We address an issue raised by Walden and Hegele [1] on the specificity of the very-low-density lipoprotein (VLDL) cholesterol-to-triglyceride ratio as a characteristic of type III hyperlipidemia (a ratio > 0.30 is considered characteristic [2]). Currently, dietary modification and lipid-lowering drugs are often used before underlying genetic defects in hyperlipidemic patients are evaluated. We assessed the VLDL-to-triglyceride ratio with and without lipid-lowering therapy to determine whether this ratio remains a reliable persistent marker of the underlying genetic defect. We reviewed charts of patients with the E (_2/E)₂ isoform and characteristics of type III hyperlipidemia who were studied by the Molecular Disease Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health. The fasting, untreated lipid levels of the 17 patients showed VLDL cholesterol levels of 349 ±336 mg/dL and fasting triglyceride concentrations of 756 ±549 mg/dL. The VLDL cholesterol-to-triglyceride ratio was 0.44 ±0.15. The patients had an average of 5 ±1 repeated full lipid profiles while receiving various forms of lipid-lowering therapy. The patients' VLDL cholesterol levels decreased by 68% (P = 0.01), and their triglyceride concentrations decreased by 59% (P = 0.004). The VLDL cholesterol-to-triglyceride ratio decreased by 16% (P = 0.1). Seventy-four ratios were measured; the baseline and mean ratios are shown in Figure 1. Of 17 patients, 3 had a baseline ratio of less than 0.30, and 5 had a mean treatment ratio of less than 0.30. This low ratio was observed in one third of the lipid profiles drawn (28 of 74 ratios), affecting about one half of the patients (8 of 17 patients) at one or more of their visits.

View larger version (40K): [in this window] [in a new window]   Figure 1. The ratios of very-low-density lipoprotein cholesterol to total plasma triglyceride concentration before and after treatment in 17 patients homozygous for the apoprotein E2 allele.

The clinical importance of these data is that if patients were screened on one of these visits, the diagnosis might not be suspected. Family screening and treatment would not be done, with deleterious effects. Therefore, a single ratio at baseline or during therapy is not a reliable marker for disease. Apolipoprotein E restriction isotyping may become an additional method in screening for the risk for type III hyperlipidemia [1], and the limitations of the VLDL cholesterol-to-triglyceride ratio should be appreciated.