Arteriolar-to-venular Diameter Ratio Research Articles

Non-Invasive Retinal Vessel Analysis as a Predictor for Cardiovascular Disease.

Cardiovascular disease (CVD) is the most frequent cause of death worldwide. The alterations in the microcirculation may predict the cardiovascular mortality. The retinal vasculature can be used as a model to study vascular alterations associated with cardiovascular disease. In order to quantify microvascular changes in a non-invasive way, fundus images can be taken and analysed. The central retinal arteriolar (CRAE), the venular (CRVE) diameter and the arteriolar-to-venular diameter ratio (AVR) can be used as biomarkers to predict the cardiovascular mortality. A narrower CRAE, wider CRVE and a lower AVR have been associated with increased cardiovascular events. Dynamic retinal vessel analysis (DRVA) allows the quantification of retinal changes using digital image sequences in response to visual stimulation with flicker light. This article is not just a review of the current literature, it also aims to discuss the methodological benefits and to identify research gaps. It highlights the potential use of microvascular biomarkers for screening and treatment monitoring of cardiovascular disease. Artificial intelligence (AI), such as Quantitative Analysis of Retinal vessel Topology and size (QUARTZ), and SIVA-deep learning system (SIVA-DLS), seems efficient in extracting information from fundus photographs and has the advantage of increasing diagnosis accuracy and improving patient care by complementing the role of physicians. Retinal vascular imaging using AI may help identify the cardiovascular risk, and is an important tool in primary cardiovascular disease prevention. Further research should explore the potential clinical application of retinal microvascular biomarkers, in order to assess systemic vascular health status, and to predict cardiovascular events.

Effects of high-intensity interval training on retinal vessel diameters and oxygen saturation in patients with hypertension: A cross-sectional and randomized controlled trial

IntroductionArterial hypertension is a global healthcare burden that affects macrovascular and microvascular structure and function and can promote vascular end-organ damage. This study aimed 1) to evaluate differences in microvascular health between normotensive individuals and patients with arterial hypertension and 2) to assess the effects of short-term high-intensity interval training (HIIT) on microvascular health in the subgroup with arterial hypertension as add-on treatment to antihypertensive medication. MethodsIn the cross-sectional part, central retinal arteriolar (CRAE) and venular diameter equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), and retinal oxygen saturation (O2-saturation) were investigated in 19 normotensive healthy controls (mean age 56 ± 7 years) and 41 patients with arterial hypertension (mean age 59 ± 7 years). In the subsequent randomized controlled trial (RCT), patients with arterial hypertension were randomized to an intervention group (HIIT 3×/week) or a control group that received standard physical activity recommendations after baseline assessment. Assessments of retinal vessel biomarkers and patients` characteristics were repeated after the intervention period of 8 weeks. ResultsIn the cross-sectional part, individuals with normal blood pressure (BP) showed lower body mass index (BMI), body fat, 24 h systolic and diastolic BP, higher peak oxygen uptake, wider CRAE (174 ± 17 μm vs. 161 ± 17 μm, p = 0.009), and higher AVR (0.84 ± 0.05 vs. 0.79 ± 0.05, p = 0.003) compared to patients with hypertension. In the RCT, patients with arterial hypertension showed reduced BMI and fasting glucose levels after HIIT and control condition. In addition, the intervention group reduced body fat percentage (27.0 ± 5.5 vs. 25.8 ± 6.1, p = 0.023) and increased peak oxygen uptake (33.3 ± 5.7 vs. 36.7 ± 5.1, p < 0.001). No changes in BP were found in either group. The intervention group showed narrower CRVE (β −4.8 [95 % CI, −8.85, −0.81] p = 0.020) and higher AVR (0.03 [0.01, 0.04] p < 0.001) after eight weeks of HIIT compared to the control group. No statistically significant changes in retinal O2-saturation were found in either group. ConclusionShort-term HIIT proved to be an effective treatment to ameliorate hypertension-induced retinal microvascular abnormalities in patients with hypertension. Retinal vessel diameters may prove to be a sensitive biomarker to quantify treatment efficacy at the microvascular level, at the earliest possible stage in patients with hypertension.

Cardiorespiratory fitness and development of childhood cardiovascular risk: The EXAMIN YOUTH follow-up study.

Background: Obesity- and hypertension-related cardiovascular (CV) risk has been shown to originate in childhood. Higher body mass index (BMI) and blood pressure (BP) have been associated with increased large artery stiffness and a lower microvascular arteriolar-to-venular diameter ratio (AVR) in children. This study aimed to investigate the association of cardiorespiratory fitness (CRF) with development of BMI, BP and vascular health during childhood. Methods: In our prospective cohort study, 1,171 children aged 6-8years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20m shuttle run test. After 4years, all parameters were assessed in 664 children using the same protocols. Results: Children with a higher CRF at baseline developed a significantly lower BMI (β [95% CI] -0.09 [-0.11 to -0.06] kg/m2, p < 0.001), a lower systolic BP (β [95% CI] -0.09 [-0.15 to -0.03]mmHg, p = 0.004) and a higher AVR (β [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4years. The indirect association of CRF with development of retinal arteriolar diameters was mediated by changes in BMI. Conclusion: Our results identify CRF as a key modulator for the risk trajectories of BMI, BP and microvascular health in children. Obesity-related CV risk has been shown to track into adulthood, and achieving higher CRF levels in children may help counteract the development of CV risk and disease not only in pediatric populations, but may also help reduce the burden of CVD in adulthood. Registration: http://www.clinicaltrials.gov/ (NCT02853747).

COFFEE CONSUMPTION RELATES TO A REDUCTION OF AORTIC STIFFNESS BUT NOT ON MICROCIRCULATION IN WELL-CONTROLLED HYPERTENSIVES

Objective: Nutritional interventions potentially preventing hypertension-related organ damage are far to be fully defined. Coffee is one of the most used beverages all over the world. Many studies tried to define the optimal amount of coffee in order to understand whether coffee has a role in cardiovascular prevention. Thus, we evaluated vascular stiffness in well controlled hypertensives according to coffee consumption. Design and method: We evaluated well-treated 449 patients (225F, 224M, aged 62.56±11.49) with essential hypertension. All patients were checked for organ damage screening including carotid-femoral pulse wave velocity (cfPWV), Augmentation Index (AI), and ankle-brachial Index (ABI). To evaluate microcirculation, amydriatic retinography was performed. Arteriolar-to-Venular diameter Ratio (AVR). The number of coffee cups per day was asked during the visit. The median coffee consumption was 2 cups per day. Results: Patients were subdivided into three groups according to tertiles of cups consumed: Group 1, 0-1 cups 148 patients (87F, 61M; 63.66±12.94), Group 2, 2 cups, 159 patients (77F; 82M; 64.75±10.09), Group 3, &gt;2 cups, 142 patients (60F; 82M; 58.96±10.54). No differences highlighted in BMI, in SBP/DBP, in cfPWV and in ABI. On the contrary, aortic stiffness evaluated as AI results significantly decreased in high coffee consumers compared to other groups (ANOVA p&lt;0.0001). In particular, Group 3 was lower than Group 1 (Group 3 9.54±15.48 vs Group 1 17.49 ± 19.56, p&lt;0.05) and (Group 3 9.54±15.48 vs Group 2 15.88 ± 16.57, p&lt;0.05). AVR was higher in less coffee consumers compared to higher (Group 1 0.91 ± 0.10 vs group 3 0.87 ± 0.11, p&lt;0.05), but no difference resulted between Group 2 and 3 or Group 1 and 2. Moreover, AVR did not correlate to Augmentation Index in any group. Conclusions: Coffee consumption may have a role in prevention of aortic remodelling and stiffness. Consumption of at least 3 cups of coffee per day reduces vascular stiffness and increase central vascular compliance, despite this effect is reduced in distal vascular circulation. Our findings need further analysis, mainly to the effects in distal/central hemodynamics due to different drug treatment.

4095Exercise and vascular ageing: a cross-sectional and randomized controlled trial

Abstract Background Vascular ageing can be quantified at subclinical stages by use of sensitive vascular biomarkers of the macro- and microcirculation. Detection of vascular impairments enables initiation of timely treatment strategies to counteract development of CV disease and improve CV outcome. Purpose To (a) compare large artery stiffness and retinal microvascular diameters in healthy life-long active and healthy sedentary older adults with CV risk patients, and (b) to assess the effects of short-term high-intensity exercise training on vascular health in these patients. Methods Seven hundred and eighty-three participants were screened for their CV risk and physical activity profile. We included 38 healthy active (HA, mean age 60±7 years) and 36 healthy sedentary (HS, mean age 60±7 years) as well as 84 sedentary patients with ≥2 CV risk factors (SR, mean age 59±6 years) in the cross-sectional approach. SR were randomized to a 12-week high-intensity interval training (HIIT) or physical activity recommendations after the baseline assessment. Carotid-femoral PWV (cfPWV) was measured as a marker of large artery stiffness and the central retinal arteriolar (CRAE) and venular (CRVE) diameters as well as the retinal arteriolar-to-venular diameter ratio (AVR) were measured as a marker of the microcirculation. Standard procedures of anthropometric measurements were implemented. Results Anthropometric parameters differed between the groups according to the inclusion criteria. cfPWV was highest in SR (8.2±1.4m/s) compared to HS (7.5±1.6m/s) and HA (7.0±1.1 m/s). HA had a lower cfPWV compared to HS (p&lt;0.05) and SR (p&lt;0.001). HA had wider CRAE (179±14μm) and narrower CRVE (204±17μm) compared to HS (CRAE: 172±11 μm; CRVE: 209±11 μm) resulting in a higher AVR in HA (0.88±0.05) compared to HS (0.83±0.04, p&lt;0.001). By contrast, SR showed narrower CRAE (171±14 μm) and wider CRVE (218±16μm, p&lt;0.05) compared to HS resulting in a lower AVR (0.79±0.05, p&lt;0.001) compared to HS and HA. HIIT in SR improved most classic CV risk factors. Additionally, CRAE increased (pre: 175±14μm vs post: 181±13μm, p=0.001) and CRVE decreased (pre: 222±14μm vs post: 220±14μm, p=0.007) in the HIIT group without changes in the cfPWV. PWV was significantly but moderately associated with AVR (r=−0.2, p=0.01). Conclusions Life-long physical activity and fitness were associated with lower arterial stiffness and favourable retinal vessel diameters in healthy individuals. CV patients had higher arterial stiffness and lower AVR. Short-term HIIT improved retinal microvascular phenotype without changes in large artery stiffness. Retinal vessel diameters are sensitive diagnostic tool for CV risk stratification and subclinical vascular disease monitoring in CV patients. Short-term HIIT may postpone development of small vessel disease in older patients. Acknowledgement/Funding Swiss National Science Foundation, Nora van Meeuwen-Häfliger Stiftung

Retinal Endothelial Function, Physical Fitness and Cardiovascular Risk: A Diagnostic Challenge.

IntroductionDynamic retinal vessel analysis (DVA) is a new non-invasive method to quantify microvascular endothelial dysfunction by flicker light-induced dilatation (FID). FID has been shown to be impaired in type 2 diabetes as well as heart failure. The aim of the study was to analyze FID in healthy active versus healthy sedentary and cardiovascular (CV) risk patients in addition to corresponding static vessel diameters.MethodsThirty-one healthy active (HA, mean age 60 ± 8 years), 33 healthy sedentary individuals (HS, 59 ± 7 years) and 76 sedentary patients with increased CV risk (SR, 58 ± 6 years) were included in this cross-sectional study. Group differences in CV risk factors and cardiorespiratory fitness, maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the arteriolar (AFarea) and venular (VFarea) area under the flicker curve were analyzed. The central retinal arteriolar and venular diameters were used to calculate the arteriolar-to-venular diameter ratio (AVR).ResultsHS [ADmax = 3.5 (2.1)%; AFarea = 48.2 (31.9)%∗s] showed higher FID compared to SR [ADmax = 2.7 (1.8)%, p = 0.021; AFarea = 34.5 (26.5)%∗s, p = 0.006] and HA [AFarea = 32.8 (23.1)%∗s, p = 0.029]. HA and SR did not significantly differ. HA had a higher AVR (0.87 ± 0.05) compared to HS (0.83 ± 0.04, p < 0.001) with further deterioration in SR (0.79 ± 0.05, p < 0.001). Interestingly, 28 participants had impaired FID but normal AVR and 43 participants had normal FID but impaired AVR.DiscussionFID can differentiate between sedentary low and high risk individuals. However, FID in healthy active persons (HA) seemed impaired with a concomitant higher AVR. We postulate that lower FID in HA may be explained by predilatated arterioles and a reduced dilatation reserve. We recommend combination of FID with analysis of retinal vessel diameters to differentiate functional non-responders from manifest microvascular endothelial dysfunction and, thereby, improve microvascular risk stratification in a personalized medicine approach.Clinical Trial RegistrationClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ ct2/show/NCT02796976).

Short- and Long-Term Effects of Bariatric Surgery on Vascular Phenotype.

Retinal microvascular diameters and large artery stiffness are valid biomarkers of cardiovascular risk. This study assessed short- and long-term micro- and macrovascular improvements after bariatric surgery (BS). Sixteen patients (44 ± 12years) underwent BS in this observational study. Two weeks before as well as 6weeks and 4years after surgery, retinal vessel analysis and assessment of brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI), and anthropometry were performed. Three patients were lost to follow-up. Six weeks after BS, retinal arteriolar diameters (CRAE) were wider (180.1μm vs. 188.1μm; p = 0.001), and the arteriolar-to-venular diameter ratio (AVR) was higher (0.82 vs. 0.86; p < 0.001) compared to baseline levels. During the 4years of follow-up, the retinal changes sustained but further improvements did not occur. Both indices of large artery stiffness, baPWV and CAVI, remained unchanged 6weeks and 4years after surgery. Retinal microvascular phenotype improved 6weeks after BS. The improvements in microvascular health were maintained during 4years of follow-up but, despite significant further reductions in body mass index, did not improve further long-term. baPWV and CAVI were unaffected after surgery indicating that BS primarily affects microvascular phenotype rather than large artery stiffness. Retinal vessel imaging seems to be a feasible diagnostic tool to monitor microvascular health after BS. Normalization of BMI and blood pressure may be necessary to achieve long-term improvement of large artery phenotype after BS.

Acute and chronic effects of soccer game on the retinal vessel diameters in middle-aged adults.

Although changes in retinal vessel diameter is a new biomarker for the evaluation of cardiovascular risk factors, limited information is available regarding the effects of endurance exercises on retinal microcirculation. Thus, we aimed to evaluate both chronic and acute effects of soccer game on the diameters of retinal vessels in middle-aged players. Retinal vessel diameters were measured in 12 middle-aged amateur players (44.4±7.0 years of age) with more than four years of soccer playing experience and 12 age-matched sedentary adults (49.7±7.1 years of age). In soccer players, diameters were also measured immediately after the soccer game. Cardiovascular risk profiles (anthropometry and body composition and blood pressure [BP]) and physical activity levels were also measured. Soccer players had wider retinal vessels than controls (P<0.05), resulting in greater arteriolar-to-venular diameter ratio (AVR) (P<0.05). Greater sports-related physical activity, lower body mass index (BMI) and fat mass were observed for soccer players compared to the controls (P<0.05), whereas BP did not differ. Physical activity level correlated positively with temporal retinal arteriolar (TRA) diameter and with AVR (P<0.05), whereas TRA diameter correlated negatively with BMI and fat mass (P<0.05). A significant correlation between temporal retinal venule (TRV) diameter and TRA diameter (P<0.05) was observed. The acute soccer game increased BP (P<0.05) and induced TRV dilatation (P<0.05). In middle-aged amateur soccer players, improvement of the retinal microcirculation was observed. Cardiovascular risk factors and physical inactivity were associated with adverse retinal microvascular alterations. In terms of acute effects, soccer play causes venular, but not arteriolar dilatation for middle-aged adults.

Effects of a cluster-randomized school-based prevention program on physical activity and microvascular function (JuvenTUM 3)

Background and aimsIt is unknown whether a school-based prevention program has the potential to improve microvascular health in children. This study investigates the impact of the school-based lifestyle intervention program JuvenTUM 3 on physical activity, physical fitness, serum biomarkers and microvascular function. MethodsWe studied 434 children (10–11 years) in a cluster-randomized setting (8 intervention schools, IG; 7 control schools, CG) over 18 months. The school-based prevention program included weekly lifestyle lessons for children with the aim to increase physical activity in and outside of school, physical fitness as well as health behavior. Anthropometric measurements and blood sampling were conducted using standard protocols, physical activity by use of a questionnaire and physical fitness by a 6-item-test battery. Central retinal arteriolar (CRAE) and venular (CRVE) vessel diameters as early marker of vascular dysfunction, as well as the arteriolar-to-venular diameter ratio (AVR), were investigated with a non-mydriatic vessel analyser. ResultsSchool-based physical activity increased in 41% of children in IG (19% in CG, p = 0.038). Improvements in vascular parameters were observed for AVR (increase in 83% of children in IG versus 50% in CG; p < 0.001) and for CRVE (43% of children with retinal venular widening in IG versus 58% in CG, p = 0.019). These vascular improvements were also seen in overweight children for CRAE (p = 0.021) and AVR (p < 0.001). ConclusionsThe school-based prevention program JuvenTUM 3 increased physical activity at school inducing favourable effects on retinal microvasculature function. These findings underline the importance of early lifestyle interventions in children for primary prevention of cardiovascular disease.

Association of cardiorespiratory fitness with retinal vessel diameters as a biomarker of cardiovascular risk

ObjectiveWe aimed to investigate the association of retinal microvascular health with cardiorespiratory fitness (VO2peak) and cardiovascular risk factors. MethodsIn a population of 260 obesity-enriched participants we investigated the association of retinal vessel diameters with cardiorespiratory fitness (CRF), body mass index (BMI) and blood pressure (BP). Retinal vessel imaging was performed by use of a fundus camera and a semi-automated processing software, calculating the central retinal arteriolar (CRAE) and venular equivalent (CRVE) as well as the arteriolar-to-venular diameter ratio (AVR). ResultsParticipants had a mean age of 45.8 ± 12.5 years and a BMI of 35.8 ± 6.8 kg/m2. 45% of patients were diagnosed with hypertension, 26% with diabetes and 30% with dyslipidemia. Increasing VO2peak was independently associated with lower CRVE (β = −0.600; CI −1.141, −0.060; p = 0.030). Higher BMI and mean arterial pressure were independently associated with narrower CRAE (β = −0.492; CI −0.909, −0.076; p = 0.021 and β = −0.268; CI −0.471, −0.066; p = 0.009, respectively) and lower AVR (β = −0.002; CI −0.003, −0.000; p = 0.026 and β = −0.001; CI −0.002, −0.000; p = 0.001, respectively). ConclusionsHigher cardiorespiratory fitness is associated with beneficial retinal microvascular health. Higher BMI and BP were associated with an impairment of retinal microvascular health. Exercise is known for its potential to improve body composition and reduce BP but may also prove to be an efficient therapy to counteract small vessel disease in cardiometabolic disease.

Effects of different endurance exercise modalities on migraine days and cerebrovascular health in episodic migraineurs: A randomized controlled trial.

Aerobic exercise training is a promising complementary treatment option in migraine and can reduce migraine days and improve retinal microvascular function. Our aim was to elucidate whether different aerobic exercise programs at high vs moderate intensities distinctly affect migraine days as primary outcome and retinal vessel parameters as a secondary. In this randomized controlled trial, migraine days were recorded by a validated migraine diary in 45 migraineurs of which 36 (female: 28; age: 36 (SD:10)/BMI: 23.1 (5.3) completed the training period (dropout: 20%). Participants were assigned (Strata: age, gender, fitness and migraine symptomatology) to either high intensity interval training (HIT), moderate continuous training (MCT), or a control group (CON). Intervention groups trained twice a week over a 12-week intervention period. Static retinal vessel analysis, central retinal arteriolar (CRAE) and venular (CRVE) diameters, as well as the arteriolar-to-venular diameter ratio (AVR) were obtained for cerebrovascular health assessment. Incremental treadmill testing yielded maximal and submaximal fitness parameters. Overall, moderate migraine day reductions were observed (ηP2=.12): HIT revealed 89% likely beneficial effects (SMD=1.05) compared to MCT (SMD=0.50) and CON (SMD=0.59). Very large intervention effects on AVR improvement (ηP2=0.27), slightly favoring HIT (SMD=-0.43) over CON (SMD=0), were observed. HIT seems more effective for migraine day reduction and improvement of cerebrovascular health compared to MCT. Intermittent exercise programs of higher intensities may need to be considered as an additional treatment option in migraine patients.

Association of body composition and blood pressure categories with retinal vessel diameters in primary school children.

Alterations in retinal vessel diameters have been shown to be predictive of cardiovascular risk in adults and children. The aim of our study was to examine the association of body composition and blood pressure (BP) categories with retinal vessel diameters in school children. We examined anthropometric parameters, BP and retinal arteriolar (CRAE) and venular (CRVE) diameters as well as the arteriolar-to-venular diameter ratio (AVR) in 391 children (age: 7.3, s.d. 0.4). Differences between the lowest and highest BP quartiles indicated that higher systolic and diastolic BP were associated with narrower CRAE (P<0.001 for both). Children in the highest weight quartile had narrower CRAE compared with the lowest quartile (P=0.05). In the regression analysis, systolic and diastolic BP were associated with arteriolar narrowing (-0.4 measuring units (mu) per mm Hg, 95% confidence interval: [-0.6; -0.3] and -0.6 mu per mm Hg [-0.7; -0.4], respectively; P<0.001 for both). An independent association was found for diastolic BP only. Compared with normotensives (NT; 74.4% of cohort), arteriolar narrowing was already seen in children categorized as pre-hypertensive (PHT) (11.5% of cohort), which was similar to HT children (14.1% of cohort) (NT: mean 207.2 [205.6; 208.7] mu; PHT: 201.7 [197.8; 205.7] mu; HT: 199.7 [196.2; 203.3] mu; P=0.01 for PHT vs. NT and P<0.001 for HT vs. NT in systolic BP). Our results suggest that systolic and diastolic BP are main determinants of retinal arteriolar diameters; and therefore, microvascular health in young children. Pre-hypertension seems to be associated with retinal microvascular alterations early in life.

Artery/Vein Discrimination Using GraphBased Approach and LDA Classifier

Analyzing the retinal blood vessels can provide very helpful information to doctors for early detection of diseases Such as diabetic retinopathy due to large number of patients. For this generalized arteriolar narrowing, which is inversely related to higher blood pressure levels is usually expressed by the Arteriolar-to-Venular diameter Ratio (AVR). The AVR value can also be an indicator of other diseases, like hypertension, and other cardiovascular conditions. Among other image processing operations, the estimation of AVR requires vessel segmentation, accurate vessel width measurement, and artery/vein (A/V) classification. This paper presents an automatic approach for A/V classification based on the analysis of a graph extracted from the retinal vasculature. The proposed method classifies the entire vascular tree deciding on the type of each intersection point (graph nodes) and assigning one of two labels to each vessel segment (graph links). Final classification of a vessel segment as A/V is performed through the combination of the graph-based labelling results with a set of intensity features. Accuracy values of 88.3%, 87.4%, and 89.8% are obtained for the images of the INSPIREAVR, DRIVE, and VICAVR databases, respectively. These results demonstrate that our method outperforms recent approaches for A/V classification.

Association of leptin and insulin with childhood obesity and retinal vessel diameters

Childhood obesity is associated with an impaired retinal microcirculation. The aim of the study was to investigate the association between specific obesity-related biomarkers, physical fitness and retinal vessel diameters in school children. We studied 381 children aged 10-11 years (body mass index (BMI): 19.3±3.7 kg m(-2)) in a school-based setting. Anthropometric measurements and blood sampling were conducted using standard protocols for children. The serum biomarkers leptin, adiponectin, insulin as well as interleukin-6 (IL-6) were analyzed. Physical fitness was determined by a six-item-test battery and physical activity by use of a questionnaire. Central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and the arteriolar-to-venular diameter ratio (AVR) were assessed with a non-mydriatic vessel analyzer (SVA-T) using a computer-based program. Compared with normal weight children (n=254), obese children (n=39) showed higher leptin (P<0.001), higher insulin (P<0.001), higher IL-6 (P<0.001) and lower adiponectin levels (P=0.013). Obese children demonstrated wider CRVE (P=0.041) and lower AVR (P<0.001). Higher leptin levels were associated with wider CRVE (P=0.032) and lower AVR (P=0.010), that was BMI dependent. Insulin levels were associated with arteriolar (P=0.045) and venular dilatation (P=0.034) after adjustment for BMI. No significant associations between adiponectin levels, IL-6 levels, physical fitness or physical activity and retinal vessel diameter were observed. Lower leptin levels were independently correlated with higher physical fitness (r=-0.33; P<0.001). Leptin and insulin levels are associated with changes of the retinal microcirculation. Especially insulin seems to be a good target marker for the cardiometabolic risk assessment in children since elevated insulin levels are independently associated with microvascular end-organ alterations at an early stage. Lifestyle intervention studies are warranted to examine whether improvement of physical fitness or weight reduction can affect cardiometabolic risk markers and reverse alterations of the retinal microcirculation.

Development of an automated system to classify retinal vessels into arteries and veins

There are some evidence of the association between the calibre of the retinal blood vessels and hypertension. Computer-assisted procedures have been proposed to measure the calibre of retinal blood vessels from high-resolution photopraphs. Most of them are in fact semi-automatic. Our objective in this paper is twofold, to develop a totally automated system to classify retinal vessels into arteries and veins and to compare the measurements of the arteriolar-to-venular diameter ratio (AVR) computed from the system with those computed from observers.Our classification method consists of four steps. First, we obtain the vascular tree structure using a segmentation algorithm. Then, we extract the profiles. After that, we select the best feature vectors to distinguish between veins and arteries. Finally, we use a clustering algorithm to classify each detected vessel as an artery or a vein.Our results show that compared with an observer-based method, our method achieves high sensitivity and specificity in the automated detection of retinal arteries and veins. In addition the system is robust enough independently of the radii finally chosen, which makes it more trustworthy in its clinical application. We conclude that the system represents an automatic method of detecting arteries and veins to measure the calibre of retinal microcirculation across digital pictures of the eye fundus.

Automated Measurement of the Arteriolar-to-Venular Width Ratio in Digital Color Fundus Photographs

A decreased ratio of the width of retinal arteries to veins [arteriolar-to-venular diameter ratio (AVR)], is well established as predictive of cerebral atrophy, stroke and other cardiovascular events in adults. Tortuous and dilated arteries and veins, as well as decreased AVR are also markers for plus disease in retinopathy of prematurity. This work presents an automated method to estimate the AVR in retinal color images by detecting the location of the optic disc, determining an appropriate region of interest (ROI), classifying vessels as arteries or veins, estimating vessel widths, and calculating the AVR. After vessel segmentation and vessel width determination, the optic disc is located and the system eliminates all vessels outside the AVR measurement ROI. A skeletonization operation is applied to the remaining vessels after which vessel crossings and bifurcation points are removed, leaving a set of vessel segments consisting of only vessel centerline pixels. Features are extracted from each centerline pixel in order to assign these a soft label indicating the likelihood that the pixel is part of a vein. As all centerline pixels in a connected vessel segment should be the same type, the median soft label is assigned to each centerline pixel in the segment. Next, artery vein pairs are matched using an iterative algorithm, and the widths of the vessels are used to calculate the AVR. We trained and tested the algorithm on a set of 65 high resolution digital color fundus photographs using a reference standard that indicates for each major vessel in the image whether it is an artery or vein. We compared the AVR values produced by our system with those determined by a semi-automated reference system. We obtained a mean unsigned error of 0.06 (SD 0.04) in 40 images with a mean AVR of 0.67. A second observer using the semi-automated system obtained the same mean unsigned error of 0.06 (SD 0.05) on the set of images with a mean AVR of 0.66. The testing data and reference standard used in this study has been made publicly available.

Automated selection of major arteries and veins for measurement of arteriolar-to-venular diameter ratio on retinal fundus images

An automated method for measurement of arteriolar-to-venular diameter ratio (AVR) is presented. The method includes optic disc segmentation for the determination of the AVR measurement zone, retinal vessel segmentation, vessel classification into arteries and veins, selection of major vessel pairs, and measurement of AVRs. The sensitivity for the major vessels in the measurement zone was 87%, while 93% of them were classified correctly into arteries or veins. In 36 out of 40 vessel pairs, at least parts of the paired vessels were correctly identified. Although the average error in the AVRs with respect to those based on the manual vessel segmentation results was 0.11, the average error in vessel diameter was less than 1 pixel. The proposed method may be useful for objective evaluation of AVRs and has a potential for detecting focal arteriolar narrowing on macula-centered screening fundus images.

Exercise-induced alterations of retinal vessel diameters and cardiovascular risk reduction in obesity

BackgroundThe retinal microcirculation is affected early in the process of atherosclerosis and retinal vessel caliber is an emerging cardiovascular risk factor. Obesity is associated with vascular dysfunction. Here, we investigate the effect of regular exercise on retinal vessel diameters in lean and obese runners. We analyze a possible link to alterations of the nitric oxide (NO)-asymmetric dimethylarginine (ADMA) pathway. MethodsRetinal vessel diameters were assessed by means of a static vessel analyzer (SVA-T) in 15 obese athletes (OA), 14 lean amateur athletes (AA) and 17 lean elite athletes (EA) following a 10 week training program. ADMA serum levels were detected by ELISA and dimethylarginine dimethylaminohydrolase (DDAH) -1/-2 mRNA-expression in peripheral mononuclear cells (PBMC) was analyzed by real time PCR. ResultsAt baseline, the mean (±SD) arteriolar to venular diameter ratio (AVR) was impaired in obese (OA: 0.81±0.05) compared to lean subjects (AA: 0.87±0.07; EA: 0.94±0.05). The individual fitness levels correlated with AVR (rho=+0.66; P<0.001) and the training program improved AVR in all groups (P<0.001), normalising AVR in the obese (OA: 0.86±0.1). A training-induced arteriolar dilatation was found in OA (P=0.01), which was accompanied by a significant decrease of ADMA levels (0.56±0.12–0.46±0.12μmoll−1; P<0.028). DDAH-1 mRNA levels in PBMC increased in all groups (P<0.01). ConclusionsCardiovascular fitness and body composition affect retinal vessel diameters. Regular exercise reverses the subclinical impairment of the retinal microvasculature in obesity by inducing retinal arteriolar dilatation. The NO/ADMA pathway may play a key role in the training-induced improvement of microvascular function, which has the potential to counteract progression of small vessel disease.

Automatic estimation of the arteriolar‐to‐venular diameter ratio (AVR) in retinal images

Abstract Purpose The Arteriolar‐to‐Venular diameter Ratio (AVR), a parameter derived from vessel caliber measurements in a specific region of retinal images, is used as a descriptor of generalized arteriolar narrowing. We developed a computerized system to compute AVR in a totally automatic way. Methods Images are at first enhanced to highlight the vessel network, which is then traced by a vessel tracking algorithm. From the detected vessel structure, the position of the optic disc is derived and the region inside which the AVR data are to be measured is determined. Vessels within this region are classified as either arteries or veins, their caliber estimated and the AVR parameter is eventually computed. Results provided by the system have been compared with manually derived AVR values on 20 eye fundus images. Results Mean and SD values from the two sets of measurements are the same, and automatic/manual ratios have an average value of 1 and 95% confidence interval of (0.98‐1.02). The correlation coefficient between the two methods is 0.88. In only two images the ratio is appreciably different from unity, 1.14 and 0.89 respectively. A detailed analysis of these cases revealed that in each image the wrong classification of one vessel only was the cause for these unsatisfactory results. When these misclassifications are manually corrected, e.g. with a quick editing tool that can be easily made available to the user, the ratios become 0.95 and 0.99, respectively, and the overall correlation coefficient becomes 0.97. Conclusion Additional evaluation on a larger set of images, acquired from subjects exhibiting wide variations of AVR, will be performed in order to fully assess the reliability and clinical applicability of this automatic procedure.

Automatic Grading of Retinal Vessel Caliber

New clinical studies suggest that narrowing of the retinal blood vessels may be an early indicator of cardiovascular diseases. One measure to quantify the severity of retinal arteriolar narrowing is the arteriolar-to-venular diameter ratio (AVR). The manual computation of AVR is a tedious process involving repeated measurements of the diameters of all arterioles and venules in the retinal images by human graders. Consistency and reproducibility are concerns. To facilitate large-scale clinical use in the general population, it is essential to have a precise, efficient and automatic system to compute this AVR. This paper describes a new approach to obtain AVR. The starting points of vessels are detected using a matched Gaussian filter. The detected vessels are traced with the help of a combined Kalman filter and Gaussian filter. A modified Gaussian model that takes into account the central light reflection of arterioles is proposed to describe the vessel profile. The width of a vessel is obtained by data fitting. Experimental results indicate a 97.1% success rate in the identification of vessel starting points, and a 99.2% success rate in the tracking of retinal vessels. The accuracy of the AVR computation is well within the acceptable range of deviation among the human graders, with a mean relative AVR error of 4.4%. The system has interested clinical research groups worldwide and will be tested in clinical studies.