Prevalence and Characteristics of Specimens with Extremely Low High-Density Lipoprotein Cholesterol

Extremely low levels of high-density lipoprotein cholesterol (HDL-C), defined as < 10 mg/dL, are rarely observed in clinical laboratories and may result from severe metabolic disorders, genetic conditions, or analytical and preanalytical interferences. Understanding the prevalence and associated findings of such results is critical for accurate interpretation.

We retrospectively analyzed 1,022,234 HDL-C test results from specimens submitted to GC Labs, a large referral laboratory in South Korea, between January and December 2023. For specimens with HDL-C < 10 mg/dL, concurrent laboratory findings were evaluated. Additional comparisons of the prevalence of HDL-C < 10 mg/dL and its associated laboratory findings were made using public datasets from KNHANES (2011 - 2023), NHIS (2023), and US NHANES (2015 - 2020).

Among all specimens, 147 (0.015%) showed HDL-C < 10 mg/dL. Out of these, 125 specimens had available concurrent test results. Common findings included abnormal liver chemistries (56.8%), decreased kidney function (31.2%), elevated CRP (20.0%), anemia, and very high triglyceride levels (≥ 500 mg/dL in 33.6%). Several patterns suggested preanalytical issues, including delayed serum separation, dilutional effects, or lipemic interference observed on gross examination (12.0%). One case showed no apparent abnormalities, raising suspicion of rare genetic or medical conditions or analytical error. Public datasets showed similarly low prevalence (0.004 - 0.009%) and comparable findings.

Extremely low HDL-C values are rare but often linked to identifiable biochemical abnormalities or preanalytical/analytical interferences. Reviewing concurrent test results and specimen handling helps distinguish true pathology from spurious results and improve diagnostic accuracy in clinical laboratories.