Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank

Purpose:Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). Methods:Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. Results:We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, P-nonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (P-nonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. Conclusions:Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.