Hyperlipidemia, Blood Lipid Level, and the Risk of Glaucoma: A Meta-Analysis

Abstract

PURPOSE. Previous studies reported that hyperlipidemia and blood lipid levels were associated with glaucoma, ocular hypertension (OHT), and intraocular pressure (IOP). However, studies aimed at investigating this association have yielded conflicting results. Therefore, to shed light on these inconclusive findings, we performed multiple distinct meta-analyses to clarify the association of hyperlipidemia and blood lipid levels with glaucoma, OHT, and IOP. METHODS. A systematic literature search from Embase, Web of Science, and PubMed was performed to identify relevant studies. To assess the association between hyperlipidemia and glaucoma, we used the pooled odds ratio (OR) with 95% confidence interval (CI). When we assessed the association between blood lipid levels and IOP levels, the pooled mean difference in IOP associated with a 10 mg/dL increase in the blood lipid level was estimated. The pooled difference in IOP was also estimated between patients with and without hyperlipidemia. All the papers that assessed the correlation between hyperlipidemia and glaucoma, between blood lipid levels and IOP levels, and between hyperlipidemia and IOP were included in this meta-analysis. RESULTS. We detected a marked association between hyperlipidemia and glaucoma (OR ¼ 1.37; 95% CI ¼ 1.16-1.61), with significant heterogeneity among studies. However, hyperlipidemia was not significantly associated with glaucoma in our analysis of only crosssectional studies, studies that reported only on hypercholesterolemia patients, studies that were conducted only in North America and Europe, or studies in which normal-tension glaucoma (NTG) patients were included only in the subgroup analyses. The pooled results showed that an increase of 10 mg/dL in blood triglyceride levels would increase the IOP by 0.016 mm Hg (95% CI ¼ 0.009-0.024), with evident heterogeneity between studies (P < 0.001; I 2 ¼ 92.0%). The pooled results showed that the blood total cholesterol and lowdensity lipoprotein-cholesterol (LDL-c) level both had a significant association with IOP. When compared to the patients with nonhyperlipidemia, those with hyperlipidemia had a significantly higher IOP of 0.51 mm Hg (95% CI ¼ 0.18-0.83) (P ¼ 0.001 for heterogeneity; I 2 ¼ 81.6%). CONCLUSIONS. The evidence suggests that hyperlipidemia is significantly associated with an increased risk of glaucoma and that hyperlipidemia and the increased blood lipid levels are associated with increased IOP.

Plasma Lipid Levels and Risk of Primary Open Angle Glaucoma: A Genetic Study Using Mendelian Randomization

“…Previous observational studies have shown contradictory results for relationships between plasma lipid levels and the risk of POAG [28][29][30]. A newly published meta-analysis performed by Wang et al [7] found a signi cant association between plasma lipid levels and the risk of POAG. However, considering these observational studies are limited by potential residual confounding and reverse causality, we should interpret these ndings with caution.…”

“…Concerning the relationship between plasma lipids levels and POAG, Wang et al [7] clari ed that hyperlipidemia is signi cantly associated with an increased risk of glaucoma based on pooled responses across 18 epidemiological studies. Wang et al speculated that the possible explanation of this association might be that excess blood lipid levels would increase the episcleral venous pressure and blood viscosity, resulting in a consequent decrease in out ow facility [7,32]. Nevertheless, despite the reasonable biological rationale, the causality for the association between plasma lipid levels and the risk of POAG has remained unclear.…”

“…With the increasing burden of POAG, it is momentous to make clear the potentially risk factors for better prevention. Up to now, multiple risk factors, such as age [4,5], diabetes [6], hyperlipidemia [7], elevated intraocular pressure (IOP) [8,9], family history [10], and ethnic background [11] have been established in connection with the risk of POAG. However, such relationships can be in uenced by confounding from unknown factors.…”

“…Several epidemiological studies have reported plasma lipid concentrations and hyperlipidemia have a signi cant association with the risk of POAG [12][13][14]. A meta-analysis aggregating data from 18 epidemiological studies identi ed that hyperlipidemia caused a 37% increase in the risk of patients developing POAG [7]. The quantitative analysis in this meta-analysis also showed that an increase of 10 mg/dl in the plasma triglyceride concentration, plasma total cholesterol concentration, or plasma lowdensity lipoprotein cholesterol (LDL-C) concentration would increase the IOP by 0.016 mm Hg, 0.032 mm Hg, or 0.050 mm Hg, respectively [7].…”

“…A meta-analysis aggregating data from 18 epidemiological studies identi ed that hyperlipidemia caused a 37% increase in the risk of patients developing POAG [7]. The quantitative analysis in this meta-analysis also showed that an increase of 10 mg/dl in the plasma triglyceride concentration, plasma total cholesterol concentration, or plasma lowdensity lipoprotein cholesterol (LDL-C) concentration would increase the IOP by 0.016 mm Hg, 0.032 mm Hg, or 0.050 mm Hg, respectively [7]. Nevertheless, these relationships may be biased because of the inherent limitations of epidemiological studies such as reverse causation, confounding, and measurement error [15].…”