TY - JOUR A1 - Kuchler, Timon A1 - Günthner, Roman A1 - Ribeiro, Andrea A1 - Hausinger, Renate A1 - Streese, Lukas A1 - Wöhnl, Anna A1 - Kesseler, Veronika A1 - Negele, Johanna A1 - Assali, Tarek A1 - Carbajo-Lozoya, Javier A1 - Lech, Maciej A1 - Adorjan, Kristina A1 - Stubbe, Hans Christian A1 - Hanssen, Henner A1 - Kotliar, Konstantin A1 - Haller, Berhard A1 - Heemann, Uwe A1 - Schmaderer, Christoph T1 - Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation N2 - Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians. Methods In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204). Measurements and main results PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters. Conclusion Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management. KW - Endothelial dysfunction KW - Long COVID KW - Post-COVID-19 syndrome KW - retinal microvasculature Y1 - 2023 U6 - http://dx.doi.org/10.1007/s10456-023-09885-6 N1 - Corresponding author: Christoph Schmaderer VL - 26 SP - 547 EP - 563 PB - Springer Nature CY - Dordrecht ER - TY - JOUR A1 - Angermann, Susanne A1 - Günthner, Roman A1 - Hanssen, Henner A1 - Lorenz, Georg A1 - Braunisch, Matthias C. A1 - Steubl, Dominik A1 - Matschkal, Julia A1 - Kemmner, Stephan A1 - Hausinger, Renate A1 - Block, Zenonas A1 - Haller, Bernhard A1 - Heemann, Uwe A1 - Kotliar, Konstantin A1 - Grimmer, Timo A1 - Schmaderer, Christoph T1 - Cognitive impairment and microvascular function in end-stage renal disease JF - International Journal of Methods in Psychiatric Research (MPR) N2 - Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention. KW - cerebral small vessel disease KW - cognitive impairment KW - dialysis KW - retinal vessels Y1 - 2022 U6 - http://dx.doi.org/10.1002/mpr.1909 SN - 1049-8931 (Print) SN - 1557-0657 (Online) VL - 31 IS - 2 SP - 1 EP - 10 PB - Wiley ER - TY - JOUR A1 - Werfel, Stanislas A1 - Günthner, Roman A1 - Hapfelmeier, Alexander A1 - Hanssen, Henner A1 - Kotliar, Konstantin A1 - Heemann, Uwe A1 - Schmaderer, Christoph ED - Guzik, Tomasz J. T1 - Identification of cardiovascular high-risk groups from dynamic retinal vessel signals using untargeted machine learning JF - Cardiovascular Research N2 - Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations. KW - Machine learning KW - Retinal vessels KW - Microcirculation KW - Haemodialysis KW - Myocardial infarction and cardiac death Y1 - 2022 U6 - http://dx.doi.org/10.1093/cvr/cvab040 SN - 0008-6363 VL - 118 IS - 2 SP - 612 EP - 621 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Morat, Mareike A1 - Faude, Oliver A1 - Hanssen, Henner A1 - Ludyga, Sebastian A1 - Zacher, Jonas A1 - Eibl, Angi A1 - Albracht, Kirsten A1 - Donath, Lars T1 - Agility Training to Integratively Promote Neuromuscular, Cognitive, Cardiovascular and Psychosocial Function in Healthy Older Adults: A Study Protocol of a One-Year Randomized-Controlled Trial JF - International Journal of Environmental Research and Public Health N2 - Exercise training effectively mitigates aging-induced health and fitness impairments. Traditional training recommendations for the elderly focus separately on relevant physiological fitness domains, such as balance, flexibility, strength and endurance. Thus, a more holistic and functional training framework is needed. The proposed agility training concept integratively tackles spatial orientation, stop and go, balance and strength. The presented protocol aims at introducing a two-armed, one-year randomized controlled trial, evaluating the effects of this concept on neuromuscular, cardiovascular, cognitive and psychosocial health outcomes in healthy older adults. Eighty-five participants were enrolled in this ongoing trial. Seventy-nine participants completed baseline testing and were block-randomized to the agility training group or the inactive control group. All participants undergo pre- and post-testing with interim assessment after six months. The intervention group currently receives supervised, group-based agility training twice a week over one year, with progressively demanding perceptual, cognitive and physical exercises. Knee extension strength, reactive balance, dual task gait speed and the Agility Challenge for the Elderly (ACE) serve as primary endpoints and neuromuscular, cognitive, cardiovascular, and psychosocial meassures serve as surrogate secondary outcomes. Our protocol promotes a comprehensive exercise training concept for older adults, that might facilitate stakeholders in health and exercise to stimulate relevant health outcomes without relying on excessively time-consuming physical activity recommendations. KW - agility KW - prevention KW - healthy aging KW - community dwelling KW - psychosocial Y1 - 2020 U6 - http://dx.doi.org/10.3390/ijerph17061853 SN - 1660-4601 VL - 17 IS - 6 SP - 1 EP - 14 PB - MDPI CY - Basel ER - TY - JOUR A1 - Streese, Lukas A1 - Kotliar, Konstantin A1 - Deiseroth, Arne A1 - Infanger, Denis A1 - Gugleta, Konstantin A1 - Schmaderer, Christoph A1 - Hanssen, Henner T1 - Retinal endothelial function in cardiovascular risk patients: A randomized controlled exercise trial JF - Scandinavian Journal of Medicine and Science in Sports N2 - The aim of this study was to investigate, for the first time, the effects of high-intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle-aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12-week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light-induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low-density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1%, post: 3.0 ± 2.2%, P = .018) and AFarea (pre: 32.6 ± 28.4%*s, post: 37.7 ± 30.6%*s, P = .016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8%, post: 2.9 ± 1.8%, P = .254; AFarea, pre: 41.6 ± 28.5%*s, post: 37.8 ± 27.0%*s, P = .186). Venular function remained unchanged after HIIT. There was a significant association between ∆-change VO2peak and ∆-changes ADmax and AFarea (P = .026, R² = 0.073; P = .019, R² = 0.081, respectively). 12-weeks of HIIT improved retinal endothelial function in middle-aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle-aged individuals with increased CV risk. Y1 - 2020 U6 - http://dx.doi.org/10.1111/sms.13560 SN - 1600-0838 VL - 30 IS - 2 SP - 272 EP - 280 PB - Wiley CY - Oxford ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Hanssen, Henner A1 - Eberhardt, Karla A1 - Vilser, Walthard A1 - Schmaderer, Christoph A1 - Halle, Martin A1 - Heemann, Uwe A1 - Baumann, M. T1 - Retinal pulse wave velocity in young male normotensive and mildly hypertensive subjects JF - Microcirculation Y1 - 2013 SN - 1549-8719 N1 - Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.) PB - Wiley CY - Malden ER - TY - JOUR A1 - Pressler, Axel A1 - Esefeld, Katrin A1 - Scherr, Johannes A1 - Ali, Mohammad A1 - Hanssen, Henner A1 - Kotliar, Konstantin A1 - Lanzl, Ines A1 - Halle, Martin A1 - Kaemmerer, Harald A1 - Schmidt-Trucksäss, Arno A1 - Hager, Alfred T1 - Structural alterations of retinal arterioles in adults late after repair of aortic isthmic coarctation JF - The American Journal of Cardiology N2 - Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 μm, first to third quartile 171 to 197; vs 197 μm, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients. Y1 - 2010 U6 - http://dx.doi.org/10.1016/j.amjcard.2009.10.070 SN - 0002-9149 VL - 105 IS - 5 SP - 740 EP - 744 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Lanzl, Ines M. A1 - Hanssen, Henner A1 - Eberhardt, Karla A1 - Vilser, Walthard A1 - Halle, Martin A1 - Heemann, Uwe A1 - Schmidt-Trucksäss, Arno A1 - Baumann, Marcus T1 - Does increased blood pressure rather than aging influence retinal pulse wave velocity? JF - Investigative Ophthalmology & Visual Science, IOVS N2 - Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself. Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated. Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains. Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV. Y1 - 2012 U6 - http://dx.doi.org/10.1167/iovs.11-8815 SN - 0146-0404 VL - 53 IS - 4 SP - 2119 EP - 2126 PB - ARVO CY - Rockville, Md. ER -