Evaluation of the Non-HDL Cholesterol to Apolipoprotein B Ratio as a Screening Test for Dysbetalipoproteinemia

BACKGROUND: Familial dysbetalipoproteinemia is associated with the accumulation of remnant lipoproteins and premature cardiovascular disease. Identification of dysbetalipoproteinemia is important because family members may be affected. Diagnostic testing involves demonstration of β-lipoprotein in the VLDL fraction or characterization of apo E 3 . These investigations are complex and relatively expensive. The ratios of apo B to total cholesterol and triglycerides have been proposed as screening tests. However, the ratio of non-HDL cholesterol to apo B (NHDLC/apoB) could offer improved performance as the confounding effect of variations in HDL cholesterol is removed. METHODS: We evaluated NHDLC/apoB as a screening test for dysbetalipoproteinemia, using β-quantification analysis as a reference standard. Data from 1637 patients referred over a 16-year period for β quantification were reviewed retrospectively. In 63 patients, diagnostic criteria for dysbetalipoproteinemia (VLDL cholesterol/triglyceride ratio ≥0.69 and presence of β-VLDL) were fulfilled, and 1574 patients had dysbetalipoproteinemia excluded. RESULTS: Mean NHDLC/apoB in patients with dysbetalipoproteinemia was 7.3 mmol/g (SD, 1.5 mmol/g) and with dysbetalipoproteinemia excluded was 4.0 mmol/g (SD, 0.5 mmol/g). The optimum cutoff of >4.91 mmol/g achieved a diagnostic sensitivity of 96.8% (95% CI, 89.0–99.6) and specificity of 95.0% (95% CI, 93.8–96.0). NHDLC/apoB offered improved performance compared to total cholesterol/apoB [diagnostic sensitivity 92.1% (95% CI, 82.4–97.4) and specificity 94.5% (95% CI, 93.2–95.6) with a cutoff of >6.55 mmol/g]. NHDL/apoB reference ranges were not sex-dependent, although there was a significant difference between men and women for total cholesterol/apoB. CONCLUSIONS: NHDLC/apoB offers a simple first-line test for dysbetalipoproteinemia in selecting patients with mixed hyperlipidemia for more complex investigations.