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Background: Attempts to raise high-density lipoprotein cholesterol (HDL-C) levels pharmacologically have failed to reduce cardiovascular risk and some studies suggest that very high HDL-C levels may paradoxically be linked to adverse outcomes. These findings have shifted focus from HDL quantity to quality, emphasizing functional properties. Because direct functional assays are difficult to implement clinically, HDL subfraction analysis has emerged as a practical alternative for evaluating heterogeneity and potential function of HDL.
Methods: A total of 172 healthy adults (85 men and 87 women) were classified into five gender-specific HDL-C percentile groups. HDL subfractions were analyzed using a commercial polyacrylamide gel electrophoresis-based assay and compared across groups and genders. The profiles of 22 patients with dyslipidemia whose HDL-C levels corresponded to Group III were compared with healthy individuals in Group III (used as controls).
Results: Among men, increased HDL-C levels were associated with a higher proportion of small HDL subfraction, whereas large and intermediate HDL subfractions remained stable. In women, the large HDL subfraction increased and intermediate HDL subfraction decreased with increasing HDL-C levels. Despite similar HDL-C levels, patients with dyslipidemia had lower large HDL subfraction and higher intermediate HDL subfraction than healthy controls, with no difference in small HDL subfraction.
Conclusions: Gender-specific reference distributions for HDL subfractions across a wide HDL-C range were established using a polyacrylamide gel electrophoresis-based method. These findings suggest that HDL subfraction analysis may reflect qualitative differences beyond HDL-C levels and offer additional value for individualized cardiovascular risk assessment and future research on HDL function.
DOI: 10.7754/Clin.Lab.2025.250840
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