IM Resident UBC North Vancouver, British Columbia, Canada
Background: Dysbetalipoproteinemia (DBL) is an underrecognized lipid disorder characterized by impaired remnant lipoprotein clearance and elevated cardiovascular risk. While classically associated with the APOE2/E2 genotype, formal DBL diagnosis remains challenging due to the need for specialized testing that is often unavailable in routine clinical settings. Therefore, clinical diagnostic criteria using basic lipid values are often employed. Although population-based studies estimate its prevalence to be below 0.2%, rates may be higher among individuals with atherosclerotic disease. We aimed to identify DBL-like dyslipidemia in patients with premature coronary artery disease (CAD) using clinical diagnostic criteria and to assess concordance with APOE genotypes.
METHODS AND RESULTS: We analyzed lipid profiles, APOB measurements, and APOE sequencing from the Study to Avoid CardioVascular Events in British Columbia (SAVE BC), a prospective registry of individuals with highly premature CAD (males ≤50 years, females ≤55 years). Of 262 patients who had complete lipid information available, we identified 33 individuals meeting ≥1 published diagnostic clinical criterion for DBL using their highest recorded non-HDL-C value, recognizing that peak values likely reflect periods of minimal treatment effect. After manually excluding 15 patients whose peak values remained within treatment ranges, 18 probable DBL cases were identified. Overall detection rates across seven diagnostic criteria ranged from 0.4% to 7.3%, with the highest rates observed using the Blom (7.3%) and Paquette (5.7%) criteria, and the lowest with the Sniderman (0.4%) and Sampson (0.8%) criteria.
Among 15 probable DBL cases with available APOE genotypes, one (6.7%) was an APOE2/E2 homozygote, presenting with markedly elevated triglycerides (14.05 mmol/L) and non-HDL cholesterol (9.85 mmol/L), consistent with the classic DBL phenotype. One patient (6.7%) was an E2/E3 heterozygote, also showing elevated triglycerides (15.43 mmol/L) and non-HDL-C (6.67 mmol/L). Five patients (33.3%) had E3/E4 genotype, with variable lipid profiles (triglycerides ranging from 1.75 to 19.77 mmol/L). The majority (8 patients, 53.3%) were E3/E3, with heterogeneous lipid values and some displaying significant hypertriglyceridemia.
Conclusion: In this cohort of patients with premature CAD, we observed a 0.4–7.3% prevalence of DBL-like dyslipidemia, substantially higher than general population estimates. Although the classic APOE2/E2 genotype was rare, a notable proportion of patients met at least one clinical diagnostic criterion based on their lipid profiles. These findings support the utility of DBL diagnostic criteria as practical screening tools in high-risk patients, potentially guiding further genetic evaluation and tailored lipid management.
