Association between hypertension and retinal vascular features in ultra-widefield fundus imaging

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Abstract

Objective

Changes to the retinal vasculature are known to be associated with hypertension independently of traditional risk factors. We investigated whether measurements of retinal vascular calibre from ultra-widefield fundus imaging were associated with hypertensive status.

Methods

We retrospectively collected and semiautomatically measured ultra-widefield retinal fundus images from a subset of participants enrolled in an ongoing population study of ageing, categorised as normotensive or hypertensive according to thresholds on systolic/diastolic blood pressure (140/90 mm Hg) measured in a clinical setting. Vascular calibre in the peripheral retina was measured to calculate the nasal–annular arteriole:venule ratio (NA-AVR), a novel combined parameter.

Results

Left and right eyes were analysed from 440 participants (aged 50–59 years, mean age of 54.6±2.9 years, 247, 56.1% women), including 151 (34.3%) categorised as hypertensive. Arterioles were thinner and the NA-AVR was smaller in people with hypertension. The area under the receiver operating characteristic curve of NA-AVR for hypertensive status was 0.73 (95% CI 0.68 to 0.78) using measurements from left eyes, while for right eyes, it was 0.64 (95% CI 0.59 to 0.70), representing evidence of a statistically significant difference between the eyes (p=0.020).

Conclusions

Semiautomated measurements of NA-AVR in ultra-widefield fundus imaging were associated with hypertension. With further development, this may help screen people attending routine eye health check-ups for high blood pressure. These individuals may then follow a care pathway for suspected hypertension. Our results showed differences between left and right eyes, highlighting the importance of investigating both eyes of a patient.

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Most cited references 18

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Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

L Hubbard, R Brothers, W King … (1999)

To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. Population-based, cross-sectional study. Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

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Retinal vessel diameters and risk of hypertension: the Rotterdam Study.

M Kamran Ikram, Jacqueline C M Witteman, Johannes R Vingerling … (2006)

Generalized retinal arteriolar narrowing is an important sign of systemic hypertension, and a lower arteriolar:venular diameter ratio predicts the risk of hypertension. We investigated whether this association was based on arteriolar or venular diameters or both. This study was based on the prospective population-based Rotterdam Study (1990-1993) and included 1900 participants (> or =55 years of age) of whom 739 persons had normal blood pressure (systolic or =140 mm Hg or diastolic blood pressure > or =90 mm Hg or use of antihypertensive medication. Adjusted for age, gender, follow-up time, body mass index, smoking, diabetes mellitus, total and high-density lipoprotein cholesterol, C-reactive protein, and intima-media thickness, arteriolar narrowing was associated with an increased risk of hypertension (odds ratio per SD: 1.38; 95% CI, 1.23 to 1.55); for venular narrowing this was less striking (OR: 1.17; 95% CI, 1.04 to 1.32). Each SD decrease in the arteriolar:venular diameter ratio significantly increased the risk of hypertension by 24%. To examine the effect of baseline blood pressure, we stratified persons into those with "normal blood pressure" or "prehypertension." Within these strata, arteriolar narrowing was still related to incident hypertension. These data show that both retinal arteriolar and venular narrowing may precede the development of systemic hypertension.

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Retinal arteriolar diameter and risk for hypertension.

David Couper, , Ronald Klein … (2004)

Narrowing of the small arterioles has been hypothesized to contribute to the pathogenesis of hypertension, but prospective clinical data are lacking. To examine the relation of retinal arteriolar narrowing to incident hypertension in healthy middle-aged persons. Prospective cohort study. The population-based Atherosclerosis Risk in Communities Study, conducted in 4 U.S. communities. 5628 persons 49 to 73 years of age without preexisting hypertension. Diameters of retinal vessels were measured from digitized retinal photographs. A summary arteriole-to-venule ratio was computed as an indicator of generalized arteriolar narrowing; a lower ratio indicated greater narrowing. Areas of focal arteriolar narrowing were defined from photographs by using a standard protocol. Incident hypertension, defined as systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medication, was identified from the cohort. After 3 years of follow-up, 811 (14.4%) persons had developed hypertension. The incidence of hypertension was higher in persons with lower arteriole-to-venule ratios (incidence of 8.9%, 12.3%, 13.7%, 14.3%, and 22.3%, comparing decreasing quintiles of the ratio) and in persons with focal arteriolar narrowing than in those without focal arteriolar narrowing (25.1% vs. 13.0%). After the authors controlled for the average systolic and diastolic blood pressures over the preceding 6 years, body mass index, waist-to-hip ratio, and other risk factors, the odds of developing hypertension were approximately 60% higher in persons with lower arteriole-to-venule ratios (odds ratio, 1.62 [95% CI, 1.21 to 2.18] comparing lowest to highest quintile; P = 0.006 for trend) and focal arteriolar narrowing (odds ratio, 1.61 [CI, 1.27 to 2.04]; P < 0.001). Smaller retinal arteriolar diameters are independently associated with incident hypertension, which suggests that arteriolar narrowing may be linked to the occurrence and development of hypertension.

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Author and article information

Journal

Journal ID (nlm-ta): Open Heart

Journal ID (iso-abbrev): Open Heart

Journal ID (hwp): openhrt

Journal ID (publisher-id): openheart

Title: Open Heart

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2053-3624

Publication date Collection: 2020

Publication date (Electronic): 8 January 2020

Volume: 7

Issue: 1

Electronic Location Identifier: e001124

Affiliations

[1 ] departmentResearch , Optos plc , Dunfermline, UK

[2 ] departmentCentre for Cardiovascular Sciences , University of Edinburgh , Edinburgh, Lothian, UK

[3 ] departmentThe VAMPIRE Project, Computer Vision and Image Processing Group, School of Science and Engineering , University of Dundee , Dundee, Dundee, UK

[4 ] departmentCentre for Public Health , Queen's University Belfast , Belfast, Belfast, UK

[5 ] departmentEdinburgh Imaging Facility QMRI , University of Edinburgh , Edinburgh, UK

[6 ] departmentThe VAMPIRE Project, Centre for Clinical Brain Sciences , University of Edinburgh , Edinburgh, UK

Author notes

[Correspondence to ] Dr Gavin Robertson; grobertson@ 123456optos.com

Author information

Gavin Robertson http://orcid.org/0000-0002-9670-930X

Enrico Pellegrini https://orcid.org/0000-0001-6913-1760

Jano van Hemert http://orcid.org/0000-0003-0834-7079

Article

Publisher ID: openhrt-2019-001124

DOI: 10.1136/openhrt-2019-001124

PMC ID: 6999694

PubMed ID: 32076560

SO-VID: d74dc503-4b7f-4829-a9c6-bfe53e280fbf

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

History

Date received : 27 June 2019

Date revision received : 27 November 2019

Date accepted : 17 December 2019

Funding

Funded by: SINAPSE (Scottish Image Network: A Platform for Scientific Excellence) Knowledge Exchange Programme;

Funded by: FundRef http://dx.doi.org/10.13039/501100006041, Innovate UK;

Award ID: 1011973

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Keywords: hypertension,imaging and diagnostics,microvascular disease

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Keywords: hypertension, imaging and diagnostics, microvascular disease

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Association between hypertension and retinal vascular features in ultra-widefield fundus imaging

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Abstract

Objective

Methods

Results

Conclusions

Related collections

Vascular Biology

Most cited references 18

Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

Retinal vessel diameters and risk of hypertension: the Rotterdam Study.

Retinal arteriolar diameter and risk for hypertension.

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Cited by 6

Most referenced authors 522