Elsevier

Atherosclerosis

Volume 233, Issue 2, April 2014, Pages 478-484
Atherosclerosis

Retinal microvascular structure and function in patients with risk factors of atherosclerosis and coronary artery disease

https://doi.org/10.1016/j.atherosclerosis.2013.12.044Get rights and content

Highlights

  • Retinal microvascular endothelial function was assessed by Dynamic Vessel Analyser (DVA).

  • The DVA measurements are reproducible in patients at risk of coronary artery disease.

  • Right and left eyes respond in a similar manner.

  • Smaller retinal vessels were associated with an increased flicker response.

  • Retinal microvascular structure changes was associated with reduced flicker response.

Abstract

Objective

Retinal microvascular signs are markers of cardiovascular disease risk. There are limited data, on relationships between retinal microvascular signs and retinal microvascular endothelial function. We sought to determine the relationship of retinal vascular signs with retinal microvascular endothelial function in patients with or at high risk of coronary artery disease.

Methods

Participants with atherosclerosis risk factors and coronary disease (n = 258; mean age 57 ± 11 years) were recruited to have static and dynamic retinal vascular assessment. Retinal arteriolar dilatation in response to flicker light (FI–RAD) was measured using the Digital Vessel Analyser and expressed as percentage increase over baseline diameter. Static retinal photographs were acquired utilising a digital fundus camera for measurement of central retinal artery and vein equivalent (CRAE and CRVE), arteriovenous nicking (AVN) and focal arteriolar narrowing (FAN).

Results

Intra-class correlation coefficient was 0.82 for flicker-light induced retinal arteriolar dilatation. There were modest associations in retinal vascular measurements between eyes. For each 10 μm decrease in retinal arteriolar diameter, the absolute increase in FI–RAD was 0.28% (95% CI 0.11, 0.45; p = 0.002) independent of age, gender and atherosclerosis risk factors. AVN and FAN were associated with attenuated FI–RAD (β = −0.67%; 95% CI −1.20, −0.15; p = 0.012) and (β = −0.83%; 95% CI −1.44, −0.23; p = 0.007) respectively after adjustment for age and gender.

Conclusion

Assessment of retinal microvascular endothelial function is reproducible and correlated with retinal microvascular structure and signs, independent of atherosclerosis risk factors. Assessment of retinal vascular structure and function may provide insights into atherosclerotic disease.

Introduction

The retinal circulation is unique as it allows a direct and non-invasive window to the health of the human circulation in vivo. Large epidemiologic studies have shown that retinal microvascular signs (e.g., arteriovenous nicking, focal arteriolar narrowing, and measurement of static retinal vascular calibre) provide information on risk of vascular complications, cardiac events and stroke in the general population [1], [2], [3], [4], [5], [6].

The mechanisms and pathways underlying these associations remain, however, unclear. Advances in retinal vascular imaging technology have allowed retinal microvascular function, a nitric oxide dependent phenomenon, to be evaluated in “real time” by non-invasive dynamic assessment of retinal vascular dilatation in response to diffuse luminance flicker light using the Dynamic Vessel Analyser (DVA) [7]. There are limited data on how static retinal microvascular signs are correlated with retinal microvascular endothelial function, particularly in subjects with or at risk for coronary heart disease [8]. Understanding the associations between static and dynamic retinal vascular markers may help in further developing a diagnostic tool capable of early detection of atherosclerosis, and assist in risk stratification of patients with cardiovascular disease.

To address these gaps, we sought to examine the feasibility of measuring retinal microvascular endothelial function using the DVA in patients with or at risk of coronary artery disease, and to study the inter-relationship between retinal vascular structure and function.

Section snippets

Study population and patient preparation

The study was approved by the Human Research Ethics Committee of Austin Health and written informed consent was obtained from all subjects. All participants (n = 258) underwent retinal photography, including static and dynamic assessment. The inclusion criteria for recruitment were that participants had to have at least two traditional cardiovascular risk factors and/or clinically evident coronary artery disease. Traditional cardiovascular risk factors included a history of hypertension,

Reproducibility and association between eyes

The characteristics of the study population are displayed in Table 1. ICC was 0.99 and 0.98 for baseline arteriolar and venular diameter respectively, and 0.82 and 0.79 for flicker-light induced retinal arteriolar and venular dilatation respectively. None of 13 baseline retinal arteriolar and venular diameter measurements were beyond the limits of agreement while at maximum dilatation, 1/13 of the arteriolar (FI–RAD), but not venular (FI–RVD), measurements were beyond the limits of agreement (

Discussion

In this study of patients with or at high risk of coronary artery disease, we investigated the reproducibility of retinal microvascular endothelial function assessment using the DVA and studied the inter-relationship between retinal vascular function and structure. The main findings are as follows. First, we showed that baseline and flicker light induced retinal arteriolar and venular dilatation, utilising the DVA, is reproducible. Second, we found modest to strong statistically significant

Financial disclosures

None.

Funding sources

Dr Al-Fiadh was supported by a co-funded Postgraduate Scholarship from the National Health and Medical Research Council (NHMRC) and National Heart Foundation of Australia (ID 567147). This work was supported in part by a Grant-in-Aid from the National Heart Foundation of Australia (G 08M 3781).

References (35)

  • G.T. Dorner et al.

    Nitric oxide regulates retinal vascular tone in humans

    Am J Physiol Heart Circ Physiol

    (2003)
  • T.T. Nguyen et al.

    Correlation of light-flicker-induced retinal vasodilation and retinal vascular caliber measurements in diabetes

    Invest Ophthalmol Vis Sci

    (2009)
  • B.U. Seifertl et al.

    Retinal vessel analyzer (rva)–design and function

    Biomed Tech Berl

    (2002)
  • R. Kawasaki et al.

    Retinal microvascular signs and risk of stroke: the multi-ethnic study of atherosclerosis (mesa)

    Stroke

    (2012)
  • J.R. Landis et al.

    The measurement of observer agreement for categorical data

    Biometrics

    (1977)
  • T.T. Nguyen et al.

    Reproducibility of the retinal vascular response to flicker light in asians

    Curr Eye Res

    (2009)
  • H.C. Chen et al.

    Vessel diameter changes during the cardiac cycle

    Eye (Lond)

    (1994)
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