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Original Investigation
May 2, 2019

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

Author Affiliations
  • 1Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston
  • 3Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor
  • 4Center for Eye Policy and Innovation, University of Michigan, Ann Arbor
  • 5Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor
  • 6National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital National Health Service Foundation Trust, University College London Institute of Ophthalmology, London, United Kingdom
  • 7Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 8now with Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York
JAMA Ophthalmol. 2019;137(7):756-765. doi:10.1001/jamaophthalmol.2019.0900
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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