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Habitual intake of dietary advanced glycation end products is not associated with generalized microvascular function-the Maastricht Study.
Linkens, AMA, Houben, AJHM, Kroon, AA, Schram, MT, Berendschot, TTJM, Webers, CAB, van Greevenbroek, M, Henry, RMA, de Galan, B, Stehouwer, CDA, et al
The American journal of clinical nutrition. 2022;(2):444-455
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Abstract
BACKGROUND Endogenously formed advanced glycation end products (AGEs) may be important drivers of microvascular dysfunction and the microvascular complications of diabetes. AGEs are also formed in food products, especially during preparation methods involving dry heat. OBJECTIVES We aimed to assess cross-sectional associations between dietary AGE intake and generalized microvascular function in a population-based cohort. METHODS In 3144 participants of the Maastricht Study (mean ± SD age: 60 ± 8 y, 51% men) the dietary AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated using the combination of our ultra-performance LC-tandem MS dietary AGE database and an FFQ. Microvascular function was determined in the retina as flicker light-induced arteriolar and venular dilation and as central retinal arteriolar and venular equivalents, in plasma as a z score of endothelial dysfunction biomarkers (soluble vascular adhesion molecule 1 and soluble intracellular adhesion molecule 1, soluble E-selectin, and von Willebrand factor), in skin as the heat-induced skin hyperemic response, and in urine as 24-h albuminuria. Associations were evaluated using multiple linear regression adjusting for demographic, cardiovascular, lifestyle, and dietary factors. RESULTS Overall, intakes of CML, CEL, and MG-H1 were not associated with the microvascular outcomes. Although higher intake of CEL was associated with higher flicker light-induced venular dilation (β percentage change over baseline: 0.14; 95% CI: 0.02, 0.26) and lower plasma biomarker z score (β: -0.04 SD; 95% CI: -0.08, -0.00 SD), the effect sizes were small and their biological relevance can be questioned. CONCLUSIONS We did not show any strong association between habitual intake of dietary AGEs and generalized microvascular function. The contribution of dietary AGEs to generalized microvascular function should be further assessed in randomized controlled trials using specifically designed dietary interventions.
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Monitoring peripheral perfusion in sepsis associated acute kidney injury: Analysis of mortality.
de Miranda, AC, de Menezes, IAC, Junior, HC, Luy, AM, do Nascimento, MM
PloS one. 2020;(10):e0239770
Abstract
Microcirculatory disorders have been consistently linked to the pathophysiology of sepsis. One of the major organs affected is the kidneys, resulting in sepsis-associated acute kidney injury (SA-AKI) that correlates considerably with mortality. However, the potential role of clinical assessment of peripheral perfusion as a possible tool for SA-AKI management has not been established. To address this gap, the purpose of this study was to investigate the prevalence of peripheral hypoperfusion in SA-AKI, its association with mortality, and fluid balance. This observational cohort study enrolled consecutive septic patients in the Intensive Care Unit. After fluid resuscitation, peripheral perfusion was evaluated using the capillary filling time (CRT) and peripheral perfusion index (PI) techniques. The AKI was defined based on both serum creatinine and urine output criteria. One hundred and forty-one patients were included, 28 (19%) in the non-SA-AKI group, and 113 (81%) in the SA-AKI group. The study revealed higher peripheral hypoperfusion rates in the SA-AKI group using the CRT (OR 3.6; 95% CI 1.35-9.55; p < 0.05). However, this result lost significance after multivariate adjustment. Perfusion abnormalities in the SA-AKI group diagnosed by both CRT (RR 1.96; 95% CI 1.25-3.08) and PI (RR 1.98; 95% CI 1.37-2.86) methods were associated to higher rates of 28-day mortality (p < 0.01). The PI's temporal analysis showed a high predictive value for death over the first 72 h (p < 0.01). A weak correlation between PI values and the fluid balance was found over the first 24 h (r = - 0.20; p < 0.05). In conclusion, peripheral perfusion was not different intrinsically between patients with or without SA-AKI. The presence of peripheral hypoperfusion in the SA-AKI group has appeared to be a prognostic marker for mortality. This evaluation maintained its predictive value over the first 72 hours. The fluid balance possibly negatively influences peripheral perfusion in the SA-AKI.
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Endothelial dysfunction assessed by digital tonometry and discrepancy between fraction flow reserve and instantaneous wave free ratio.
Jerabek, S, Zemanek, D, Pudil, J, Bayerova, K, Kral, A, Kopriva, K, Kawase, Y, Omori, H, Tanigaki, T, Chen, Z, et al
Acta cardiologica. 2020;(4):323-328
Abstract
Background: We tested whether the level of endothelial dysfunction assessed by digital tonometry, and expressed as reactive hyperemia index (RHI), is related to occurrences of a discrepancy between fractional flow reserve (FFR) and the instantaneous wave free ratio (iFR) (ClinicalTrials.gov identifier: NCT03033810).Methods: We examined patients with coronary stenosis in the range of 40-70%, assessed by both FFR and iFR (system Philips-Volcano) for stable angina. We included consecutive patients with FFR and iFR in one native coronary artery, and who had had no previous intervention.Results: We included 138 patients. Out of those, 24 patients (17.4%) had a negative FFR (with an FFR value >0.8) and positive iFR (with a iFR value ≤0.89) - designated the FFRn/iFRp discrepancy group, and 22 patients (15.9%) had a positive FFR (≤0.8) and negative iFR (>0.89) - designated the FFRp/iFRn discrepancy. RHI was higher in the discrepancy groups compared the group without discrepancy (1.73 ± 0.79 vs. 1.48 ± 0.50, p = 0.025). However, this finding was not confirmed in multivariant logistic regression analyses. Patients with any type of discrepancy differed from the agreement group by having a higher occurrence of diabetes mellitus [9 patients (21.4%) vs. 36 patients (39.6%), p = 0.029], active smoking (23 patients or 54.8% vs. 26 patients or 28.6%, p = 0.003) and lower use of calcium channel blockers (9 patients, 21.4%, vs. 43 patients, 46.7%, p = 0.004).Conclusion: The presence of endothelial dysfunction can be associated with a discrepancy in FFR/iFR. However, RHI correlated with risk factors of atherosclerosis, not with FFR or iFR.
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Classification of Regions of Nonperfusion on Ultra-widefield Fluorescein Angiography in Patients with Diabetic Macular Edema.
Fang, M, Fan, W, Shi, Y, Ip, MS, Wykoff, CC, Wang, K, Falavarjani, KG, Brown, DM, van Hemert, J, Sadda, SR
American journal of ophthalmology. 2019;:74-81
Abstract
PURPOSE To classify retinal nonperfusion regions (NPRs) in patients with diabetic macular edema (DME) and assess the relationship with severity of DME. DESIGN Prospective, observational case series. METHODS Forty eyes of 29 patients with treatment-naïve center-involved macular edema secondary to diabetes mellitus were included (The DAVE study, NCT01552408) in this analysis. Ultra-widefield fluorescein angiography (UWF FA) images were transmitted to the Doheny Image Reading Center, where they were corrected using stereographic projection to adjust for peripheral distortion. Two independent, certified graders manually evaluated the NPR and classified the nonperfusion as being associated with leakage or without leakage. The size of these 2 subtypes of NPR were computed in mm2 and assessed across the entire retina and within 3 concentric retinal zones. The relationship between subtype of NPR and the severity of DME was assessed. RESULTS In 40 eyes with treatment-naïve DME, visual acuity was significantly correlated with central macular thickness (CMT) and macular volume (MV). The NPR with leakage was positively correlated with CMT (R = 0.408, P = .009) and MV (R = 0.399, P = .011), whereas the NPR without leakage was negatively correlated with CMT (R = -0.468, P = .002) and MV (R = -0.473, P = .002). The NPR with leakage in the posterior region was significantly greater compared to the mid-periphery and the far periphery (P < .001), whereas the NPR without leakage was significantly greater in the mid-periphery compared with the far periphery or the posterior region (P = .001). CONCLUSION In patients with DME, the severity of DME appears to be positively correlated with NPR with leakage but negatively correlated with NPR without leakage. These findings may have implications for the pathophysiology of DME and the design of protocols for targeted laser in these eyes.
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Evaluation of systemic microvascular reactivity in adults with congenital heart disease.
Marino, P, de Oliveira Lopes, G, Pereira Borges, J, Carolina Terra Cola, M, Arkader Kopiler, D, Tibirica, E
Congenital heart disease. 2018;(6):978-987
Abstract
OBJECTIVE Adults with congenital heart disease share some features with those with chronic heart failure. Although microvascular endothelial dysfunction has been described in chronic heart failure, evaluation of the microcirculation in adults with congenital heart disease is lacking. The present study aimed to investigate systemic microvascular reactivity in adults with congenital heart disease. INTERVENTIONS The patients initially underwent cardiopulmonary exercise testing. Then, the cutaneous microvascular reactivity was evaluated in these patients using a laser speckle contrast imaging system coupled with skin iontophoresis of endothelial-dependent (acetylcholine) or -independent (sodium nitroprusside) vasodilators and postocclusive reactive hyperemia (PORH) and compared with healthy controls matched for age and sex. RESULTS Thirty-one patients and 29 healthy controls were evaluated. The basal microvascular flow (P < .0001) and area under the curve in response to acetylcholine (P < .0001) were higher in the patients than in the healthy volunteers. The increase in cutaneous vascular conductance in response to sodium nitroprusside was reduced in the patients compared to the healthy volunteers (P = .0031). No difference in the microvascular response was observed during postocclusive reactive hyperemia. The basal microvascular flow of patients with peak oxygen consumption below 16.0 mL kg-1 min-1 was superior to that of patients with values greater than 16.0 mL kg-1 min-1 (P = .0046). CONCLUSIONS Adults with congenital heart disease present a higher baseline cutaneous microvascular blood flow than healthy controls and do not present systemic microvascular endothelial dysfunction. Nevertheless, endothelium-independent microvascular reactivity is blunted, suggesting an altered vascular smooth muscle response or vascular structural alterations. Finally, patients with a lower functional capacity presented a greater microvascular basal blood flow than subjects with a higher functional capacity.
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Pregnancy-associated plasma protein-A is positively correlated with first-trimester skin microvascular reactivity.
Iacobaeus, C, Kahan, T, Jörneskog, G, Bremme, K, Andolf, E, Thorsell, M
Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2018;(3):361-367
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Abstract
OBJECTIVE To investigate the relationship between levels of circulating maternal pregnancy-associated plasma protein-A (PAPP-A) and first-trimester maternal vascular function. METHODS This was a cross-sectional study of 53 healthy, non-smoking, nulliparous pregnant women in Stockholm, Sweden. PAPP-A levels and vascular function were assessed during gestational weeks 11-14. Forearm skin microcirculation was investigated by laser Doppler perfusion imaging during iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess endothelium-dependent and -independent microvascular vasodilatation, respectively. Microvascular endothelial function index was calculated as peak ACh/peak SNP. Endothelium-dependent and -independent vasodilatation in the brachial artery was evaluated, respectively, by postischemic hyperemia-induced flow-mediated vasodilatation (FMD) and by response to sublingual intake of glyceryl trinitrate (GTN). RESULTS PAPP-A was correlated with skin microvascular endothelial function index (β = 1.008 (95% CI, 0.34-1.68), r2 = 0.17, P = 0.004). PAPP-A also correlated inversely with FMD (β = -0.052 (95% CI, -0.094 to -0.011), r2 = 0.13, P = 0.014) but did not relate to forearm endothelial function index (i.e. FMD/GTN). The results were retained in multivariate analyses including known confounding factors. CONCLUSIONS First-trimester endothelium-dependent skin microvascular reactivity was positively related to PAPP-A levels. If confirmed, these novel findings suggest that first-trimester skin microvascular reactivity could be a useful early pregnancy marker of placental function. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
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Coronary microvascular dysfunction may be related to IGF-1 in acromegalic patients and can be restored by therapy.
Tellatin, S, Maffei, P, Osto, E, Dassie, F, Famoso, G, Montisci, R, Martini, C, Fallo, F, Marra, MP, Mioni, R, et al
Atherosclerosis. 2018;:100-105
Abstract
BACKGROUND AND AIMS Acromegaly increases the risk of cardiovascular mortality. Data on the cardiovascular risk in asymptomatic acromegaly are limited. In particular, data on coronary microvascular abnormalities are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic acromegaly. METHODS We studied 40 acromegalic patients (23 male, age 52 ± 11 years) without clinical evidence of cardiovascular disease, and 40 control subjects matched for age and sex. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperaemic to resting diastolic flow velocity. RESULTS CFR was lower in patients than in controls (2.9 ± 0.8 vs. 3.7 ± 0.6, p < 0.0001) and was abnormal (≤2.5) in 13 patients (32.5%) compared with any control subjects (0%) (p < 0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels (r = -0.5, p < 0.004). In patients with CFR≤2.5, IGF-1 was higher (756 [381-898] μg/l versus 246 [186-484] μg/l, p < 0.007) whereas growth hormone (GH) levels were similar (6.3 [2.8-13.7] μg/l versus 5 [2.8-8.9] μg/l, p = 0.8). In multivariable linear regression analysis, IGF-1 was independently associated with CFR (p < 0.0001). In multiple logistic regression analysis, IGF-1 independently increased the probability of CFR≤2.5 (p = 0.009). In four patients with active disease (all with CFR<2.5), treatment with somatostatin analogues normalized CFR. However the other four patients with active disease were not responder. CONCLUSIONS Acromegalic patients have coronary microvascular dysfunction that may be restored by therapy with somatostatin analogues. IGF-1 independently correlates with the coronary microvascular impairment, suggesting the pivotal role of this hormone in explaining the increased cardiovascular risk in acromegaly.
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Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury.
La Fountaine, MF, Cirnigliaro, CM, Azarelo, F, Hobson, JC, Tascione, O, Swonger, KN, Dyson-Hudson, T, Bauman, WA
Experimental physiology. 2017;(9):1234-1244
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Abstract
What is the central question of this study? What impact does insulin resistance have on cutaneous perfusion responses to insulin iontophoresis in vascular beds with markedly reduced or functionally ablated sympathetic nervous system vasomotor function resulting from spinal cord injury? What is the main finding and its importance? Persons with spinal cord injury have sublesional microvascular endothelial dysfunction, as indicated by a blunted cutaneous perfusion response to acetylcholine iontophoresis, and the presence of insulin resistance has a further confounding effect on endothelium-mediated changes to cutaneous perfusion in the lower extremities. Endothelium-mediated mechanisms that regulate skin blood flow might play an integral role in optimizing skin perfusion in vascular beds with sympathetic nervous system vasomotor impairment, such as in spinal cord injury (SCI). Insulin is a vasoactive hormone and second messenger of nitric oxide that facilitates endothelium-mediated dilatation. The effects of insulin resistance (IR) on sublesional cutaneous perfusion responses to insulin provocation have yet to be described in persons with SCI. Persons with SCI and an able-bodied (AB) cohort were divided into subgroups based upon fasting plasma insulin concentration cut-offs for IR (≥13.13 mIU ml-1 ) or insulin sensitivity (IS; <13.13 mIU ml-1 ), as follows: AB, IS (ABIS, n = 21); SCI, IS (SCIS, n = 21); AB, IR (ABIR, n = 9); and SCI, IR (SCIR, n = 11). Laser Doppler flowmetry characterized peak blood perfusion unit (BPU) responses (percentage change from baseline) to insulin, acetylcholine or placebo iontophoresis in the lower extremities; BPU responses were log10 transformed to facilitate comparisons, and the net insulin response (NetIns) BPU response was calculated (insulin minus placebo BPU response). The NetIns was significantly greater in both IS groups compared with their corresponding IR group. The acetylcholine-mediated BPU responses in the SCI subgroups were significantly lower than those in the ABIS group. The proportional BPU responses of NetIns to acetylcholine in the IS cohorts (i.e. ABIS and SCIS) were significantly greater (P < 0.05) than that of each IR subgroup. The presence of IR has a confounding effect on sublesional microvascular endothelium-mediated cutaneous perfusion responses to provocation. Preservation of endothelial sensitivity to its agonists appears to be an important modifiable risk factor to optimize cutaneous perfusion in the lower extremities of persons with SCI.
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Multimarker approach for the prediction of microvascular obstruction after acute ST-segment elevation myocardial infarction: a prospective, observational study.
Feistritzer, HJ, Reinstadler, SJ, Klug, G, Reindl, M, Wöhrer, S, Brenner, C, Mayr, A, Mair, J, Metzler, B
BMC cardiovascular disorders. 2016;(1):239
Abstract
BACKGROUND Presence of microvascular obstruction (MVO) derived from cardiac magnetic resonance (CMR) imaging is among the strongest outcome predictors after ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the comparative predictive values of different biomarkers for the occurrence of MVO in a large cohort of reperfused STEMI patients. METHODS This study included 128 STEMI patients. CMR imaging was performed within the first week after infarction to assess infarct characteristics, including MVO. Admission and peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were measured. RESULTS MVO was detected in 69 patients (54%). hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations showed similar prognostic value for the prediction of MVO (area under the curve (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.05), whereas the prognostic utility of NT-proBNP was weakly lower (AUC = 0.64, p < 0.05). Combination of these biomarkers did not increase predictive utility compared to hs-cTnT alone (p = 0.349). CONCLUSIONS hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations provided similar prognostic value for the prediction of MVO. The prognostic utility of NT-proBNP was lower. Combining these biomarkers could not further improve predictive utility compared to hs-cTnT alone.
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Metabolic syndrome and retinal microvascular calibre in a high cardiovascular disease risk cohort.
Wang, SB, Mitchell, P, Plant, AJ, Phan, K, Liew, G, Thiagalingam, A, Burlutsky, G, Gopinath, B
The British journal of ophthalmology. 2016;(8):1041-6
Abstract
AIMS: To investigate the independent associations between metabolic syndrome and retinal vessel calibre in a high cardiovascular risk cohort, and to determine whether these associations also exist in patients without diabetes, hypertension or coronary artery disease (CAD). METHODS The Australian Heart Eye Study is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program. Retinal arteriolar calibre narrowing and retinal venular calibre widening were measured from retinal photographs. CAD was quantified using severity (Gensini) and extent scores. Diabetes and hypertension were defined from clinical investigation (fasting plasma glucose >7.0 mmol/L and blood pressure >130/85 mm Hg) or from self-reported clinical diagnosis, including the use of medications. RESULTS A total of 979 participants had complete information on metabolic syndrome components and were included in cross-sectional analyses. After adjusting for age, sex, smoking status and fellow vessel calibre, persons with metabolic syndrome (compared with persons without metabolic syndrome) had narrower retinal arteriolar calibre (mean difference 4.3 µm, p<0.0001). No significant difference in venular calibre was observed (p=0.05). This association persisted in persons without diabetes (mean arteriolar calibre difference 4.4 µm, p=0.0006) but not in participants without CAD and those without hypertension. CONCLUSIONS Metabolic syndrome is independently associated with narrower retinal arterioles but not wider retinal venules among those at high risk of CAD. The association between metabolic syndrome and narrower retinal arterioles is likely due to the presence of CAD or hypertension in individuals with this syndrome, as the association is not significant in individuals without hypertension or without CAD.