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

<div><p>Background</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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<b>,</b> 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.</p><p>Conclusions</p><p>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.</p></div

Plasma lipid levels according to genetic characteristics in subjects of the Alienor study (N = 825).

<p>Abbreviations: TC: Total cholesterol; TG: Triglycerides;</p><p>*ANOVA or Student t-tests were performed for means comparison;</p>†<p>Statistically significant p-value <0.0055 (Bonferroni corrected, P = 0.05/9 = 0.0055).</p

Odds ratio for occurrence of CIND for practicing cognitively stimulating activities and multilingualism during lifespan.

<p>Multilingualism was studied through its two classifications: ¹subjects using 2 languages versus more than two; ²subjects using only 3, only 4 or more than four languages; CSC: cognitively stimulating component.</p

Statin and fibrate drug use according to genetic characteristics in subjects of the Alienor study (N = 825).

<p>* Use of statin at one examination or more;</p>†<p>Use of fibrate at one examination or more;</p>‡<p>χ² tests were performed for frequency comparison;</p>§<p>Statistically significant p-value <0.0055 (Bonferroni corrected, P = 0.05/9 = 0.0055).</p

Associations of AMD with statin and fibrate drug use in the Alienor study (odds-ratios (OR) and [95% confidence interval (CI)] for 1 mmol/L increase).

<p>Abbreviations: AMD: age-related macular degeneration;</p><p>*adjusted for age and gender;</p>†<p>adjusted for age, gender, educational level, smoking, BMI, hypertension, HDL, LDL, triglycerides, cardiovascular disease, and diabetes;</p>‡<p>adjusted for age, gender, educational level, smoking, BMI, hypertension, HDL, LDL, triglycerides, cardiovascular disease, diabetes, ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC(rs10468017<b>)</b>, LIPC(rs493258<b>)</b> LPL, ABCA1 and CETP polymorphisms;</p>∥<p>Use of statin at one examination or more;</p>#<p>Statistically significant p-value <0.025 (Bonferroni corrected, P = 0.05/2 = 0.025);</p>β<p>Use of fibrate at one examination or more.</p

Time course of the percentage of % False Positive Nogo in the Go/Nogo task of the young and the older group under SD and NAP conditions (mean values ± SEM).

<p>SD  =  Sleep deprivation.</p

Associations of AMD with plasma lipids levels in the Alienor study (odds-ratios (OR) and [95% confidence interval (CI)] for 1 mmol/L increase).

<p>Abbreviations: AMD: age-related macular degeneration; TC: Total cholesterol; TG: Triglycerides;</p><p>*adjusted for age and gender;</p>†<p>adjusted for age, gender, educational level, smoking, BMI, hypertension, hypolipidemic drug, cardiovascular disease, and diabetes;</p>‡<p>adjusted for age, gender, educational level, smoking, BMI, hypertension, hypolipidemic drug, cardiovascular disease, diabetes, ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC(rs10468017), LIPC(rs493258) LPL, ABCA1 and CETP polymorphisms;</p>§<p>Statistically significant p-value <0.0125 (Bonferroni corrected, P = 0.05/4 = 0.0125).</p

Acquisition of multilingualism in the studied population.

<p><u>Part A. Typical progression: sequential and increasing process of learning and practicing multilingualism.</u> (For each stage of multilingualism, either individuals stayed at a specified level, or they progressed to the next step i.e. they learned an additional language.) Description of the 6 models of progression found among the 168 individuals for which the learning process represents the acquisition of one language after another (keeping the practice of all of them). <u>Part B. Atypical and unordered progression of learning and practicing multilingualism</u>. Illustration of the 6 models of atypical progression exhibited by the 64 subjects learning 2 or 3 languages in the same period of time and/or losing the practice of one or 2 languages at some point in their lives.</p

Characteristics of participants.

<p>Data are given as mean (standard deviation) unless otherwise stated. a: Chi-square test; b: Mann-Whitney test; c: Student t-test; d: Fisher test. For each component, the total scores could potentially vary between 0 and the component specific value, indicating the highest contribution to the component: 0–280 for the social component, 0–467 for the cognitively stimulating component, 0–130 for the productive component, 0–76 for the recreational and passive component, 0–206 for the physical component (non-sport).</p

Association between different stages of multilingualism and CIND.

<p>Forest plot of the OR comparing different stages of multilingualism over lifetime, to bilingualism, trilingualism and/or quadrilingualism. The solid vertical line shows an OR of 1 (no effect). Each multilingual status is represented by a square, the size of which shows the corresponding sample size in the analysis. The symbols represent the four different analysis performed. The lozenge at the top shows the overall effect of speaking “more than two languages” versus “exactly two languages”. The CL for each situation is represented by a horizontal line and the lower and upper control limits are indicated next (LCL, UCL).</p