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Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma

Educational Objective
To assess the association of elevated cholesterol levels and statin use with incident primary open-angle glaucoma (POAG).
1 Credit CME
Key Points

Question  Are self-reported elevated cholesterol level and statin use associated with risk of primary open-angle glaucoma?

Findings  In this population-based cohort study of 886 incident cases of primary open-angle glaucoma from 136 782 participants who contributed person-time for up to 15 or more years and provided repeated updated data on statin use and cholesterol levels, 5 or more years of statin use was associated with a 21% lower risk of primary open-angle glaucoma, while every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of primary open-angle glaucoma.

Meaning  Statin use, which is highly prevalent among older persons at risk for primary open-angle glaucoma, was associated with a lower risk of primary open-angle glaucoma.

Abstract

Importance  The use of statins (hydroxymethylglutaryl coenzyme A inhibitors) has been associated with a lower risk of primary open-angle glaucoma (POAG); however, results have been conflicting, and little is known about the association between high cholesterol levels and POAG.

Objective  To assess the association of elevated cholesterol levels and statin use with incident POAG.

Design, Setting, and Participants  This study used data collected biennially from participants aged 40 years or older who were free of glaucoma and reported eye examinations, within 3 population-based cohorts: the Nurses’ Health Study (N = 50 710; followed up from 2000 to 2014), the Nurses’ Health Study 2 (N = 62 992; 1999-2015), and the Health Professionals Follow-up Study (N = 23 080; 2000-2014). Incident cases of POAG were confirmed by medical record review. The analyses were performed in January 2019.

Exposures  Biennially updated self-reported information on elevated cholesterol level status, serum cholesterol levels, and duration of statin use.

Main Outcomes and Measures  Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression models on pooled data, with stratification by cohort.

Results  Among the 136 782 participants in the 3 cohorts (113 702 women and 23 080 men), 886 incident cases of POAG were identified. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of POAG (RR, 1.07 [95% CI, 1.02-1.11]; P = .004). Any self-reported history of elevated cholesterol was also associated with a higher risk of POAG (RR, 1.17 [95% CI, 1.00-1.37]). A history of any statin use was associated with a 15% lower risk of POAG (RR, 0.85 [95% CI, 0.73-0.99]). Use of statins for 5 or more years vs never use of statins was associated with a 21% lower risk of POAG (RR, 0.79 [95% CI, 0.65-0.97]; P = .02 for linear trend). The association between use of statins for 5 or more years vs never use of statins and risk of POAG was more inverse in those who were older (≥65 years: RR, 0.70 [95% CI, 0.56-0.87] vs <65 years: RR, 1.05 [95% CI, 0.68-1.63]; P = .01 for interaction).

Conclusions and Relevance  Among adults aged 40 years or older, higher serum cholesterol levels were associated with higher risk of POAG, while 5 or more years of statin use compared with never use of statins was associated with a lower risk of POAG.

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Article Information

Accepted for Publication: February 5, 2019.

Corresponding Author: Jae H. Kang, ScD, Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, 181 Longwood Ave, Boston, MA 02115 (nhjhk@channing.harvard.edu).

Published Online: May 2, 2019. doi:10.1001/jamaophthalmol.2019.0900

Author Contributions: Dr Kang had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kang, Boumenna, Khawaja, Pasquale.

Acquisition, analysis, or interpretation of data: Kang, Stein, Khawaja, Rosner, Wiggs, Pasquale.

Drafting of the manuscript: Kang, Pasquale.

Critical revision of the manuscript for important intellectual content: Boumenna, Stein, Khawaja, Rosner, Wiggs, Pasquale.

Statistical analysis: Kang, Rosner.

Obtained funding: Wiggs, Pasquale.

Administrative, technical, or material support: Boumenna, Pasquale.

Supervision: Pasquale.

Conflict of Interest Disclosures: Dr Stein reported receiving grants from the National Institutes of Health and grants from Research to Prevent Blindness during the conduct of the study. Dr Khawaja reported receiving personal fees from Allergan, Novartis, Thea, Grafton Optical, and Santen outside the submitted work. Dr Rosner reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Kang reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Wiggs reported receiving grants from the National Eye Institute during the conduct of the study and grants from the National Eye Institute outside the submitted work. Dr Pasquale reported receiving personal fees from Bausch & Lomb, Eyenovia, and Verily Inc outside the submitted work. No other disclosures were reported.

Funding/Support: This work was supported by grants UM1 CA186107, UM1 CA176726, UM1 CA167552, EY09611, and EY015473 from the National Institutes of Health (Dr Pasquale).

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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