By association: Statins, cholesterol and glaucoma risk

By association: Statins, cholesterol and glaucoma risk

Statins, the gold standard for high cholesterol treatment, may be associated with a lower risk of primary open-angle glaucoma (POAG) when used over time, per new research into cholesterol's interplay with glaucoma.

"This is another study that supports statin use being associated with a reduced risk of the development of glaucoma. What is not clear is the reason why."

Published online in JAMA Ophthalmology, the study found a 21% lower risk of POAG among adults using statins for five or more years and, conversely, a 7% greater risk of POAG for every 20 mg/dL increase in total serum cholesterol. The described association lends itself to ongoing debate about statins' overall effect on glaucoma progression as well as high cholesterol's role.

A leading cause of irreversible blindness in the United States, glaucoma is a group of eye disorders-  POAG, the most common-that cause progressive optic neuropathy. While a characteristic elevation in intraocular pressure (IOP) is often but not always a tell-tale sign of the disorder and a primary point of management, the exact pathophysiological mechanisms responsible for glaucoma remain unclear. Likely multifactorial, these primary and secondary mechanisms range from the genetic to structural and vascular. Toward that end, this latest research adds perspective on how one of the most commonly prescribed cardiovascular drugs in America may affect glaucoma risk.

Per this population-based cohort study, researchers analyzed 886 incident cases of POAG among 136,782 participants age 40 and older in three cohorts who contributed biennial data on statin use and cholesterol levels for 15 years or more. Notably, individuals who used statins for five or more years were more likely to report a history of elevated cholesterol levels, higher total serum cholesterol levels and a higher prevalence of cardiovascular disease or risk factors.

Researchers observed not only a 7% increase in POAG risk for every 20 mg/dL increase in total serum cholesterol in all participants, particularly those with total serum cholesterol levels of 250 mg/dL or more, but also a 6% increase in POAG risk among those who never used cholesterol-lowering drugs.

Additionally, researchers noted inverse associations with POAG and longer statin use. While each year of statin use was associated with a 3% lower risk of POAG compared to "never-users" of statins, the inverse association was "slightly stronger" at five or more years of statin use and stronger among those 65 years and older versus those younger than 65. Significantly, this study is the first to show that five or more years of statin use was associated with a 21% lower risk of POAG and 10 or more years use associated with a 40% lower risk.

This observed association is attributed to statins' potential IOP-lowering and neuroprotective mechanisms, researchers believe. Statins increase nitric oxide production, which may assist in aqueous outflow, as well as stimulating blood flow to the optic nerve. So, too, statins also contain anti-excitotoxic, anti-apoptotic and anti-inflammatory properties that may protect retinal ganglion cells.

"As high cholesterol and statin use have been associated with other neurodegenerative diseases, the interrelationships between cholesterol, glaucoma and these outcomes is also fertile ground for further scientific inquiry," notes study author Jae Hee Kang, Sc.D., assistant professor of medicine at Brigham and Women's Hospital, in a news release.

Statins for glaucoma? Not quite

Although evidence is growing that statins may protect against the development or progression of POAG, definitive clinical trials are lacking to conclusively elucidate any observed associations. That said, this isn't the first study to show an association between statin use and glaucoma, says Murray Fingeret, O.D., chief of the optometry section, Brooklyn/St. Albans campus of the VA New York Harbor Healthcare System, and clinical professor at State University of New York College of Optometry.

"This is another study that supports statin use being associated with a reduced risk of the development of glaucoma," Dr. Fingeret writes. "What is not clear is the reason why. Statins could be neuroprotective, may have a relaxing effect on the trabecular meshwork, which should lead to lower IOP (which was not evaluated in this study), being anti-inflammatory or enhance blood flow. We don't know what [statins] are doing to reduce the development of glaucoma."

While glaucoma research continues with theories abounding as to the disease's genesis and progression, clinicians search for any modifiable risk factors that may help allay the disease. Recently, several studies demonstrated how certain activities linked to cardiovascular health may affect one such modifiable trait: IOP. Last year, a study concluded that simply meeting physical activity guidelines might reduce risk of glaucoma development by as much as 40%, while another found mindfulness-based stress reduction via meditation might reduce risk, too. Both activities resulted in lowered IOP and add to the growing body of evidence that suggests blood flow may contribute to the multifactorial disorder.

For the meantime, Dr. Fingeret suggests more research is necessary to determine the proposed mechanisms for statins' association with glaucoma, be they possible IOP-lowering effects or a neuroprotective response.

Additionally, the AOA Evidence-Based Optometry Committee is currently developing an evidence-based clinical practice guideline on glaucoma. The committee is currently reviewing, grading and collaborating the current global literature and developing the comprehensive guideline for a targeted release of 2020.

To learn more about abnormal sleep's association with glaucoma, click here.

July 16, 2019

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