Monocyte related haematological indices in acute exacerbations of COPD - a new biomarker?

C-reactive protein (CRP) and leukocyte count are standard tools for recognising inflammation in COPD patients. This study aimed to find if there is a pattern in monocyte related haematological indices - monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR) - which could be helpful in differentiating COPD patients in need for hospitalization due to acute exacerbation of COPD or differentiating frequent COPD exacerbators from non-frequent COPD exacerbators. The study included 119 patients with COPD and 35 control subjects, recruited at the Clinic for Respiratory Diseases Jordanovac, University Hospital Centre Zagreb, Croatia. Complete blood count was performed on Sysmex XN-1000, CRP on Cobas c501, and Fbg on BCS XP analyser. Data were analysed with MedCalc statistical software. The COPD patients were divided into three groups - frequent exacerbators (FE), non-frequent exacerbators (NFE), patients hospitalized for acute COPD exacerbations (HAE) and the control group were healthy smokers (HS). A statistically significant difference was found in the values of MNR while comparing these groups of patients: FE vs HAE (p<0.000), NFE vs HAE (p<0.000) and HS vs HAE (p<0.001); and for the values of MLR: FE vs HAE (p<0.022), NFE vs HAE (p<0.000) and HS vs HAE (p<0.000). As MLR and MNR have shown the statistical difference comparing the group of HAE to NFE, FE and HS, MLR and MNR could be valuable and available markers of acute COPD exacerbations and need for hospitalization.

Simple predictors of the re- occurrence of severe febrile neutropenia episode: a single-center retrospective cohort study in pediatric patients with malignant diseases.

AIM: To identify the risk factors of a repeated episode of severe febrile neutropenia (FN) and to build an accurate and easy-to-use predictive model. METHODS: This single-center retrospective cohort study conducted at the Clinical Hospital Center Children's Hospital Rijeka from January 1, 2008 to December 31, 2016 included pediatric patients with malignant diseases who experienced at least one FN episode. The association of the second severe FN episode appearance with relevant clinical and laboratory data was analyzed by logistic regression. RESULTS: Out of 45 patients with one FN episode, 25 (56%) had severe FN and 11 (24%) had repeated severe FNs. Significant predictors of a repeated severe FN episode were the first FN episode duration of 9 or more days and red blood cells ≤3.0×1012/L. The predictive model constructed by crossing these two indicators had the accuracy of 87% (95% confidence interval [CI] 73%-94%), sensitivity of 82% (95% CI 53%-97%), and specificity of 88% (95% CI 79%-93%). CONCLUSION: The first FN episode duration and anemia are significantly associated with the risk for severe FN re-occurrence. These factors may be useful in the identification of children with cancer who are at high risk for adverse outcome at any future fever onset and may benefit from early intensive treatment.

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women. AIM: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. PATIENTS AND METHODS: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. RESULTS: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. CONCLUSIONS: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

Validation of the Croatian version of CIVIQ quality of life questionnaire in patients with chronic venous disorders.

AIM: To test the psychometric properties of the Croatian version of the Chronic Venous Insufficiency Quality of Life (CIVIQ) Questionnaire and to assess the quality of life in patients with chronic venous disorders of all stages. METHODS: This cross-sectional study performed between 2014 and 2015 in a private family practice assessed the factorial validity, cross-sectional validity, and reliability of the Croatian CIVIQ 20-item questionnaire completed by 428 adult patients (78% women) with chronic venous disorders classified according to the Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) C classification as stages C1-C6. RESULTS: Median patient age was 52 years (5th-95th percentile, 30-77). The distribution according to the clinical stages of chronic venous disorders was as follows: C1 (n=78, 18%), C2 (n=192, 45%), C3 (n=53, 12%), C4 (n=44, 10%), C5 (n=13, 3%), and C6 (n=48, 11%). The CIVIQ-20 factorial structure was unstable, and six items were excluded from the analysis to test the psychometric properties of the shortened version (CIVIQ-14). CIVIQ-14 has three dimensions (physical, psychological, and pain). Internal consistency reliability is high for the entire CIVIQ-14 (Cronbach α=0.92) and for all CIVIQ-14 dimensions (α≥0.80). The median quality of life significantly decreased with higher CEAP C stages as follows: C1/C2 (86, 50-100); C3/C4 (75, 36-98); C5/C6 (67, 31-95) (P<0.001). Post-hoc analysis showed a higher quality of life in C1/C2 than in other groups (P<0.001). CONCLUSION: The shortened CIVIQ-14 version is useful for assessing the quality of life in patients with chronic venous disorders in everyday clinical practice. To achieve a stable validated instrument, we recommend a cross-cultural validation of items that have loadings on more than one factor.

Cardiac manifestations in alcoholic liver disease.

Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.

Erectile function in cardiovascular patients: its significance and a quick assessment using a visual-scale questionnaire.

PURPOSE: The aim of this study was to investigate the connection between erectile dysfunction (ED) and cardiovascular diseases and to test a novel visual-scale questionnaire (VEF) we propose for the assessment of erectile function. SUBJECTS AND METHODS: Erectile function was assessed in 170 male cardiovascular patients under the age of 70 by the use of several self-administered questionnaires: the International Index of Erectile Function-5 (IIEF-5); the Massachusetts Male Aging Study questionnaires (MMAS Sexual Activity Questionnaire and MMAS Single Question), and finally, VEF. RESULTS: Patients' mean age was 55.65 ± 9.97 y. The most common indications for hospitalization were coronary artery disease (CAD) (n = 82, 48%), and decompensated chronic heart failure (n = 30, 18%). The prevalence of ED as determined by IIEF-5 was 58% (n = 99). Patients with ED were on average 5.7 years older (P = 0.0001), had a higher frequency of diabetes (by 19%, P < 0.01), and a somewhat higher level of uric acid (by 72 µmol/l, P < 0.01). Results of the VEF correlated significantly with those of other questionnaires. Three different machine learning algorithms demonstrated a greater accuracy of VEF than IIEF-5 and MMAS Sexual Activity Questionnaire in predicting ED severity. CONCLUSION: ED is highly prevalent among cardiovascular patients. The Visual Scale Erectile Function questionnaire (VEF) is a simple and valid tool, suitable for quick screening of this condition.

Comparative Study of Intragastric Balloon and Cognitive-Behavioral Approach for Non-Morbid Obesity.

BACKGROUND/AIMS: Intragastric balloon (IGB) and cognitive-behavioral therapy (CBT) are possible options for weight reduction. The aim of our study was to compare their effectivness in inducing weight loss and metabolic changes accompanying weight loss in non-morbidly obese patients. METHODOLOGY: Subjects were required to be between 18 and 55 years old and to have a BMI between 30 and 45 to be eligible. Exclusion criteria, besides those for IGB placement, were the presence of diabetes, depression, binge-eating disorder and the use of medications that affect body weight. Anthropometric, biochemical and blood pressure measurements were performed at baseline and after 6 months. A total of 114 subjects were recruited to the study and assigned to IGB (n = 60) or CBT group (n = 54). All patients completed the study. RESULTS: After 6 months, patients treated with IGB lost significantly (P < 0.01) more weight (%EWL = 44.6 ± 23.9) than patients who participated in CBT (%EWL = 24.3 ± 16.0). In IGB group 75% of patients achieved ≥ 10% loss of initial weight, and 42.6% of patients in CBT group respectively. A significant improvement in all indices of metabolic syndrome except HDL cholesterol was seen in both treatment groups but much more in subjects treated with IGB. CONCLUSIONS: Our results confirmed that intragastric balloon is useful method for promoting weight loss. Due to improvement of metabolic parameters and substantial benefit on liver function, obese people with metabolic syndrome appear to be the best candidates for IGB placement. Combining intragastric balloon treatment with cognitive-behavioral approach might prove valuable for even greater weight loss.

ANDRIJA STAMPAR AS PRESIDENT OF THE INTERIM COMMISSION OF THE WORLD HEALTH ORGANIZATION

This paper provides an analysis of Andrija Stampar's activities after World War II on the establishment of effective international health. Analyzed archival materials have confirmed with numerous evidence that Stampar as the president of the Interim Commission of the World Health Organization (WHO) played a crucial role in the establishment of the ideological starting points and organization of the WHO system, which remain relevant to date. Apart from the strategic foundations, it has been shown that his principles regarding the need for practical action based on the best professional knowledge and experience have no alternatives. The above is presented in the paper with the details of Stampar's activities during the cholera epidemic in Egypt and associated with the experiences of the recent global crisis caused by the COVID pandemic.

Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis.

The objective of the present study was to investigate possible changes in granulysin (GNLY)-mediated cytotoxicity of peripheral blood lymphocytes in psoriatic arthritis (PsA) patients with respect to different phases of the disease. We prospectively enrolled 25 PsA patients in the active phase, 26 PsA patients in remission and 24 healthy controls. The simultaneous detection of intracellular GNLY and cell surface antigens (CD3 and CD56) was performed with flow cytometry. GNLY apoptotic protein was visualised by immunocytochemistry. Natural killer (NK) cell cytotoxicity was analysed with a cytotoxicity assay against human erythroleukaemia K-562 cells. The percentage of GNLY(+) cells did not differ significantly between PsA patients in the acute phase and those in remission; however, it was always higher than in healthy examinees due to the increased percentage of GNLY(+) cells within T cells, NKT cells, and both, and in the CD56(+dim) and CD56(+bright) NK subsets. The mean fluorescence intensity for GNLY was higher in all lymphocyte subpopulations in the acute phase than in remission and in healthy controls. Accordingly, GNLY-mediated NK cell cytotoxicity against K-562 cells of active phase PsA patients was significantly higher than that in patients in remission or in healthy controls. These findings demonstrated the involvement of GNLY in the worsening of PsA and suggested that GNLY mediated the development of joint lesions.

Detection of myocardial ischemia in diabetic patients: the limitations of myocardial perfusion imaging.

In the study of 286 patients with suspected coronary artery disease and recent exercise single photon emission computed tomography (SPECT) test, we performed coronary angiography with coronary fractional flow reserve (FFR) measurement and tested the differences between diabetic (103) and non-diabetic (183) patients in ischemia detection by this two methods. The diabetic patients had a higher prevalence of hypertension, higher BMI and cholesterol levels, as well as longer duration of hospitalization than non-diabetic patients. There was no difference found between groups according to the exercise SPECT test, but, there were significantly more negative results in the non-diabetic group than in the diabetic group according to the FFR test, also, the percentage of stenosis was higher in diabetic patients. The concordance between the two methods was found, it was fair in diabetic patients (kappa = 0.25, 95% C.I. 0.06-0.45) and moderate in non-diabetic patients (kappa = 0.49, 95% C.I. 0.36-0.62).

Total knee replacement surgery is followed by transitory endothelial dysfunction.

Acute coronary syndrome (ACS) presents today the leading group of post-operative cardiovascular complications, while endothelial dysfunction (ED) is one of the key elements in its development. The chronic ED represents thus the basis for the gradual development of atherosclerotic changes, while its sudden aggravation leads to ACS. The persistent ED occurs due to the effects of chronic cardiovascular risk factors, while according to the available studies it can also develop or aggravate under the impact of different acute events. We have directed this study to the investigation of the dynamic of endothelial function before and after a major orthopaedic surgical intervention. This randomised prospective study included 19 patients that underwent the intervention of total knee replacement and 20 healthy examinees of the adequate age and gender High-resolution ultrasound test based on the flow mediated dilatation of the brachial artery is what at we carried out at the beginning of the research, respectively 12, 24, 48 and 72 hours, as well as 7 days after the surgical intervention. The starting values of the FMD test were within the normal range in both groups, although the ability of dilatation upon stimulus was significantly lower in the investigated group. The FMD percentage change in the total sample was negatively connected with the body weight, not having shown additional connections with other cardiovascular risk factors. During the early post-operative period, a significant transitory lowering of the FMD percentage change was recorded, having reached the lowest value 24 hours after the surgery. During the seven-day prospective surveillance, no significant cardiovascular complications were recorded. Further research is necessary in order to confirm these results as well as the testing of the possible connection of the described post-operative transitory endothelial dysfunction with the development of cardiovascular complications and the adverse event.

[Volume assessment in the acute heart and renal failure]. / Odredivanje volumnog statusa u akutnom zatajivanju srca i bubrega.

Acute kidney injury (AKI) is an important clinical issue, especially in the setting of critical care. It has been shown in multiple studies to be a key independent risk factor for mortality, even after adjustment for demographics and severity of illness. There is wide agreement that a generally applicable classification system is required for AKI which helps to standardize estimation of severity of renal disfunction and to predict outcome associated with this condition. That's how RIFLE (Risk-Injury-Failure-Loss-End-stage renal disease), and AKIN (Acute Kidney Injury Network) classifications for AKI were found in 2004 and 2007, respectively. In the clinical setting of heart failure, a positive fluid balance (often expressed in the literature as weight gain) is used by disease management programs as a marker of heart failure decompensation. Oliguria is defined as urine output less than 0,3 ml/kg/h for at least 24 h. Since any delay in treatment can lead to a dangerous progression of the AKI, early recognition of oliguria appears to be crucial. Critically ill patients with oliguric AKI are at increased risk for fluid imbalance due to widespread systemic inflammation, reduced plasma oncotic pressure and increased capillary leak. These patients are particulary at risk of fluid overload and therefore restrictive strategy of fluid administration should be used. Objective, rapid and accurate volume assessment is important in undiagnosed patients presenting with critical illness, as errors may result in interventions with fatal outcomes. The historical tools such as physical exam, and chest radiography suffer from significant limitations. As gold standard, radioisolopic measurement of volume is impractical in the acute care enviroment. Newer technologies offer the promise of both rapid and accurate bedside estimation of volume status with the potential to improve clinical outcomes. Blood assessment with bioimpendance vector analysis, and bedside ultrasound seem to be promising technologies for this need.

Regular dog-walking improves physical capacity in elderly patients after myocardial infarction.

Various positive effects of pet ownership on cardiovascular health are well known. The aim of this prospective and controlled longitudinal study was to determine the effects of everyday dog-walking on physical capacity in elderly patients during the first year after myocardial infarction. Regularly dog-walking for at least 15 minutes three times a day is related to significantly higher work load on the bicycle exercise test (72.5 +/- 10.75 versus 67.6 +/- 11.6 W p < 0.05) in the "dog-walking" group (N = 29, mean age 72.5 years) at 12 months compared to the control group (N = 30, mean age 71.7 years). Our results suggest that dogs may help to maintain continuous physical activity in elderly cardiovascular patients promoting their physical capacity. Further researches are needed to confirm this association as well to identify other possible influences of dog ownership on the cardiovascular health and on the outcome in patients after myocardial infarction.

Perforin expression after acute myocardial infarction--a pilot study.

Perforin is an important mediator of inflammatory reactions. It is a quick-action cytotoxic mediator accumulated in the cytoplasmic granules of effector immunity cells (T lymphocytes, NK and NKT cells) which provide death signal in infected or transformed cells. Perforin-positive cells were previously detected in myocardial tissue during Trypanosoma cruzi infection and viral myocarditis while its role in chronic and progressive cardiovascular inflammatory disease such as atherosclerosis is almost completely unexplored. The perforin activity is also untested during acute coronary events that represent unexpected atherosclerotic complications due to the inflammatory destabilisation and atherosclerotic plaque rupture. The aim of this study was to investigate the presence of perforin, an important immunological inflammatory molecule in peripheral blood lymphocytes during the early period after acute myocardial infarction. We analyzed three subject groups: women with ST-segment elevation acute myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), conservatively treated women with acute myocardial infarction without ST-segment elevation (NSTEMI) and a control group of healthy volunteers. The STEMI and NSTEMI groups did not basically differ in medication neither in levels of routine laboratory tests, while troponin I were significantly higher in the STEMI group. In the study, we detected an early decrease of perforin-positive lymphocytes in STEMI patients that were in contrast with their persisting elevation among NSTEMI patients. Despite greater myocardial necrosis in the STEMI group, results of this pilot-study indicated the prolonged perforin-mediated inflammatory response in patients with NSTEMI. This perforin down-regulation that follows the coronary interventional reperfusion in STEMI emphasized the possible anti-inflammatory role of primary PCI among patients with acute myocardial infarction. Given that the issue of routine primary PCI in NSTEMI is nowadays highly topical, the results we expect in the wake of this pilot study could demonstrate a significant impact on clinical practice. Further research is needed to confirm these results, compare the perforin-mediated activity to other inflammatory mediators in acute coronary events and to examine their impact on the long-term outcome.

Liver disease in the era of COVID-19: Is the worst yet to come?

The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.

[Dietary habits and cardiovascular diseases]. / Prehrambene navike i kardiovaskularne bolesti.

Cardiovascular diseases are a major public health problem worldwide. They are the main cause of death in industrialized countries, while the mortality associated with cardiovascular disease is increasing in less developed countries. The modifiable risk factors for cardiovascular disease are cigarette smoking, hypertension, hyperlipidemia, diabetes mellitus and obesity. Obesity has been recorded in 10%-25% of the population, indicating that poor or inappropriate diet is one of the most common causes of cardiovascular disease. Unhealthy dietary habits including place and way of taking meals, number of daily meals and excessive salt intake from processed foods also contribute to body mass gain. In the present study, dietary habits were assessed in cardiovascular patients versus control group by use of Dietary Habits Questionnaire. Study results showed a statistically significantly higher (P < 0.05) prevalence of inappropriate eating habits in cardiovascular patients (lower number of daily meals, more often skipping breakfast and having dinner) than in control group. In conclusion, many lifestyle and individual behavior modifications are needed in most patients with or at a high risk of cardiovascular disease.

Iron deficiency anaemia influences cognitive functions.

Many diseases, different nutritional, metabolic and hormonal changes, ageing and drugs can alter cognitive functions. Anemia via cerebral hypoxia and other possible mechanisms has been suggested to have a great influence on cognition. Iron deficiency anemia, the most common form of anemia, has been suggested to result in cognitive deterioration and alteration of neurological functions. Previous studies resulted in significant discrepancies considering correlation between anemia and cognitive achievement mainly because different or not sensitive enough tests used to measure cognition. We suggest a significant influence of iron deficiency anemia on dynamic properties and functional features of the central nervous system activity. Cognitive achievement is strongly related to hemoglobin level and could be expected in all patients. Higher hemoglobin level results in better CNS function. As a first step in confirming or refuting our hypotheses we suggest standardization of the method used to measure cognition, such as a very sensitive apparatus like Complex reactiometer Drenovac (CRD).

Efficacy of healthy weight loss program in obesity treatment: Croatian experience.

We evaluated the efficiency of a six-month outpatient weight loss treatment program combining healthy diet, fat reduction, psychological counseling, exercise, and orlistat treatment, by measuring body weight and levels of cardiovascular risk factors in 476 subjects with BMI over 30 or 28 with increased blood pressure, cholesterol, and sugar at the baseline and at the end of program. After four weeks of adjustment to a mild low-calorie diet (1600 kcal/day) and counseling, subjects started receiving orlistat (120 mg TID). The mean weight loss after 6 months was 10.9%. Systolic pressure dropped by 6.7%, diastolic by 4.2%, fasting blood glucose by 10.1%, and total cholesterol by 9.8%. Only 9 subjects (7.8%) poorly tolerated the treatment. More men than women were able to maintain the achieved weight loss six months after the program (70.6% vs. 58.3%, respectively). The healthy weight loss program was an efficient approach to obesity treatment.

Anti-inflammatory effects of exercise training in the early period after myocardial infarction.

The aim of this investigation was to determine the effect of exercise training on the levels of plasma cytokines and acute phase reactants in the early post acute myocardial infarction (AMI) period. Sixty patients were enrolled into this three-week cardiac rehabilitation study. The mean time from AMI was 7.08 +/- 1.60 days, and the patient mean age was 60 +/- 10 years. Subjects were randomly assigned to one of the two groups: the control group treated with standard measures, and the group with additional regular moderate-intensity exercise training. Physical activity was based on the ergospirometry test results. Apart from clinical follow-up and routine laboratory analysis we determined the levels of plasma cytokines: tumor necrosis factor (TNF-alpha), soluble TNF-alpha receptor 1 (TNF-alphaSR1), interleukin (IL)-8, IL-10, and acute phase reactants: high sensitivity C-reactive protein (hsCRP) and fibrinogen. The obtained results confirmed the hypothesis that the early post AMI period is an inflammatory state the intensity of which gradually decreases with standard treatment during the first month after AMI, while including patients into early exercise training improves their inflammatory profile by decreasing the level of acute phase reactant and TNF-alphaSR1.

Exercise induced von Willebrand Factor release -- new model for routine endothelial testing.

Endothelial dysfunction (ED) is actively involved in the mechanism of occurrence, development and progression of all the degrees of atherosclerosis. The established impact of ED on the progress and outcome of cardiovascular diseases, together with convincing indications of a possible successful therapeutic modification, necessitate the changeover of ED assessment from experimental to a routine practice. As there is no appropriate method for a clinical practice, scientists anticipate significant research efforts in the further development. Among numerous methods already available, von Willebrand Factor (vWF) stands out significantly. In accordance with the accepted leading diagnostic role of vWF baseline levels in the group of peripheral endothelial markers, and earlier scientific observations on the absence of its expected reactivation during physical exercise, we hypothesised this promising theory. We believe that a constant stronger release of vWF in endothelial cell injury leads to the exhaustion of its stores in Weibel-Palade bodies with the consequent absence of the expected rise of concentration during the exercise. Therefore, we hypothesised that ED could be exhaustible vWF endothelopathy and the exercise induced release of vWF a new, simple, safe and reliable test for the detection of ED and monitoring of the expected therapeutic effect. In order to have a final clinical usability of the proposed diagnostic model, it is necessary to test its reliability in different pathological and risk states, and establish susceptibility in therapeutic procedures. The correlation with invasive functional angiographic tests and the flow mediated dilatation test of peripheral arteries also needs to be validated. We expect the proposed test of vWF inducibility to find its place in clinical practice, i.e. in prevention, prediction and therapy of cardiovascular diseases.