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Retinal vessel narrowing: an early predictor of future arteriosclerosis?

Benetos, Athanase

doi: 10.1097/HJH.0000000000001644
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Department of Geriatrics, University Hospital of Nancy, Vandoeuvre les Nancy, France

Correspondence to Athanase Benetos, MD, PhD, Department of Geriatrics, University Hospital of Nancy, 54511 Vandoeuvre les Nancy, France. E-mails: a.benetos@chru-nancy.fr

For several decades, fundoscopy was one of the most reliable clinical tools for assessing the vascular impact of major cardiovascular risk factors such as diabetes mellitus and hypertension. However, in most European countries, this examination is no longer part of medical routine because of the subjectivity of the evaluation and the fact that other methodological approaches have since been developed such as carotid echography, aortic pulse wave velocity (PWV), and so forth, providing more accurate information on structural and functional vascular alterations. Interestingly, in these last years, and owing to technological advances, several devices have been proposed to measure retinal vessel calibre with accuracy and in a noninvasive manner. Using these methods, several cohort studies have shown that retinal artery narrowing (RAN) is a marker of microvascular dysfunction and is associated with chronic hypertension [1–3] and arterial stiffness [4]. In addition, narrowing of the retinal vessel lumen has been associated with a higher incidence of cardiovascular events [5] independently of blood pressure levels [6]. The study by Kawashima-Kumagai et al.[7] with RAN exhibit, over a period of 5 years, a more pronounced increase in aortic pulse wave velocity.

Compared with previous published reports on this topic, this study presents two major interests:

  1. a large study population of over 6000 individuals, and
  2. a longitudinal design assessing the evolution of arterial stiffness over a period of 5 years in relation to retinal artery calibre.

Owing to these characteristics, the findings of Kawashima-Kumagai et al., add significant information to prior studies, which had observed cross-sectional relationships between RAN and arterial stiffness [4]. In effect, by showing that RAN may precede large artery stiffness by several years, the present data suggest that the negative long-term prognostic effect of RAN on the cardiovascular system may be related to accelerated arterial aging.

Only a few longitudinal studies to date have assessed the determinants of arterial stiffening over a long period of time. These latter studies were able to demonstrate that hemodynamic and biological parameters can accelerate the annual increase in arterial stiffness measured by PWV, which include frequent conditions such as diabetes, metabolic syndrome, obesity, chronic elevation in BP and increased heart rate [8–10]. Genetic determinants (e.g. genes of the renin–angiotensin–aldosterone system, telomere dynamics, etc.) also appear to influence the pace of age-related increase in arterial stiffness [11–13]. This accelerated increase in arterial stiffness pertains essentially to aortic and other central arteries, whereas much less stiffness is observed in peripheral arteries, particularly of the upper and lower limbs [14,15]. The increase in aortic and other central artery stiffness may in turn explain the more pronounced elevation in pulse pressure in individuals presenting the above conditions with an increased risk of cardiovascular morbidity and mortality [14,16].

The present study conducted in a large population sample was able to show that RAN occurred earlier in age than large artery stiffening, which indicates that either retinal artery alterations precede aortic alterations or that the tools currently used to detect RAN are more sensitive than those used for the detection of large artery stiffness. Indeed, clinical cross-sectional and longitudinal studies have shown that increases in arterial stiffness with age is not linear, being more pronounced after the age of 55–60 [9], whereas the present study shows that RAN mainly occurs between the ages of 35–50 years.

Early detection of the risk of arterial stiffening could be of major interest as:

  1. arterial stiffness is an independent factor for adverse cardiovascular outcomes [14,16] and
  2. once established, arterial stiffness is very difficult to reverse.

According to the results of the present analysis by Kawashima-Kumagai et al.[7], one could suggest that individuals in their early 40s, especially those with a family history of early cardiovascular disease or those presenting modifiable cardiovascular risk factors, may benefit from measurements of retinal artery calibre. Presence of RAN could, thus, be a very early sign of future systematic arteriosclerosis at an age when other markers of arterial stiffness are not yet present. Therefore, future studies should essentially focus on younger individuals (i.e. <50 years old) as, in older patients, PWV is a safe, relatively inexpensive and easy-to-perform method to detect arteriosclerosis and high cardiovascular risk.

Several issues, however, need to be investigated in order to establish the diagnostic and predictive interest of this approach. Of particular note, in the present study, a large number of individuals (approximately 15%) had unsuccessful measurements and were thus, excluded from the analysis. Further studies should hence better define the feasibility, reproducibility and cost of retinal artery measurements in real-life conditions.

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ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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