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JAMA OphthalmolOctober 202320 citations

Calcium Channel Blocker Use and Associated Glaucoma and Related Traits Among UK Biobank Participants.

Kastner Alan, Stuart Kelsey V, Montesano Giovanni, De Moraes C Gustavo, Kang Jae H, Wiggs Janey L, Pasquale Louis R, Hysi Pirro, Chua Sharon Y L, Patel Praveen J


AI Summary

This study found calcium channel blocker use linked to 39% higher glaucoma odds and thinner retinal nerve layers, suggesting an IOP-independent neurodegenerative mechanism.

Abstract

Importance

Calcium channel blocker (CCB) use has been associated with an increased risk of glaucoma in exploratory studies.

Objective

To examine the association of systemic CCB use with glaucoma and related traits among UK Biobank participants.

Design, setting, and participants: This population-based cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis of glaucoma status, intraocular pressure (IOP), and optical coherence tomography (OCT)-derived inner retinal layer thicknesses. Data analysis was conducted in January 2023.

Exposure: Calcium channel blocker use was assessed in a baseline touchscreen questionnaire and confirmed during an interview led by a trained nurse.

Main outcomes and measures: The primary outcome measures included glaucoma status, corneal-compensated IOP, and 2 OCT-derived inner retinal thickness parameters (macular retinal nerve fiber layer [mRNFL] and macular ganglion cell-inner plexiform layer [mGCIPL] thicknesses). We performed logistic regression and linear regression analyses to test for associations with glaucoma status and IOP and OCT-derived inner retinal thickness parameters, respectively.

Results

This study included 427 480 adults. Their median age was 58 (IQR, 50-63) years, and more than half (54.1%) were women. There were 33 175 CCB users (7.8%). Participants who had complete data for glaucoma status (n = 427 480), IOP (n = 97 100), and OCT-derived inner retinal layer thicknesses (n = 41 023) were eligible for respective analyses. After adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors, use of CCBs (but not other antihypertensive agents) was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001). Calcium channel blocker use was also associated with thinner mGCIPL (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and mRNFL (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03) thicknesses but not IOP (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84).

Conclusions and relevance: In this study, an adverse association between CCB use and glaucoma was observed, with CCB users having, on average, 39% higher odds of glaucoma. Calcium channel blocker use was also associated with thinner mGCIPL and mRNFL thicknesses, providing a structural basis that supports the association with glaucoma. The lack of association of CCB use with IOP suggests that an IOP-independent mechanism of glaucomatous neurodegeneration may be involved. Although a causal relationship has not been established, CCB replacement or withdrawal may be considered should glaucoma progress despite optimal care.


MeSH Terms

AdultHumansFemaleMiddle AgedMaleCalcium Channel BlockersCross-Sectional StudiesBiological Specimen BanksUK BiobankRetinal Ganglion CellsGlaucoma

Key Concepts4

In a population-based cross-sectional study of 427,480 UK Biobank participants, calcium channel blocker (CCB) use was associated with greater odds of glaucoma (odds ratio [OR], 1.39 [95% CI, 1.14 to 1.69]; P = .001), after adjustment for key sociodemographic, medical, anthropometric, and lifestyle factors.

PrognosisCross-sectionalPopulation-based cross-sectional studyn=427,480 adultsCh10Ch28

In a population-based cross-sectional study of 41,023 UK Biobank participants, calcium channel blocker (CCB) use was associated with thinner macular ganglion cell-inner plexiform layer (mGCIPL) thickness (-0.34 μm [95% CI, -0.54 to -0.15 μm]; P = .001) and thinner macular retinal nerve fiber layer (mRNFL) thickness (-0.16 μm [95% CI, -0.30 to -0.02 μm]; P = .03).

MechanismCross-sectionalPopulation-based cross-sectional studyn=41,023 adults with OCT dataCh5Ch28

In a population-based cross-sectional study of 97,100 UK Biobank participants, calcium channel blocker (CCB) use was not associated with intraocular pressure (IOP) (-0.01 mm Hg [95% CI, -0.09 to 0.07 mm Hg]; P = .84).

MechanismCross-sectionalPopulation-based cross-sectional studyn=97,100 adults with IOP dataCh3Ch28

A population-based cross-sectional study included 427,480 UK Biobank participants with complete data for glaucoma status, 97,100 for intraocular pressure (IOP), and 41,023 for optical coherence tomography (OCT)-derived inner retinal layer thicknesses.

MethodologyCross-sectionalPopulation-based cross-sectional studyn=427,480 adults (glaucoma status); 97,…Ch10

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