Higher Levels of ‘Good’ Cholesterol Linked to Increased Glaucoma Risk

Higher levels of high-density lipoprotein cholesterol (HDL-C) were associated with an increased risk of glaucoma, while high levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides were associated with a reduced risk, a prospective study showed.

Among over 400,000 older U.K. Biobank participants, higher levels of HDL-C were associated with an increased risk of glaucoma (HR for 1-SD increase 1.05, 95% CI 1.02-1.08, P=0.001), while high levels of the other commonly used serum lipid measures were all linked to a reduced risk:

• LDL-C: HR 0.96, 95% CI 0.94-0.99, P=0.005
• Total cholesterol: HR 0.97, 95% CI 0.94-1.00, P=0.037
• Triglycerides: HR 0.96, 95% CI 0.94-0.99, P=0.008

“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 Zhenzhen Liu, MD, PhD, of Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science in China, and colleagues in the British Journal of Ophthalmology.

After adjusting for confounders, a 1-SD increment in HDL-C genetic risk was associated with a 5% greater hazard of glaucoma (HR 1.05, 95% CI 1.00-1.11, P=0.031). However, the polygenic risk score for LDL-C, total cholesterol, and triglycerides did not show a significant association with glaucoma.

Jeremy Sivak, PhD, of Krembil Research Institute at Toronto Western Hospital, told MedPage Today that “the results are surprising because the team found that so-called ‘good’ cholesterol is associated with greater risk of developing glaucoma, and ‘bad’ cholesterol is associated with lower risk. This result challenges some earlier studies that have reported the opposite association.”

Sivak said that the concepts of “good” and “bad” cholesterol come from cardiovascular disease. “The role of these types of blood lipids in glaucoma is likely to be very different, and might be related to the regulation of fluid flow and pressure in the eye. One important take-away from this study is that these ‘good’ and ‘bad’ labels might need to be reassessed in the context of other diseases.”

As for the findings about risk, the “differences are highly statistically significant, but the absolute differences in lipid levels are relatively small, revealed only by the large numbers of participants,” Sivak noted. The data suggest that “there are variables in play that are still not accounted for and, as noted by the authors, correlations do not necessarily mean causation.”

Sivak said one strength of the study is that it’s prospective and follows the same population over time, while other research compared different patients at one point in time. “There seems to be good justification for further research in this area given the prospective study design and high statistical significance of the analyses,” he added.

Victoria L. Tseng, MD, PhD, of the University of California Los Angeles Stein Eye Institute, noted that it is currently suspected that “vascular disease resulting from high cholesterol could compromise blood flow to the optic nerve and potentially be a risk factor to develop glaucoma or for it to get worse.”

Is there a message for clinicians from this research? “I don’t think we have sufficient evidence to recommend medication changes based on these findings,” Tseng said. “Patients would benefit from continued chronic disease monitoring and management with their primary care providers to maximize systemic health in conjunction with their ocular conditions.”

For this study, the researchers included 400,229 U.K. Biobank participants. Mean age was 56.4, 54% were women, and 94.9% were white. Of these patients, 26.8% had hypertension, 3.5% had diabetes, 3.3% had heart disease, and most (84.7%) had not used statins.

Over a mean 14.44 years of follow-up, 1.72% of patients were diagnosed with glaucoma. They were more likely to be older, non-white, and have a higher waist-to-hip ratio. They also had higher rates of diabetes (5.4%), hypertension (33.4%), and heart disease (4.8%).

The authors noted limitations to their study, including the almost entirely white patient population and the possibility that glaucoma cases were missed due to reliance on hospital records and self-assessments.

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