Association of Retinal Microvascular Abnormalities with All-Cause and Specific-Cause Mortality Among U.S. Adults

Abstract

Abstract Background: Retinal microvascular abnormalities (RMA) reflect cumulative microvascular damage from systemic diseases and aging. However, little is known about the association between RMA and long-term survival outcomes. This study aimed to examine the relationships between RMA and the risk of all-cause and specific-cause mortality among U.S. adults. Methods: Individuals aged >40 years were included from the U.S. National Health and Nutrition Examination Survey, 2005-2008. RMA and its subtypes, including retinopathy, arteriovenous nicking (AVN), focal arteriolar narrowing (FAN) and Hollenhorst plaque (HP), were manually graded from retinal photographs. Associations between RMA and the risk of all-cause and cause-specific mortality were examined with Cox regression analysis. Results: This cohort study of 5775 adults included 2881 women (weighted proportion, 52.6%) and 2894 men (weighted, 47.4%), with a weighted mean (SE) age of 56.6 (0.4) years. RMA were present in 1251 participants (weighted, 17.9%), of whom 710 (weighted, 9.8%) had retinopathy, 635 (weighted, 9.3%) had AVN, 64 (weighted, 1.0%) had FAN, and 21 (weighted, 0.3%) had HP. During a median of 12.2 years (range, 0.1-15.0 years) of follow-up, 1488 deaths occurred, including 452 associated with cardiovascular disease (CVD), 341 associated with cancer, and 695 associated with other causes. After adjusting confounding factors, the presence of any RMA and retinopathy at baseline was associated with higher risk of all-cause mortality (HR, 1.26; 95%CI, 1.07-1.47; HR, 1.36; 95%CI, 1.09-1.71, respectively), CVD mortality (HR, 1.36; 95%CI, 1.06-1.73; HR, 1.53; 95%CI, 1.04-2.26, respectively) and other-cause mortality (HR, 1.33; 95%CI, 1.06-1.67; HR, 1.55; 95%CI, 1.20-2.01, respectively). Additionally, FAN was significantly associated with an increased risk of other-cause mortality (HR, 2.06; 95%CI, 1.16-3.65). Although AVN was not associated with mortality in the whole population, it was significantly related to higher risks of all-cause and CVD death in those with obesity (HR, 1.68; 95%CI, 1.12-2.52; HR, 1.96; 95%CI, 1.23-3.13, respectively). Conclusions: This study revealed that the presence of RMA is independently associated with greater risks of all-cause, CVD and other-cause mortality in adults aged 40 years or older.