Association of Statin Use and High Serum Cholesterol Levels With 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.

Figure.. Association Between Total Serum Cholesterol Level and Risk of Primary Open-Angle Glaucoma

A Cox proportional hazards regression cubic spline plot showing the association (with 95% CI bands) between total serum cholesterol and relative risk of primary open-angle glaucoma using 3 knots and increments of 20 mg/dL (to convert to millimoles per liter, multiply by 0.0259). The test for whether a nonlinear association vs a simple linear association is a better fit to the data was not significant (P = .44); therefore, a linear association can be considered a good fit to the data. Every 20-mg/dL increase in total serum cholesterol was associated with a 7% increase in risk of primary open-angle glaucoma (relative risk, 1.07; 95% CI, 1.02-1.11; P = .004).