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Objective: Our study focuses on the role of psychological states in the development of cardiovascular disease (CVD) and explores the potential of positive psychological factors in reducing CVD risk. While existing research has predominantly examined negative mental states and risk behavior, this longitudinal study takes a novel approach by investigating positive psychological wellbeing and its impact on sustained health behavior. Method: The research involved participants (n = 502) with medium to high cardiovascular risk who underwent a comprehensive risk assessment in 2012, followed by written risk communication. Health behavior and psychological variables were measured in 2012 and 2019. A cross-lagged panel was employed to repeat measures of a cardiovascular health index with latent factors. Results: Results indicated an excellent fit for the model (RMSEA = 0.0644, CFI = 0.936, TLI = 0.921, SRMR = 0.050), with significant associations between the observed variables (p < 0.05) and created latent factors. Furthermore, the model implied significant bivariate correlations (p < 0.05) between latent constructs of sustained health behavior and positive psychological states in 2012 and 2019. A significant regression relationship between Health Awareness Index 2012 and 2019, between Psychological wellbeing in 2012 and 2019 (B = 1.103 p = 0.038), latent factors could be identified (B = 1.103 p = 0.038) using cross-lagged panel model. Results highlighted the importance of cardiovascular health awareness, subjective risk perception, and self-directed efforts in facilitating health behavior change. Conclusion: Relationships between psychological wellbeing and health awareness emphasize that positive experiences and reinforcement are crucial in sustaining optimal health behavior. Our findings offer a new perspective on cardiovascular risk screening and preventive interventions. Extending cardiovascular risk screening with psychological measures may broaden prevention opportunities by including psychological elements reinforcing positive psychological states. The findings suggest that an effective prevention program must consider stabilizing and maintaining positive psychological states to achieve lasting improvements in cardiovascular health.

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Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and atherosclerosis is the key factor promoting its development. Carotid intima-media thickening and the presence of carotid plaques are important indices of cardiovascular risk. In addition, inflammation is a major and complex factor in the development of atherosclerosis. The relationships between carotid atherosclerosis and certain inflammatory markers have rarely been studied in healthy individuals. Therefore, we aimed to investigate the associations between subclinical carotid atherosclerosis and various inflammatory biomarkers in a large Caucasian population free of evident CVD. In addition to recording study participants' demographic characteristics, anthropometric characteristics, and atherosclerotic risk factors, laboratory tests were performed to measure levels of hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and inflammatory cytokines/chemokines, including interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, interferon (IFN)-α2, IFN-γ, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP)-1. This study included 264 asymptomatic individuals with a median age of 61.7 years (interquartile range, 54.5-67.5 years); 45.7% of participants were male. Participants were divided into two groups according to their carotid status: the normal carotid group, comprising 120 participants; and the pathological carotid group, comprising 144 participants. Compared with the normal carotid group, hypertension and diabetes mellitus were significantly more common and serum levels of HbA1c, IL-8, and MCP-1 were significantly higher in the pathological carotid group. Multivariate regression analysis revealed significant positive associations between pathological carotid findings and serum levels of IL-8 (highest tertile, OR: 2.4, p = 0.030) and MCP-1 (highest tertile, OR: 2.4, p = 0.040). Our results suggest that IL-8 and MCP-1 may serve as early indicators of subclinical atherosclerosis, thereby helping to identify individuals at increased risk of CVD before the onset of clinical symptoms.

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Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

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BACKGROUND: The rapid growth of web-based symptom checkers (SCs) is not matched by advances in quality assurance. Currently, there are no widely accepted criteria assessing SCs' performance. Vignette studies are widely used to evaluate SCs, measuring the accuracy of outcome. Accuracy behaves as a composite metric as it is affected by a number of individual SC- and tester-dependent factors. In contrast to clinical studies, vignette studies have a small number of testers. Hence, measuring accuracy alone in vignette studies may not provide a reliable assessment of performance due to tester variability. OBJECTIVE: This study aims to investigate the impact of tester variability on the accuracy of outcome of SCs, using clinical vignettes. It further aims to investigate the feasibility of measuring isolated aspects of performance. METHODS: Healthily's SC was assessed using 114 vignettes by 3 groups of 3 testers who processed vignettes with different instructions: free interpretation of vignettes (free testers), specified chief complaints (partially free testers), and specified chief complaints with strict instruction for answering additional symptoms (restricted testers). κ statistics were calculated to assess agreement of top outcome condition and recommended triage. Crude and adjusted accuracy was measured against a gold standard. Adjusted accuracy was calculated using only results of consultations identical to the vignette, following a review and selection process. A feasibility study for assessing symptom comprehension of SCs was performed using different variations of 51 chief complaints across 3 SCs. RESULTS: Intertester agreement of most likely condition and triage was, respectively, 0.49 and 0.51 for the free tester group, 0.66 and 0.66 for the partially free group, and 0.72 and 0.71 for the restricted group. For the restricted group, accuracy ranged from 43.9% to 57% for individual testers, averaging 50.6% (SD 5.35%). Adjusted accuracy was 56.1%. Assessing symptom comprehension was feasible for all 3 SCs. Comprehension scores ranged from 52.9% and 68%. CONCLUSIONS: We demonstrated that by improving standardization of the vignette testing process, there is a significant improvement in the agreement of outcome between testers. However, significant variability remained due to uncontrollable tester-dependent factors, reflected by varying outcome accuracy. Tester-dependent factors, combined with a small number of testers, limit the reliability and generalizability of outcome accuracy when used as a composite measure in vignette studies. Measuring and reporting different aspects of SC performance in isolation provides a more reliable assessment of SC performance. We developed an adjusted accuracy measure using a review and selection process to assess data algorithm quality. In addition, we demonstrated that symptom comprehension with different input methods can be feasibly compared. Future studies reporting accuracy need to apply vignette testing standardization and isolated metrics.

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Age-related disorders are closely linked to the accumulation of senescent cells. The senescence-associated secretory phenotype (SASP) sustains and progresses chronic inflammation, which is involved in cellular and tissue dysfunction. SASP-related growth and differentiation factor-15 (GDF-15) is an immunoregulatory cytokine that is coupled to aging and thus may have a regulatory role in the development and maintenance of atherosclerosis, a major cause of cardiovascular disease (CVD). Although the effects of GDF-15 are tissue-specific and dependent on microenvironmental changes such as inflammation, available data suggest that GDF-15 has a significant role in CVD. Thus, GDF-15 is a promising biomarker and potential therapeutic target for atherosclerotic CVD.

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Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35-65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging).

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Cardiovascular diseases (CVDs) are the leading cause of death among elderly people. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator of cholesterol metabolism. Herein, we investigated the role of PCSK9 in age-related CVD. Both in humans and rats, blood PCSK9 level correlated positively with increasing age and the development of cardiovascular dysfunction. Age-related fatty degeneration of liver tissue positively correlated with serum PCSK9 levels in the rat model, while development of age-related nonalcoholic fatty liver disease correlated with cardiovascular functional impairment. Network analysis identified PCSK9 as an important factor in age-associated lipid alterations and it correlated positively with intima-media thickness, a clinical parameter of CVD risk. PCSK9 inhibition with alirocumab effectively reduced the CVD progression in aging rats, suggesting that PCSK9 plays an important role in cardiovascular aging.

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BACKGROUND: Data harmonisation is essential in real-world data (RWD) research projects based on hospital information systems databases, as coding systems differ between countries. The Hungarian hospital information systems and the national claims database use internationally known diagnosis codes, but data on medical procedures are recorded using national codes. There is no simple or standard solution for mapping the national codes to a standard coding system. Our aim was to map the Hungarian procedure codes (OENO) to SNOMED CT as part of the European Health Data Evidence Network (EHDEN) project. METHODS: We recruited 25 professionals from different specialties to manually map the procedure codes used between 2011 and 2021. A mapping protocol and training material were developed, results were regularly revised, and the challenges of mapping were recorded. Approximately 7% of the codes were mapped by more people in different specialties for validation purposes. RESULTS: We mapped 4661 OENO codes to standard vocabularies, mostly SNOMED CT. We categorized the challenges into three main areas: semantic, matching, and methodological. Semantic refers to the occasionally unclear meaning of the OENO codes, matching to the different granularity and purpose of the OENO and SNOMED CT vocabularies. Lastly, methodological challenges were used to describe issues related to the design of the above-mentioned two vocabularies. CONCLUSIONS: The challenges and solutions presented here may help other researchers to design their process to map their national codes to standard vocabularies in order to achieve greater consistency in mapping results. Moreover, we believe that our work will allow for better use of RWD collected in Hungary in international research collaborations.

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Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity.

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INTRODUCTION: Even though preventive measures have been taken to reduce cardiovascular risk, cardiovascular mortality is increasing. Cardiovascular screening can be a population strategy that contributes to the reduction of mortality over the long term when implemented in a systematic, protocol-based, expanded manner. OBJECTIVE: In this study, we examine changes in participants' health behavior between 2012 and 2019 as a follow-up to the Budakalász Epidemiological Study (BEV). METHOD: A cardiovascular health index was developed to enable effective follow-up. This study included subjects with medium and high cardiovascular risks who participated in the BEV complex cardiovascular risk assessment in 2012 (n = 502). Besides the basic data from the BEV baseline study (demographics, healthy lifestyle, risk behavior, diseases treated by medicine), the 2019 follow-up questionnaire included newly added psychological questionnaires (Perceived Stress, WHO Well-being, Beck Hopelessness Scale, Health-Related Social Support, ABCD Risk Questionnaire). RESULTS: All factors of the cardiovascular health index created in our analysis showed an improvement of over 70% between 2012 and 2019. 37.6% of the participants did something for their health, according to their confession, by 30.3%, BEV had a big or very big impact on their lives from the 2012 BEV test in the year after the test, and by 24.7%, BEV had and still has a big or very big impact on their lives. The improving health indices show a significant correlation with psychological factors. Psychological factors showed a positive correlation with well-being (tau_b = 0.344) and a negative correlation with perceived stress (tau_b = -0.225) and hopelessness (tau_b = -0.206). CONCLUSION: The participants in the study showed a significant change in health behavior seven years after the BEV cardiovascular risk assessment. A higher level of mental well-being is associated with improved values. By analyzing the impact of BEV on the health behavior change and the lifestyle, we can conclude that the cardiovascular risk assessment facilitates health behavior change. Orv Hetil. 2023; 164(4): 119-131.

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Despite the well-known importance of left atrial (LA) mechanics in diastolic function, data are scarce regarding the prognostic power of LA longitudinal strain and its potential added value in the risk stratification of an elderly population. Accordingly, our aim was to determine the long-term prognostic importance of 2D speckle-tracking echocardiography-derived peak atrial longitudinal strain (PALS) in a community-based screening sample. Three hundred and fourteen volunteers were retrospectively identified from a population-based screening program (mean age 62 ± 11 years; 58% female) with a median follow-up of 9.5 years. All subjects who participated in the screening program underwent 2D echocardiography to measure left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and PALS, as well as low-dose cardiac CT to determine the Agatston score. The primary endpoint was all-cause mortality. Thirty-nine subjects (12.4%) met the primary endpoint. Subjects with adverse outcomes had significantly lower LV GLS (dead vs. alive; - 19.2 ± 4.3 vs. - 20.6 ± 3.5%, p < 0.05) and PALS (32.3 ± 12.0 vs. 41.8 ± 14.2%, p < 0.001), whereas LV EF did not show a difference between the two groups (51.1 ± 7.0 vs. 52.1 ± 6.2, %, p = NS). By multivariable Cox regression analysis, PALS was found to be a significant predictor of adverse outcomes independent of LV GLS, and Agatston and Framingham scores. In subjects with PALS values below the standard cut-off of 39%, the risk of all-cause mortality was almost 2.5 times higher (hazard ratio: 2.499 [95% confidence interval: 1.334-4.682], p < 0.05). Beyond the assessment of LV EF and LV GLS, PALS offers incremental value in cardiovascular risk stratification in a community-based elderly cohort. PALS was found to be a significant and independent predictor of long-term mortality among other classical cardiovascular risk estimators.

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BACKGROUND: Oxidative stress is an important factor in the pathomechanism of atherosclerosis. Advanced oxidation protein products (AOPPs) are considered markers of oxidative stress. Thickening of the carotid intima-media layers indicates subclinical atherosclerosis and can be detected by carotid ultrasound. OBJECTIVE: Our aim was to examine the association between carotid intima-media thickness (CIMT) and the level of AOPPs. METHODS: Carotid duplex scans and measurements of AOPPs were performed on 476 participants of a cardiovascular population study. The presence of conventional cardiovascular risk factors was investigated with a questionnaire, physical examination, and laboratory tests. RESULTS: There was a positive correlation between maximum CIMT and the level of AOPPs only in the male population (r = 0.219, p = 0.033). Multivariate analysis has revealed that the association between AOPPs and mean or maximum CIMT was independent of cardiovascular risk factors (OR = 1.458, p = 0.004, and OR = 2.038, p < 0.001). CONCLUSIONS: Among males, the elevated level of AOPPs as a marker of oxidative stress may signal the existence of early atherosclerotic alterations.

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AlphaN-catenin gene CTNNA2 has been implicated in intrauterine brain development, as well as in several psychiatric disorders and cardiovascular diseases. Our present aim was to investigate CTNNA2 gene-wide associations of single-nucleotide polymorphisms (SNPs) with psychiatric and cardiovascular risk factors to test the potential mediating role of rumination, a perseverative negative thinking phenotype in these associations. Linear mixed regression models were run by FaST-LMM within a sample of 795 individuals from the Budakalasz Health Examination Survey. The psychiatric outcome variables were rumination and its subtypes, and ten Brief Symptom Inventory (BSI) scores including, e.g., obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, and paranoid ideation. Cardiovascular outcome variables were BMI and the Framingham risk scores for cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We found nominally significant CTNNA2 associations for every phenotype. Rumination totally mediated the associations of CTNNA2 rs17019243 with eight out of ten BSI scores, but none with Framingham scores or BMI. Our results suggest that CTNNA2 genetics may serve as biomarkers, and increasing the expression or function of CTNNA2 protein may be a potential new therapeutic approach in psychiatric disorders with perseverative negative thinking including, e.g., depression. Generally, an antiruminative agent could be a transdiagnostic and preventive psychopharmacon.

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OBJECTIVES: Reliable and valid assessment of subjective risk perception is a crucial part of cardiovascular disease (CVD) prevention and rehabilitation. Since the recently developed Attitudes and Beliefs about Cardiovascular Disease (ABCD) Risk Questionnaire complies with these requirements, the aim of the present study was to investigate the psychometric properties of the Hungarian version of the measure. DESIGN AND SETTING: Community-based cross-sectional observational study PARTICIPANTS: In sum, 410 (M=49.53 years, SD=8.09) Hungarian adults (inclusion criteria: aged 35 and above, not under treatment with a psychiatric disorder) were included in the present study (female: n=277, 67.6%; college or university-level education: n=247, 60.2%). METHODS: We translated the ABCD Risk Questionnaire into Hungarian and checked its psychometric properties and validity indices. PRIMARY OUTCOME MEASURES: Internal consistency, explorative and confirmative factorial validity. Associations with sociodemographic and health-related characteristics, as well as with measures of mental health (depressive symptoms, perceived stress and well-being). RESULTS: Exploratory and confirmatory factor analyses supported a three-factor solution, corresponding to the original subscales of Risk Perception, Perceived Benefits and Healthy Eating Intentions, with a moderate correlation between the latent constructs. The respondents' level of knowledge on CVD risk factors was largely independent of their subjective risk perception. The results also provided evidence on the weak-to-medium associations between mental health indices and CVD-related perceptions. Based on the results, a shortened scale version was also suggested. CONCLUSION: This study confirms the factorial structure, internal consistency and validity of the Hungarian version of the ABCD Risk Questionnaire in a non-English-speaking community sample. The ABCD Risk Perception Questionnaire is a parsimonious and psychometrically adequate measure to assess CVD-related attitudes and knowledge in the general population. Further research is needed in socioeconomically more diverse and in clinical samples, as well as in longitudinal intervention studies.

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BACKGROUND AND AIMS: Visceral obesity is a marker of dysfunctional adipose tissue and ectopic fat infiltration. Many studies have shown that visceral fat dysfunction has a close relationship with cardiovascular disease. For a better identification of visceral adiposity dysfunction, the visceral adiposity index (VAI) is used. Coronary artery calcium score (CACS) is known to have a strong correlation with the total plaque burden therefore provides information about the severity of the coronary atherosclerosis. CACS is a strong predictor of cardiac events and it refines cardiovascular risk assessment beyond conventional risk factors. Our aim was to evaluate the association between VAI and CACS in an asymptomatic Caucasian population. METHODS AND RESULTS: Computed tomography scans of 460 participants were analyzed in a cross-sectional, voluntary screening program. A health questionnaire, physical examination and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. Mean VAI was 1.41 ± 0.07 in men and 2.00 ± 0.15 in women. VAI showed a positive correlation with total coronary calcium score (r = 0.242) in males but not in females. VAI was stratified into tertiles by gender. In males, third VAI tertile was independently associated with CACS>100 (OR: 3.21, p = 0.02) but not with CACS>0 after the effects of conventional risk factors were eliminated. CONCLUSION: VAI tertiles were associated with calcium scores and the highest VAI tertile was an independent predictor for the presence of CACS>100 in males but not in females.

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Introduction: Cardiovascular disease is the leading cause of death accounting for 4 million deaths per year in Europe. Psychosocial factors explain at least 25-40% of the disease's prevalence beyond the well-known lifestyle factors. Isolation in adulthood is one of the main sources of chronic stress that raises the incidence of the disease. The low level of social support and social isolation are increasing the risk of depression and high blood pressure hence the incidence of cardiovascular diseases. Aim: Our aim was to observe the correlation between social isolation and health behaviour. Furthermore, we have adapted the earlier validated Multidimensional Social Support Scale to the domain of health. Method: The data from 507 persons were collected online in 2018. Multidimensional Social Support Scale adapted to health, self-rated health, subjective means, short version of Beck Depression, shortened version of WHO Wellbeing, and Perceived Stress Scales were recorded. Results: Factor analysis verified the scale construction of the original 3-subscale structure (Cronbach alpha values = 0.945, 0.950 and 0.905). According to the regression models, social support received from friends we have observed to have moderately positive correlation with intensive exercises (B = 0.205, beta = 0.096, p = 0.093). Logistic regression model revealed that health-connected social support does not correlate with smoking, only education variable was related with it strongly, statistically significantly (B = -1.284, OR = 0.277, p<0.001). Conclusion: Multidimensional Social Support Scale has satisfactory stability and consistency to measure health-related social support. Social support showed correlation with the measures of mental health (depression, stress-level, wellbeing), and moderate association with intense exercises. Orv Hetil. 2020; 161(4): 129-138.

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Introduction: Relaxin-1 (RLN1) has emerged as a possible therapeutic target in myocardial fibrosis due to its anti-fibrotic effects. Previous randomized clinical trials investigated therapeutic role of exogenous relaxin in patients with acute-on-chronic heart failure (HF) and failed to meet clinical endpoints. Here, we aimed to assess endogenous, circulating RLN1 levels in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic origin. Furthermore, we analyzed relation of RLN1 and left ventricular diastolic function, left and right ventricular fibrosis, and invasive hemodynamic measurements. Unique feature of our study is the availability of ex vivo human myocardial tissue. Methods: Human myocardial samples were available from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University after local ethical approval and informed consent of all participants (n = 47). Tissue was collected immediately after heart explantations; peripheral blood was collected before induction of anesthesia. Myocardial sections were stained for Masson's trichrome and Picrosirius red staining to quantify fibrosis. Medical records were analyzed (ECG, anthropometry, blood tests, medication, echocardiography, and invasive hemodynamic measurements). Results: Average RLN1 levels in HFrEF population were significantly higher than measured in age and gender matched healthy control human subjects (702 ± 283 pg/ml in HFrEF vs. 44 ± 27 pg/ml in control n = 47). We found a moderate inverse correlation between RLN1 levels and degree of myocardial fibrosis in both ventricles (r = -0.357, p = 0.014 in the right ventricle vs. r = -0.321, p = 0.028 in the left ventricle with Masson's trichrome staining). Parallel, a moderate positive correlation was found in left ventricular diastolic function (echocardiography, E/A wave values) and RLN1 levels (r = 0.456, p = 0.003); a negative correlation with RLN1 levels and left ventricular end-systolic diameter (r = -0.373, p = 0.023), and diastolic pulmonary artery pressure (r = -0.894, p < 0.001). RLN1 levels showed moderate correlation with RLN2 levels (r = 0.453, p = 0.0003). Conclusion: Increased RLN1 levels were accompanied by lower myocardial fibrosis rate, which is a novel finding in our patient population with coronary artery disease and HFrEF. RLN1 can have a biomarker role in ventricular fibrosis; furthermore, it may influence hemodynamic and vasomotor activity via neurohormonal mechanisms of action. Given these valuable findings, RLN1 may be targeted in anti-fibrotic therapeutics and in perioperative care of heart transplantation.

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Detecting early-stage atherosclerosis is an important step towards cardiovascular disease prevention. Coronary artery calcium (CAC) score is a sensitive and non-invasive tool for detecting coronary atherosclerosis. Higher serum uric acid (SUA) levels are known to be associated with cardiovascular diseases. However, there is inconsistency regarding the independence of the association. The aim of our study was to assess the association of CAC and SUA in an asymptomatic population. CAC scans of 281 participants were analyzed in a voluntary screening program. A health questionnaire, physical examination, and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. 36.3% (n = 102) of the participants had no detectable CAC and 13.9% (n = 39) had a CAC score of > 300. SUA showed positive correlation with CAC score (0.175, p < 0.01). SUA was independently associated with Ca score > 300 (OR 5.17, p = 0.01) after the effects of conventional risk factors were eliminated.

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BACKGROUND AND PURPOSE: To develop an evidence-based, standardized structured reporting (SR) method for brain MRI examinations in neonatal hypoxic-ischemic encephalopathy (HIE) suitable both for clinical and research use. METHODS: SR template development was based on comprehensive review of the pertinent literature with the basic sections and subdivisions of the template defined according to MRI sequences (both conventional and diffusion-weighted, MR-spectroscopy (MRS), and T2*-weighted imaging), and the items targeted on age-related imaging patterns of HIE. In order to evaluate the usability of the proposed SR template we compared data obtained from the brain MR image analysis of 87 term and 19 preterm neonates with the literature. The enrolled 106 infants were born between 2013 and 2015, went through therapeutic hypothermia according to the TOBY criteria due to moderate to severe asphyxia and had at least one brain MRI examination within the first two weeks of life. Ethical approval was obtained for this retrospective study. Descriptive statistical analysis was also performed on data exported from the structured reporting system as feasibility test. RESULTS: The mean gestational age of the study population was 38.3±2.2 weeks; brain MRI was performed on 5.8±2.9 day of life, hence in 78% of our patients after the conclusion of therapeutic hypothermia. Our main imaging findings were concordant to the pertinent literature. Moreover, we identified a characteristic temporal evolution of diffusion changes. Interestingly 18% (n=19/106) of the clinically asphyxiated infants had isolated axial-extraaxial haemorrhage without any imaging sign of HIE. CONCLUSION: In this article our approach of reporting HIE cases with our novel SR template is described. The SR template was found suitable for reporting HIE cases, moreover it uncovered time and location dependent evolution of diffusion abnormalities (and pseudonormalization, as well), suggesting its usefulness in clinical research applications. The high number of isolated intracranial haemorrhages, and the changing diffusion pattern emphasizes the importance of early imaging in HIE.

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The present paper provides novel findings on the temporo-spatial correlation of perivascular laminin immunoreactivity with the early postnatal astrocyte development. The cerebrovascular laminin immunoreactivity gradually disappears during development. The fusion of the glial and vascular basal laminae during development makes the laminin epitopes inaccessible for antibody molecules (Krum et al., 1991, Exp Neurol 111:151). The fusion is supposed to correlate with the maturation of the glio-vascular connections. Glial development was followed by immunostaining for GFAP (glial fibrillary acidic protein), S100 protein, glutamine synthetase as glial markers and for nestin to visualize the immature glial structures. Our investigation focused on the period from postnatal day (P)2 to P16, on the dorso-parietal pallium. In the wall of the telencephalon the laminin immunoreactivity disappeared between P5 and P10; in subcortical structures it persisted to P12 or even to P16. Its disappearance overlapped the period when GFAP-immunopositive astrocytes were taking the place of radial glia. Despite the parallel time courses, however, the spatial patterns of the two processes were just the opposite: disappearance of the laminin immunoreactivity progressed from the middle zone whereas the appearance of GFAP from the pial surface and the corpus callosum. Rather, the regression of the vascular laminin immunoreactivity followed the progression of the immunoreactivities of glutamine synthetase and S100 protein. Therefore, the regression really correlates with a 'maturation' of astrocytes which, however, affects other astrocyte functions rather than cytoskeleton.

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