrophoretic populations of very low density lipoproteins (VLDLs, d <1.006 g/mL), ie, normal pre–β-migrating VLDL and slow pre–β VLDL. Slow pre–β VLDL represents remnant lipoproteins derived from the hydrolysis of triglyceride (TG)-rich lipoproteins (TRLs), and thus DPBL is a characteristic of plasma remnant lipoprotein accumulation. To determine the prevalence of DPBL in our lipid clinic population, patients (n=2501) were selected who (1) had an unambiguous VLDL electrophoretic phenotype and could be classified as having either DPBL (DPBL+), β-migrating VLDL (β-VLDL+), or an absence of both (DPBL/β-VLDL −/−) and (2) had hypercholesterolemia (HC: plasma cholesterol ≥6.2 mmol/L, n=1017), hypertriglyceridemia (HTG: plasma TG ≥2.3 mmol/L but <15 mmol/L, n=554) or combined hyperlipidemia (HC+HTG, n=930). Patients with TG <2.3 mmol/L and cholesterol <5.2 mmol/L acted as control subjects (n=343). Using a commercially available agarose gel electrophoresis system, we identified 220 hyperlipidemic patients (8.8%) with DPBL (versus <1% of control). The prevalence of DPBL was higher in (1) male than in female patients (10.7% versus 6.7%), (2) postmenopausal than in premenopausal females (7.3% versus 4.1%), and (3) patients with HC+HTG than in those with HTG or HC alone (15.8% versus 8.3% versus 2.7%, respectively). Patients with an ε2 allele had a higher prevalence of DPBL; ie, 26.9% of apoE 3/2 and 26.2% of apoE 4/2 patients had DPBL compared with 6.5%, 6.8%, and 7.4% of apoE 3/3, 4/3, and 4/4 patients, respectively. DPBL patients consistently had increased levels of VLDL-C and (LDL+HDL)-TG and decreased levels of LDL-C, and their plasma lipid profiles were intermediate between those of β-VLDL+ and DPBL/β-VLDL−/− patients. These results demonstrate that male sex, postmenopausal status in women, and the presence of an apoE 3/2 or apoE 4/2 phenotype are associated with an increased incidence of DPBL in hyperlipidemic patients.