Elevated High-Density Lipoprotein Cholesterol and Age-Related Macular Degeneration: The Alienor Study

Background: Lipid metabolism and particularly high-density lipoprotein (HDL) may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. Methods: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247); late AMD (n = 40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. Results: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95% CI: 1.54-3.90; P = 0.0002) and any AMD (OR = 2.29, 95% CI: 1.46-3.59; P = 0.0003). Association with late AMD was far from statistical significance (OR = 1.58, 95% CI: 0.48-5.17; p = 0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. Conclusions: This study suggests that elderly patients with high HDL concentration may be at increased risk for AMD and, further, that HDL dysfunction might be implicated in AMD pathogenesis.