Abstract P243: Retinal Microvascular Findings and Future Risk of Peripheral Artery Disease: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: Lower-extremity peripheral artery disease (PAD) is often considered as a subtype of macrovascular disease. For the development of critical limb ischemia (CLI), a severe form of PAD, microvascular disease is indicated to play a crucial role by impairing collateral formation and wound healing. However, the contribution of microvascular disease to the development of PAD has not been systematically evaluated in a large cohort study. Hypothesis: Microvascular disease, as represented by retinal findings, will be associated with future PAD risk, and its association will be stronger for CLI. Methods: Retinal photographs were taken at the 3 rd examination (1993-1995) of the ARIC Study. We investigated 9390 participants free of clinical history of PAD and quantified the associations of each retinal finding with PAD risk using Cox models. PAD was defined as hospitalizations with PAD diagnosis (ICD-9: 440.2x, 440.3, 440.4) or leg revascularization (38.18, 39.25, 39.29, 39.50). Of PAD cases, those with ulcer (707.1), gangrene (785.4) or leg amputation (84.1x) were considered CLI. Results: During a median follow-up of 19 years, 304 participants developed PAD, of which 92 were considered CLI. Retinal hemorrhages, exudates, microaneurysms and any retinopathy demonstrated independent associations with PAD (Table) beyond potential confounders including diabetes, while generalized arteriolar narrowing did not. These significant retinal findings were more strongly associated with CLI than with PAD (HR range 3.1-6.5 vs. 2.2-3.3, with all p-values for difference in HR from seemingly unrelated regression <0.05 except soft exudates). Also, these retinal findings tended to have stronger associations with PAD outcomes among persons with diabetes than those without. Conclusions: Retinal hemorrhages, exudates, microaneurysms and any retinopathy were independently associated with PAD, especially its severe form, CLI. Our results suggest the importance of microvascular wall fragility/permeability in the development of PAD.