The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study

2020 ◽  
Author(s):  
Xikun Han ◽  
Jue-Sheng Ong ◽  
Alex W Hewitt ◽  
Puya Gharahkhani ◽  
Stuart MacGregor
Keyword(s):  
Macular Degeneration ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipid Biomarkers ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Lipoprotein Cholesterol ◽  
European Descent ◽  
Age Related

Abstract Background Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear. Methods Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64–407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium. Results Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD.

scholarly journals Casual Effect of Serum Lipid Biomarkers On Early Age-Related Macular Degeneration Using Mendelian Randomization

2021 ◽  
Author(s):  
Fen-Fen Li ◽  
Yuqin Wang ◽  
Qi Chen ◽  
Lue Xiang ◽  
Feng-Qin Rao ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Serum Lipid ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipid Biomarkers ◽  
Age Related Macular Degeneration ◽  
Lipoprotein Cholesterol ◽  
European Ancestry ◽  
Age Related ◽  
Increased Risk

Abstract Background Age-related macular degeneration (AMD) is one of the major causes of vision loss. Early AMD needs to be taken seriously, whereas lipid biomarkers’ casual effects on early AMD remain unclear. Methods In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between seven serum lipid biomarkers, consisting of apolipoprotein A (ApoA), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], and triglycerides (TG), and the risk of early AMD. Totally, 14,034 cases and 91,214 controls of European ancestry were included in the analysis (Number of SNPs = 11,304,110). Results MR estimates showed that a higher HDL-C level was strongly associated with increased risk of early AMD (OR = 1.25, 95% CI: 1.15-1.35, P = 2.61 × 10−8). In addition, the level of ApoA was also positively associated with the risk of early AMD (OR = 2.04, 95% CI: 1.50-2.77, P = 6.27 × 10−6). Conversely, higher LDL-C levels significantly decreased the risk of early AMD (OR = 0.90, 95% CI: 0.85-0.96, P = 2.03 × 10−3). In addition to LDL-C, higher levels of ApoB and TG were found to be positively associated with early AMD risk. Sensitivity analyses further supported these associations. Moreover, multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results. Conclusion This study addresses the question of causality relationships that elevated circulating HDL-C/ApoA levels and increased risk of early AMD, whereas LDL-C, ApoB, and TG specifically reduce the risk of early AMD. These findings contribute to our better understanding of the role of lipid metabolism in drusen formation, particularly in early AMD development.

Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

2021 ◽  
Author(s):  
Liv Tybjærg Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Ruth Frikke-Schmidt ◽  
Børge Grønne Nordestgaard
Keyword(s):  
Macular Degeneration ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Age Related Macular Degeneration ◽  
Apolipoprotein A1 ◽  
Age Related ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Plasma Apolipoprotein

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

Effect of intravitreal injection of aflibercept on cardiovascular risk parameters in patients with neovascular age related macular degeneration

2020 ◽  
Vol 15 ◽  
Author(s):  
Constantinos D. Georgakopoulos ◽  
Athina Pallikari ◽  
Panagiotis Plotas ◽  
Konstantinos Kagkelaris ◽  
Stylianos Mastronikolis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Macular Degeneration ◽  
Intravitreal Injection ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Age Related Macular Degeneration ◽  
Lipoprotein Cholesterol ◽  
Age Related ◽  
Increased Risk ◽  
Oncologic Patients

Objective: Systemic administration of anti-vascular endothelial growth factors (anti-VEGFs) has been associated with severe cardiovascular adverse events in oncologic patients. The purpose of this pilot study is to evaluate the short-term effect of a single intravitreal injection of aflibercept on biomarkers related to increased risk of cardiovascular disease. Patients and Methods: Forty-seven treatment naïve patients with neovascular age related macular degeneration in one eye were enrolled in the study. The patients underwent treatment with one intravitreal injection of aflibercept in the affected eye. Laboratory biomarkers of cardiovascular disease were evaluated before the first intravitreal injection of aflibercept and at 7 and 30 days after aflibercept administration. More precisely, we evaluated the levels of homocysteine, total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol and C-reactive protein. Results: There was not any statistically significant change in the levels of the evaluated parameters up to one month after the first intravitreal injection of aflibercept. Conclusions: According to our study, administration of a single dose of aflibercept in eyes with neovascular age-related macular degeneration does not seem to affect the evaluated biomarkers that are related to cardiovascular disease.

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

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e90973 ◽  
Author(s):  
Audrey Cougnard-Grégoire ◽  
Marie-Noëlle Delyfer ◽  
Jean-François Korobelnik ◽  
Marie-Bénédicte Rougier ◽  
Mélanie Le Goff ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Macular Degeneration ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Age Related Macular Degeneration ◽  
Lipoprotein Cholesterol ◽  
Age Related
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