Retinal Microvascular Caliber Research Articles

Effects of long-term almond consumption on markers for vascular function and cardiometabolic risk in men and women with prediabetes: results of a randomized, controlled cross-over trial.

The aim of this study was to investigate the long-term effects of almond consumption on peripheral vascular function, ambulant blood pressure profiles (ABP), and serum/plasma markers reflecting endothelial dysfunction and inflammation in participants with overweight/obesity and prediabetes. Thirty-four participants completed this single-blinded, randomized, cross-over trial with 5-month intervention and control periods, separated by a 2-month wash-out. During the intervention period, participants consumed 50g of whole almonds daily. At the end of each intervention period, peripheral vascular function was assessed by measuring the carotid-to-femoral and carotid-to-radial pulse wave velocities (PWVc-f and PWVc-r, respectively) and retinal microvascular calibers. Serum/plasma concentrations of soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNFα), serum amyloid A protein (SAA) and high-sensitivity C-reactive protein (hs-CRP) and 24-hour ABP were also analyzed. Almond consumption did not significantly affect arterial stiffness (PWVc-f and PWVc-r), while central retinal venular equivalent (CRVE) was minimally increased by 2μm (P = 0.019). Central retinal arteriolar equivalent (CRAE), the arteriolar-to-venular ratio (AVR), and endothelial and inflammatory serum/plasma markers showed no significant changes after almond consumption. Almond consumption reduced systolic blood pressure (SBP; -3 mmHg 24-hour P = 0.035, -4 mmHg daytime P = 0.046, and - 4 mmHg during nighttime P = 0.029), SBP variability during 24-hour, daytime, and nighttime (P = 0.005, P = 0.019, and P = 0.003, respectively), and diastolic blood pressure variability during nighttime (P ≤ 0.001). Almond consumption did not affect arterial stiffness, retinal microvasculature calibers, or serum and plasma markers for endothelial dysfunction and inflammation in participants with prediabetics, while BP and BP variability were improved. This clinical trial was registered in February 2018 as NCT03419702.

Advances in Structural and Functional Retinal Imaging and Biomarkers for Early Detection of Diabetic Retinopathy.

Diabetic retinopathy (DR), a vision-threatening microvascular complication of diabetes mellitus (DM), is a leading cause of blindness worldwide that requires early detection and intervention. However, diagnosing DR early remains challenging due to the subtle nature of initial pathological changes. This review explores developments in multimodal imaging and functional tests for early DR detection. Where conventional color fundus photography is limited in the field of view and resolution, advanced quantitative analysis of retinal vessel traits such as retinal microvascular caliber, tortuosity, and fractal dimension (FD) can provide additional prognostic value. Optical coherence tomography (OCT) has also emerged as a reliable structural imaging tool for assessing retinal and choroidal neurodegenerative changes, which show potential as early DR biomarkers. Optical coherence tomography angiography (OCTA) enables the evaluation of vascular perfusion and the contours of the foveal avascular zone (FAZ), providing valuable insights into early retinal and choroidal vascular changes. Functional tests, including multifocal electroretinography (mfERG), visual evoked potential (VEP), multifocal pupillographic objective perimetry (mfPOP), microperimetry, and contrast sensitivity (CS), offer complementary data on early functional deficits in DR. More importantly, combining structural and functional imaging data may facilitate earlier detection of DR and targeted management strategies based on disease progression. Artificial intelligence (AI) techniques show promise for automated lesion detection, risk stratification, and biomarker discovery from various imaging data. Additionally, hematological parameters, such as neutrophil-lymphocyte ratio (NLR) and neutrophil extracellular traps (NETs), may be useful in predicting DR risk and progression. Although current methods can detect early DR, there is still a need for further research and development of reliable, cost-effective methods for large-scale screening and monitoring of individuals with DM.

Short-term Aronia melanocarpa extract supplementation improves cognitive performance: a randomized, double-blind, placebo-controlled cross-over study in healthy young adults

PurposeEvidence on the potential beneficial effects of anthocyanin-rich foods and supplements on cognitive performance is mainly based on acute or long-term studies in older adults. However, short-term studies focusing on a younger population are lacking. Therefore, short-term effects of Aronia melanocarpa extract (AME) supplementation on cognitive performance were investigated in healthy young adults. Potential underlying mechanisms were also addressed.MethodsA randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180 mg anthocyanins/day) or a placebo for 1 week, separated by at least 2 weeks of wash-out. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Furthermore, arterial stiffness (carotid-to-femoral pulse wave velocity), retinal microvascular calibers (fundus photography), and serum brain-derived neurotrophic factor (BDNF) concentrations were measured at baseline and after 1 week.ResultsParticipants had a mean age of 25 ± 4 years and an average BMI of 23.4 ± 2.7 kg/m2. Compliance was excellent and the study product was well-tolerated. As compared to placebo, movement time was significantly reduced by 4.8% within the five-choice reaction time test after 1 week of AME supplementation (intervention effect: – 12 ms; p < 0.05). Memory and executive function did however not change. Serum BDNF concentrations were significantly higher after AME supplementation as compared to placebo (+ 5.7%; intervention effect: 1.8 ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected.ConclusionShort-term AME supplementation beneficially affected cognitive performance as attention and psychomotor speed improved. Serum BDNF concentrations were increased, but vascular function markers were not affected.Clinical trial registrationThe study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

Retinal Microvascular Caliber and Incident Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis.

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. The retina allows for visualization of a microvascular bed that shares similarities with the cerebral microvasculature. We investigated the associations between baseline retinal arteriolar and venular calibers (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively) and incident depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA). We used longitudinal data on 4,366 participants (mean age = 63.2 years; 48.5% women, 28.4% Black) without baseline depressive symptoms. Depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale score ≥16 and/or use of antidepressant medication, were determined between 2002 and 2004 (baseline; MESA visit 2) and at 3 follow-up examinations conducted every 1.5–2 years thereafter. Fundus photography was performed at baseline. After a mean follow-up period of 6.1 years, 21.9% (n = 958) had incident depressive symptoms. After adjustment for sociodemographic, lifestyle, and cardiovascular factors, a 1–standard-deviation larger baseline CRVE was associated with a higher risk of depressive symptoms (hazard ratio = 1.10, 95% confidence interval: 1.02, 1.17), and a 1–standard-deviation larger baseline CRAE was not statistically significantly associated with incident depressive symptoms (hazard ratio = 1.04, 95% confidence interval: 0.97, 1.11). In this study, larger baseline CRVE, but not CRAE, was associated with a higher incidence of depressive symptoms.

Microvascular changes at different stages of chronic kidney disease.

Patients with progressing chronic kidney disease (CKD) are more likely to experience cardio‐ and cerebrovascular events than progressing to end‐stage renal disease. The authors explored whether retinal microvascular calibers differed with the degree of renal impairment and between the standard and extended optic disk and may serve as a simple additional tool for risk stratification in this highly vulnerable patient cohort. The authors analyzed central retinal arteriolar and venular equivalent calibers (CRAE, CRVE) at different retinal zones (zone B&C) using digital retinal imaging in hypertensive patients with stage 2 (n = 66) or stage 3 CKD (n = 30). Results were adjusted for age, sex, HbA1c, and 24‐hour diastolic blood pressure. Mean eGFR was 77.7 ± 8.9 and 48.8 ± 7.9 ml/min/1.73 m2 for stage 2 and 3 CKD, respectively. CRAE and CRVE in zones B and C were significantly lower in patients with stage 3 CKD compared to patients with stage 2 CKD (CRAE‐B:141.1 ± 21.4 vs. 130.5 ± 18.9 µm, p = .030; CRAE‐C:137.4 ± 19.4 vs 129.2 ± 18.2 µm, p = .049; CRVE‐B:220.8 ± 33.0 vs. 206.0 ± 28.4 µm, p = .004; and CRVE‐C:215.9 ± 33.0 vs. 201.2 ± 25.1µm, p = .003). In patients with stage 2 CKD, CRAE‐B was higher than CRAE‐C (141.1 ± 21.4 vs. 137.4 ± 19.4µm, p < .001). In contrast, such a difference was not found in patients with stage 3 CKD. CRAE of both retinal zones correlated with eGFR for the entire cohort. In patients with stage 3 CKD, retinal narrowing is more pronounced compared to patients with stage 2 CKD. Whether the novel observation of difference in arteriolar caliber between zones B and C in stage 2 CKD could serve as an early marker of CKD progression warrants further investigation.

YI 1.3 Retinal Microvascular Calibers and Incident Depressive Symptoms: The Multi-Ethnic Study of Atherosclerosis

BackgroundCerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is scarce. The retina allows for direct visualisation of a microvascular bed that shares anatomical and physiological similarities with the cerebral microvasculature. We investigated the association between baseline central retinal arteriolar and venular calibers (CRAE and CRVE) and 7.8-year change of CRAE and CRVE and incident depressive symptoms.MethodsLongitudinal data are from the Multi-Ethnic Study of Atherosclerosis (MESA) of 3,999 participants (62.3 ± 9.7 years; 48.2% women; 26.6% black) without depressive symptoms at baseline. Presence of depressive symptoms, defined as Centre for Epidemiological Studies Depression Scale score ≥16 and/or use of antidepressant medication, was determined in 2002–2004 (baseline, MESA exam 2) and at three follow-up examinations every 1.5–2 years thereafter. Fundus photography was performed at MESA exam 2 and exam 5 after a mean of 7.8 years.ResultsAfter a mean follow-up of 6.1 years, 21.7% (n = 869) had incident depressive symptoms. After adjustment for socio-demographic, lifestyle and cardiovascular factors, one SD larger baseline CRVE (21.8 µm) was associated with a higher risk of depressive symptoms (hazard ratio: 1.10; 95% confidence interval: 1.02–1.18), but one SD larger baseline CRAE (14.1 µm) was not (hazard ratio: 1.05; 0.98–1.13). Neither 7.8-year change of CRAE nor CRVE were associated with depressive symptoms (odds ratios: 1.06; 0.90–1.24, and 1.06; 0.91–1.23, respectively).ConclusionsLarger baseline CRVE is associated with a higher incidence of depressive symptoms. This might support the hypothesis that cerebral microvascular dysfunction contributes to the development of depression.

A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 μm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

Retinal microvasculature and masked hypertension in young adults: the African-PREDICT study.

Masked hypertension is known to induce microvascular complications. However, it is unclear whether early microvascular changes are already occurring in young, otherwise healthy adults. We therefore investigated whether retinal microvascular calibers and acute responses to a flicker stimulus are related to masked hypertension. We used the baseline data of 889 participants aged 20-30 years who were taking part in the African Prospective study on the Early Detection and Identification of Cardiovascular Disease and Hypertension. Clinic and 24-h ambulatory blood pressure were measured. The central retinal artery equivalent (CRAE) and central retinal vein equivalent were calculated from fundus images, and retinal vessel dilation was determined in response to flicker light-induced provocation. A smaller CRAE was observed in those with masked hypertension vs. those with normotension (157.1 vs. 161.2 measuring units, P < 0.001). In forward multivariable-adjusted regression analysis, only CRAE was negatively related to masked hypertension [adjusted R2 = 0.267, β = -0.097 (95% CI = -0.165; -0.029), P = 0.005], but other retinal microvascular parameters were not associated with masked hypertension. In multivariable logistic regression analyses, masked hypertension [OR = 2.333, (95% CI = 1.316; 4.241), P = 0.004] was associated with a narrower CRAE. In young healthy adults, masked hypertension was associated with retinal arteriolar narrowing, thereby reflecting early microvascular alterations known to predict cardiovascular outcomes in later life.

Effects of a High-Protein Diet on Cardiometabolic Health, Vascular Function, and Endocannabinoids-A PREVIEW Study.

An unfavorable lipid profile and being overweight are known mediators in the development of cardiovascular disease (CVD) risk. The effect of diet, particularly high in protein, remains under discussion. Therefore, this study examines the effects of a high-protein (HP) diet on cardiometabolic health and vascular function (i.e., endothelial function, arterial stiffness, and retinal microvascular structure), and the possible association with plasma endocannabinoids and endocannabinoid-related compounds in overweight participants. Thirty-eight participants (64.5 ± 5.9 (mean ± SD) years; body mass index (BMI) 28.9 ± 4.0 kg/m2) were measured for 48 h in a respiration chamber after body-weight maintenance for approximately 34 months following weight reduction. Diets with either a HP (n = 20) or moderate protein (MP; n = 18) content (25%/45%/30% vs. 15%/55%/30% protein/carbohydrate/fat) were provided in energy balance. Validated markers for cardiometabolic health (i.e., office blood pressure (BP) and serum lipoprotein concentrations) and vascular function (i.e., brachial artery flow-mediated vasodilation, pulse wave analysis and velocity, and retinal microvascular calibers) were measured before and after those 48 h. Additionally, 24 h ambulatory BP, plasma anandamide (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and pregnenolone (PREG) were analyzed throughout the day. Office and ambulatory BP, serum lipoprotein concentrations, and vascular function markers were not different between the groups. Only heart rate (HR) was higher in the HP group. HR was positively associated with OEA, while OEA and PEA were also positively associated with total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations. Vascular function markers were not associated with endocannabinoids (or endocannabinoid-related substances). In conclusion, the HP diet did not affect cardiometabolic health and vascular function in overweight participants after completing a weight-loss intervention. Furthermore, our data indicate a possible association between OEA and PEA with TC and LDL cholesterol.

Effects of diet-induced weight loss on postprandial vascular function after consumption of a mixed meal: Results of a randomized controlled trial with abdominally obese men.

Effects of weight loss on postprandial vascular function have not been studied so far. We therefore examined (i) effects of diet-induced weight loss on postprandial changes in various vascular function markers after consumption of a mixed meal and (ii) differences between normal-weight and abdominally obese men of comparable age at baseline and after weight loss. Fifty-four apparently healthy abdominally obese (waist circumference: 102-110cm) and 25 normal-weight men (waist circumference: <94cm) participated. The abdominally obese men were randomly allocated to a diet-induced weight-loss program or a no-weight loss control group. Men assigned to the weight-loss program followed a calorie-restricted diet for six weeks targeting a waist circumference of less than 102cm, followed by a weight-maintenance period for two weeks. The control group maintained their habitual diet and physical activity levels. Measurements were performed before and two hours after consumption of the test meal consisting of two muffins (containing 56.6g fat) and 300mL low-fat milk. The mean weight loss was 10.3kg in the weight-loss compared with the control group. The postprandial change in flow-mediated vasodilation of the brachial artery (FMD) was significantly higher at baseline in normal-weight as compared with the postprandial change in abdominally obese men (1.89±2.52 versus 0.48±2.50 percentage points; P=0.027). However, no differences in postprandial changes were observed in the abdominally obese men after weight loss compared with the control treatment. Also, weight reduction did not affect postprandial changes in carotid-to-femoral pulse wave velocity, retinal microvascular caliber properties, or plasma markers of microvascular endothelial function. Even though postprandial increases in triacylglycerol (P=0.028), insulin (P=0.029) and C-peptide concentrations (P<0.001) were reduced in the abdominally obese men following weight loss, postprandial changes in FMD at the end of the weight-loss treatment were still more unfavorable as compared with those observed in normal-weight individuals. In this trial with abdominally obese men, we did not find effects of diet-induced weight loss on postprandial changes in vascular endothelial function, arterial stiffness and markers of microvascular function. This trial was registered on ClinicalTrials.gov under study number NCT01675401.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60±8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10g of refined cold-pressed flaxseed oil, providing 4.7g ALA (n=29), or 10g of high-oleic sunflower (control) oil (n=30) for 12 weeks. As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58μmol/L (P=0.02) and 0.14pg/mL (P=0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

A Systematic Review of Vascular Structure and Function in Pre-eclampsia: Non-invasive Assessment and Mechanistic Links.

Hypertensive disorders of pregnancy, such as pre-eclampsia, are known to be independently associated with the development of premature cardiovascular disease (CVD) in women. In pre-eclampsia, the placenta secretes excess anti-angiogenic factors into the maternal circulation, leading to widespread endothelial damage, and inflammation. This endothelial damage is evidenced to persist beyond the acute illness. However, whether it is permanent and responsible for the elevated rates of premature CVD seen in this at-risk group remains unclear. A systematic review of the available literature with respect to vascular structure and function prior to, during and after a pregnancy complicated by pre-eclampsia was performed. Studies non-invasively assessing vascular structure using carotid intima-media thickness (CIMT), retinal microvasculature caliber, CT coronary angiogram, or coronary calcium scores were included. Vascular function was assessed using brachial flow-mediated dilation (FMD), pulse wave analysis (PWA), and peripheral arterial tonometry (PAT). In total 59 articles were included (13 CIMT, 5 CTCA/Ca score, five retinal microvasculature, 27 FMD, 7 PAT, and 14 PWV/PWA), consisting of prospective and retrospective cohort, and case-control studies. Change in vascular structure was evidenced with significant increases in CIMT by 73–180 μm greater than that of non-affected women. This is tempered by other studies reporting resolution of structural changes postpartum, highlighting the need for further research. Accelerated coronary calcification and plaque deposition was identified, with greater rates of increased calcium scores and subclinical coronary artery disease shown by CTCA in women with a history of pre-eclampsia at 30 years postpartum. Impaired endothelial function was consistently reported prior to, during and immediately after pregnancy as evidenced by differences in FMD of 1.7–12.2% less than non-affected women, an increase in PWV by 13.2–26%, and reduced retinal microvascular caliber and arterial elasticity indices. The evidence was less conclusive for the persistence of long-term endothelial dysfunction. Understanding the underlying mechanistic links between pre-eclampsia and CVD is a key step to identifying targeted therapies aimed at “repairing the endothelium” and attenuating risk. This review has highlighted the need for a greater understanding of vascular structure and function following pre-eclampsia through high quality studies with large sample sizes, particularly in the longer postpartum period when clinical CVD disease starts to manifest.

P5340HIV-infected participants on combination ART (tenofovir, emtricitabine, efavirenz) have improved endothelial function and smaller retinal venular calibers compared to treatment naive participants

Abstract Background Cumulative data from several studies suggest that HIV-infected populations have a 2-fold increased cardiovascular risk. Evidence is also pointing to a link between HIV and early vascular changes, including endothelial dysfunction and subclinical atherosclerosis. There is a paucity of data from sub-Saharan Africa (the epicenter of the global HIV burden and a region with a rapidly increasing cardiovascular disease [CVD] incidence); furthermore, the contribution of specific combination ART (c-ART) regimens to HIV-related CVD and early vascular changes remain unclear. Purpose To investigate the association between HIV-infection, c-ART (TDF+FTC+EFV), CVD risk and vascular markers of CVD in an adult cohort in South Africa. Methods Cross-sectional study, participants assigned to 3 groups: HIV-free (HIV−), HIV-infected ART naïve (HIV+/−) and HIV-infected on ART (HIV+/+). Data collection: demographic information, anthropometrics, CVD risk factors, and blood chemistry. Vascular endpoints assessed: brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (C-IMT) and retinal microvascular calibers. Results Cohort size: n=427 (HIV− n=148; HIV+/− n=69; HIV+/+ n=210), mean age: 39.4 years, 68.9% females. Analysis of cardiovascular risk showed no differences in smoking and alcohol consumption, and blood pressure was unaffected by HIV-status. The untreated HIV group had a high % participants with clinically low HDL-cholesterol levels, whereas c-ART seemed to reduce the prevalence (HIV+/−: 58% vs 31% in HIV− and 26% in HIV+/+; p&lt;0.01). Prevalence of hyper-LDL-cholesterolemia and hypertriglyceridemia were similar. High sensitivity CRP levels were unaffected by HIV-status. Markers of end-organ damage showed renal involvement in the HIV+ groups (median regression of urine albumin-creatinine ratio in HIV+/+ and HIV+/− vs HIV−: Beta±SEM: 0.5±0.3 and 0.8±0.2 in HIV+/+ and HIV+/− respectively, p=0.02; adjusted for age, gender and ethnicity), as well as hepatic injury in the treated group (gamma-GT in HIV+/+ vs HIV−: Beta±SEM: 23.3±4.4, p&lt;0.01, adjustment as above). Multiple regression of vascular markers showed increased FMD in HIV+/+ vs HIV+/− (Beta±SEM: 1.8±0.8, p=0.01; adjusted for age, gender, ethnicity and BMI), and decreased central retinal venular equivalent (CRVE) in HIV+/+ vs HIV+/− (Beta±SEM: −11.9±3.8, p=0.002) and vs HIV− (Beta±SEM: −7.1±3.2, p=0.03), adjustment as above. Carotid IMT was not affected by HIV or treatment status. Conclusions Combination ART consisting of TDF+FTC+EFV conferred vascular protection in HIV-infected participants as shown by improved endothelial function (increased FMD) and smaller CRVE compared to ART naïve counterparts. There was no evidence of subclinical atherosclerosis involvement (C-IMT). The vasculoprotective effects in the treated group were supported by a favourable HDL-cholesterol profile, despite unchanged inflammation (hs-CRP), and evidence of renal and hepatic impairment. Acknowledgement/Funding Dept of Science and Technology (South Africa); National Research Foundation (South Africa); Belgian Science Policy, Belgium; Austrian Grants Agency.

Associations of retinal microvascular caliber with intermediate phenotypes of large arterial function and structure: A systematic review and meta-analysis.

Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta-analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole-to-venule ratio) and preclinical CV measures (large arterial function and structure). We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study-specific correlation estimates were combined into meta-analysis where possible. Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta-analysis. Most studied middle-aged adults cross-sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima-media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) -0.17, 95% CI -0.25 to -0.10) and greater (poorer) intima-media thickness (r -0.05, 95%CI -0.09 to -0.02) across all adult participants. Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.

Abstract WP562: Retinal Vessel Caliber is Associated With Cognitive Function Independent of Cerebrovascular and Renal Disease: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Microvascular retinal abnormalities may be markers of cerebrovascular and renal microvascular disease and are associated with cognitive impairment. Hypothesis: Stroke and albuminuria mediate the association of retinal abnormalities with cognitive performance. Methods: In a racially diverse longitudinal MESA cohort, we used retinal imaging from MESA exams 2 (2002-2004) and 5 (2010-2012) to determine the association of retinal microvascular changes with global cognitive function (Cognitive Abilities Screening Instrument; CASI version 2), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) scores at MESA Exam 5 after adjusting for vascular risk factors and interactions with albuminuria at Exam 2 and incident stroke (ischemic or hemorrhagic). Results: A total of 4,392 participants were included. At Exam 5, the mean (±SD) age of participants was 69.5 (9.3), 46.6% were women, 41.3% were non-Hispanic White. Albuminuria was present in 373 and stroke occurred in 77 participants. Over the 8-year period, the mean change in central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) was -2.9 (11.4) μm and -7.6 (14.8) μm, respectively. The CRAE at Exam 5, change in CRAE between Exam 2 and 5, and CRVE at Exam 2 were associated with a poorer CASI score (Table). Greater CRVE at Exam 2 and 5 was associated with a poorer DSC (Table) and no associations were found with DS scores (all p&gt;0.05). Stroke and albuminuria were associated with CASI and DSC. The interaction of stroke with the change in CRAE and with CRVE at exam 5 in predicting DSC was significant. However, albuminuria and incident stroke did not mediate or significantly interact with microvascular retinal changes to predict CASI (all p&gt;0.05). Conclusions: Stroke and albuminuria do not explain the association between retinal microvascular caliber and global cognitive performance but the interaction with stroke in predicting processing speed is significant.

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 ± 5years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5years; 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.

The effect of pre-eclampsia on retinal microvascular caliber at delivery and post-partum.

The retinal microcirculation provides a unique view of microvessel structure by means of non-invasive, retinal image analysis. The aim of the study was to compare the retinal vessel caliber at delivery and one-year post-partum between women who have had pre-eclampsia during pregnancy to a normotensive control group. Digital photos of the eye were taken at delivery and one-year post-partum. Retinal vessels were analysed and summarised as the corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent. The corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent were significantly lower in the pre-eclamptic group compared to the control group both at delivery and one-year post-partum (p < 0.001). Retinal artery and venular caliber changes that occur during pregnancies affected by pre-eclampsia persist for up to one-year post-partum. These changes may reflect a permanent, long-term microvascular dysfunction and may be useful as a biomarker of future vascular risk.

The retinal microcirculation in migraine: The Rotterdam Study.

BackgroundTo explore the role of microvascular pathology in migraine, we investigated the association between migraine and retinal microvascular damage.MethodsWe included 3270 participants (age ≥ 45 years, 63% women) from the population-based Rotterdam Study (2006–2009). Participants with migraine were identified using a validated questionnaire based on ICHD-II criteria (n = 562). Retinopathy signs were graded on fundus photographs. Retinal arteriolar and venular caliber were measured by semi-automatic assessment of fundus photographs. Associations of migraine with retinopathy and retinal microvascular calibers were examined using logistic and linear regression models, respectively, adjusting for age, sex, and cardiovascular risk factors.ResultsMigraine was not associated with the presence of retinopathy (odds ratio (OR): 1.09, 95% confidence interval (CI) 0.62; 1.92). In the fully adjusted model, adjusting for the companion vessel, persons with migraine did not differ in retinal arteriolar or venular caliber compared to persons without migraine (mean difference in standardized arteriolar caliber −0.05 (95%CI −0.13; 0.03); in standardized venular caliber −0.00 (95%CI −0.09; 0.08)). Migraine subtypes, including migraine with aura, were also not associated with retinal microvascular damage.ConclusionsOur findings suggest that migraine is not associated with retinopathy or difference in retinal microvascular caliber. Further studies are needed to confirm these results.

Effects of long-term magnesium supplementation on endothelial function and cardiometabolic risk markers: A randomized controlled trial in overweight/obese adults

Long-term magnesium supplementation improves arterial stiffness, a cardiovascular disease risk marker. Effects on endothelial function may be another mechanism whereby increased magnesium intakes affect cardiovascular risk. Therefore, a 24-week, randomized, double-blind, placebo-controlled trial was performed to examine effects of magnesium supplementation on endothelial function and cardiometabolic risk markers. Fifty-two overweight and obese subjects (30 men and 22 women, age 62 ± 6 years) were randomized to receive either three times daily magnesium (total dose: 350 mg) or placebo capsules. Endothelial function was assessed at the start and at the end of the study. Cardiometabolic risk markers were measured at baseline, after 12 weeks, and at week 24. Brachial artery flow-mediated vasodilation did not change following long-term magnesium supplementation (0.49 pp; 95% CI: −0.38 to 1.36 pp; P = 0.26). Changes in reactive hyperemia index, retinal microvascular caliber and plasma markers for microvascular endothelial function (sVCAM-1, sICAM-1 and sE-selectin) were also not different. In addition, no effects on serum lipids, plasma glucose, insulin sensitivity, and low-grade systemic inflammation were observed. In conclusion, a daily magnesium supplement of 350 mg for 24 weeks does not improve endothelial function and cardiometabolic risk markers in overweight and obese middle-aged and elderly adults.

Diet-induced weight loss improves not only cardiometabolic risk markers but also markers of vascular function: a randomized controlled trial in abdominally obese men

Background: Many trials assessing effects of dietary weight loss on vascular function have been performed without no–weight loss control groups and in individuals with obesity-related morbidities. Usually a limited set of vascular function markers has been investigated.Objective: The objective of this study was to examine effects of diet-induced weight loss on various vascular function markers and differences between normal-weight and abdominally obese men at baseline and after weight reduction.Design: Twenty-five healthy, normal-weight men (waist circumference: <94 cm) and 54 abdominally obese men (waist circumference: 102–110 cm) participated. Abdominally obese participants were randomly allocated to a dietary weight-loss or a no–weight loss control group. Individuals from the weight-loss group followed a calorie-restricted diet for 6 wk to obtain a waist circumference <102 cm followed by a weight-maintenance period of 2 wk. The control group maintained their habitual diet and physical activity levels. The primary outcome was the change in brachial artery flow-mediated vasodilation (FMD).Results: Compared with the control group, FMD did not change in the weight-loss group, but carotid-to-femoral pulse wave velocity tended to decrease by 0.5 m/s (P = 0.065). The retinal arteriolar caliber increased by 5 μm (P < 0.001) and the arteriolar-to-venular ratio by 0.02 (P < 0.01). Soluble endothelial selectin and soluble intercellular adhesion molecule concentrations decreased (P < 0.001). Also, total cholesterol, low–density lipoprotein cholesterol, triacylglycerol, glucose, insulin, C-peptide, homeostasis model assessment of insulin resistance, and blood pressure improved (P < 0.05 for all variables). Except for FMD, these markers differed at baseline between normal-weight and abdominally obese men but became comparable after weight loss.Conclusions: In abdominally obese men, dietary weight loss targeting a waist circumference of <102 cm improved retinal microvascular caliber, plasma biomarkers of microvascular endothelial function, and the more conventional cardiometabolic risk markers. Aortic stiffness tended to decrease, but FMD was not changed. This trial was registered at clinicaltrials.gov as NCT01675401.