Xue He,1,* Cong Li,1,2,* Yan Wang,1,3,* Zhenchao Du,1,4 Jianrong Jiang,1,5 Wenli Zhang,1,4 Jingyan Peng,1,5 Zhishen Peng,1,5 Tengda Huang,1,3 Heng Li,1,4 Yu Kuang,1 Honghua Yu,1 Lei Liu,1 Xiaohong Yang1,3 

1Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Sciences, Guangzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 4School of Medicine, Shantou University Medical College, Shantou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiaohong Yang, Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China, Email syyangxh@scut.edu.cn Lei Liu, Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China, Email liulei@gdph.org.cn

Background: Coronary heart disease (CHD) and depression are highly comorbid and increase mortality risk. Although age-related eye diseases (AREDs) are independently associated with CHD and depression, their link to comorbidity remains unknown. Therefore, we aim to investigate the association between AREDs and the comorbidity of CHD and depression.
Methods: Using UK Biobank data, we conducted a prospective cohort analysis with baseline assessments from March 2006 to December 2010 and follow-up until July 2021. AREDs include age-related macular degeneration, glaucoma, cataract, and diabetes-related eye diseases (DRED). Incident cases were identified via self-reports and hospital records. Multivariable Cox proportional hazard regression models were applied to investigate the association between AREDs and comorbidity risk.
Results: Among 116,501 participants free of CHD and depression at baseline, 7,750 (6.65%), 3,682 (3.16%), and 741 (0.64%) developed CHD, depression, and their comorbidity over a mean of 11.82 years (inter-quartile range: 11.51– 13.11) of follow-up. After adjusting for confounders, individuals with AREDs had a higher risk of developing CHD (hazard ratio [HR] 1.10, 95% confidence interval [CI]: 1.03– 1.17), depression (HR 1.28, 95% CI: 1.16– 1.42), and comorbidity (HR 1.37, 95% CI: 1.12– 1.67). Compared to those without AREDs, individuals with cataract were associated with increased risks of comorbidity (HR 1.57, 95% CI: 1.23– 2.03) and depression (HR 1.26, 95% CI: 1.10– 1.43), while those with DRED had an increased risk of incident CHD (HR 1.33, 95% CI: 1.13– 1.56).
Conclusion: The study found that individuals with AREDs had a higher risk of comorbid CHD and depression than of either condition independently. Our findings highlighted the importance of screening for the comorbidity of CHD and depression in the longitudinal management of AREDs.

Keywords: age-related eye diseases, coronary heart disease, depression, comorbidity