Prevalence, clinical characteristics, and etiologic spectrum of extremely low levels of high-density lipoprotein cholesterol in Thai patients: a single-center study

Background Extremely low high-density lipoprotein cholesterol (HDL-C) is uncommon and may result from secondary conditions or rare genetic disorders. Data on persistently low HDL-C in Southeast Asians remain limited. We aim to determine the prevalence, clinical characteristics, underlying etiologies, and clinical outcomes of patients with persistent low HDL-C.Methods This retrospective cohort study evaluated adults with persistently low HDL-C (<30 mg/dL) identified via laboratory and electronic medical records between January 2020 and December 2024. Patients were stratified into two phenotypes based on baseline HDL-C severity: markedly low (20–29 mg/dL) or extremely low (<20 mg/dL).Results Among 217,481 individuals undergoing lipid testing (1,053,662 HDL-C measurements), 164 patients had persistently low HDL-C (mean age, 56.9 years; 68.9% male). The prevalence of persistently low and extremely low HDL-C was 0.08% and 0.008%, respectively. Concomitant hypertriglyceridemia affected ∼75% of patients. Most cases were associated with secondary conditions. Extremely low HDL-C was more frequently associated with liver disease (41.2%) and active malignancy (29.4%), whereas metabolic syndrome predominated among patients with markedly low HDL-C (42.2%). During a median follow-up of 2.57 years, all-cause mortality was higher in the extremely low HDL-C group (29.4% vs. 11.6%; hazard ratio, 4.33; 95% CI, 1.58–11.91; p = 0.004), while atherosclerotic cardiovascular disease rates were similar between groups (35.3% vs. 32.0%).Conclusions Persistently low HDL-C is an exceedingly rare phenotype driven primarily by secondary systemic conditions. An extremely low HDL-C level appears to be a marker of severe underlying systemic illness and was associated with higher short-term mortality.