Small dense LDL-cholesterol determined by a simple precipitation assay for screening familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL), the most prevalent genetic hyperlipidemia, is associated with a several-fold increased risk of cardiovascular events. In spite of its prevalence and risk, no method has been developed to diagnose FCHL using conventional lipid markers. In an earlier study, our group established a simple precipitation assay for small dense low density-lipoprotein-cholesterol (sd-LDL-C) directly in serum. We conducted the present study to examine whether sd-LDL-C serves as a useful diagnostic marker for FCHL. When subjects (n = 1661, M/F = 1183/478) were stratified into normolipidemia, hypercholesterolemia, hypertriglyceridemia, and combined hyperlipidemia (CHL) groups, sd-LDL-C was higher in the CHL group than in the other groups, and higher in FCHL cases with family histories of hyperlipidemia than in CHL cases without family histories. FCHL is characterized by increased apolipoprotein (apo) B and small-sized LDL. Ninety-four percent of the subjects with both hyperapoB (>120 mg/dl) and small-LDL (diameter <25.5 nm) were classified into the top quartile of sd-LDL-C (>33 mg/dl). These results suggest that sd-LDL-C determined by the simple precipitation method is useful for screening FCHL in large populations. However, the number of females included in the study is small, making it difficult to draw conclusions especially in females.