Elevated serum high-density lipoprotein is positively associated with incident glaucoma among middle-aged and older adults: a national cohort in China

Emerging evidence challenges the traditional view of high-density lipoprotein (HDL) as uniformly protective in ocular health. This study aimed to evaluate the association between serum HDL levels and glaucoma in a middle-aged and older Chinese population. We conducted a retrospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 7,510 participants aged over 45 years without baseline glaucoma were included. Serum HDL was measured at baseline (2011), and incident glaucoma was ascertained via self-report during follow-up (2013–2018). Cox proportional hazards models and restricted cubic spline (RCS) analyses were used to assess the association, with adjustment for demographic and clinical covariates. Over a 7 years’ follow-up, 224 participants (2.98%) developed glaucoma. After multivariable adjustment, each 1 mmol/L increase in HDL was associated with a 57% higher risk of glaucoma (HR = 1.57; 95% CI: 1.10–2.26; p = 0.014). Participants with low HDL level (< 1.0 mmol/L) had a significantly lower glaucoma risk compared to those with normal HDL level (HR = 0.63; 95% CI: 0.38–0.89; p = 0.012). RCS analysis indicated a steeper increase in risk at serum HDL ≤ 1.501 mmol/L. Subgroup analyses revealed consistency across most strata, with a stronger association observed in participants with liver disease (p for interaction = 0.035). Elevated serum HDL levels were associated with an increased risk of glaucoma in Chinese middle-aged and older adults, particularly at lower HDL concentrations. These findings challenge the conventional “good cholesterol” paradigm in glaucoma and underscore the need for further research into lipid-related pathways in its pathogenesis.