Association between very high HDL-C levels and cardiovascular mortality

OBJECTIVE: To evaluate the association between very high high-density lipoprotein cholesterol (HDL-C) levels and cardiovascular mortality in a general adult population. METHODS: In this retrospective cohort study, 3,758 adults undergoing lipid profiling at a tertiary care center were categorized into five HDL-C groups: Very Low (< 30 mg/dL), Low (30-49 mg/dL), Normal (50-69 mg/dL), High (70-89 mg/dL), and Very High (≥ 90 mg/dL in men or ≥ 110 mg/dL in women). Demographic, clinical, and laboratory data were collected. The primary outcome was cardiovascular mortality over a median follow-up of 5.9 years. Kaplan-Meier survival curves and Cox proportional hazards models were used to assess associations, adjusting for age, sex, comorbidities, and medications. RESULTS: The Very High HDL-C group demonstrated the highest cardiovascular mortality rate (11.3 per 1,000 person-years) and significantly reduced survival compared to the Normal group (log-rank p = 0.00028). Multivariable analysis revealed that very high HDL-C was associated with increased cardiovascular mortality (adjusted HR: 1.52; 95% CI 1.04-2.24; p = 0.03). Subgroup analyses showed elevated risk in older adults, diabetics, and non-statin users. CONCLUSION: Extremely high HDL-C levels were independently associated with increased cardiovascular mortality, suggesting a U-shaped relationship. These findings warrant cautious interpretation of high HDL-C values in clinical practice.