Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease

By Theuerle JD, Al-Fiadh AH et al

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. Theuerle et al sought to determine whether retinal microvascular endothelial dysfunction predicts long-term major adverse cardiovascular events (MACE).

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.
  • After adjustment for traditional risk factors, patients within the lowest quintile of FI-RAD had the highest risk of MACE.
  • Patients with lower FI-RAD were also more likely to die.
  • 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.

This study is the first to confirm that an uncomplicated measurement of retinal arteriolar endothelial dysfunction, as measured by FI-RAD at a single time point, is a strong and independent predictor of long-term MACE in patients with CAD and cardiovascular risk factors. Dynamic retinal vessel analysis may provide added benefit to traditional risk factors in stratifying patients at risk for cardiovascular events.

Additional clinical studies and validation of this novel marker of microvascular dysfunction are required to establish the applicability of this method to the clinical arena.

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Theuerle JD, Al-Fiadh AH, Amirul Islam FM, Patel SK, Burrell LM, Wong TY, Farouque O. Impaired retinal microvascular function predicts long-term adverse events in patients with cardiovascular disease. Cardiovasc Res. 2021 Jul 7;117(8):1949-1957. doi: 10.1093/cvr/cvaa245. PMID: 32750111.