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Statin use was associated with a higher likelihood of glaucoma in adults with hyperlipidemia, even those whose "bad" cholesterol was at optimal levels, according to a cross-sectional, population-based study.

Among over 79,000 patients ages 40 and older in the All of Us (AoU) Research Program, statin use was associated with increased glaucoma prevalence compared with non-use (adjusted OR 1.13, 95% CI 1.01-1.26), reported Victoria L. Tseng, MD, PhD, of the David Geffen School of Medicine at the University of California Los Angeles, and colleagues.

Stratifying by low-density lipoprotein cholesterol (LDL-C) levels, statin use was significantly associated with glaucoma among participants with optimal levels (aOR 1.39, 95% CI 1.05-1.82) and high levels (aOR 1.37, 95% CI 1.09-1.70), they noted in .

There was also a positive association between statin use and prevalence of glaucoma in participants ages 60-69 years (aOR 1.28, 95% CI 1.05-1.56).

"Most previous studies have suggested no association or a protective association between statins and glaucoma. Our finding of increased glaucoma in statin users suggests that things may be more complicated than previously discussed," Tseng told MedPage Today.

Tens of millions of people in the U.S. take statins to prevent heart disease. In a with a grade of B, the U.S. Preventive Services Task Force advises that clinicians prescribe statins in patients ages 40-75 who have at least one risk factor such as diabetes or dyslipidemia, and an estimated 10-year cardiovascular event risk of 10% or more.

"High cholesterol can affect the quality of circulation in blood vessels throughout the body, and poor blood circulation to the optic nerve can make glaucoma worse," Tseng said. "Statins work to lower cholesterol levels so the question is whether they can also alter the risk of glaucoma."

One large tracked 524,109 people with hyperlipidemia, including 316,182 with statin prescriptions, and showed that use of statins for 2 years was tied to a decreased risk of progressing from glaucoma to open-angle glaucoma relative to those who received no statin therapy (adjusted HR 0.907, 95% CI 0.846-0.973).

The new study is unique since it relies on a database that includes a high number of minority participants (35.9%), Tseng said. In the 2012 study, only 12.6% of participants were not white.

Tseng and colleagues stratified their results based on whether patients had optimal, near optimal, borderline high, high, or very high levels of LDL-C. According to Tseng, those with healthier levels may have reached them by using statins.

"Those in the optimal and high ranges had associations between statin use and increased likelihood of glaucoma, while those in the other ranges did not have an association," she said. "It could be that statin users had worse hyperlipidemia, which is why they needed statins. So, the statins could be a proxy for worse circulation to the optic nerve."

If statins themselves are responsible for higher glaucoma rates, it's not clear why that might be the case. To understand a connection, Tseng said, "we would need to more comprehensively understand the associations between different types of lipid measurements, vascular circulation in the optic nerve, and changes that result with statin use."

For now, ophthalmologists should understand the cardiovascular status of patients and their use of related medications, Tseng noted. "These may all be factors contributing to glaucoma risk either positively or negatively and may make the glaucoma disease not behave as typically as expected."

She explained that clinicians typically expect glaucoma to not worsen if eye pressure is reduced and controlled. But "sometimes, even with low eye pressure, glaucoma continues to progress. Then we think about things like blood perfusion to the optic nerve. Somebody with poor vasculature who may require statin use could fall in this latter category."

For this study, the researchers examined 2017-2022 AoU Research Program data for 79,742 participants with hyperlipidemia, 8% of whom were taking statins. Mean age was 66.2, 57.3% were women, and 64.1% were white.

Statin users had higher mean LDL-C levels than non-users (144.9 mg/dL vs 136.3 mg/dL, respectively). Glaucoma was more common in those with LDL-C levels ≥100 mg/dL (9.2%) compared with <100 mg/dL (7.9%; P<0.001).

The authors noted limitations to their study, including its observational nature and the possibility of miscoding. In addition, the prevalence of glaucoma in the research population was higher than other population-based studies in the U.S.

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