Lipoprotein Subclasses Independently Contribute to Subclinical Variance of Microvascular and Macrovascular Health.

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

Changes in physical activity behavior and development of cardiovascular risk in children.

The study aimed to investigate the association of changes in physical activity, screen time, and cardiorespiratory fitness (CRF) with development of body mass index (BMI), blood pressure (BP), and retinal microvascular health in children over four years. In 2014, 391 children aged 6-8 years were screened, and thereof 262 children were reexamined after four years following standardized protocols. Retinal arteriolar (CRAE) and venular diameters were measured by a retinal vessel analyzer. CRF was objectively assessed by a 20 m shuttle run, physical activity, and screen time by use of a questionnaire. Children who achieved higher CRF levels reduced their BMI (ß [95% CI] -0.35 [-0.46 to -0.25] kg/m2 per stage, P ≤ .001) and thereby developed wider CRAE (ß [95% CI] 0.25 [0.24 to 0.48] µm per stage, P = .03) at follow-up. Moreover, children with elevated or high systolic BP at baseline, but lower levels of screen time during the observation period, had wider CRAE at follow-up (ß [95% CI] -0.37 [-0.66 to -0.08] µm per 10 min/d, P = .013). Change in CRF was not directly associated with better microvascular health at follow-up. However, an increase of CRF over four years was associated with a reduced BMI and consequently wider retinal arterioles at follow-up. In children with elevated or high systolic BP, a reduction of screen time significantly improved retinal microvascular health as a primary prevention strategy to promote childhood health and combat development of manifest CV disease later in life.

Hand and knee osteoarthritis are associated with reduced diameters in retinal vessels: the AGES-Reykjavik study.

To investigate the association between osteoarthritis (OA) and microvascular pathology, we examined the relationship between retinal microvascular caliber and osteoarthritis of the hand and knee in an elderly population. The AGES-Reykjavik is a population-based, multidisciplinary longitudinal cohort study of aging. Retinal vessel caliber, hand osteoarthritis and total knee joint replacements due to OA were examined in 4757 individuals (mean age 76 ± 5 years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5 years; 58% female) were also assessed. Logistic regression analysis, adjusting for age, sex, and body mass index, showed an association between narrow arteriolar caliber and hand OA, as well as knee replacement. After adjustment for other covariates, including statin therapy, this association was significant for both hand OA in men and women [OR 1.10(1.03-1.17), p < 0.01] (per unit standard deviation decrease in CRAE) and TKR prevalence [OR 1.15 (1.01-1.32), p = 0.04], especially for men [OR 1.22 (1.00-1.51) p = 0.04] and also for incident TKRs in men [OR 1.50 (1.07-2.10), p = 0.04]. Narrow venular caliber was associated with hand OA in women [OR 1.10 (1.01-1.21), p = 0.03]. Retinal arterial narrowing in hand and knee OA is present in males as well as females. Venular narrowing in hand OA in women was an unexpected finding and is in contrast with the venular widening usually observed in cardiovascular diseases.

Cross-sectional association between oral health and retinal microcirculation.

AIM: To investigate the relation between oral health status and microcirculation, we analysed the association between periodontitis and number of teeth with retinal vessel diameters in a population-based study. METHODS: We analysed data from the Study of Health in Pomerania-TREND (SHIP-TREND). All subjects (3,183 for number of teeth, 3,013 for mean probing depth and 2,894 for mean attachment level) underwent nonmydriatic funduscopy and dental examination. We measured central retinal arteriolar (CRAE), venular (CRVE) vessel diameters and calculated arterio-venous ratio (AVR) from static vessel analysis (SVA). Periodontal status was assessed using the case definition of the Center for Disease Control and Prevention/American Academy of Periodontology (CDC/AAP). Data were analysed by linear (CRAE, CRVE, AVR) and logistic regression (AVR < 0.8) adjusted for age, sex, smoking status, alcohol consumption, body mass index, systolic blood pressure, hsCRP and type-2-diabetes mellitus. RESULTS: Only in men, significant associations were found between periodontal and retinal conditions. Severe periodontitis [ß = -0.0120 (-0.0218; -0.0007 95%-CI)] and mean probing depth [ß = -0.0054 (-0.0105; -0.0002 95%-CI)] were inversely associated with AVR; severe periodontitis [ß = 3.80 (0.61; 6.98 95%-CI)], mean probing depth [ß = 1.86 (0.23; 3.49 95%-CI)] and mean attachment level [ß = 1.31 (0.34; 2.27 95%-CI)] with CRVE and mean attachment level with CRAE [ß = 0.91 (0.14; 1.69 95%-CI)]. CONCLUSIONS: Our results point towards an association between periodontal conditions and AVR in men. Periodontitis may impact microvascular endothelium function. Improving oral health to reduce periodontitis might lead to reduced risk for other age-related diseases.

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.

Diameter Changes of Retinal Vessels in Diabetic Retinopathy.

PURPOSE OF REVIEW: The diameter of retinal vessels is an important source of information about retinal blood flow and metabolism. The purpose of the present study is to review how diameter changes of retinal vessels contribute to the development of diabetic retinopathy and may be a marker of the prognosis of the disease. RECENT FINDINGS: The early stages of diabetic retinopathy are accompanied with dilatation of the diameter of retinal vessels and reduced autoregulation. Diabetic retinopathy also shows regional differences in the macular area and the retinal periphery and accompanying differences in vascular reactivity in these areas. These differences may potentially become an important source of insight into the pathophysiology of the disease in the future. Diabetic retinopathy is accompanied with changes in the diameter regulation of retinal vessels. The potential of newly developed techniques for assessing retinal blood flow and metabolism, such as Doppler techniques, adaptive optics, and retinal oximetry, is promising and may potentially contribute to significant advances in our understanding of diabetic retinopathy which remains a major cause of visual impairment.

Greenspace exposure and the retinal microvasculature in healthy adults across three European cities.

BACKGROUND: Emerging evidence points to the beneficial role of greenspace exposure in promoting cardiovascular health. Most studies have evaluated such associations with conventional cardiovascular endpoints such as mortality, morbidity, or macrovascular markers. In comparison, the microvasculature, a crucial compartment of the vascular system where early subclinical signs of cardiovascular problems appear, has not been studied in association with greenspace exposure. The current study assessed the association between surrounding greenness and microvascular status, as assessed by retinal vessel diameters. METHODS: This study included a sample of healthy adults (n = 114 and 18-65 years old) residing in three European cities [Antwerp (Belgium), Barcelona (Spain), and London (UK)]. The exposures to greenspace at the home and work/school locations were characterized as average surrounding greenness [normalized difference vegetation index (NDVI)] within buffers of 100 m, 300 m, and 500 m. The central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were calculated from fundus pictures taken at three different time points. We developed linear mixed-effect models to estimate the association of greenspace exposure with indicators of retinal microvasculature, adjusted for relevant individual and area-level covariates. RESULTS: We observed the most robust associations with CRVE. Higher levels of greenspace at work/school were associated with smaller retinal venules [(seasonal NDVI) 300m: 3.85, 95%CI -6.67,-1.03; 500m: 5.11, 95%CI -8.04, -2.18]. Findings for surrounding greenness and CRAE were not conclusive. CONCLUSION: Our study suggests an association of greenspace exposure with better microvascular status, specifically for retinal venules. Future research is needed to confirm our findings across different contextual settings.

Subcutaneous advanced glycation end products, cardiovascular risk factors and vascular health during childhood development in a Swiss population.

Background: Skin-derived advanced glycation end products (sAGEs) have been associated with cardiovascular (CV) risk and mortality in adults. We hypothesize that cardiorespiratory fitness (CRF), body mass index (BMI) and vascular health are associated with development of sAGEs during childhood. Methods: In our prospective cohort study, 1171 children aged 6-8 years were screened for sAGEs, BMI, retinal arteriolar diameters (CRAE) and pulse wave velocity (PWV), using standardized procedures. To determine CRF a 20 m shuttle run was performed. After four 4 years, all parameters were assessed in 675 children using the same protocols. Results: Higher initial CRF levels were significantly associated with lower sAGEs (ß [95 CI] -0.02 [-0.03 to -0.002] au, p = 0.022) levels at follow-up, although they showed a greater change from baseline to follow-up (ß [95 CI] 0.02 [0.002 to 0.03] au, p = 0.027). Moreover, individuals with higher sAGEs at baseline showed narrower CRAE (ß [95% CI] -5.42 [-8.76 to -2.08] µm, p = 0.001) at follow-up and showed a greater change in CRAE (ß [95% CI] -3.99 [-7.03 to -0.96] µm, p = 0.010) from baseline to follow-up. Conclusion: Exercise and higher CRF may help mitigate the formation of AGEs during childhood, thereby reducing the risk for development of CV disease associated with AGEs-induced damage. Preventive strategies may need to target CRF early in life to achieve improvement of CV risk factors and may counteract the development of CV disease later in life.

Alterations in Retinal Vessel Diameters in Patients with Retinal Vein Occlusion before and after Treatment with Intravitreal Ranibizumab.

Purpose: To investigate the alterations of retinal vessel diameters in patients with macular edema secondary to retinal vein occlusion (RVO), before and after treatment with intravitreal ranibizumab. Methods: Digital retinal images were obtained from 16 patients and retinal vessel diameters were measured before and three months after treatment with intravitreal ranibizumab with validated software to determine central retinal arteriolar and venular equivalents, as well as arteriolar to venular ratio. Results: In 17 eyes of 16 patients with macular edema secondary to RVO (10 with branch RVO and 6 with central RVO) aged 67 ± 10.2 years, we found that diameters of both retinal arterioles and venules were significantly decreased after intravitreal ranibizumab treatment. Specifically, the central retinal arteriolar equivalent was 215.2 ± 11.2 µm at baseline and 201.2 ± 11.1 µm at month 3 after treatment (p < 0.001), while the central retinal venular equivalent was 233.8 ± 29.6 µm before treatment versus 207.6 ± 21.7 µm at month 3 after treatment (p < 0.001). Conclusions: A significant vasoconstriction in both retinal arterioles and venules in patients with RVO was found at month 3 after intravitreal ranibizumab treatment compared to baseline. This could be of clinical importance, since the degree of vasoconstriction might be an early marker of treatment efficacy, compatible with the idea that hypoxia is the major trigger of VEGF in RVO. Further studies should be conducted to confirm our findings.

Bivariate relation of vascular health and blood pressure progression during childhood.

BACKGROUND AND AIMS: Hypertension is a major risk factor for the development of cardiovascular disease (CVD) in adulthood. High blood pressure (BP) is associated with subclinical vascular impairments as early as childhood. We aimed to assess the association of retinal microvascular diameters and large artery pulse wave velocity (PWV) with progression of childhood BP. METHODS: In our prospective Basel cohort study, 1171 children aged 6-8 years were screened for BP, body mass index, retinal vessel diameters and PWV using standardized protocols. After 4 years, all parameters were assessed in 749 children using the same protocols. RESULTS: Children with narrower central retinal arteriolar diameters (CRAE) and higher PWV at baseline developed higher systolic BP after 4 years (ß [95% CI] 0.6 [0.072 to 1.164] mmHg per 10 µm decrease, p = 0.026 and ß [95% CI] 0.6 [0.331 to 0.838] mmHg per 0.1 m/s increase, p < 0.001, respectively). Children with increased systolic BP at baseline developed narrower CRAE and higher PWV at follow-up (ß [95% CI] -3.3 [-4.43 to -2.09] µm per 10 mmHg increase, p < 0.001 and ß [95% CI] 0.13 [0.10 to 0.16] m/s per 10 mmHg increase, p < 0.001, respectively). CONCLUSIONS: Retinal arteriolar diameter and PWV independently predict progression of childhood BP, while initial BP is linked to development of micro- and macrovascular impairments, describing a bivariate temporal relationship between vascular health and BP. Childhood may present a window of opportunity for initiation of primary prevention strategies for the treatment of high BP to help prevent manifestation of CVD later in life.

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 6-8 years were screened for CRF, BMI, BP, retinal vessel diameters and pulse wave velocity using standardized protocols. Endurance capacity was assessed by 20 m shuttle run test. After 4 years, all parameters were assessed in 664 children using the same protocols. Results: Children with a higher CRF at baseline developed a significantly lower BMI (ß [95% CI] -0.09 [-0.11 to -0.06] kg/m2, p < 0.001), a lower systolic BP (ß [95% CI] -0.09 [-0.15 to -0.03] mmHg, p = 0.004) and a higher AVR (ß [95% CI] 0.0004 [0.00004 to 0.0007] units, p = 0.027) after 4 years. 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).

Lower fractal dimension of retinal vessel for patients with Birdshot chorioretinopathy.

PURPOSE: To identify the retinal vessel vasculature parameters associated with birdshot chorioretinopathy (BSCR). METHODS: This retrospective observational study included 28 prevalent cases of BSCR with a median time from diagnosis of 6 years and 28 controls matched for age, arterial hypertension, diabetes and refraction. Forty-five-degree fundus images of both dilated eyes were acquired with a fundus camera (Canon CR-2, Tokyo, Japan). The summary diameter of the arterial retinal vessels (central retinal artery equivalent, CRAE), venous retinal vessels (central retinal vein equivalent, CRVE), vascular tortuosity and fractal dimension (FD) were measured using VAMPIRE software. Retinal vasculitis was characterized using fluorescein angiography and active choroiditis using indocyanine green angiography. RESULTS: At baseline, BSCR was associated with lower FD compared with matched controls (mean difference, -0.04; 95% confidence interval [CI], -0.06 to -0.02, p < 0.001). No other VAMPIRE parameters (CRAE, CRVE, arterial and venous tortuosity) differed. Among BSCR patients, retinal vein vasculitis was associated with higher CRAE (mean difference, 21 µ; 95% CI, 2.6-40, p = 0.03), venous tortuosity (geometric mean ratio, 1.79; 95% CI, 1.18-2.72, p = 0.007) and FD (mean difference, -0.04; 95% CI, -0.06 to -0.01, p = 0.007). Resolution of retinal vein vasculitis during follow-up was paralleled by decrease in CRAE, CRVE and venous tortuosity values and increase in venous FD, respectively. CONCLUSION: BSCR is associated with lower FD value, suggesting that chronic retinal inflammation induces microvascular remodelling. Efficient treatment of retinal vasculitis may reverse changes in retinal vascular parameters. Changes in retinal vascular parameters could be potentially useful for assessing patients with BSCR disease.

Assessment of the impact of N95 respirators or surgical masks use on the retinal microvasculature.

PURPOSE: To determine the possible impact of wearing N95 respirator or surgical masks on retinal vessel diameters and choroidal thickness in healthy healthcare workers. METHODS: Diameters of peripapillary retinal arteries and veins and choroidal thickness values at the foveal center and at 1000 µm distances from the foveal center in both nasal and temporal directions were measured before mask wearing using a spectral-domain optical coherence tomography. After four hours (h) of N95 or surgical mask wearing vessel diameter and choroidal thickness measurements were repeated. RESULTS: A total of 52 eyes from 52 participants (28 F [53.8%]; 24 M [46.2%]) were enrolled in this study. The mean age of patients was 34.58 ± 5.24 years (25-44 years). The diameters of all measured arteries [inferior temporal artery (p = 0.003), superior temporal artery (p < 0.001), inferior nasal artery (p = 0.003), and superior nasal artery (p = 0.004)] and veins,with the exception of superior nasal vein, (inferior temporal vein (p = 0.031), superior temporal vein (p = 0.027), inferior nasal vein (p < 0.001), and superior nasal vein (p = 0.063)] increased significantly after four hour use of N95 respirators and surgical maskswhen compared to baseline. There was also a significant diameter increase of the superior temporal (p < 0.001), inferior nasal veins (p < 0.001), and superior temporal artery (p = 0.037) for N95 respirators and surgical masks use, respectively. The differences in central subfoveal, temporal, and nasal choroidal thickness between baseline and after 4 h use of N95 respirators were statistically significant (From 366.73 ± 70.81 µm to 381.23 ± 69.29µm,p < 0.001 for the subfoveal; from 324.00 ± 64.13µm to 335.40 ± 61.35 µm, p = 0.007 for the temporal; from 297.40 ± 68.18 µm to 308.23 ± 74.51µm, p = 0.002 for the nasal thicknesses). Choroidal thickness values were also increased with surgical mask use. But only the increase in central subfoveal thickness was statistically significant (From 366.78 ± 71.00 µm to 372.58 ± 76.56 µm, p = 0.031 for the central subfoveal; from 297.42 ± 68.35 µmto 302.79 ± 73.05 µm, p = 0.068 for the nasal; from 324.01 ± 64.21µm to 330.33 ± 65.84, p = 0.117 for the temporal thicknesses). CONCLUSION: With four hours use of N95 respirators or surgical face masks, retinal vessel diameters and choroidal thicknesses showed an increase in comparison to baseline measurements. Hemodynamic changes seen secondary to hypercapnia due to prolonged use of N95 respirators or surgical masks may also be observed in the retinal and choroidal circulation. Furthermore, the use of face masks should be taken into account while assessing the retinal microvasculature.

Retinal vessel diameters and function in cardiovascular risk and disease.

In the last two decades evidence has gradually accumulated suggesting that the eye may be a unique window for cardiovascular risk stratification based on the assessment of subclinical damage of retinal microvascular structure and function. This can be facilitated by non-invasive analysis of static retinal vessel diameters and dynamic recording of flicker light-induced and endothelial function-related dilation of both retinal arterioles and venules. Recent new findings have made retinal microvascular biomarkers strong candidates for clinical implementation as reliable risk predictors. Beyond a review of the current evidence and state of research, the article aims to discuss the methodological benefits and pitfalls and to identify research gaps and future directions. Above all, the potential use for screening and treatment monitoring of cardiovascular disease risk are highlighted. The article provides fundamental comprehension of retinal vessel imaging by explaining anatomical and physiological essentials of the retinal microcirculation leading to a detailed description of the methodological approach. This allows for better understanding of the underlying retinal microvascular pathology associated with the prevalence and development of cardiovascular disease. A body of new evidence is presented on the clinical validity and predictive value of retinal vessel diameters and function for incidence cardiovascular disease and outcome. Findings in children indicate the potential for utility in childhood cardiovascular disease prevention, and the efficacy of exercise interventions highlight the treatment sensitivity of retinal microvascular biomarkers. Finally, coming from the availability of normative data, solutions for diagnostic challenges are discussed and conceptual steps towards clinical implementation are put into perspective.

Changes in retinal vascular diameters in senior and geriatric cats in association with variation in systemic blood pressure.

OBJECTIVES: Early diagnosis of arterial hypertension is essential to prevent target organ damage. In humans, retinal arteriolar narrowing predicts hypertension. This blinded prospective observational study investigated the retinal vessel diameters in senior and geriatric cats of varying systolic blood pressure (SBP) status and evaluated retinal vascular changes in hypertensive cats after treatment. METHODS: Cats with a median age of 14 years (range 9.1-22 years) were categorised into five groups: group 1, healthy normotensive (SBP <140 mmHg; n = 40) cats; group 2, pre-hypertensive (SBP 140-160 mmHg; n = 14) cats; group 3, cats with chronic kidney disease (CKD) and normotensive (n = 26); group 4, cats with CKD and pre-hypertensive (n = 13); and group 5, hypertensive cats (SBP >160 mmHg, n = 15). Colour fundus images (Optibrand ClearView) were assessed for hypertensive lesions. Retinal vascular diameters and bifurcation angles were annotated and calculated using the Vascular Assessment and Measurement Platform for Images of the Retina annotation tool (VAMPIRE-AT). When available, measurements were obtained at 3 and 6 months after amlodipine besylate treatment. RESULTS: Ten hypertensive cats had retinal lesions, most commonly intraretinal haemorrhages and retinal exudates. Arteriole and venule diameters decreased significantly with increasing age (-0.17 ± 0.05 pixels/year [P = 0.0004]; -0.19 ± 0.05 pixels/year). Adjusted means ± SEM for arteriole and venule diameter (pixels) were 6.3 ± 0.2 and 8.9 ± 0.2 (group 1); 7.6 ± 0.3 and 10.1 ± 0.4 (group 2); 6.9 ± 0.2 and 9.5 ± 0.3 (group 3); 7.4 ± 0.3 and 10.0 ± 0.4 (group 4); and 7.0 ± 0.3 and 9.8 ± 0.4 (group 5). Group 1 arteriole and venule diameters were significantly lower than those of groups 2 and 4. Group 2 arteriole bifurcation angle was significantly narrower than those of groups 1 and 3. Post-treatment, vessel diameters decreased significantly at 3 and 6 months in seven hypertensive cats. CONCLUSIONS AND RELEVANCE: Increased age was associated with reduced vascular diameters. Longitudinal studies are required to assess if vessel diameters are a risk indicator for hypertension in cats.

Retinal oxygen saturation and vessel diameter in patients with chronic kidney disease.

PURPOSE: To investigate changes in retinal oximetry and the diameter of retinal vasculature in patients with chronic kidney disease (CKD) and relationships between retinal vasculature and the estimated glomerular filtration rate (eGFR), provide a scientific basis for the early detection and diagnosis of CKD. METHODS: Eighty-three patients with CKD and 103 healthy individuals were included after providing informed consent. All participants were examined using a noninvasive technology (Oxymap Inc., Reykjavik, Iceland) for measuring the arterial (SaO2 ) and venous (SvO2 ) oxygen saturation and the arteriovenous difference in oxygen saturation (Sa-vO2 ). The corresponding retinal vessel diameters of these arterioles (D-A) and venules (D-V) were measured. The eGFR of patients with CKD was calculated from the serum creatinine concentration. RESULTS: In general, patients with CKD had higher mean SaO2 values than healthy individuals (100.15 ± 4.68% versus 97.14 ± 4.22%; p < 0.001, mean ± SD). The mean SaO2 in the superior temporal, superior nasal and inferior nasal quadrants significantly increased. There was no significant difference measured in the SvO2 when patients with CKD (63.66 ± 5.29%) and healthy individuals (62.70 ± 5.27%) were compared. The mean Sa-vO2 of the CKD group (36.49 ± 4.98%) was increased compared with normal subjects (34.44 ± 4.76%) (p = 0.005). The retinal arteriole diameter was narrower in patients with CKD than in normal individuals (117.53 ± 14.88 µm versus 126.87 ± 14.98 µm; p < 0.001, mean ± SD), and the arteriovenous ratio was smaller than in normal individuals (0.71 ± 0.09 versus 0.77 ± 0.09; p < 0.001, mean ± SD). Pearson's two-tailed correlation showed a significant correlation between the SaO2 and eGFR (R = -0.363, p = 0.001), and narrower retinal arterial calibre was significantly associated with a lower eGFR (R = 0.415, p < 0.001). CONCLUSION: Based on our results, there were alterations in retinal oxygen saturation and vascular diameter in patients with CKD. Further studies are needed to determine whether such changes play a role in the development of CKD.

Blood Pressure Increase and Microvascular Dysfunction Accelerate Arterial Stiffening in Children: Modulation by Physical Activity.

BACKGROUND: Atherosclerotic remodeling starts early in life and can accelerate in the presence of cardiovascular risk (CV) factors. Regular physical activity (PA) can mitigate development of large and small artery disease during lifespan. We aimed to investigate the association of changes in body mass index (BMI), blood pressure (BP), PA behavior and retinal microvascular diameters with large artery pulse wave velocity (PWV) in prepubertal children over 4 years. METHODS: The school-based prospective cohort study included 262 children initially aged 6-8 years, assessing the above CV risk factors and retinal vessels by standardized procedures at baseline (2014) and follow-up (2018). PWV was assessed by an oscillometric device at follow-up. RESULTS: Children with increased systolic BP over 4 years showed higher PWV at follow-up (ß [95% CI] 0.006 [0.002 to 0.011] mmHg per unit, P = 0.002). In contrast, increased vigorous PA corresponded to a lower PWV at follow-up (ß [95% CI] -0.009 [-0.018 to <0-0.001] 10 min/day per unit, P = 0.047). Progression of retinal arteriolar narrowing and venular widening were linked to a higher PWV after 4 years (ß [95% CI] -0.014 [-0.023 to -0.004] 0.01 changes per unit, P = 0.003). CONCLUSION: Increase in systolic BP and progression of microvascular dysfunction were associated with higher PWV after 4 years. Children with increasing levels of vigorous PA were found to have lower PWV at follow-up. Habitual vigorous PA has the potential to decelerate the process of early vascular aging in children and may thus help counteract CV disease development later in life. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03085498.

Physical activity and exercise improve retinal microvascular health as a biomarker of cardiovascular risk: A systematic review.

BACKGROUND AND AIMS: Physical activity (PA) and fitness are important modulators of vascular ageing and may therefore help expand individual health span. We aimed to systematically review the association of PA and fitness, as well as the effects of exercise interventions on the new microvascular biomarkers retinal arteriolar (CRAE) and venular (CRVE) diameters and the retinal flicker light-induced dilatation (FID) in children and adults. METHODS: PubMed, Ovid, The Cochrane, EMBASE and Web of Science were searched. 805 studies were found, and 25 full-text articles analysed. Twenty-one articles were included in this systematic review. RESULTS: Higher PA levels were associated with narrower CRVE in children and adults. Physical inactivity was associated with wider CRVE in both age groups. Combined aerobic and motor skill training in school settings lead to wider CRAE in children. Aerobic exercise interventions in adults with or without CV risk factors induced wider CRAE and narrower CRVE. Studies on the effect of exercise on FID are scarce. In a twelve-week randomized controlled trial, high-intensity interval training significantly improved FID in older patients with CV risk factors. CONCLUSIONS: Higher PA and fitness levels were associated with improved retinal microvascular health in children and adults. Short-term exercise interventions in healthy children and adults, as well as CV risk patients, improved retinal microvascular structure and function. Exercise has the potential to counteract microvascular remodelling and development of small vessel disease during lifespan. Retinal vessel analysis can differentiate the beneficial effects of exercise on target microvascular organ damage.

Associations of cardiovascular risk factors and retinal vessel dimensions at present and their evolution over time in a healthy working population.

PURPOSE: The aim of this study was to investigate whether an association between retinal vessel diameters with blood pressure and other risk factors exists in a healthy working population and whether current risk factors can be used as predictors for retinal vessel changes over time. METHODS: Retinal photographs and medical data were obtained during a voluntary work health check in 2010 and 2013. The central retinal arterial equivalent (CRAE) and central retinal venular equivalent (CRVE) were assessed using a semi-automated software. Linear regression analysis was carried out to determine associations with systemic parameters and cardiovascular risk factors. RESULTS: A total of 1685 participants had gradable photographs and full medical data with a mean age of 44.8 years (SD: 10.2) and 80.8% being male; full data were obtained in both 2010 and 2013 for 365 participants allowing for longitudinal analysis. In the cross-sectional analysis, a mean CRAE of 171.2 ±18.3 µm and a mean CRVE 215.8 ± 18.6 µm were found. A significant negative association for CRAE was seen for age, mean arterial blood pressure (MABP), body mass index (BMI) and high-density lipoprotein (HDL), while triglycerides, spherical equivalent (SAE) and being a current smoker were positively associated. For CRVE age, MABP, HbA1c and HDL were negatively associated, while being female, low-density lipoprotein, white blood cell count, SAE and being a current smoker showed a positive association. The linear regression model for the cross-sectional analysis explained 31% and 21% of the variance of CRAE and CRVE, respectively. The longitudinal analysis showed a mean decrease of -1.6 µm (p = 0.04) for CRAE and -2.0 (p = 0.005) for CRVE within the three-year time frame. Linear regression analysis with longitudinal data showed a significant association for HDL and CRAE, while for other factors no statistically significant association between current risk factors and changes in CRAE and CRVE was observed. CONCLUSION: The width of both arterial and venous retinal vessels shows associations not only with arterial blood pressure but also with biochemical markers of cardiovascular risk. While such effects are partially established for elderly persons, our study results indicate that they apply also in a young population in working age with seemingly unimpaired health.

Spectral-domain optical coherence tomography of retinal vessels in Waldenström's macroglobulinemia.

PURPOSE: To image retinal blood vessels in patients with Waldenström's macroglobulinemia using optical coherence tomography (OCT). METHODS: Retrospective case series examining fundus photographs and OCT scans of 16 eyes in eight patients with Waldenström's macroglobulinemia. Analyses included intravascular OCT reflectivity profiles and vessel diameters, and their relation to total immunoglobulin M (IgM) levels. RESULTS: In six out of eight patients, cross-sectional OCT scans of larger retinal vessels (diameter > 100 µm) showed normal intravascular reflectivity and retrovascular shadowing. In two patients with the highest total IgM > 60 g/l, altered intravascular reflectivity, distinct anterior and posterior vessel wall reflexes, and retrovascular hyposhadowing were seen. Normalization of the OCT reflectivity in these patients occurred after reduction of total IgM to < 17 g/l and was accompanied by decreasing venous tortuosity and disappearance of retinal haemorrhages and cotton wool spots. CONCLUSION: This study found that Waldenström's macroglobulinemia and total IgM > 60 g/l were associated with abnormal intravascular reflectivity and retrovascular shadowing on OCT. Awareness of these signs of hyperviscosity could potentially enable earlier detection of critical conditions in patients with Waldenström's macroglobulinemia and improve the assessment of severity and treatment effect.