Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.
The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.
The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.
‘A Little Unusual’
Drawing any clinically relevant conclusions from this latest study would be premature, Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study, said. “I certainly would not be telling my patients on statins to stop their statins,” Tseng said.
Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established, she added.
A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.
“It’s a little unusual that we found the opposite,” Tseng told Medscape Medical News.
One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.
Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma,” she said. “Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”
While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”
Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).
Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).
Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, Tseng said, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.
Database Strengths and Limitations
The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, told Medscape Medical News.
The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.
“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.
“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.
However, the database has limitations as well, Wang noted, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”
The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.
Richard Mark Kirkner is a medical journalist based in the Philadelphia area.
