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BackgroundPhysical activity (PA) protects against cardiovascular disease. However, previous research has shown that high PA is associated with an increased carotid intima-media-thickness (cIMT), an independent predictor for future cardiovascular disease. Our aim was to further investigate this unexpected association with two different measurement methods of PA and two established markers for Early Vascular Ageing: cIMT and carotid-femoral pulse-wave velocity (cfPWV).MethodsThe community-based Early Vascular Ageing-Tyrol cohort study included adolescents in western Austria and northern Italy. Medical examinations included anthropometric measurements, fasting blood analysis, a physician guided interview to assess lifestyle factors, measurement of cIMT and cfPWV. PA was rated by an in-person interview on the basis of average minutes of moderate- or vigorous sports per day and by the Baecke questionnaire expressed as Baecke score (BS).ResultsComplete data set was available for 1,001 adolescents with a mean age of 17.8 years (standard deviation ±0.9 years). 558 (55.7%) of participants were female. cIMT was positively associated with both measures of PA in univariate (minutes sports per day: p

ObjectiveIn patients with complex coronary artery disease (CAD) undergoing cardiac surgery, myocardial protection might be impaired due to microvascular obstruction, resulting in myocardial injury and subsequent biomarker release. Therefore, this study investigated the correlation between the complexity of CAD, reflected by the SYNTAX Score, and the release of cardiac biomarkers after CABG.MethodsIn a consecutive series of 919 patients undergoing isolated CABG SYNTAX scores I and II were calculated to assess the complexity of CAD. Levels of high sensitivity cardiac troponin T (hs-cTnT) and creatine kinase-myocardial band (CK-MB) were routinely measured once before and serially after surgery. Patients were divided into tertiles according to their SYNTAX Scores I and II. Spearman correlations and regression models were performed to measure the degree of association between the release of hs-cTnT and CK-MB and the SYNTAX Scores.ResultsPatients with a higher SYNTAX Score I had more comorbidities reflected in a higher EuroSCORE II. Preoperatively, higher levels of cardiac biomarkers were found in patients with higher SYNTAX Score II. No correlation was observed between hs-cTnT, CK-MB and SYNTAX Score I or II. Regression models did not show any association between cardiac biomarkers and the complexity of CAD.ConclusionThe complexity of CAD is not associated with the release of cardiac biomarkers after CABG. Factors influencing postoperative biomarker release need to be elucidated in future trials to include postoperative biomarker release into risk stratification models predicting outcome after cardiac surgery.

AimTo determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing.MethodsIn the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV.ResultsA total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291).ConclusionIn our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome.

Background: Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are partly overlapping, innate and adaptive immune responses are induced, which can be quantified using the determination of specific biomarkers. Among these, C-reactive protein (CRP) has been established as a marker of innate immune function, whereas Neopterin, which is mainly produced upon stimulation with interferon-gamma, reflects cellular immune activation. Aim: We investigated inflammation markers in patients with microbiologically confirmed viral or bacterial pneumonia, and studied the potential of CRP, Neopterin, and the CRP/Neopterin ratio to distinguish between viral and bacterial pathogenesis. Furthermore, we examined, how often neuropsychiatric symptoms occur in patients suffering from different kinds of pneumonia. Patients and method: A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), Influenza infection (n = 10), Influenza and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot study. Clinical as well as laboratory parameters were determined shortly after admission. Results: We found significantly higher CRP/Neopterin ratios in patients with bacterial pneumonia (median: 0.34) and lower CRP/Neopterin ratios in patients hospitalized with COVID-19 infection (median: 0.03; p < 0.001). Both in men and in women, the CRP/Neopterin ratio was able to distinguish between viral and bacterial pathogens, but also was able to detect bacterial super-infection (BSI) in subjects with initial viral pneumonia (p < 0.001). Patients with BSI presented with significantly lower CRP/Neopterin ratios (median 0.08) than patients with bacterial infection only (median 0.34; p < 0.001). Interestingly, COVID-19 patients had a decreased physical functioning (as reflected in the ECOG score) and a higher frequency of fatigue (84.1%) and neurological symptoms (54.8%) than patients with pneumonia, due to other underlying pathogens. Patients that reported fatigue during viral and bacterial pneumonia presented with lower CRP concentrations than patients without it. Conclusions: The CRP/Neopterin ratio is useful to differentiate between viral and bacterial pathogenesis. The occurrence of neuropsychiatric symptoms in pneumonia appears to depend on the kind of pathogen causing the infection. Lower CRP concentrations at admission appear to be related to fatigue during acute viral and bacterial infection.

BackgroundHomocysteine (Hcy) has been associated with an adverse cardiovascular risk profile in adolescents. Assessment of the association between plasma Hcy levels and clinical/laboratory factors might improve our understanding of the pathogenesis of cardiovascular disease.MethodsHcy was measured in 1,900 14- to 19-year-old participants of prospective population-based EVA-TYROL Study (44.3% males, mean age 16.4 years) between 2015 and 2018. Factors associated with Hcy were assessed by physical examination, standardized interviews, and fasting blood analysis.ResultsMean plasma Hcy was 11.3 ± 4.5 µmol/L. Distribution of Hcy was characterized by extreme right skew. Males exhibited higher Hcy and sex differences increased with increasing age. Univariate associations with Hcy emerged for age, sex, body mass index, high-density lipoprotein cholesterol, and for factors pertaining to blood pressure, glucose metabolism, renal function, and diet quality, whereas the most important multivariate predictors of Hcy were sex and creatinine.DiscussionClinical and laboratory factors associated with Hcy in adolescents were manifold, with sex and high creatinine identified as strongest independent determinants. These results may aid when interpreting future studies investigating the vascular risk of homocysteine.

Abstract Background Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted. Methods We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3–6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management. Discussion This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

ABSTRACT Determination of antibody levels against the nucleocapsid (N) and spike (S) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to estimate the humoral immune response after SARS-CoV-2 infection or vaccination. Differences in the design and specification of antibody assays challenge the interpretation of test results, and comparative studies are often limited to single time points per patient. We determined the longitudinal kinetics of antibody levels of 145 unvaccinated coronavirus disease 2019 (COVID-19) patients at four visits over 1 year upon convalescence using 8 commercial SARS-CoV-2 antibody assays (from Abbott, DiaSorin, Roche, Siemens, and Technoclone), as well as a virus neutralization test (VNT). A linear regression model was used to investigate whether antibody results obtained in the first 6 months after disease onset could predict the VNT results at 12 months. Spike protein-specific antibody tests showed good correlation to the VNT at individual time points (rS, 0.74 to 0.92). While longitudinal assay comparison with the Roche Elecsys anti-SARS-CoV-2 S test showed almost constant antibody concentrations over 12 months, the VNT and all other tests indicated a decline in serum antibody levels (median decrease to 14% to 36% of baseline). The antibody level at 3 months was the best predictor of the VNT results at 12 months after disease onset. The current standardization to a WHO calibrator for normalization to binding antibody units (BAU) is not sufficient for the harmonization of SARS-CoV-2 antibody tests. Assay-specific differences in absolute values and trends over time need to be considered when interpreting the course of antibody levels in patients. IMPORTANCE Determination of antibodies against SARS-CoV-2 will play an important role in detecting a sufficient immune response. Although all the manufacturers expressed antibody levels in binding antibody units per milliliter, thus suggesting comparable results, we found discrepant behavior between the eight investigated assays when we followed the antibody levels in a cohort of 145 convalescent patients over 1 year. While one assay yielded constant antibody levels, the others showed decreasing antibody levels to a varying extent. Therefore, the comparability of the assays must be improved regarding the long-term kinetics of antibody levels. This is a prerequisite for establishing reliable antibody level cutoffs for sufficient individual protection against SARS-CoV-2.

Aim: To determine the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) among Western Austrian adolescents and its association with arterial stiffness as a marker of early vascular ageing. Methods: In the cross-sectional Early Vascular Ageing in the YOUth study, liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan (Echosense, Paris, France) in 14- to 19-year-old Austrian adolescents. Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV) and cardiovascular risk factors by a face-to-face interview, physical examination, and fasting blood analyses. Linear regression models and one-way analysis of variance were performed to analyze the association between liver fat content, MASLD and cfPWV. Results: A total of 1292 study participants (65.2% female) aged 17.2 ± 1.3 years were included. MASLD was detected in 62 (4.8%) adolescents. CAP value showed a significant association with cfPWV in the unadjusted model (p < 0.001) but lost its significant influence in the multivariable model after adjusting for sex, age and cardiovascular risk criteria (increased BMI or waist circumference, impaired glucose metabolism, elevated blood pressure, elevated plasma triglycerides, and decreased HDL cholesterol; p = 0.540). In the analysis of variance, a significant increase in cfPWV was observed in adolescents with any of the five cardiovascular risk criteria for MASLD (p < 0.001), but not with the additional presence of steatotic liver disease (p = 0.291). Conclusion: In our adolescent cohort, liver fat content and MASLD were not found to be independent predictors for early vascular ageing. Nevertheless, the determination of liver fat content can be a useful tool to identify adolescents at high risk for cardiovascular disease and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Oral contraception is one of the most popular contraceptive methods both in adults and adolescents. However, the effects of oral contraception on lipids in adolescents are not well studied. Lipid profiles were measured and contraceptive use was assessed in 14- to 19-year-old female participants of the prospective population-based Early Vascular Ageing-Tyrol Study between 2015 and 2018, twice on average 22 months apart. For this analysis, data from 828 young women with a median age of 17.0 years were available. Of them, 317 (38%) used oral contraceptives (OCs). OC users had a slightly higher systolic and diastolic blood pressure and larger changes over time and were more likely to use cigarettes than nonusers. Total cholesterol (179.6 vs. 162.4 mg/dL), low-density lipoprotein-cholesterol (106.4 vs. 94.6 mg/dL), and triglycerides (104.0 vs. 67.0 mg/dL) were significantly higher in OC users after multivariable adjustment in linear regression models. No difference in high-density lipoprotein-cholesterol between the two groups was found. In 558 females, follow-up data were available. Those who initiated OC use had on average 15.4 mg/dL higher low-density lipoprotein-cholesterol and 36.2 mg/dL higher triglyceride level changes between baseline and follow-up than never users. Duration of OC use did not show a significant association with lipid levels and changes. We showed an independent association between OC use and blood lipids as well as lipid trajectories over time in a large cohort of healthy adolescents. These changes are especially relevant to consider in adolescents with other risk factors for dyslipidemia or other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Abstract The diagnosis of COVID-19 relies on the direct detection of SARS-CoV-2 RNA in respiratory specimens by RT-PCR. The pandemic spread of the disease caused an imbalance between demand and supply of materials and reagents needed for diagnostic purposes including swab sets. In a comparative effectiveness study, we conducted serial follow-up swabs in hospitalized laboratory-confirmed COVID-19 patients. We assessed the diagnostic performance of an in-house system developed according to recommendations by the US CDC. In a total of 96 serial swabs, we found significant differences in the accuracy of the different swab systems to generate a positive result in SARS-CoV-2 RT-PCR, ranging from around 50 to 80%. Of note, an in-house swab system was superior to most commercially available sets as reflected by significantly lower Ct values of viral genes. Thus, a simple combination of broadly available materials may enable diagnostic laboratories to bypass global limitations in the supply of swab sets.

The presence of neutralizing antibodies against SARS-CoV-2 in a large number of people is – besides cellular immunity – important to overcome the SARS-CoV-2 pandemic. While determination of neutralizing antibodies via virus neutralization tests are laborious, assays to determine the antibody levels serologically are fully automated and widely available. Correlations between these methodologies were recently given by the manufacturers, however performance in samples close to the cut off value have not yet been fully validated.Thus, we analysed 22 borderline and low positive (

Background Cardiovascular disease depends on the duration and time course of risk factor exposure. Previous reports on risk factors of progression of carotid intima‐media thickness (cIMT) in the young were mostly restricted to high‐risk populations or susceptible to certain types of bias. We aimed to unravel a risk factor signature for early vessel pathology based on repeated ultrasound assessments of the carotid arteries in the general population. Methods and Results Risk factors were assessed in 956 adolescents sampled from the general population with a mean age of 15.8±0.9 years, 56.2% of whom were female. cIMT was measured at baseline and on average 22.5±3.4 months later by high‐resolution ultrasound. Effects of baseline risk factors on cIMT progression were investigated using linear mixed models with multivariable adjustment for potential confounders, which yielded significant associations (given as increase in cIMT for a 1‐SD higher baseline level) for alanine transaminase (5.5 μm; 95% CI: 1.5–9.5), systolic blood pressure (4.7 μm; 0.3–9.2), arterial hypertension (9.5 μm, 0.2–18.7), and non‐high‐density (4.5 μm; 0.7–8.4) and low‐density lipoprotein cholesterol (4.3 μm; 0.5–8.1). Conclusions Systolic blood pressure, arterial hypertension, low‐density and non‐high‐density lipoprotein cholesterol, and alanine transaminase predicted cIMT progression in adolescents, even though risk factor levels were predominantly within established reference ranges. These findings reemphasize the necessity to initiate prevention early in life and challenge the current focus of guideline recommendations on high‐risk youngsters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03929692.

Abstract Background According to the World Health Organization, cardiovascular diseases (CVDs) are the leading non-communicable cause of death. Awareness of the individual risk profile is crucial to implement a healthy lifestyle and prevent CVDs. Multiple studies demonstrated that atherosclerosis, the main cause of CVDs, begins early in life. Therefore, it may be necessary to start prevention programs already in childhood. Methods The EVA-Tyrol study is a population-based non-randomized controlled trial that will prospectively enroll 2000 participants from high schools and training companies in North- and East-Tyrol (Austria) and South-Tyrol (Italy). Participants will be assigned to either an intervention (n = 1500) or a control (n = 500) group. Intervention group participants will be enrolled at the 10th school grade (mean age 15–16 years), undergo two examinations within a two-year interval, with follow-up at the 12th grade (mean ages 17–18 years). Control group participants will be enrolled at the 12th grade (mean age 17–18 years). Medical examination will include anthropometric measurements, comprehensive lifestyle and dietary questionnaires, a fasting blood sample, high-resolution ultrasound of the carotid arteries, and measurement of carotid-femoral pulse wave velocity. Active intervention will consist of (1) enhancing knowledge about CVDs, (2) individual medical counseling based on the results of the baseline examination, (3) an online health promotion tool and (4) involvement of participants in planning and implementation of health promotion projects. Effectiveness of the intervention will be assessed by comparing the proportion subjects with ideal health metrics as defined by the American Heart Association between study groups. Discussion This study aims to improve cardiovascular health in Tyrolean adolescents by demonstrating the efficacy of a multi-layer health promotion program and may yield novel insights into the prevalence of vascular risk conditions and mechanisms of early vascular pathologies in adolescents. Trial registration EVA-Tyrol has been retrospectively registered at clinicaltrials.gov under NCT03929692 since April 29, 2019.

BackgroundMale sex is related to increased COVID-19 severity and fatality although confirmed infections are similarly distributed between men and women. The aim of this retrospective analysis was to investigate the impact of sex hormones on disease progression and immune activation in men with COVID-19.Patients and MethodsWe studied for effects of sex hormones on disease severity and immune activation in 377 patients (230 men, 147 women) with PCR-confirmed SARS-CoV-2 infections hospitalized at the Innsbruck University Hospital between February and December 2020.ResultsMen had more severe COVID-19 with concomitant higher immune system activation upon hospital admission when compared to women. Men with a severe course of infection had lower serum total testosterone (tT) levels whereas luteinizing hormone (LH) and estradiol (E2) levels were within the normal range. tT deficiency was associated with elevated CRP (rs = - 0.567, p < 0.001), IL-6 levels (rs = - 0.563, p < 0.001), lower cholesterol levels (rs = 0.407, p < 0.001) and an increased morbidity and mortality. Men with tT levels < 100 ng/dL had a more than eighteen-fold higher in-hospital mortality risk (OR 18.243 [95%CI 2.301 – 144.639], p = 0.006) compared to men with tT levels > 230 ng/dL. Moreover, while morbidity and mortality showed a positive correlation with E2 levels at admission, we detected a negative correlation with the tT/E2 ratio upon hospital admission.ConclusionHospitalized men with COVID-19 present with rather low testosterone levels linked to more advanced immune activation, severe clinical manifestations translating into an increased risk for ICU admission or death. The underlying mechanisms remain elusive but may include infection driven hypogonadism as well as inflammation mediated cholesterol reduction causing gonadotropin suppression and impaired androgen formation. Finally, in elderly late onset hypogonadism might also contribute to lower testosterone levels.

T cells play a fundamental role in the early control and clearance of many viral infections of the respiratory system. In SARS-CoV-2-infected individuals, lymphopenia with drastically reduced CD4+ and CD8+ T cells correlates with Coronavirus disease 2019 (COVID-19)-associated disease severity and mortality. In this study, we characterized cellular and humoral immune responses induced in patients with mild, severe and critical COVID-19. Peripheral blood mononuclear cells of 37 patients with mild, severe and critical COVID-19 and 10 healthy individuals were analyzed by IFNγ ELISpot and multi-color flow cytometry upon stimulation with peptide pools covering complete immunodominant SARS-CoV-2 matrix, nucleocapsid and spike proteins. In addition SARS-CoV-2 antibody levels, neutralization abilities and anaphylatoxin levels were evaluated by various commercially available ELISA platforms. Our data clearly demonstrates a significantly stronger induction of SARS-CoV-2 specific CD8+ T lymphocytes and higher IFNγ production in patients with mild compared to patients with severe or critical COVID-19. In all patients SARS-CoV-2-specific antibodies with similar neutralizing activity were detected, but highest titers of total IgGs were observed in critical patients. Finally, elevated anaphylatoxin C3a and C5a levels were identified in severe and critical COVID-19 patients probably caused by aberrant immune complex formation due to elevated antibody titers in these patients. Crucially, we provide a full picture of cellular and humoral immune responses of COVID-19 patients and prove that robust polyfunctional CD8+ T cell responses concomitant with low anaphylatoxin levels correlate with mild infections. In addition, our data indicates that high SARS-CoV-2 antibody titers are associated with severe disease progression.

Abstract Background Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of future cardiovascular events. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. Moreover, stroke is a leading cause of disability and morbidity which partly emerges from post-stroke complications. Methods/design We designed a block-randomised (2:1 ratio) open pragmatic trial [NCT02156778] with blinded outcome assessment comparing STROKE-CARD to usual post-stroke-patient care. STROKE-CARD is a multifaceted post-stroke disease management program with the objective of reducing recurrent cardiovascular events and improving quality of life in ischaemic stroke and TIA-patients. It combines intensified multi-domain secondary prevention, systematic detection and treatment of post-stroke complications, and patient self-empowerment. Enrolment of 2160 patients with acute ischaemic stroke or TIA (ABCD2-Score ≥ 3) is planned at two study centres in Austria. The co-primary efficacy endpoints are (i) the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) occurring within 12 months after the index event and (ii) one-year health-related quality-of-life measured with the European Quality of Life-5 Dimensions (EQ-5D-3 L) questionaire. Secondary endpoints include all-cause mortality, functional outcome, and target-level achievement in risk factor management. Discussion This trial will provide evidence on whether the pragmatic post-stroke intervention program STROKE-CARD can help prevent cardiovascular events and improve quality-of-life within the setting of a high-quality acute stroke care system. In case of success, STROKE-CARD may be implemented in daily clinical routine and serve as a model for other disease management initiatives. Trial registration ClinicalTrials.gov: NCT02156778. (June 5, 2014, retrospectively registered).

Abstract Background Bright light (BL) has been shown to be effective in enhancing both cognitive and physical performances. Alterations in nighttime melatonin levels have also been observed. However, evaluations of light-induced changes in the preceding biochemical processes are absent. Therefore, the impact of a single morning BL exposure on sensorimotor and visuomotor performance, as well as tryptophan (trp) and trp metabolites, was evaluated in this study. Methods In a crossover design, 33 healthy volunteers were randomly exposed to 30 min of

The objectives of this study were to develop age- and sex-specific reference percentiles for fat mass index (FMI) and fat-free mass index (FFMI) in adolescents aged 14 to 19 years and to determine differences in overweight/obesity classification by FMI and body mass index (BMI). The EVA4YOU study is a single-center cross-sectional study conducted in western Austria. Cardiovascular risks including anthropometric measurements and bioelectrical impedance analysis were assessed in adolescents (mean age 17 years). FMI and FFMI were calculated as the ratio of fat mass (FM) and fat-free mass (FFM) to the square of height and compared to study population–specific BMI percentiles. One thousand four hundred twenty-two adolescents were included in the analysis. Girls had a significantly higher mean FM and FMI and a significantly lower mean FFM, FFMI (p < 0.001, each), and mean BMI (p = 0.020) than boys. Body composition classification by FMI and BMI percentiles shows a concordance for the < 75th and > 97th percentile, but a significant difference in percentile rank classifications between these two cut-off values (all p < 0.05). Based on FMI, 15.5% (221/1422) of the whole population and 29.4% (92/313) of those between the 75th and 97th percentiles are classified one category higher or lower than those assigned by BMI. Conclusion: Classification of normal or pathologic body composition based on BMI and FMI shows good accordance in the clearly normal or pathologic range. In an intermediate range, FMI reclassifies categories based on BMI in more than a quarter of adolescents. Cut-off values to differentiate normal from pathologic FMI values on a biological basis are needed. Trial registration: The study is registered at www.clinicaltrials.gov (Identifier: NCT04598685; Date of registration: October 22, 2020). What is Known: • Chronic non-communicable diseases (NCDs) are the leading cause of morbidity and mortality globally, with major risk factors including unhealthy diets, harmful behaviors, and obesity. Obesity in children and adolescents is a key risk factor for later NCDs, which is commonly measured by Body Mass Index (BMI). • BMI can be misleading as it doesn't distinguish between fat mass (FM) and fat-free mass (FFM), leading to potential misclassification of obesity in children. Previous studies have already suggested the use of the Fat Mass Index (FMI) and Fat-Free Mass Index (FFMI) as a more accurate measures of body composition. What is New: • This study adds the first age- and sex-specific reference values for FMI and FFMI in Austrian adolescents using bioelectrical impedance analysis (BIA) as a safe and secure measurement method of a large representative cohort. • We found percentile misclassification between BMI and FMI when categorizing for obesity, especially in intermediate categories of body composition. Furthermore, when comparing the new reference values for FMI and FFMI to existing ones from the US, UK, and Germany we could show a good alignment within the European cohorts and major differences with American values, indicating and confirming the difference of FMI and FFMI for different populations of different ethnical background, living on different continents. [ABSTRACT FROM AUTHOR]