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Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Publicatiejaar 2019
Gepubliceerd in Ophthalmology
Auteur(s) Johanna Maria Colijn, Anneke I den Hollander, Ayse Demirkan, Audrey Cougnard-Grégoire, Timo Verzijden, Eveline Kersten, Magda A Meester-Smoor, Benedicte M J Merle, Grigorios Papageorgiou, Shahzad Ahmad, Monique T Mulder, Miguel Angelo Costa, Pascale Benlian, Geir Bertelsen, Alain M Bron, Birte Claes, Catherine Creuzot-Garcher, Maja Gran Erke, Sascha Fauser, Paul J Foster, Christopher J Hammond, Hans-Werner Hense, Carel B Hoyng, Anthony P Khawaja, Jean-Francois Korobelnik, Stefano Piermarocchi, Tatiana Segato, Rufino Silva, Eric H Souied, Katie M Williams, Cornelia M van Duijn, Cécile Delcourt, Caroline C W Klaver, T.G.M.F. Gorgels

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset.

DESIGN: Pooled analysis of cross-sectional data.

PARTICIPANTS: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data.

METHODS: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations.

MAIN OUTCOME MEASURES: AMD features and stage; lipid measurements.

RESULTS: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10-6 and P = 1.6 × 10-4).

CONCLUSIONS: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

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