High HDL-C Levels Linked to Notable Risk of Glaucoma, Study Finds

Zhenzhen Liu, MD, PhD

Credit: Eye Science

A new investigation linked elevated levels of high-density lipoprotein cholesterol (HDL-C) to an increased risk of glaucoma, contrary to its beneficial role on cardiovascular health, while raised low-density lipoprotein cholesterol (LDL-C) exhibited a lower risk of the blinding eye disease.¹

Using a large, population-representative sample from the UK Biobank, involving more than 400,000 people with long-term follow-up of 14 years, a team of investigators found these associations between serum lipids and glaucoma differed based on sex and age, with a persistent association in people older than 55 years.

“Given that most contradictory studies were cross-sectional, the causal relationship between blood lipids and glaucoma deserves further exploration, and it is recommended that age- and sex-specific effects be taken into account when assessing the relationship between lipids and glaucoma,” wrote the investigative team, led by Zhenzhen Liu, MD, PhD, and Guangming Jin, MD, PhD, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University.

Multiple eye diseases, including age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic retinopathy, have been correlated with dyslipidemia. Recent evidence pointed to a potential link between serum lipid levels and glaucoma, but Liu and colleagues noted these data were not confirmatory.²

An improved perception of the link between serum lipids and glaucoma could elucidate the pathophysiology of the ocular disease, and offer evidence for novel treatments with available medications.³ This analysis examined the association between glaucoma and commonly used serum lipid measures, including HDL-C, LDL-C, total cholesterol, and triglycerides.

Glaucoma status was determined using self-reported data and hospital inpatient records – any person with any type of glaucoma at baseline or a history of glaucoma surgery on the baseline questionnaire was excluded from the analysis. For this examination, investigators used a set of polygenic risk scores for 28 diseases and 25 traits, including the serum lipid measures, designed for the UK Biobank cohort.¹

Among 400,229 individuals in the UK Biobank without glaucoma at baseline, 6868 (1.72%) developed glaucoma over a mean follow-up of approximately 14 years. People with incident glaucoma were older, more likely to be non-White, had higher HDL-C and lower LDL-C, with a higher prevalence of diabetes, hypertension, and cardiovascular disease (CVD), than those without glaucoma.

After performing multivariate Cox regression analysis, Liu and colleagues found higher levels of HDL-C associated with an elevated risk for glaucoma (hazard ratio [HR], 1.05; 95% CI, 1.02–1.08; P =.001). Notably, increasing levels of LDL-C were also linked to a reduced risk for glaucoma (HR, 0.96; 95% CI, 0.94–0.99; P =.005), as were lower levels of total cholesterol (HR, 0.97; 95% CI, 0.94–1.00; P = .037) and triglycerides (HR, 0.96; 95% CI, 0.94–0.99; P = .008).

Upon further analysis, examining the connection between the polygenic risk score of serum lipids and glaucoma risk, each 1-SD increase in HDL-C genetic risk was correlated with a greater risk for glaucoma (HR, 1.05; 95% CI, 1.00–1.11; P = .031). The polygenic risk score of LDL-C, total cholesterol, and triglycerides did not reveal a significant relationship with glaucoma.

Liu and colleagues found the associations between serum lipids and glaucoma stratified by age persisted among participants aged ≥55 years, and lost significance in patients aged 40–55 years (P >.05). Higher levels of HDL-C and lower triglycerides were each linked to a higher risk of glaucoma in males (P <.001), but not female participants (P >.05), while higher LDL-C and total cholesterol showed a lower risk of glaucoma in females only (P <.05).

“HDL-C has been regarded as the ‘good cholesterol’ for seven decades,” they wrote. “However, this study demonstrates that high levels of HDL-C are not consistently associated with a favorable prognostic outcome. Further studies are needed to investigate the mechanisms behind these associations.”

References

1. _{Ma Y, Wu Y, Hu L, et al. Associations between serum lipids and glaucoma: A cohort study of 400 229 UK Biobank participants. Br J Ophthalmol. February 4, 2025. doi:10.1136/bjo-2024- 326062}
2. _{Ahola-Olli AV, Mustelin L, Kalimeri M, et al. Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts. Diabetologia. 2019;62(12):2298-2309. doi:10.1007/s00125-019-05001-w}
3. _{Joshi RS, Adatiya VH. Study of the relationship between serum lipid levels and primary open-angle glaucoma. Indian J Ophthalmol. 2023;71(5):1948-1952. doi:10.4103/IJO.IJO_3233_22}