James D Theuerle1,2, Ali H Al-Fiadh1,2, Fakir M Amirul Islam3, Sheila K Patel2, Louise M Burrell1,2, Tien Yin Wong4, Omar Farouque1,2. 1. Department of Cardiology, Austin Health, 145 Studley Road, Melbourne, Victoria 3084, Australia. 2. Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Australia. 3. Department of Statistics, Data Science and Epidemiology, Swinburne University of Technology, Melbourne, Australia. 4. Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical, School, National University of Singapore, Singapore, Singapore.
Abstract
AIMS: Endothelial dysfunction is a precursor to the development of symptomatic atherosclerosis. Retinal microvascular reactivity to flicker light stimulation is a marker of endothelial function and can be quantified in vivo. We sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE). METHODS AND RESULTS: In a single-centre prospective observational study, patients with coronary artery disease (CAD) or cardiovascular risk factors underwent dynamic retinal vessel assessment in response to flicker light stimulation and were followed up for MACE. Retinal microvascular endothelial dysfunction was quantified by measuring maximum flicker light-induced retinal arteriolar dilatation (FI-RAD) and flicker light-induced retinal venular dilatation (FI-RVD). In total, 252 patients underwent dynamic retinal vessel assessment and 242 (96%) had long-term follow-up. Of the 242 patients, 88 (36%) developed MACE over a median period of 8.6 years (interquartile range 6.0-9.1). After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE [odds ratio (OR) 5.21; 95% confidence interval (CI) 1.78-15.28]. Patients with lower FI-RAD were also more likely to die (OR 2.09; 95% CI 1.00-4.40, per standard deviation decrease in FI-RAD). In Kaplan-Meier analysis, patients with FI-RAD responses below the cohort median of 1.4% exhibited reduced MACE-free survival (55.5 vs. 71.5%; log-rank P = 0.004). FI-RVD was not predictive of MACE. CONCLUSION: Retinal arteriolar endothelial dysfunction is an independent predictor of MACE in patients with CAD or cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Endothelial dysfunction is a precursor to the development of symptomatic atherosclerosis. Retinal microvascular reactivity to flicker light stimulation is a marker of endothelial function and can be quantified in vivo. We sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE). METHODS AND RESULTS: In a single-centre prospective observational study, patients with coronary artery disease (CAD) or cardiovascular risk factors underwent dynamic retinal vessel assessment in response to flicker light stimulation and were followed up for MACE. Retinal microvascular endothelial dysfunction was quantified by measuring maximum flicker light-induced retinal arteriolar dilatation (FI-RAD) and flicker light-induced retinal venular dilatation (FI-RVD). In total, 252 patients underwent dynamic retinal vessel assessment and 242 (96%) had long-term follow-up. Of the 242 patients, 88 (36%) developed MACE over a median period of 8.6 years (interquartile range 6.0-9.1). After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE [odds ratio (OR) 5.21; 95% confidence interval (CI) 1.78-15.28]. Patients with lower FI-RAD were also more likely to die (OR 2.09; 95% CI 1.00-4.40, per standard deviation decrease in FI-RAD). In Kaplan-Meier analysis, patients with FI-RAD responses below the cohort median of 1.4% exhibited reduced MACE-free survival (55.5 vs. 71.5%; log-rank P = 0.004). FI-RVD was not predictive of MACE. CONCLUSION: Retinal arteriolar endothelial dysfunction is an independent predictor of MACE in patients with CAD or cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events. Published on behalf of the European Society of Cardiology. All rights reserved.
Authors: Lukas Streese; Joséphine Gander; Justin Carrard; Christoph Hauser; Timo Hinrichs; Arno Schmidt-Trucksäss; Konstantin Gugleta; Henner Hanssen Journal: BMJ Open Date: 2022-06-06 Impact factor: 3.006