Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

Concomitant occurrence of Wernicke's encephalopathy and sarcopenia due to vitamin D depletion in patients with alcohol use disorder: a case report.

Individuals with alcohol use disorder frequently suffer from vitamin D deficiency, in addition to deficiencies in vitamins B12, folic acid and B1. This is due to inadequate dietary intake and behavioural changes. Each of these deficiencies results in different clinical symptoms. Subacute spinal cord degeneration, together with radicular and sensorimotor peripheral neuropathy, arises from B12 vitamin and folic acid deficiencies. B1 vitamin deficiency leads to Wernicke's encephalopathy, which can include the classical triad of symptoms (i.e. cognitive changes, ataxia and ophthalmoplegia). Sarcopenia is a consequence of a long-term deficiency of vitamin D. This current case report describes a 43-year-old female patient with alcohol use disorder who complained of dizziness, postural disturbance and episodes of intermittent paraesthesia. She was subsequently shown to have concomitant Wernicke's encephalopathy and sarcopenia due to vitamin D deficiency. This case report presents the diagnostic process undertaken to exclude conditions related to ataxia and paraparesis other than vitamins D and B1 deficiencies. It also emphasizes the importance of concomitant replacement of the depleted vitamins because the vitamin deficiency may occur simultaneously, which causes the accompanying manifestations of several clinical syndromes.

IGF-1 and IGFBP3 as indirect markers of hepatic insulin resistance and their relation to metabolic syndrome parameters in liver steatosis patients.

Objective. The aim of the present study was to assess insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP3) as markers of insulin resistance in patients with prediabetes and type 2 diabetes mellitus (TDM2). Patients and Methods. This observational clinical study included 76 obese/overweight patients at the age of 45-75 years with T2DM on oral diabetic medication and ultrasonographically or by a computerized tomography (CT) diagnosed liver steatosis. Correlation analysis was performed between plasma levels of insulin, C-peptide, IGF-1, IGFBP3 and HOMA indexes on the one hand and between plasma levels of ALT, AST, triglyceride, cholesterol, and HDL cholesterol and body mass index (BMI) of patients on the other hand. In case of significant partial correlation coefficients, a multiple linear regression model with IGF-1 and IGFBP3 used as outcome variables adjusted for age and sex groups was calculated. According to these regression models, ROC curves were prepared with HOMA index=3 used as a classificator of insulin resistance. Results. Significant correlation was found between C-peptide and IGF-1 (r=0.24, p≤0.05), C-peptide and IGFBP3 (r=0.24, p≤0.05), IGFBP3 and cholesterol (r=0.22, p≤0.05) IGFBP3 and ALT (r=0.19, p≤0.05), HOMA index and triglycerides (r=0.22, p≤0.05), and HOMA index and ALT (r=0.23, p≤0.05). Significant correlation adjusted for age and gender was found between C-peptide and IGF-1 plasma levels (R2=0.20, p<0.05) with AUROC 0.685 (p≤0.01) and C-peptide and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.684 (p≤0.01). Significant correlation adjusted for age and gender was found between triglyceride and IGFBP3 plasma levels (R2=0.28, p<0.05) with AUROC 0.616 (p≤0.01). After the distribution of patients according to their IGFBP3 levels, we found a difference between the 1st and the 4th quartiles in terms of triglyceride levels. Conclusion. Our results demonstrate a fundamental role of IGF-1 and IGFBP3 in the patho-physiology of hepatic insulin resistance and suggest them as indirect indicators of the hepatic insulin resistance.

Theories and Molecular Basis of Vascular Aging: A Review of the Literature from VascAgeNet Group on Pathophysiological Mechanisms of Vascular Aging.

Vascular aging, characterized by structural and functional alterations of the vascular wall, is a hallmark of aging and is tightly related to the development of cardiovascular mortality and age-associated vascular pathologies. Over the last years, extensive and ongoing research has highlighted several sophisticated molecular mechanisms that are involved in the pathophysiology of vascular aging. A more thorough understanding of these mechanisms could help to provide a new insight into the complex biology of this non-reversible vascular process and direct future interventions to improve longevity. In this review, we discuss the role of the most important molecular pathways involved in vascular ageing including oxidative stress, vascular inflammation, extracellular matrix metalloproteinases activity, epigenetic regulation, telomere shortening, senescence and autophagy.

Pathophysiology of Circulating Biomarkers and Relationship With Vascular Aging: A Review of the Literature From VascAgeNet Group on Circulating Biomarkers, European Cooperation in Science and Technology Action 18216.

Impairment of the arteries is a product of sustained exposure to various deleterious factors and progresses with time; a phenomenon inherent to vascular aging. Oxidative stress, inflammation, the accumulation of harmful agents in high cardiovascular risk conditions, changes to the extracellular matrix, and/or alterations of the epigenetic modification of molecules, are all vital pathophysiological processes proven to contribute to vascular aging, and also lead to changes in levels of associated circulating molecules. Many of these molecules are consequently recognized as markers of vascular impairment and accelerated vascular aging in clinical and research settings, however, for these molecules to be classified as biomarkers of vascular aging, further criteria must be met. In this paper, we conducted a scoping literature review identifying thirty of the most important, and eight less important, biomarkers of vascular aging. Herein, we overview a selection of the most important molecules connected with the above-mentioned pathological conditions and study their usefulness as circulating biomarkers of vascular aging.

[Carbohydrate-deficient transferrin in doping and non-doping athletes]. / A szénhidrátszegény transzferrin értékének változásai doppingoló és nem doppingoló sportolóknál.

UNLABELLED: The determination of carbohydrate deficient transferrin (CDT) concentration is primarily used in social security studies as a proof of regular alcohol consumption exceeding the amount of 60 grams per day. AIMS: The present study was performed to investigate into how carbohydrate deficient transferrin CDT values in serum are affected by the so-called food supplements and chemicals included in doping lists. METHODS: The investigation was carried out in 15 bodybuilders of two sport clubs and in 10 boxers. All sportsmen were males. In both groups serum carbohydrate deficient transferrin (CDT%), median red blood cell volume and (MCV) gamma-glutamyl-transpeptidase (GGT) values were measured. RESULTS: The authors found a significant difference between the two groups only in carbohydrate deficient transferrin CDT% that was the CDT% value in bodybuilders was twice as high as in boxers. CONCLUSION: Not all the details of the specificity of carbohydrate deficient transferrin (CDT) concentration are known, however, the remarkably high sensitivity of the method makes it suitable and probably economically effective as a pre-screening tool in doping tests.

[Does carbohydrate-deficient transferrin have diagnostic value in non-alcoholic fatty liver disease?]. / Diagnosztikus értékû-e a szénhidrátszegény transzferrin nem alkoholos zsírmájban?

UNLABELLED: Non-alcoholic fatty liver disease (NAFLD) is an acquired metabolic liver disease in the consequence of triglyceride accumulation within liver cells. It is accompanied by necrobiotic inflammatory reaction, fibrosis and also by liver cirrhosis. Its distinction from alcoholic fatty liver disease (AFLD) can be difficult. Clear anamnesis may help, but if the patient does not inform us about the alcohol consumption, the differentiation is not easy. AIM: Our aim was to determine the value of carbohydrate deficient transferrin (CDT) in patients with non-alcoholic fatty liver disease, as well as to analyze the background of high CDT values, according to the anamnesis. PATIENTS AND METHODS: 39 patients (21 female and 18 male) with ultrasound signs of fatty liver disease were studied. CDT, body mass index (BMI) and HOMA index were determined. RESULTS: Mean value of CDT was: 2.39+/-0.52% (in male 2.51+/-0.61, in female 2.28+/-0.4). No significant difference was found among the two sexes. The diversity of CDT values was normal. The value of BMI belonged to the overweight area without any significant difference between the two sexes. CONCLUSION: On the basis of the results, NAFLD and AFLD can be differentiated according to the CDT value, and this value could be a higher specific value than the activity of gammaglutamyl transpeptidase, however, anamnesis and other factors are as well very important in achieving the correct diagnosis.

[Common occurrence of non-alcoholic fatty liver disease and cholecystolithiasis]. / A nem alkoholos zsírmáj és az epekövesség együttes elofordulásának megfigyelése.

INTRODUCTION: Non-Alcoholic Fatty Liver Disease is an acquired metabolic disease of the liver caused by accumulation of triglycerides in hepatocytes that is followed by necrobiotic inflammatory reaction, fibrosis and cirrhosis. Obesity, insulin resistance, diabetes mellitus and hyperlipidaemia are important pathogenetic factors of the process. It is known that among patients with cholecystolithiasis and diabetes mellitus in their anamnesis complications of cholecystolithiasis occur much more frequently like among patients without diabetes. AIM: The aim of the study is observation of the incidence of cholecystolithiasis and its complications in patients with Non-Alcoholic Fatty Liver Disease and comparison of cholecystolithiasis incidence between healthy population and population with Non-Alcoholic Fatty Liver Disease. METHODS: Abdominal ultrasonographical findings were analysed in patients hospitalised at our department and in outpatients, patients with severe accompanied diseases were excluded of the analysis. The analysed basic file of patients could be considered as a selected file. The independence of the two examined variables was measured by chi(2) test. RESULTS: Steatosis was described in 38% of the examined patients, cholecystolithiasis was described in 16% of patients. Cholecystolithiasis and its complications occur two times more frequently in patients with Non-Alcoholic Fatty Liver Disease (33%) like Non-Alcoholic Fatty Liver Disease in patients with cholecystolithiasis (16%). Complications of cholecystolithiasis occur more frequently among patients with Non-Alcoholic Fatty Liver Disease like in healthy individuals. The chi(2) test did not bring significant results concerning the independence of cholecystolithiasis and Non-Alcoholic Fatty Liver Disease. CONCLUSION: Pathogenetic factors of Non-Alcoholic Fatty Liver Disease participate in the pathogenesis of cholecystolithiasis. Their common pathogenetic factors bring about that the formation of cholecystolithiasis is probably faster than the progression of steatosis.

[Hepatorenal syndrome]. / Hepatorenalis szindróma.

Hepatorenal syndrome. Hepatorenal syndrome is a functional renal failure in state of portal hypertension caused by splanchnic vasodilatation that brings decrease of renal perfusion. The inductive factors include acute alcoholic hepatitis, non-adequate diuretic therapy, infections and bleeding from upper parts of gastrointestinal tract. Recognition of pathophysiological mechanisms of hepatorenal syndrome helped the elaboration of therapeutic schemes. The treatment is successful in improvement of renal functions in many patients but it is very expensive.

[Role of lipid peroxidation in non-alcoholic steatohepatitis]. / A lipidperoxidáció szerepe a nem alkoholos steatohepatitis kialakulásában.

The liver steatosis is a frequent human disease. The most frequent cause of the process is the alcohol consumption. But it also may arise without significant alcohol abuse. This pathogenetic process is called non-alcoholic steatohepatitis (NASH), that is characterized by the same conditions like the alcoholic steatohepatitis. In the pathogenesis of the NASH various factors participate i.e. obesity, diabetes mellitus type II, hyperlipidaemia, pregnancy, variable chemotoxins, parenteral nutrition, jejunoileal bypass, chronic inflammatory diseases, protein deficient nutrition and inborn metabolic diseases. Pathobiochemically the process consists of oxidative stress and lipid peroxidation. This condition comes from the progressive accumulation of the free fatty acids in mitochondria and from the induction of cytochrome P450, CYP 2E1 isoform in hepatocytes and Kupffer cells. The free fatty acids and ketons can cause the induction of CYP 2E1 system, that is why diabetes mellitus and obesity are the two most important factors in the NASH pathogenesis. This article is concerned mainly in the explanation of NASH pathomechanism.