Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: a randomized double-blind, placebo-controlled trial.

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.

Association of aortic stiffness early post myocardial infarction with left ventricular remodelling.

BACKGROUND: Adverse left ventricular (LV) remodelling after myocardial infarction is associated with heart failure. We investigated whether aortic stiffness during acute ST-segment elevation myocardial infarction is associated with LV remodelling at long-term follow-up. METHODS: In 109 patients within 48 h of myocardial infarction post-primary percutaneous coronary intervention and after 2 years, we measured: (a) carotid to femoral pulse wave velocity (PWV), (b) LV global longitudinal strain (GLS) and left atrial strain using speckle-tracking echocardiography, (c) PWV/GLS ratio as a surrogate marker of ventricular-arterial interaction, and (d) LV end-diastolic and end-systolic volumes. A > 15% decrease from the baseline in LV end-systolic volume at 2-year follow-up was considered as a criterion of reverse LV remodelling. RESULTS: Compared with baseline, all patients had reduced PWV, LV end-diastolic and end-systolic volumes while PWV/GLS, GLS and reservoir left atrial strain were improved (p < .05) after 2 years. Baseline values of PWV, GLS, PWV/GLS ratio and reservoir left atrial strain were associated with percentage change of LV end-systolic volume at 2 years (p < .05). Multivariable analysis revealed that lower baseline values of PWV and a less impaired GLS and PWV/GLS were independently associated with reverse LV remodelling at 2 years with a C-statistic of .748, .711 and .787, respectively. CONCLUSION: Aortic stiffness early post-infarction determines LV remodelling after 2 years of the ischemic event despite post successful revascularization. CLINICAL TRIAL REGISTRATION-URL: http://www. CLINICALTRIALS: gov. Unique identifier: NCT03984123, 30/04/2020.

The Effect of a Ketogenic Diet versus Mediterranean Diet on Clinical and Biochemical Markers of Inflammation in Patients with Obesity and Psoriatic Arthritis: A Randomized Crossover Trial.

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.

Effects of Liraglutide, Empagliflozin and Their Combination on Left Atrial Strain and Arterial Function.

Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are cardioprotective drugs. We investigated their effects on left atrial function, a major determinant of cardiac diastolic dysfunction in type 2 diabetes mellitus. We also explored the association of changes in arterial stiffness with those of the LA strain after treatment. Materials and Methods: A total of 200 patients (59.5 ± 9.1 year old, 151 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n = 50 served as controls), liraglutide (n = 50), empagliflozin (n = 50) or their combination (liraglutide + empagliflozin) (n = 50). We measured at baseline and 6 months post-treatment: (a) left atrial and global left ventricular longitudinal strain by speckle tracking echocardiography; (b) pulse wave velocity (PWV) and central systolic blood pressure. Results: At baseline, there was a correlation of the LA reservoir strain with PWV (r = -0.209, p = 0.008), central SBP (r = -0.151, p = 0.030), EF (r = 0.214, p = 0.004) and GLS (r = -0.279, p = 0.009). The LA reservoir change 6 months post-treatment was correlated with the PWV change in all groups (r = -0.242, p = 0.028). The LA reservoir change 6 months post-treatment was correlated with the GLS change in all groups (r = -0.322, p = 0.004). Six months after intervention, patients treated with liraglutide, empagliflozin and their combination improved the left atrial reservoir strain (GLP1RA 30.7 ± 9.3 vs. 33.9 ± 9.7%, p = 0.011, SGLT2i 30 ± 8.3 vs. 32.3 ± 7.3%, p = 0.04, GLP1&SGLT2i 29.1 ± 8.7 vs. 31.3 ± 8.2, p = 0.007) compared to those treated with insulin (33 ± 8.3% vs. 32.8 ± 7.4, p = 0.829). Also, patients treated with liraglutide and the combination liraglutide and empagliflozin had improved left atrial conduction strain (p < 0.05). Empagliflozin or the combination liraglutide and empagliflozin showed a greater decrease of PWV and central and brachial systolic blood pressure than insulin or GLP-1RA. (p < 0.05). Conclusions: Impaired aortic elastic properties are associated with a decreased LA strain in type 2 diabetics. Treatment with liraglutide, empagliflozin and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with the improvement of arterial and myocardial functions.

Treatment with Umbilical Cord Blood Platelet Lysate Gel Improves Healing of Diabetic Foot Ulcer.

BACKGROUND: This study was conducted to examine the hypothesis that umbilical cord blood platelet lysate (UCB-PL) gel has a significant impact on the healing rate of DFU. Μethods: In this open-labeled, randomized controlled trial, 110 patients were randomized to treatment with UCB-PL gel (UCB-PL group, n = 52) every three days for one month or dressing with normal saline (control group, n = 58). All participants were followed up for 20 weeks post treatment. Ulcer surface area was assessed with the imitoMeasure application at two, four, and six weeks, and two, four and six months. This study's main outcome was the reduction in ulcer size over the six-month study period. RESULTS: The mean ulcer area at baseline was 4.1 cm2 in the UCB-PL group and 1.7 cm2 in the control group. At six months post treatment, patients on the UCB-PL treatment displayed a significant reduction in ulcer size compared to baseline 0.12 (0-8.16) in contrast to a more modest change in the control group 1.05 (0-24.7). The ulcer area was decreased at the end of the study in 40 patients (97.6%) in the UCB-PL group and 27 (73%) in the control group (Fisher's p = 0.002). CONCLUSIONS: The application of UCB-PL gel in DFU resulted in a significant reduction in ulcer size compared to regular saline dressing.

Risk of major adverse cardiovascular events and stroke associated with treatment with GLP-1 or the dual GIP/GLP-1 receptor agonist tirzepatide for type 2 diabetes: A systematic review and meta-analysis.

INTRODUCTION: Mounting evidence suggests that glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) attenuate cardiovascular-risk in type-2 diabetes (T2DM). Tirzepatide is the first-in-class, dual glucose-dependent-insulinotropic-polypeptide GIP/GLP-1 RA approved for T2DM. PATIENTS AND METHODS: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate: (i) the incidence of major adverse cardiovascular events (MACE); and (ii) incidence of stroke, fatal, and nonfatal stroke in T2DM-patients treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). RESULTS: Thirteen RCTs (9 and 4 on GLP-1 RAs and tirzepatide, respectively) comprising 65,878 T2DM patients were included. Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs. Additionally, GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%) and nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%), whereas no association between fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%). In secondary analyses, GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%) and MACE-recurrence, but not hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%). There was no association between GLP-1RAs or GIP/GLP-1 RAs and fatal or nonfatal myocardial infarction. DISCUSSION AND CONCLUSION: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and mortality in T2DM. While there is solid evidence that GLP-1 RAs significantly attenuate the risk of ischemic stroke in T2DM, dedicated RCTs are needed to evaluate the efficacy of novel GIP/GLP-1 RAs for primary and secondary stroke prevention.

Impairment in Right Ventricular-Pulmonary Arterial Coupling in Overweight and Obesity.

Background: The association of obesity with right ventricular function and the interplay between right heart and pulmonary circulation is incompletely understood. We evaluate the role of obesity as a determinant of right ventricular-pulmonary artery coupling (RVAC). Methods: We retrospectively studied consecutive subjects without overt cardiovascular or pulmonary disease. Subjects were stratified according to body mass index (BMI) as normal weight, overweight, or obese. A transthoracic echocardiographic study was used to assess left and right heart functional and structural parameters. RVAC was assessed using the ratio of peak systolic velocity of the tricuspid annulus to pulmonary artery systolic pressure (PASP). Results: A total of 145 subjects were enrolled with diabetes mellitus incidence higher in obese. There was no difference in left ventricular global longitudinal strain and in PASP or markers of right ventricular systolic function based on BMI. RVAC was significantly lower in the presence of obesity (normal weight: 0.52 (0.19) cm·(sec·mmHg)-1 vs. overweight: 0.47 (0.16) cm·(sec·mmHg)-1 vs. obese: 0.43 (0.14) cm·(sec·mmHg)-1, p = 0.03), even after adjustment for confounders (ß: -0.085, 95% confidence interval: -0.163, -0.009, p = 0.029). Conclusions: Our findings highlight the relationship between metabolic impairment and RVAC, suggesting additional mechanisms for heart failure development observed in obese subjects.

The Effect of 4-Month Treatment with Glycocalyx Dietary Supplement on Endothelial Glycocalyx Integrity and Vascular Function in Patients with Psoriasis.

Psoriasis predisposes to cardiovascular dysfunction. We investigated whether glycocalyx dietary supplement (GDS), which contains glycosaminoglycans and fucoidan, improves endothelial glycocalyx and arterial stiffness in psoriatic patients. Fifty participants with psoriasis under biological agents were randomly assigned to GDS (n = 25) or placebo (n = 25) for 4 months. We measured at baseline and at follow-up: (a) perfused boundary region (PBR) of the sublingual microvessels (range 4 to 25 µm), a marker of endothelium glycocalyx integrity; (b) carotid-femoral pulse wave velocity (PWV-Complior SP-ALAM) and augmentation index (AIx), markers of arterial stiffness and (c) psoriasis area and severity index (PASI) score. Both groups displayed a similar decrease in PASI at four months (p < 0.05), and no significant differences were found between groups (p > 0.05). Compared to the placebo, participants in the GDS showed a greater percentage reduction in PBR4-25 µm (-9.95% vs. -0.87%), PBR 4-9 µm (-6.50% vs. -0.82%), PBR10-19 µm (-5.12% vs. -1.60%), PBR 20-25 µm (-14.9% vs. -0.31%), PWV (-15.27% vs. -4.04%) and AIx (-35.57% vs. -21.85%) (p < 0.05). In the GDS group, the percentage reduction in PBR 4-25 µm was associated with the corresponding decrease in PWV (r = 0.411, p = 0.015) and AΙx (r = 0.481, p = 0.010) at follow-up. Four-month treatment with GDS improves glycocalyx integrity and arterial stiffness in patients with psoriasis. Clinical trial Identifier: NCT05184699.

Semaglutide Concurrently Improves Vascular and Liver Indices in Patients With Type 2 Diabetes and Fatty Liver Disease.

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.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. RESULTS: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). CONCLUSIONS: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry.

AIMS: Three physical signs, namely tendon xanthomas, corneal arcus and xanthelasma, have been associated with heterozygous familial hypercholesterolemia (heFH). The prevalence and clinical significance of these signs are not well established among contemporary heFH individuals. This study explored the frequency as well as the association of these physical signs with prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH individuals. METHODS: Data from the Hellenic Familial Hypercholesterolemia Registry were applied for this analysis. The diagnosis of heFH was based on the Dutch Lipid Clinic Network Score. Multivariate logistic regression analysis was conducted to examine the association of heFH-related physical signs with prevalent ASCVD. RESULTS: Adult patients ( n  = 2156, mean age 50 ±â€Š15 years, 47.7% women) were included in this analysis. Among them, 14.5% had at least one heFH-related physical sign present. The prevalence of corneal arcus before the age of 45 years was 6.6%, tendon xanthomas 5.3%, and xanthelasmas 5.8%. Among physical signs, only the presence of corneal arcus before the age of 45 years was independently associated with the presence of premature coronary artery disease (CAD). No association of any physical sign with total CAD, stroke or peripheral artery disease was found. Patients with physical signs were more likely to receive higher intensity statin therapy and dual lipid-lowering therapy, but only a minority reached optimal lipid targets. CONCLUSION: The prevalence of physical signs is relatively low in contemporary heFH patients. The presence of corneal arcus before the age of 45 years is independently associated with premature CAD.

Obesity and atherosclerotic cardiovascular disease in adults with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry.

BACKGROUND: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown. OBJECTIVE: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). METHODS: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded. RESULTS: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease [PAD]), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD. CONCLUSIONS: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population.