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

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 65; no. 2; pp. 313 - 320
• Main Authors: Boot, Christopher S, Middling, Elizabeth, Allen, Joy, Neely, Robert D G
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2019
• Subjects: Algorithms; Apolipoprotein B; Apolipoproteins; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Data collection; Diagnostic systems; High density lipoprotein; Hyperlipidemia; Lipids; Lipoproteins; Lipoproteins (very low density); Low density lipoprotein; Medical screening; Metabolism; Mutation; Organic chemistry; Patients; Ratios; Sensitivity; Triglycerides; United Kingdom > UK
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2018.292425

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 . 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. 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. 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. NHDLC/apoB offers a simple first-line test for dysbetalipoproteinemia in selecting patients with mixed hyperlipidemia for more complex investigations.