Association between high-density lipoprotein subfractions and low-grade inflammation, insulin resistance, and metabolic syndrome components: The ELSA-Brasil study

Background: High-density lipoprotein cholesterol (HDL-C) can be divided into subfractions, which may have variable effects in atherogenesis. The results about the association between HDL-C subfractions and risk factors for cardiovascular disease are mixed.

Objective: The objective of this study was to analyze the association between HDL-C subfractions and each metabolic syndrome component, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and C-reactive protein (CRP).

Methods: Four thousand five hundred thirty-two individuals between 35 and 74 years old without previous manifest cardiovascular disease not using fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (vertical auto profile-in mg/dL) into HDL₂-C and HDL₃-C. HDL₂-C/HDL₃-C ratio, HOMA-IR, and high-sensitivity CRP were also included in the analysis.

Results: Mean age of participants was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL₂-C, and HDL₃-C were all inversely associated with each of the metabolic syndrome defining factors, HOMA-IR values, and serum CRP. We also observed a negative association between HDL₂-C/HDL₃-C ratio with the variables aforementioned even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (P < .01).

Conclusion: HDL-C and its subfractions (HDL₂-C and HDL₃-C) are inversely associated with the defining features of metabolic syndrome, insulin resistance, and systemic inflammation. In addition, the HDL₂-C/HDL₃-C ratio measured by vertical auto profile is significantly associated with the former factors even after comprehensive adjustment for HDL-C and other confounding variables.