Ophthalmologist and Physician-Scientist
High Cholesterol Levels Linked to Greater Glaucoma Risk

High Cholesterol Levels Linked to Greater Glaucoma Risk

With an aging population, the number of cases of glaucoma continues to rise. This fact has pushed researchers to look for more effective strategies for screening and to focus on controllable risk factors. Currently, physicians have little understanding of why glaucoma develops in most cases, so linking the disease to other conditions could help people control their risk, especially individuals with a genetic predisposition.

A recent study published in JAMA Ophthalmology in May 2019, found elevated cholesterol levels may result in higher risk of developing glaucoma. Ultimately, the researchers found a 20 mg/dL increase in total serum cholesterol was associated with a seven percent increase in risk of developing primary open-angle glaucoma.

Findings of the May 2019 JAMA Ophthalmology Study

The study relied on information collected biennially from a cohort of individuals aged 40 years or older who did not have primary open-angle glaucoma (POAG) at the time of recruitment. Three total populations were used: the Nurses’ Health Study, the Nurses’ Health Study II and the Health Professionals Follow-up Study. In January 2019, the researchers analyzed the medical records of participants to confirm cases of POAG. During the course of the study, participants self-reported information about elevated cholesterol levels, as well as their use of statins and serum cholesterol values. The study participants provided this information over the course of 15 years. 

Altogether, the three cohorts in the study included 136,782 patients, among whom 886 cases of POAG were identified. Any self-reported history of elevated cholesterol was associated with a higher risk of POAG, with a relative risk of 1.17, although the 95 percent confidence interval ranged from 1.00 to 1.37. The 1.07 relative risk associated with every 20 mg/dL increase in total serum cholesterol had a 95 percent confidence interval of 1.02 to 1.11 with a p-value of .004, representing a much more promising finding.

This study provides yet another reason for controlling cholesterol levels, especially among people at risk of developing POAG. However, it is important to recognize the study has limitations, especially the fact that data was self-reported by participants. At the same time, the large number of incident cases and long follow-up period are strengths. The findings warrant further investigation.


Long-term Statin Use Could Help Lower Risk of POAG

The study not only found that higher cholesterol levels increase the risk of POAG, but also showed the risk can be controlled by the use of statins. Statins are a class of drug used to reduce cholesterol levels. In general, statins work by blocking an enzyme in the liver that produces cholesterol, and physicians regularly prescribe them to treat and prevent cardiovascular disease.

The researchers followed the use of statins among participants to investigate how these drugs might affect the risk of developing POAG. The study reports that statin use for five or more years, when compared to no history of statin use, lowered the risk of POAG by 21 percent, with a 95 percent confidence interval of 0.65 and 0.97 and a p-value of .02. This protective effect became even more pronounced in patients aged 65 years or older.

The connection between statins and POAG actually drove the study, with the connection between cholesterol and POAG part of a secondary analysis. Prior in vitro studies have showed statins may lower intraocular pressure, the primary driver of most types of glaucoma. However, prior observational studies examining statins and glaucoma have produced varying and inconsistent results. Some have claimed an inverse association, some a null association and a small number have showed an adverse association.

For the most part, data about long-term use of statins and glaucoma risk was lacking until the May 2019 JAMA Ophthalmology study was published. Any association with hyperlipidemia and glaucoma was also unclear. The researchers in the study sought to provide more definitive data on statin use and POAG risk, and their findings demonstrate a protective effect, albeit modest, that is worth exploring further.

The Protective Role of Statins in Patients with POAG Risk

Several mechanisms could explain how statins lower the risk of POAG, including reducing intraocular pressure and offering neuroprotection. In the past, researchers have shown that statins have an effect on rho kinase and myosin II adenosine triphosphatase, both of which are found in the eye’s trabecular meshwork. Statins cause increased release of nitric oxide, as well as greater aqueous outflow, according to the findings of previous studies.

In addition, previous research has suggested statins have anti-excitotoxic, anti-inflammatory and anti-apoptotic effects that can assist in the protection of retinal ganglion cells. The destruction of these cells leads to permanent blindness in patients with POAG. Furthermore, several genes linked to cholesterol metabolism have been associated with intraocular pressure and POAG in genome-wide association studies. More investigation into the specifics of these mechanisms and associations may help point to new treatments for POAG.