Life's Essential 8, Genetic Susceptibility, and the Risk of Age-Related Macular Degeneration: A Prospective Cohort Study

Abstract

Purpose: We determined the association between Life's Essential 8 (LE8) scores and AMD incidence and ascertained whether genetic susceptibility modifies it.

Methods: This prospective cohort study included 268,634 UK Biobank study participants with high, moderate, or low cardiovascular health based on LE8 scores. High and low cardiovascular health corresponded to the lowest and highest cardiovascular disease risks, respectively. The hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD were estimated using Cox proportional hazards models. The dose-response relationships were evaluated using restricted cubic spline analysis. Stratified analyses using the AMD-polygenic risk score categories were used to assess potential modification. A composite variable combined LE8 and AMD-polygenic risk to examine their joint effects.

Results: Over an average of 13.76 years, 5253 participants developed AMD. Compared with the lowest cardiovascular health, moderate and high cardiovascular health had adjusted HRs of 0.86 (95% CI, 0.76, 0.97) and 0.79 (0.69, 0.91), respectively. Each standard deviation increase in the LE8 score corresponded to an HR of 0.93 (0.91, 0.96). The LE8 behavior (HR = 0.94 [0.91, 0.96]) and biological (HR = 0.97 [0.95, 1.00]) subscale scores were inversely associated with AMD, whereas the blood lipids component was positively associated (HR = 1.07 [1.04, 1.10]). The AMD-polygenic risk and LE8 scores showed no significant interaction. The HR for having low AMD-polygenic risk and high cardiovascular health relative to having high AMD-polygenic risk and low cardiovascular health was 0.47 (0.37, 0.58).

Conclusions: Maintaining good cardiovascular health can reduce AMD incidence regardless of genetic background.

Figure 1.

Results of the Restricted Cubic Spline Analysis. Associations of the Life's Essential 8 score (a), behavior subscale score (b), and biological subscale score (c) with the risk of age-related macular degeneration, analyzed using Cox models with restricted cubic splines. The model was adjusted for age, sex, the Townsend deprivation index, education, ethnicity, drinking status, surgery, and the polygenic risk score, the first 10 genetic principal components, and genotype measurement.

Figure 2.

Joint associations of LE8 and genetic predisposition with the risk of AMD. The model was adjusted for age, sex, the Townsend deprivation index, education, ethnicity, drinking status, surgery, polygenic risk score, the first 10 genetic principal components, and genotype measurement.