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Background: We investigated the effects of the combined treatment with glucagon like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on NT-proBNP (N-terminal pro-brain natriuretic peptide), GDF-15 (growth differentiation factor 15), and MOTS-c (mitochondrial-derived peptide-c) in patients with type 2 diabetes (T2D) and high or very high cardiovascular risk., Methods: We studied 163 consecutive patients with type 2 diabetes who were treated with insulin (n=40), liraglutide (n=41), empagliflozin (n=42), or their combination (GLP-1RA+SGLT-2i) (n=40) and were matched using propensity score analysis. We measured the following at baseline and 4 and 12 months of treatment: (1) NT-proBNP, GDF-15, and MOTS-c; (2) 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and (3) left ventricular global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index using speckle-tracking imaging., Results: At 12 months, GLP-1RA, SGLT-2i, and their combination showed a greater reduction of NT-proBNP (-43.1% versus -54.2% versus -56.9% versus -14.7%) and GDF-15 than insulin. Only treatment with SGLT-2i and GLP-1RA+SGLT-2i improved MOTS-c. GLP-1RA, SGLT-2i, or GLP-1RA+SGLT-2i provided an increase of global longitudinal strain, left atrial strain, and global work index compared with insulin. In all patients, the reduction of NT-proBNP was associated with the improvement of global longitudinal strain, left atrial strain during atrial reservoir phase, and global work index; the decrease of GDF-15 with the increase of ABTS and MOTS-c; and the increase of MOTs-c with improved global longitudinal strain and constructive myocardial work at 12 months ( P <0.05)., Conclusions: Twelve-month treatment with combination of GLP-1RA+SGLT-2i was associated with a greater reduction of neurohumoral markers and increase of antioxidant ability than each treatment alone and insulin. SGLT-2i appear more effective in the improvement of neurohumoral and mitochondrial activation., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03878706.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV., Competing Interests: The authors declare no conflicts of interest.

Background : Retinal vein occlusion (RVO) is a relatively uncommon condition with a complex pathophysiology. However, its association with traditional cardiovascular risk factors is well established. In this study, we compared arterial stiffness and endothelial function between patients with RVO and healthy controls. Methods : We enrolled 28 consecutive patients with RVO, either central (CRVO) or branch (BRVO), and 30 healthy controls. We measured: (i) perfused boundary region of the sublingual arterial microvessels (a marker of endothelial glycocalyx thickness), (ii) pulse wave velocity (PWV), augmentation index (AIx), and central systolic blood pressure (cSBP). Results : No statistically significant differences regarding age, gender, and major cardiovascular risk factors were noted between patients and controls. Compared to controls, patients with RVO had higher PBR, PWV, AIx, and cSBP values ( p < 0.05). For each of these indices, no statistically significant differences were noted between patients with CRVO and BRVO ( p > 0.05). Conclusions : Patients with RVO demonstrated reduced endothelial glycocalyx thickness and increased arterial stiffness compared to healthy controls. These findings further elucidate the role of atherosclerosis and endothelial dysfunction in the pathophysiology of the disease and indicate the need for the evaluation of subclinical cardiovascular disease in such patients.

Background : The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. Methods : Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). Results : After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, p < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, p < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, p < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). Conclusions : Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients.

A disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) belongs to the family of metalloproteinases that contributes to tissue homeostasis during morphogenesis and reproduction. These metalloproteinases regulate various cell functions such as cell proliferation, are important regulators in tissue regeneration, and play a role in vascular remodelling, which is involved in atherosclerosis development. Despite the well-established association between ADAMTS-7 and atherosclerotic disease, data regarding the metalloproteinase's association with LV function remain scarce. The aim of this study was to investigate the association of ADAMTS-7 levels with diastolic dysfunction and various echocardiographic parameters in patients with type 2 diabetes mellitus. All patients underwent a clinical, vascular, and echocardiographic examination during their visit. Plasma ADAMTS-7 levels were measured in all patients. The results showed that diastolic dysfunction was strongly associated with age, but had no statistically significant association with ADAMTS-7. When individual echocardiographic parameters were examined, ADAMTS-7 levels showed a positive tendency only with deceleration time (DT), with the other echocardiographic parameters being positively associated only with age. The possible role of ADAMTS-7 in diastolic dysfunction and in the development and progression of heart failure in patients with type 2 diabetes mellitus deserves further investigation.

Background/objectives: To investigate the potential association between the endothelial dysfunction and arterial stiffness with retinal changes observed through optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with retinal vein occlusion (RVO)., Methods: Participants in this cross-sectional study were 28 patients with RVO. The demographic and clinical characteristics of all participants were recorded. Comprehensive ophthalmologic examinations were performed, including fundus photography, OCT and OCT-A. Endothelial dysfunction was assessed by measuring the endothelial glycocalyx thickness via the perfused boundary region (PBR5-25). Arterial stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (PWV), the central systolic and diastolic blood pressures (cSBP and cDBP) and the augmentation index (Aix). For each ophthalmological outcome, we generated a saturated linear regression model with demographic and systemic vascular parameters serving as independent variables. Regression coefficients with the corresponding 95% confidence intervals (CIs) were reported. A p value < 0.05 was considered as statistically significant., Results: A 1 m/s increase in PWV was associated with a 0.6% reduction in inferior macular vessel density (VD) ( p = 0.050). A 10 mmHg increase in cSBP was associated with a 0.03 mm 2 increase in foveal avascular zone (FAZ) area ( p = 0.033). A 1% increase in Aix was associated with a 0.005 mm 2 increase in FAZ area ( p = 0.008). A 1 μm increase in PBR5-25 was associated, on average, with a 4.4% decrease in superior peripapillary VD ( p = 0.027)., Conclusions: In patients with RVO, structural and microvascular retinal parameters were significantly associated with markers of endothelial dysfunction and arterial stiffness.

Introduction: Wearable Activity Trackers (WATs) offer real-time feedback on activity levels. We assessed the impact of WAT usage on physicians' exercise habits., Methods: Physicians from the Athens Medical Association, Greece (n = 742) responded to a self-administered questionnaire evaluating usage of WAT, demographic characteristics, specialty, and physical exercise habits. WHO guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in Users of WATs (Group A), and Non-Users of WATs (Group B). This is an observational, cross-sectional study., Results: There was no difference in baseline characteristics between the two groups (age, sex, body mass index). WATs were used by 38%. Between Group A and B, there was difference in mean exercise training time (302 ± 304 min vs. 210 ± 268 min, p < 0.001), higher percentage of WHO goal achievement (66.3% vs. 50.7%, p < 0.001), and greater awareness of WHO Guidelines (59.9% vs. 47.4%, p < 0.001). WATs were mostly used by four main specialties, with higher use from Cardiologists: Cardiology (47%), Endocrinology (44%), Surgery (35%) and Internal Medicine (25%), with a p = 0.045. Finally, users of WATs compared to non-users showed higher willingness to reduce body weight (58.5% vs. 48%, p = 0.01), apply dietary restrictions (36.5% vs. 29.6%, p = 0.05), and greater motivation for weekly physical exercise (74.1% vs. 32.4%, p < 0.001); Conclusion: Physicians using WATs demonstrate increased exercise training time, greater awareness of WHO guidelines and a higher propensity to implement dietary restrictions compared to non-users. Variations in WAT usage across medical specialties emphasize the need for targeted interventions to promote physical activity and enhance healthcare professionals' health.

Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, with significant variations in presentation characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Beyond reproductive health, it may also pose crucial long-term cardiometabolic risks, especially for women with specific types of PCOS, contributing to early subclinical cardiovascular atherosclerotic alterations such as endothelial dysfunction, increased arterial stiffness, and coronary artery calcium levels, respectively. Moreover, the precise relationship between clinical cardiovascular disease (CVD) and PCOS remains debated, with studies demonstrating an elevated risk while others report no significant association. This review investigates the pathophysiology of PCOS, focusing on insulin resistance and its link to subclinical and clinical cardiovascular disease. Diagnostic challenges and novel management strategies, including lifestyle interventions, medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), hormonal contraceptives, and bariatric surgery, are further discussed. Recognizing the cardiometabolic risks associated with PCOS, a comprehensive approach and early intervention should address both the reproductive and cardiometabolic dimensions of the syndrome.

Background: Diabetes mellitus (DM) is a prevalent disease in the general population and also a well-established risk factor for the development of ischemic stroke. Patients who have been diagnosed with diabetes have a 20% higher risk for developing ischemic stroke in comparison to non-diabetic individuals. The aim of the current systematic review is to provide the latest evidence regarding the association between antidiabetic treatment and the prevention of ischemic stroke. Methods: A comprehensive search in scientific literature databases PUBMED, COCHRANE, and SCOPUS was conducted. The studies that were deemed as eligible for this review were those that examined the clinical benefits of therapeutic strategies in terms of preventing ischemic strokes. Results: A total of 32 studies met the established selection criteria. The included studies showed that pioglitazone treatment significantly reduced the risk for recurrent stroke in patients with DM. Furthermore, in the context of primary prevention, the improvement in glycemic control after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RA) semaglutide and dulaglutide was associated with a reduction in the risk of ischemic stroke in diabetic subjects. Metformin monotherapy may reduce stroke risk, while dipeptidyl peptidase 4 inhibitors, sodium-glucose co-transporter 2 inhibitors, and insulin do not seem to affect the incidence of stroke. Conclusions: The findings of the present systematic review suggest that pioglitazone and GLP-1RA may decrease the risk of stroke. Further studies are needed to provide additional data regarding the preventive effect of novel antidiabetic drugs, such as dual glucose-dependent insulinotropic polypeptide/GLP-1RA agents, on stroke.

Purpose: To evaluate the potential association between endothelial glycocalyx damage, as well as arterial stiffness, and the retinal changes on optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with type 2 diabetes mellitus (DM)., Methods: Participants in this cross-sectional study were 65 patients with DM type 2 and 42 age- and gender-matched controls without DM. The demographic and clinical characteristics of the participants were recorded. All patients underwent a thorough ophthalmological examination and multimodal imaging, including fundus photography, OCT, and OCT-A. In addition, evaluation of the endothelial glycocalyx thickness by measuring the perfused boundary region (PBR5-25) of the sublingual microvessel, as well as of the arterial stiffness, by measuring the carotid-femoral pulse wave velocity (PWV), the central aortic pressures and the augmentation index (Aix) was performed. Univariate and multivariate logistic regression analysis was performed for the examination of the potential association between the eye imaging variables and the cardiovascular-related variables. The odds ratios (OR) with the respective 95% confidence intervals (CI) were calculated. A p -value < 0.05 was considered statistically significant., Results: Patients with DM presented significantly higher PBR5-25 compared to controls without DM ( p = 0.023). At the univariate analysis, increased PBR5-25 (≥2.19 μm vs. <2.19 μm) was associated with decreased peripapillary VD at the superior quadrant (univariate OR (95% CI) = 0.34 (0.12-0.93), p = 0.037). Multivariate logistic regression analysis showed that increased PWV (≥13.7 m/s vs. <13.7 m/s) was associated with an increased foveal avascular zone (FAZ) area on OCT-A ( p = 0.044) and increased FAZ perimeter ( p = 0.048). Moreover, increased Aix (≥14.745% vs. <14.745%) was associated with diabetic macular edema (DME) presence ( p = 0.050) and increased perifoveal and parafoveal superior and temporal thickness on OCT ( p < 0.05 for all associations)., Conclusions: Markers of endothelial damage and arterial stiffness were associated with structural and microvascular retinal alterations in patients with DM, pointing out that OCT-A could be a useful biomarker for detecting potential cardiovascular risk in such patients.

Backround: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) has been associated with increased cardiovascular risk. The aim of this Randomized Double-blind clinical Trial was to evaluate the effects of coenzyme-Q10 supplementation in patients with MASLD in terms of endothelial, vascular and myocardial function., Methods: Sixty patients with MASLD were randomized to receive daily 240 mg of coenzyme-Q10 or placebo. At baseline and at 6-months, the a)Perfused boundary region of sublingual vessels using the Sideview Darkfield imaging technique, b)pulse-wave-velocity, c)flow-mediated dilation of the brachial artery, d)left ventricular global longitudinal strain, e)coronary flow reserve of the left anterior descending coronary artery and f)controlled attenuation parameter for the quantification of liver steatosis were evaluated., Results: Six months post-treatment, patients under coenzyme-Q10 showed reduced Perfused boundary region (2.18 ± 0.23vs.2.29 ± 0.18 μm), pulse-wave-velocity (9.5 ± 2vs.10.2 ± 2.3 m/s), controlled attenuation parameter (280.9 ± 33.4vs.304.8 ± 37.4dB/m), and increased flow-mediated dilation (6.1 ± 3.8vs.4.3 ± 2.8%), global longitudinal strain (-19.6 ± 1.6vs.-18.8 ± 1.9%) and coronary flow reserve (3.1 ± 0.4vs.2.8 ± 0.4) compared to baseline (p < 0.05). The placebo group exhibited no improvement during the 6-month follow-up period (p > 0.05). In patients under coenzyme-Q10, the reduction in controlled attenuation parameter score was positively related to the reduction in Perfused boundary region and pulse wave velocity and reversely related to the increase in coronary flow reserve and flow-mediated dilation (p < 0.05 for all relations)., Conclusions: Six-month treatment with high-dose coenzyme-Q10 reduces liver steatosis and improves endothelial, vascular and left ventricle myocardial function in patients with MASLD, demonstrating significant improvements in micro- and macro-vasculature function., Trial Registration: NCT05941910., (© 2024. The Author(s).)

Context: The cardiovascular benefits of semaglutide are established; however, its effects on surrogate vascular markers and liver function are not known., Objective: To investigate the effects of semaglutide on vascular, endothelial, and liver function in patients with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD)., Methods: Overall, 75 consecutive subjects with T2DM and NAFLD were enrolled: 50 patients received semaglutide 1 mg (treatment group) and 25 patients received dipeptidyl peptidase 4 inhibitors (control group). All patients underwent a clinical, vascular, and hepatic examination with Fibroscan elastography at 4 and 12 months after inclusion in the study., Results: Treatment with semaglutide resulted in a reduction of Controlled Attenuation Parameter (CAP) score, E fibrosis score, NAFLD fibrosis score, Fibrosis-4 (FIB-4) score and perfused boundary region (PBR) at 4 and at 12 months ( P < .05), contrary to controls. Patients treated with semaglutide showed a greater decrease of central systolic blood pressure (SBP) (-6% vs -4%, P = .048 and -11% vs -9%, P = .039), augmentation index (AIx) (-59% vs -52%, P = .041 and -70% vs -57%, P = .022), and pulse wave velocity (PWV) (-6% vs -3.5%, P = .019 and -12% vs -10%, P = .036) at 4 and at 12 months, respectively. In all patients, ΔPWV and ΔPBR were correlated with a corresponding reduction of CAP, E fibrosis, NAFLD fibrosis, and FIB-4 scores., Conclusion: Twelve-month treatment with semaglutide simultaneously improves arterial stiffness, endothelial function, and liver steatosis and fibrosis in patients with T2DM and NAFLD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

The effect of different diet patterns on psoriasis (PSO) and psoriatic arthritis (PSA) is unknown. Τhe aim of our study was to evaluate the effectiveness of a Mediterranean diet (MD) and Ketogenic diet (KD), in patients with PSO and PSA. Twenty-six patients were randomly assigned to start either with MD or KD for a period of 8 weeks. After a 6-week washout interval, the two groups were crossed over to the other type of diet for 8 weeks. At the end of this study, MD and KD resulted in significant reduction in weight ( p = 0.002, p < 0.001, respectively), in BMI ( p = 0.006, p < 0.001, respectively), in waist circumference (WC) ( p = 0.001, p < 0.001, respectively), in total fat mass ( p = 0.007, p < 0.001, respectively), and in visceral fat ( p = 0.01, p < 0.001, respectively), in comparison with baseline. After KD, patients displayed a significant reduction in the Psoriasis Area and Severity Index (PASI) ( p = 0.04), Disease Activity Index of Psoriatic Arthritis (DAPSA) ( p = 0.004), interleukin (IL)-6 ( p = 0.047), IL-17 ( p = 0.042), and IL-23 ( p = 0.037), whereas no significant differences were observed in these markers after MD ( p > 0.05), compared to baseline. The 22-week MD-KD diet program in patients with PSO and PSA led to beneficial results in markers of inflammation and disease activity, which were mainly attributed to KD.

Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.

Background and Objectives : The effects of gender differences on cardiac parameters have been well-established. In this study, we aimed to evaluate the possible associations of plasma levels of different sex hormones with premature atrial or ventricular contractions in premenopausal women. Materials and Methods : We conducted a prospective study which included women in late reproductive age who presented with palpitations during an eight-month period. A 12-lead electrocardiography, a transthoracic echocardiogram, blood samples, and 24-hour rhythm Holter were conducted on the third day of the menstrual cycle. Results Overall, 93 healthy premenopausal women with a median age of 42 years were enrolled. QTc interval was within normal limits in all patients. The 24 h range of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) was 0-6450 and was 0-21,230, respectively. The median number of PVCs was 540 and the median number of PACs was 212, respectively. In total, 51 patients (54.8%) had a frequency of PVCs > 500/24 h and 37 patients (39.8%) had a frequency of PACs > 500/24 h, respectively. No statistically significant association was shown between any hormone and the frequency of PACs. Regarding PVCs, patients with a PVCs frequency > 500/24 h had higher estradiol levels compared to patients with PVCs less than 500/24 h (median 60 pg/mL versus 42 pg/mL, p = 0.02, OR: 1.01). No association was found between PVCs and other hormones. Conclusions : In premenopausal healthy women, higher estradiol levels are independently associated with increased PVCs. This suggests that estradiol in late reproductive stages may exert proarrhythmic effects.