Blood and Salivary Cortisol Variations in Athletes in Relation to Cardiopulmonary Exercise Testing.

Background and Objectives: Cortisol is a valuable marker for assessing the body's response to any form of stress. We conducted this study in order to evaluate the variations of salivary and serum cortisol levels in professional football players in relation to cardiopulmonary exercise testing (CPET) and their significance in potentially evaluating overtraining in athletes. Also, the question of whether salivary cortisol determination could fully substitute serum sampling was addressed. Materials and Methods: A total of 19 male professional football players were evaluated by measuring serum cortisol levels at rest (T0) and immediately after a CPET (T1) and salivary cortisol levels at rest (T0), 10 min after a CPET (T2), and 30 min after a CPET (T3). Results: T0 serum cortisol showed a statistically significant correlation with the oxygen uptake at the anaerobic threshold divided by the body weight (VO2-AT/weight), as did the T2 salivary cortisol with the maximum oxygen uptake at the anaerobic threshold (VO2-AT) and VO2-AT/weight. T0 salivary cortisol was significantly correlated with the subjects' height and the predicted O2 pulse. Conclusions: While some correlations were discovered, they are insufficient to recommend cortisol as a routine biomarker in athletes' evaluation. However, significant correlations were established between salivary and serum determinations, meaning that the non-invasive procedure could substitute venous blood sampling.

Evaluation of cardiovascular risk factors in patients with familial hypercholesterolemia from the North-Eastern area of Romania.

BACKGROUND: Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. METHODS: This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. RESULTS: Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: "possible" FH identified in 39.4%, "probable" FH in 45.9% and "definite" FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. CONCLUSIONS: In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

Multifractality through Non-Markovian Stochastic Processes in the Scale Relativity Theory. Acute Arterial Occlusions as Scale Transitions.

By assimilating biological systems, both structural and functional, into multifractal objects, their behavior can be described in the framework of the scale relativity theory, in any of its forms (standard form in Nottale's sense and/or the form of the multifractal theory of motion). By operating in the context of the multifractal theory of motion, based on multifractalization through non-Markovian stochastic processes, the main results of Nottale's theory can be generalized (specific momentum conservation laws, both at differentiable and non-differentiable resolution scales, specific momentum conservation law associated with the differentiable-non-differentiable scale transition, etc.). In such a context, all results are explicated through analyzing biological processes, such as acute arterial occlusions as scale transitions. Thus, we show through a biophysical multifractal model that the blocking of the lumen of a healthy artery can happen as a result of the "stopping effect" associated with the differentiable-non-differentiable scale transition. We consider that blood entities move on continuous but non-differentiable (multifractal) curves. We determine the biophysical parameters that characterize the blood flow as a Bingham-type rheological fluid through a normal arterial structure assimilated with a horizontal "pipe" with circular symmetry. Our model has been validated based on experimental clinical data.

The Effect of Vitamin Supplementation on Subclinical Atherosclerosis in Patients without Manifest Cardiovascular Diseases: Never-ending Hope or Underestimated Effect?

Micronutrients, especially vitamins, play an important role in the evolution of cardiovascular diseases (CVD). It has been speculated that additional intake of vitamins may reduce the CVD burden by acting on the inflammatory and oxidative response starting from early stages of atherosclerosis, when the vascular impairment might still be reversible or, at least, slowed down. The current review assesses the role of major vitamins on subclinical atherosclerosis process and the potential clinical implications in patients without CVD. We have comprehensively examined the literature data for the major vitamins: A, B group, C, D, and E, respectively. Most data are based on vitamin E, D and C supplementation, while vitamins A and B have been scarcely examined for the subclinical atherosclerosis action. Though the fundamental premise was optimistic, the up-to-date trials with vitamin supplementation revealed divergent results on subclinical atherosclerosis improvement, both in healthy subjects and patients with CVD, while the long-term effect seems minimal. Thus, there are no conclusive data on the prevention and progression of atherosclerosis based on vitamin supplementation. However, given their enormous potential, future trials are certainly needed for a more tailored CVD prevention focusing on early stages as subclinical atherosclerosis.

Anethole and Its Role in Chronic Diseases.

Anethole is the main fragrance and bioactive compound of anise, fennel, and star anise spices and more than other 20 plant species. It is widely used as flavor agent in food industry and other industries, in cosmetics, perfumery, and pharmaceuticals. In the last few years, various studies have revealed multiple beneficial effects of anethole for human health, such as anti-inflammatory, anticarcinogenic and chemopreventive, antidiabetic, immunomodulatory, neuroprotective, or antithrombotic, that are mediated by the modulation of several cell signaling pathways, mainly NF-kB and TNF-α signaling, and various ion channels. This chapter aims to review the scientific data and attempts to provide an insight into pharmacological activity of anethole and its therapeutic potential in human chronic diseases.

Risk Scores for Prediction of Major Cardiovascular Events in Non-Alcoholic Fatty Liver Disease: A No Man's Land?

Over the past 100 years, cardiovascular disease (CVD) has become a leading cause of mortality and morbidity in developed countries, and similar trends have occurred for chronic liver disease. Subsequent research also indicated that people with non-alcoholic fatty liver disease (NAFLD) had a twofold increased risk of CV events and that this risk was doubled in those with liver fibrosis. However, no validated CVD risk score specific for NAFLD patients has yet been validated, as traditional risk scores tend to underestimate the CV risk in NAFLD patients. From a practical perspective, identifying NAFLD patients and assessing severity of liver fibrosis when concurrent atherosclerotic risk factors are already established may serve as an important criterion in new CV risk scores. The current review aims to assess current risk scores and their utility for the prediction of CV events among patients with NAFLD.

Ischemia with Nonobstructive Coronary Artery Disease and Atrial Cardiomyopathy-Two Sides of the Same Story?

Ischemia with nonobstructive coronary artery disease (INOCA) is increasingly recognized as a significant cause of angina, myocardial remodeling, and eventually heart failure (HF). Coronary microvascular dysfunction (CMD) is a major endotype of INOCA, and it is caused by structural and functional alterations of the coronary microcirculation. At the same time, atrial cardiomyopathy (ACM) defined by structural, functional, and electrical atrial remodeling has a major clinical impact due to its manifestations: atrial fibrillation (AF), atrial thrombosis, stroke, and HF symptoms. Both these pathologies share similar risk factors and have a high comorbidity burden. CMD causing INOCA and ACM frequently coexist. Thus, questions arise whether there is a potential link between these pathologies. Does CMD promote AF or the reverse? Which are the mechanisms that ultimately lead to CMD and ACM? Are both part of a systemic disease characterized by endothelial dysfunction? Lastly, which are the therapeutic strategies that can target endothelial dysfunction and improve the prognosis of patients with CMD and ACM? This review aims to address these questions by analyzing the existing body of evidence, offering further insight into the mechanisms of CMD and ACM, and discussing potential therapeutic strategies.

Direct Oral Anticoagulants for Stroke and Systemic Embolism Prevention in Patients with Left Ventricular Thrombus.

In recent years, direct oral anticoagulants (DOAC) have accumulated evidence of efficacy and safety in various clinical scenarios and are approved for a wide spectrum of indications. Still, they are currently used off-label for left ventricular thrombus owing to a paucity of evidence. For the same reason, there is a lack of guideline indication as well. Our work is based on an exhaustive analysis of the available literature and provides a structured and detailed update on the use of DOACs in patients with left ventricle thrombus. The safety and efficacy of DOACs were analyzed in particular clinical scenarios. As far as we know, this is the first paper that analyzes DOACs in this approach.

Syndecan-1: From a Promising Novel Cardiac Biomarker to a Surrogate Early Predictor of Kidney and Liver Injury in Patients with Acute Heart Failure.

(1) Background: Acute heart failure (HF) represents a complex clinical syndrome burdened by increased mortality and a high rate of systemic complications. Although natriuretic peptides (e.g., NT-proBNP) currently represent the diagnostic and prognostic gold standard in acute HF, those molecules do not accurately reflect all the pathophysiological mechanisms involved in the progression of this pathology when determined independently. Therefore, the current paradigm tends to focus on a multi-marker approach for the risk stratification of patients with acute HF. Syndecan-1 is a less studied biomarker in cardiovascular diseases; its assessment in patients with acute HF being potentially able to reflect the myocardial pathological changes, such as fibrosis, inflammation, endothelial dysfunction or global wall stress. (2) Methods: We conducted a single center prospective study that enrolled 173 patients (120 patients admitted for acute HF, compared to 53 controls with stable chronic HF). A complete standardized clinical, echocardiography and laboratory evaluation was performed at admission, including serum samples for the determination of syndecan-1 by the enzyme-linked immunosorbent assay (ELISA) method. (3) Results: The serum concentration of syndecan-1 was significantly higher in patients with acute HF, compared to controls [121.4 (69.3-257.9) vs. 72.1 (41.4-135.8) ng/mL, p = 0.015]. Syndecan-1 was a significant predictor for the diagnosis of acute HF, expressed by an area under the curve (AUC) of 0.898, similar to NT-proBNP (AUC: 0.976) or cardiac troponin (AUC: 0.839). Moreover, syndecan-1 was independently associated with impaired kidney and liver function at admission, being also a predictor for early, subclinical organ dysfunction in patients with normal biological parameters at admission. When included in the multi-marker model, syndecan-1 levels influenced mortality more significantly than NT-proBNP or troponin. A multivariable regression including syndecan-1, NT-proBNP and troponin provided additional prognostic value compared to each independent biomarker. (4) Conclusions: Syndecan-1 can be considered a promising novel biomarker in acute HF, exhibiting adequate diagnostic and prognostic value. Additionally, syndecan-1 can be used as a surrogate biomarker for non-cardiac organ dysfunction, as its highs levels can accurately reflect early acute kidney and liver injury.

Cardiac Reverse Remodeling in Ischemic Heart Disease with Novel Therapies for Heart Failure with Reduced Ejection Fraction.

Despite the improvements in the treatment of coronary artery disease (CAD) and acute myocardial infarction (MI) over the past 20 years, ischemic heart disease (IHD) continues to be the most common cause of heart failure (HF). In clinical trials, over 70% of patients diagnosed with HF had IHD as the underlying cause. Furthermore, IHD predicts a worse outcome for patients with HF, leading to a substantial increase in late morbidity, mortality, and healthcare costs. In recent years, new pharmacological therapies have emerged for the treatment of HF, such as sodium-glucose cotransporter-2 inhibitors, angiotensin receptor-neprilysin inhibitors, selective cardiac myosin activators, and oral soluble guanylate cyclase stimulators, demonstrating clear or potential benefits in patients with HF with reduced ejection fraction. Interventional strategies such as cardiac resynchronization therapy, cardiac contractility modulation, or baroreflex activation therapy might provide additional therapeutic benefits by improving symptoms and promoting reverse remodeling. Furthermore, cardiac regenerative therapies such as stem cell transplantation could become a new therapeutic resource in the management of HF. By analyzing the existing data from the literature, this review aims to evaluate the impact of new HF therapies in patients with IHD in order to gain further insight into the best form of therapeutic management for this large proportion of HF patients.

Atrial Fibrillation and Chronic Coronary Ischemia: A Challenging Vicious Circle.

Atrial fibrillation, the most frequent arrhythmia in clinical practice and chronic coronary syndrome, is one of the forms of coronary ischemia to have a strong dual relationship. Atrial fibrillation may accelerate atherosclerosis and may increase oxygen consumption in the myocardium, creating a mismatch between supply and demand, thus promoting the development or worsening of coronary ischemia. Chronic coronary syndrome alters the structure and function of gap junction proteins, affecting the conduction of action potential and leading to ischemic necrosis of cardiomyocytes and their replacement with fibrous tissue, in this way sustaining the focal ectopic activity in atrial myocardium. They have many risk factors in common, such as hypertension, obesity, type 2 diabetes mellitus, and dyslipidemia. It is vital for the prognosis of patients to break this vicious circle by controlling risk factors, drug therapies, of which antithrombotic therapy may sometimes be challenging in terms of prothrombotic and bleeding risk, and interventional therapies (revascularization and catheter ablation).

Acute Myocardial Infarction in Patients with Hereditary Thrombophilia-A Focus on Factor V Leiden and Prothrombin G20210A.

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden.

An Overview of the Impact of Bacterial Infections and the Associated Mortality Predictors in Patients with COVID-19 Admitted to a Tertiary Center from Eastern Europe.

1. BACKGROUND: Literature data on bacterial infections and their impact on the mortality rates of COVID-19 patients from Romania are scarce, while worldwide reports are contrasting. 2. MATERIALS AND METHODS: We conducted a unicentric retrospective observational study that included 280 patients with SARS-CoV-2 infection, on whom we performed various microbiological determinations. Based on the administration or not of the antibiotic treatment, we divided the patients into two groups. First, we sought to investigate the rates and predictors of bacterial infections, the causative microbial strains, and the prescribed antibiotic treatment. Secondly, the study aimed to identify the risk factors associated with in-hospital death and evaluate the biomarkers' performance for predicting short-term mortality. 3. RESULTS: Bacterial co-infections or secondary infections were confirmed in 23 (8.2%) patients. Acinetobacter baumannii was the pathogen responsible for most of the confirmed bacterial infections. Almost three quarters of the patients (72.8%) received empiric antibiotic therapy. Multivariate logistic regression has shown leukocytosis and intensive care unit admission as risk factors for bacterial infections and C-reactive protein, together with the length of hospital stay, as mortality predictors. The ROC curves revealed an acceptable performance for the erythrocyte sedimentation rate (AUC: 0.781), and C-reactive protein (AUC: 0.797), but a poor performance for fibrinogen (AUC: 0.664) in predicting fatal events. 4. CONCLUSIONS: This study highlighted the somewhat paradoxical association of a low rate of confirmed infections with a high rate of empiric antibiotic therapy. A thorough assessment of the risk factors for bacterial infections, in addition to the acknowledgment of various mortality predictors, is crucial for identifying high-risk patients, thus allowing a timely therapeutic intervention, with a direct impact on improving patients' prognosis.

Atherosclerosis in Patients with Congenital Hemophilia: A Focus on Peripheral Artery Disease.

Advances in the treatment of hemophilia have increased the life expectancy of this population and we are currently facing diseases associated with aging, including cardiovascular ones. Coronary atherosclerosis, with acute myocardial infarction as the most severe form of manifestation, has been recognized as part of the comorbidities of hemophiliacs. However, little is known about peripheral artery disease. Available data show that hemophiliacs have cardiovascular risk factors and atherosclerosis similar to the general population. Impaired thrombus formation and phenotype of atheroma plaque rather than the burden of atherosclerosis explains their lower cardiovascular mortality. Since the effect of traditional cardiovascular risk factors overpowers that of decreased coagulability and promotes the onset and progression of atherosclerotic lesions, screening for traditional cardiovascular risk factors and peripheral artery disease should be integrated into standard hemophilia care. There is evidence that invasive treatments and long-term antithrombotic therapy are generally safe, provided that coagulation factor levels are taken into account and replacement therapy is given when necessary.

Inflammatory Pathways in Overweight and Obese Persons as a Potential Mechanism for Cognitive Impairment and Earlier Onset Alzeihmer's Dementia in the General Population: A Narrative Review.

The overweight status or obesity can be confirmed through classical methods such as the body mass index (BMI) and the waist-to-hip ratio (WHR). Apart from metabolic issues such as atherosclerosis, liver steatosis, or diabetes mellitus, long-term obesity or overweight status can pose a risk for cardiovascular and neurovascular complications. While some acute adverse events like coronary syndromes of strokes are well-documented to be linked to an increased body mass, there are also chronic processes that, due to their silent onset and evolution, are underdiagnosed and not as thoroughly studied. Through this review, we aimed to collect all relevant data with regard to the long-term impact of obesity on cognitive function in all ages and its correlation with an earlier onset of dementia such as Alzheimer's disease (AD). The exact mechanisms through which a decline in cognitive functions occurs in overweight or obese persons are still being discussed. A combination of factors has been acknowledged as potential triggers, such as a sedentary lifestyle and stress, as well as a genetic predisposition, for example, the apolipoprotein E (ApoE) alleles in AD. Most research highlights the impact of vascular dysfunction and systemic inflammation on the nervous system in patients with obesity and the subsequent neurological changes. Obesity during the early to mid-ages leads to an earlier onset of cognitive dysfunction in various forms. Also, lifestyle intervention can reverse cognitive dysfunction, especially dieting, to encourage weight loss.

Novel Biomarkers for Atherosclerotic Disease: Advances in Cardiovascular Risk Assessment.

Atherosclerosis is a significant health concern with a growing incidence worldwide. It is directly linked to an increased cardiovascular risk and to major adverse cardiovascular events, such as acute coronary syndromes. In this review, we try to assess the potential diagnostic role of biomarkers in the early identification of patients susceptible to the development of atherosclerosis and other adverse cardiovascular events. We have collected publications concerning already established parameters, such as low-density lipoprotein cholesterol (LDL-C), as well as newer markers, e.g., apolipoprotein B (apoB) and the ratio between apoB and apoA. Additionally, given the inflammatory nature of the development of atherosclerosis, high-sensitivity c-reactive protein (hs-CRP) or interleukin-6 (IL-6) are also discussed. Additionally, newer publications on other emerging components linked to atherosclerosis were considered in the context of patient evaluation. Apart from the already in-use markers (e.g., LDL-C), emerging research highlights the potential of newer molecules in optimizing the diagnosis of atherosclerotic disease in earlier stages. After further studies, they might be fully implemented in the screening protocols.

T-Wave Analysis on the 24 h Holter ECG Monitoring as a Predictive Assessment of Major Adverse Cardiovascular Events in Patients with Myocardial Infarction: A Literature Review and Future Perspectives.

Myocardial ischemia is a pathophysiological state characterized by inadequate perfusion of the myocardium, resulting in an imbalance between myocardial oxygen demand and supply. It is most commonly caused by coronary artery disease, in which atherosclerotic plaques lead to luminal narrowing and reduced blood flow to the heart. Myocardial ischemia can manifest as angina pectoris or silent myocardial ischemia and can progress to myocardial infarction or heart failure if left untreated. Diagnosis of myocardial ischemia typically involves a combination of clinical evaluation, electrocardiography and imaging studies. Electrocardiographic parameters, as assessed by 24 h Holter ECG monitoring, can predict the occurrence of major adverse cardiovascular events in patients with myocardial ischemia, independent of other risk factors. The T-waves in patients with myocardial ischemia have prognostic value for predicting major adverse cardiovascular events, and their electrophysiological heterogeneity can be visualized using various techniques. Combining the electrocardiographic findings with the assessment of myocardial substrate may offer a better picture of the factors that can contribute to cardiovascular death.

Anticoagulation for Atrial Fibrillation in Patients with Decompensated Liver Cirrhosis: Bold and Brave?

Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.

Could Endothelin-1 Be a Promising Neurohormonal Biomarker in Acute Heart Failure?

Acute heart failure (AHF) is a life-threatening condition with high morbidity and mortality. Even though this pathology has been extensively researched, there are still challenges in establishing an accurate and early diagnosis, determining the long- and short-term prognosis and choosing a targeted therapeutic strategy. The use of reliable biomarkers to support clinical judgment has been shown to improve the management of AHF patients. Despite a large pool of interesting candidate biomarkers, endothelin-1 (ET-1) appears to be involved in multiple aspects of AHF pathogenesis that include neurohormonal activation, cardiac remodeling, endothelial dysfunction, inflammation, atherosclerosis and alteration of the renal function. Since its discovery, numerous studies have shown that the level of ET-1 is associated with the severity of symptoms and cardiac dysfunction in this pathology. The purpose of this paper is to review the existing information on ET-1 and answer the question of whether this neurohormone could be a promising biomarker in AHF.

Chronic Kidney Disease Associated with Ischemic Heart Disease: To What Extent Do Biomarkers Help?

Chronic kidney disease represents a complex and multifaceted pathology characterized by the presence of structural or functional renal anomalies associated with a persistent reduction in renal function. As the disease progresses, complications arise due to the chronic inflammatory syndrome, hydro-electrolytic disorders, and toxicity secondary to the uremic environment. Cardiovascular complications are the leading cause of death for these patients. Ischemic cardiac pathology can be both a consequence and complication of chronic kidney disease, highlighting the need to identify specific cardiorenal dysfunction biomarkers targeting pathophysiological mechanisms common to both conditions. This identification is crucial for establishing accurate diagnoses, prognoses, and risk stratifications for patients. This work is intended to elucidate the intricate relationship between chronic kidney disease and ischemic heart disease and to investigate the roles of cardiorenal biomarkers, including cardiac troponin, natriuretic peptides, galectin-3, copeptin, fibroblast growth factor 23 and its co-receptor Klotho, soluble suppression of tumorigenicity 2, and plasma growth differentiation factor 15.