Prognostic Significance of the Wall to Lumen Ratio of Retinal Arterioles Evaluated by Adaptive Optics in Human Hypertension

Abstract

Objective: Structural alterations in the microcirculation may be considered an important mechanism of hypertension-mediated organ damage. An increased media to lumen ratio of subcutaneous small resistance arteries evaluated with locally invasive techniques (biopsies of subcutaneous fat, micromyography) may predict the subsequent development of cardiovascular events. However, it is not presently known whether structural alterations of retinal arterioles evaluated with a non-invasive approach (adaptive optics) may have a prognostic meaning. Design and method: Two-hundred and thirty-seven subjects were included in the present study. They were normotensive subjects (n = 65, 27,4%) and patients with essential hypertension (n = 163, 68,8%) or primary aldosteronism (n = 9, 3,8%). All subjects were submitted to a non-invasive evaluation or retinal arteriolar morphology (evaluation of the wall/lumen ratio: WLR) by adaptive optics. The subjects were re-evaluated after an average follow-up time of 5.5 years on order to assess the occurrence of death or cardio-cerebrovascular events. Results: Fifty-four total events occurred in the population enrolled, of which 29 were cardio-cerebrovascular event (ischemic or hemorragic stroke, atrial fibrillation, heart failure, coronary artery disease, peripheral artery disease, including aneurism requiring intervention, cardiac valvular disease) while the remaining were events or deaths for any cause, including neoplastic disease. The event-free survival was significantly less in those with a WLR above the median value of the population (0.28) according to Kaplan-Mayer survival curves and multivariate analysis (p < 0.001 by both the Mantel-Cox test and the Breslow test). Subjects with events had a WLR of retinal arterioles significantly greater than those without events. The evidence was confirmed after restricting the analysis to cardiovascular events, excluding events or deaths of neoplastic origin. The average follow-up time of our subjects was 4.6 ± 1.6 years for a total of 1090 patients-years. Patients with cardiovascular events were older and with more elevated levels of circulating glucose. Conclusions: Structural alterations of retinal arterioles evaluated by adaptive optics may predict cardio-cerebral events and total mortality.

Microcirculation in Hypertension: A Therapeutic Target to Prevent Cardiovascular Disease?

“…The evidence was confirmed after restricting the analysis to cardiovascular events, excluding deaths and neoplastic diseases [82]. Therefore, the structural alterations of retinal arterioles evaluated by adaptive optics may predict total and cardiovascular events [82].…”

“…Most recently, the prognostic role of WLR evaluated with adaptive optics was demonstrated [80]. The event-free survival was significantly worse in 230 normotensive subjects and hypertensive patients with a baseline WLR higher than the median value of the population (0.28) according to Kaplan-Meier survival curves and multivariate analysis (Cox's proportional hazard model) [82]. The evidence was confirmed after restricting the analysis to cardiovascular events, excluding deaths and neoplastic diseases [82].…”

“…The event-free survival was significantly worse in 230 normotensive subjects and hypertensive patients with a baseline WLR higher than the median value of the population (0.28) according to Kaplan-Meier survival curves and multivariate analysis (Cox's proportional hazard model) [82]. The evidence was confirmed after restricting the analysis to cardiovascular events, excluding deaths and neoplastic diseases [82]. Therefore, the structural alterations of retinal arterioles evaluated by adaptive optics may predict total and cardiovascular events [82].…”

Retinal Microcirculation Measurements in Response to Endurance Exercises Analysed by Adaptive Optics Retinal Camera

“…Only SLDF and AO can estimate the wall thickness-tointernal diameter ratio (wall/lumen ratio, WLR) of retinal arterioles, and they are used in the analysis of microvascular changes in cardiometabolic diseases, such as hypertension, diabetes, and obesity, and to predict the risk of cerebrovascular events [2,6,10,11]. AO provides a more accurate and precise estimation of the WLR of retinal arterioles compared to SLDF and allows for differentiation between functional narrowing (due to autoregulation) and structural remodelling of a vessel [6,11]. Multiple studies reported a strong relationship between retinal vessel calibre in hypertension and diabetes mellitus [2,6,7,[10][11][12].…”

“…AO provides a more accurate and precise estimation of the WLR of retinal arterioles compared to SLDF and allows for differentiation between functional narrowing (due to autoregulation) and structural remodelling of a vessel [6,11]. Multiple studies reported a strong relationship between retinal vessel calibre in hypertension and diabetes mellitus [2,6,7,[10][11][12]. In these two primary systemic diseases, micro-and macrovascular changes occur in longterm observation, and narrowing of retinal arterioles is a commonly described sign of retinopathy [2,6,[11][12][13][14][15][16][17][18][19].…”