1. In a cohort of 100,000 patients, increased levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were associated with increased intraocular pressure (IOP).
2. An increase by one standard deviation in these cholesterol levels was associated with an increase of 0.07-0.19 mmHg in IOP.
Evidence Rating Level: 2 (Good)
Study Rundown: Serum lipid levels are commonly monitored for assessment of cardiovascular risk. Other cardiovascular risk factors have been associated with increased intraocular pressure (IOP), which itself is a key risk factor for glaucoma. The relationship between hyperlipidemia and elevated IOP has remained unclear but could provide information about glaucoma risk and pathophysiology. This study aimed to assess the relationship between serum lipid levels and corneal-corrected IOP in about 100,000 patients from the UK Biobank and EPIC-Norfolk databases, with adjustment for other factors including age, body mass index (BMI), blood pressure, smoking history, and diabetes status. In this multivariable analysis, higher levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol were significantly associated with higher IOP in both cohorts. UK Biobank subjects with higher TG had significantly lower IOP. The magnitude of these differences was small, with changes between 0.05 and 0.19 mmHg for an increase in serum lipid level by one standard deviation. Lipid levels were significantly linearly associated with IOP over both normal and abnormal lipid levels. This study provides compelling evidence of a correlation of IOP with both cholesterol components and individual lipid fractions, independent of many potential confounders. Elevated IOP, then, joins diabetic retinopathy as an ocular condition potentially affected by systemic hyperlipidemia. While several gene loci have been implicated in both IOP regulation and cholesterol metabolism, the mechanism of this linkage will require further study.
Relevant Reading: Biomarkers for glaucoma: From the lab to the clinic
In-Depth [cross-sectional study]: 94,323 subjects from the UK Biobank and 6,230 from EPIC-Norfolk were included. Subjects had serum lipid levels collected between 2006 and 2009. Patients with a history of glaucoma surgery or laser therapy were excluded. IOP was measured using an ocular response analyzer (ORA) noncontact tonometer. For patients on IOP-lowering medications, pre-treatment IOP was approximated by dividing by 0.7. Univariate and multivariable linear regression models were performed for analysis using average IOP over both eyes for each subject. Multivariable models included adjustment for age, sex, ethnicity, Townsend deprivation index reflecting indicators of poverty, BMI, systolic blood pressure, height, history of any smoking, current alcohol use, diabetes status, statin use, beta blocker use, and spherical equivalent refractive error. UK Biobank and EPIC-Norfolk subjects differed significantly in several demographic and medical factors. ApoA and ApoB levels were positively associated with IOP for UK Biobank subjects.
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