Association of HDL cholesterol with incident age-related macular degeneration and mortality: Using an illness-death model for interval-censored data to account for the competing risk of death

Elevated high-density lipoprotein cholesterol (HDL-C) has been regularly associated with age-related macular degeneration (AMD). However, this association could be due to longer life expectancy in subjects with high HDL-C. Thus, we assessed the association of HDL-C with incident AMD, using an illness-death model (IDM) for interval-censored data to account for death as a competing risk. The ALIENOR study included 963 participants aged 73 and older from Bordeaux, France. Plasma HDL-C was measured at baseline. AMD was assessed repeatedly using multimodal retinal imaging (2006-2020). The IDM estimated adjusted hazard ratios (aHR [95% confidence interval]) of incident AMD, and mortality in AMD-free and AMD-affected individuals. Analyzed samples included individuals at risk of intermediate (n = 472) and advanced (n = 690) AMD. HDL-C (1-standard deviation increase) was not significantly associated with the hazard of intermediate (aHR: 1.15 [0.97–1.37]) and advanced (aHR: 1.16 [0.90–1.49]) AMD onset. Additionally, in the intermediate AMD analysis, HDL-C was significantly associated with lower mortality in AMD-free (aHR: 0.74 [0.56–0.97]) and higher mortality AMD-affected individuals (aHR: 1.55 [1.17–2.05]). Future research should leverage robust statistical methods, such as the IDM, to mitigate survival bias and enhance the accuracy of hazard ratios estimation to confirm our findings.