Dysbetalipoproteinemia: differentiating multifactorial remnant cholesterol disease from genetic apoE deficiency.

BACKGROUND Dysbetalipoproteinemia (DBL) is characterized by the accumulation of remnant lipoprotein particles and associated with an increased risk of cardiovascular and peripheral vascular disease (PVD). DBL is thought to be mainly caused by the presence of an E2/E2 genotype of the apolipoprotein E (APOE) gene, in addition to environmental factors. However, there exists considerable variability in the phenotype of these patients. OBJECTIVE The objectives were to verify the proportion of DBL subjects diagnosed using the gold standard Fredrickson criteria who did not carry E2/E2 and to compare the clinical characteristics of DBL patients with vs without E2/E2. METHODS A total of 12 432 patients with lipoprotein ultracentrifugation as well as APOE genotype or apoE phenotype data were included in the present retrospective study. RESULTS Among the 12 432 patients, 4% (n=524) were positive for Fredrickson criteria (F+), and only 38% (n=197) of the F+ individuals were E2/E2. The F+ E2/E2 group had significantly higher remnant cholesterol concentration (3.44 vs 1.89 mmol/L) and had higher frequency of DBL-related xanthomas (24% vs 2%) and floating beta (95% vs 11%) than the F+ non-E2/E2 group (p<0.0001). The F+ E2/E2 group had an independent higher risk of PVD (OR 11.12 (95% CI 1.87-66.05) p=0.008) events compared to the F+ non-E2/E2 group. CONCLUSION In the largest cohort of DBL worldwide, we demonstrated that the presence of E2/E2 was associated with a more severe DBL phenotype. We suggest that two dysbetalipoproteinemia phenotypes should be distinguished: the multifactorial remnant cholesterol disease and the genetic apoE deficiency disease.