Determinants of non-alcoholic fatty liver disease in young people: Maternal, neonatal, and adolescent factors.

AIM: To assess the impact of maternal, neonatal, and adolescent factors on the development of non-alcoholic fatty liver disease (NAFLD) in a cohort of 14- to 19-year-old adolescents. METHODS: This study is part of the Early Vascular Ageing in the YOUth study, a single-center cross-sectional study conducted in western Austria. Maternal and neonatal factors were extracted from the mother-child booklet, adolescent factors were evaluated by a face-to-face interview, physical examination, and fasting blood analyses. Liver fat content was assessed by controlled attenuation parameter (CAP) using signals acquired by FibroScan® (Echosense, Paris, France). The association of maternal, neonatal, and adolescent factors with CAP values was analyzed using linear regression models. RESULTS: In total, 595 adolescents (27.2% male) aged 17.0 ± 1.3 years were included. 4.9% (n = 29) showed manifest NAFLD with CAP values above the 90th percentile. Male sex (p < 0.001), adolescent triglyceride levels (p = 0.021), Homeostatic Model Assessment for Insulin Resistance index and BMI z-score (p < 0.001, each) showed a significant association with liver fat content in the multivariable analysis. Maternal pre-pregnancy BMI was associated with CAP values after adjustment for sex, age, and birth weight for gestational age (p < 0.001), but this association was predominantly mediated by adolescent BMI (indirect effect b = 1.18, 95% CI [0.69, 1.77]). CONCLUSION: Components of the metabolic syndrome were the most important predictors of adolescent liver fat content. Therefore, prevention of NAFLD should focus on lifestyle modification in childhood and adolescence.

Determinants of Diet Quality in Adolescents: Results from the Prospective Population-Based EVA-Tyrol and EVA4YOU Cohorts.

(1) Background: Unhealthy dietary behaviors are estimated to be one of the leading causes of death globally and are often shaped at a young age. Here, we investigated adolescent diet quality and its predictors, including nutrition knowledge, in two large Central European cohorts. (2) Methods: In 3056 participants of the EVA-Tyrol and EVA4YOU prospective population-based cohort studies aged 14 to 19 years, diet quality was assessed using the AHEI-2010 and DASH scores, and nutrition knowledge was assessed using the questionnaire from Turconi et al. Associations were examined utilizing multivariable linear regression. (3) Results: The mean overall AHEI-2010 score was 42%, and the DASH score was 45%. Female participants (60.6%) had a significantly higher diet quality according to the AHEI-2010 and DASH score. AHEI-2010 and DASH scores were significantly associated (p < 0.001) with sex, school type, smoking, and total daily energy intake. The DASH score was additionally significantly associated (p < 0.001) with age, socioeconomic status, and physical activity. Participants with better nutrition knowledge were more likely to be older, to attend a general high school, to live in a high-income household, to be non-smokers, and to have a higher diet quality according to the AHEI-2010 and DASH score. (4) Conclusions: Predictors of better diet quality included female sex, physical activity, educational level, and nutrition knowledge. These results may aid focused interventions to improve diet quality in adolescents.

Striatal Lacunar Infarction in a Late Preterm Infant Born to a Mother with Active Peripartum SARS-CoV-2 Infection.

Background: The current literature suggests that neonatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections generally have a mild course. Data on how in utero exposure to maternal infection affects neonatal health outcomes are limited, but there is evidence that neurological damage to the fetus and thromboembolic events may occur. Case Presentation. We describe the case of a late preterm infant, who presented with striatal lacunar infarction in the neonatal period, born to a mother with active peripartum SARS-CoV-2 infection. Diagnostic workup did not identify risk factors apart from the maternal SARS-CoV-2 infection. Repeated reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2 using oropharyngeal swab specimens of the patient were negative. IgG, but not IgM antibodies against spike protein S1 receptor-binding domain (S1RBD) epitope were detectable in umbilical cord blood and neonatal serum collected at 48 hours of life. Anti-SARS-CoV-2 total antibody titers against nucleocapsid protein in umbilical cord blood were negative. Conclusions: Bearing in mind a possible association of in utero exposure to SARS-CoV-2 and neonatal thromboembolic events, neonatologists should be aware of these complications even in well-appearing preterm infants.

Early Vascular Ageing in adolescents with migraine with aura: a community-based study.

BACKGROUND: Migraine with aura is associated with an increased risk of cardiovascular disease, yet the pathophysiology is unknown. Suggested underlying mechanisms of aura formation point into the direction of an abnormal vasoreactivity that also extends to the extracranial vasculature. METHODS: In the Early Vascular Ageing Tyrol study, a community-based non-randomized controlled trial conducted in 45 schools and companies in Tyrol (Austria) and South-Tyrol (Italy) between May 2015 and September 2018 aiming to increase cardiovascular health in adolescents, headache syndromes were classified according to the International Classification of Headache Disorders in a face-to-face interview. Carotid-femoral pulse-wave-velocity was measured by applanation tonometry and carotid intima-media-thickness by high-resolution ultrasound of the distal common carotid arteries. Differences in pulse-wave-velocity and carotid intima-media-thickness in youngsters with migraine with aura were compared respectively to those without headache and with other headaches by multivariable linear regression analysis. RESULTS: Of the 2102 study participants 1589 were aged 14 to 19 (mean 16.8) years and had complete data. 43 (2.7%) reported migraine with aura and 737 (46.4%) other headaches. Mean pulse-wave-velocity was 6.17 m/s (± 0.85) for migraine with aura, 6.06 m/s (± 0.82) for all other headaches and 6.15 (0.95) m/s for participants without headaches. Carotid intima-media-thickness was 411.3 µm (± 43.5) for migraine with aura, 410.9 µm (± 46.0) for all other headaches and 421.6 µm (± 48.4) for participants without headaches. In multivariable linear regression analysis, we found no differences in carotid-femoral pulse-wave-velocity or carotid intima-media-thickness in young subjects with migraine with aura, all other headaches, or no headaches. CONCLUSIONS: In line with previous large-scale studies in adults, we could not demonstrate relevant associations of migraine with aura with markers of arterial stiffness or subclinical atherosclerosis making early vascular ageing an unlikely pathophysiological link between migraine with aura and cardiovascular diseases. TRIAL REGISTRATION: First registered on ClinicalTrials.gov 29/04/2019 (NCT03929692).

Plasma homocysteine levels and associated factors in community-dwelling adolescents: the EVA-TYROL study.

Background: Homocysteine (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. Methods: Hcy 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. Results: Mean 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. Discussion: Clinical 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.

Cardiovascular health profiles in adolescents being born term or preterm-results from the EVA-Tyrol study.

BACKGROUND AND AIMS: Preterm birth has been linked with an increased risk of cardiovascular (CV) disease from childhood into adolescence and early adulthood. In this study, we aimed to investigate differences in CV health profiles between former term- and preterm-born infants in a cohort of Tyrolean adolescents. METHODS: The Early Vascular Aging (EVA)-Tyrol study is a population-based non-randomized controlled trial, which prospectively enrolled 14- to 19-year-old adolescents in North Tyrol, Austria and South Tyrol, Italy between 2015 and 2018. Metrics of CV health (body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), smoking, physical activity, dietary patterns, total cholesterol and fasting blood glucose) were assessed and compared between former term- and preterm-born girls and boys. RESULTS: In total, 1,491 study participants (59.5% female, mean age 16.5 years) were included in the present analysis. SBP and DBP were significantly higher in former preterm-born adolescents (mean gestational age 34.6 ± 2.4 weeks) compared to term-born controls (p < 0.01). In the multivariate regression analysis these findings remained significant after adjustment for potential confounders in all models. No differences were found in all other CV health metrics. The number of participants meeting criteria for all seven health metrics to be in an ideal range was generally very low with 1.5% in former term born vs. 0.9% in former preterm born adolescents (p = 0.583). CONCLUSIONS: Preterm birth is associated with elevated SBP and DBP in adolescence, which was even confirmed for former late preterm-born adolescents in our cohort. Our findings underscore the importance of promoting healthy lifestyles in former term- as well as preterm-born adolescents. In addition, we advise early screening for hypertension and long-term follow-up in the group of preterm-born individuals.

The association of allergic asthma and carotid intima-media thickness in adolescence: data of the prospective early vascular ageing (EVA)-Tyrol cohort study.

BACKGROUND: In recent years, there has been increasing evidence that asthma is associated with atherosclerosis and cardiovascular disease. However, data in children and adolescents are scarce and conflicting. We aimed to assess the impact of asthma with and without an allergic component on the carotid intima-media thickness in a large pediatric population. METHODS: The community-based early vascular ageing-Tyrol cohort study was performed between May 2015 and July 2018 in North, East (Austria) and South Tyrol (Italy) and recruited youngster aged 14 years and above. Medical examinations included anthropometric measurements, fasting blood analysis, measurement of the carotid intima-media thickness by high-resolution ultrasound, and a physician guided interview. RESULTS: The mean age of the 1506 participants was 17.8 years (standard deviation 0.90). 851 (56.5%) participants were female. 22 subjects had a physician diagnosis of non-allergic asthma, 268 had inhalative allergies confirmed by a positive radio-allergo-sorbent-test and/or prick test, and 58 had allergic asthma. Compared to healthy controls, participants with non-allergic asthma (411.7 vs. 411.7 µm; p = 0.932) or inhalative allergy (420.0 vs. 411.7 µm; p = 0.118) did not have significantly higher carotid intima-media thickness (cIMT). However, participants with allergic asthma had significantly higher cIMT (430.8 vs. 411.7; p = 0.004) compared to those without and this association remained significant after multivariable adjustment for established cardiovascular risk factors. CONCLUSION: Allergic asthma in the youth is associated with an increased carotid intima-media thickness. Physicians should therefore be aware of allergic asthma as a potential cardiovascular risk factor in children and adolescents. Trial Registration Number The EVA-Tyrol Study has been retrospectively registered at clinicaltrials.gov under NCT03929692 since April 29, 2019.

Association of adolescent lipoprotein subclass profile with carotid intima-media thickness and comparison to adults: Prospective population-based cohort studies.

BACKGROUND AND AIMS: Assessment of comprehensive lipoprotein subclass profiles in adolescents and their relation to vascular disease may enhance our understanding of the development of dyslipidemia in early life and inform early vascular prevention. METHODS: Nuclear magnetic resonance was used to measure lipoprotein profiles, including lipids (cholesterol, free cholesterol, triglycerides, phospholipids) and apolipoproteins (apoB-100, apoA1, apoA2) of 17 lipoprotein subclasses (from least dense to densest: VLDL-1 to -6, IDL, LDL-1 to -6, HDL-1 to -4) in n = 1776 14- to 19-year olds (56.6% female) and n = 3027 25- to 85-year olds (51.5% female), all community-dwelling. Lipoprotein profiles were related to carotid intima-media thickness (cIMT) as ascertained by sonography. RESULTS: Adolescents compared to adults had lower triglycerides, total, LDL, and non-HDL cholesterol, and apoB, and higher HDL cholesterol. They showed 26.6-59.8% lower triglyceride content of all lipoprotein subclasses and 21.9-51.4% lower VLDL lipid content. Concentrations of dense LDL-4 to LDL-6 were 36.7-40.2% lower, with also markedly lower levels of LDL-1 to LDL-3, but 24.2% higher HDL-1 ApoA1. In adolescents, only LDL-3 to LDL-5 subclasses were associated with cIMT (range of differences in cIMT for a 1-SD higher concentration, 4.8-5.9 µm). The same associations emerged in adults, with on average 97 ± 42% (mean ± SD) larger effect sizes, in addition to LDL-1 and LDL-6 (range, 6.9-11.3 µm) and HDL-2 to HDL-4, ApoA1, and ApoA2 (range, -7.0 to -17.7 µm). CONCLUSIONS: Adolescents showed a markedly different and more favorable lipoprotein profile compared to adults. Dense LDL subclasses were the only subclasses associated with cIMT in adolescents, implicating them as the potential preferred therapeutic target for primary prevention of cardiovascular disease at this age. In adults, associations with cIMT were approximately twice as large as in adolescents, and HDL-related measures were additionally associated with cIMT.

Diagnostic Yield of a Systematic Vascular Health Screening Approach in Adolescents at Schools.

PURPOSE: A significant proportion of noncommunicable diseases in adults has its roots in adolescence, and this is particularly true for cardiovascular disease and stroke. Detection of vascular and metabolic risk factors at young ages may aid disease prevention. METHODS: In 2,088 adolescents sampled from the general population of Tyrol, Austria, and South Tyrol, Italy, we systematically assessed the frequency of yet unknown vascular and metabolic risk conditions that require further diagnostic workup or intervention (lifestyle counselling or pharmacotherapy). The health screening included medical history taking, fasting blood analysis, and blood pressure and body measurements and was performed at schools. To recruit a representative sample of adolescents, equal proportions (about 67%) of schools were invited per school type and region. RESULTS: Adolescents were on average 16.4 (standard deviation 1.1) years old, and 56.4% were female. A proportion of 22.8% (95% confidence interval [CI], 19.6-26.3) had previous or current physician-confirmed diseases. The health screening newly detected relevant medical conditions in 45.4% [95% CI, 41.5-49.4] (55.8% [95% CI, 52.7-58.7] in boys and 37.4% [95% CI, 35.0-39.8] in girls, p < .001). The most prevalent were elevated blood pressure and hypertension, metabolic syndrome, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, and subclinical hypothyroidism. Detection of risk conditions did not depend on socioeconomic status but increased with age and body mass index. CONCLUSIONS: Vascular health screening in adolescents at schools has a high diagnostic yield and may aid guideline-recommended prevention in the youth. Implementation should carefully consider national differences in healthcare systems, resources, and existing programs.

Predictors of Carotid Intima-Media Thickness Progression in Adolescents-The EVA-Tyrol Study.

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.

Cardiovascular health behaviors and associations of sex, age, and education in adolescents - Results from the EVA Tyrol study.

BACKGROUND AND AIMS: Ideal cardiovascular health (CVH) behaviors in adolescents are defined by body mass index (BMI), diet, physical activity and smoking, and are directly associated with better health in later life. To further improve health prevention programs we investigated the prevalence of these behaviors in a cohort of healthy adolescents and focused on the associations with sex, age, and education. METHODS AND RESULTS: The Early Vascular Aging Tyrol study is a cross-sectional study assessing 14- to 19-year-old pupils and apprentices in Western Austria and South Tyrol. Between May 2015 and July 2018 2047 adolescents (43.6% males, mean age 16.4 years) with complete data for all 4 health behaviors were included. The prevalence of ideal body mass index (BMI) was 78.3%, of ideal physical activity 42.5%, of non-smoking 70.4% and of ideal diet 8.1%. Females showed a higher smoking prevalence and a lower physical activity, but better dietary habits than males. Older adolescents of both sexes had lower prevalence of ideal smoking and diet. Apprentices and pupils of vocational schools had a higher BMI and a less favorable diet compared to secondary academic school students. Smoking prevalence was highest in apprentices. Non-ideal BMI was independently associated with smoking. CONCLUSION: In our cohort, only a minority showed ideal CVH behaviors which were best in adolescents younger than 16 years. We observed significant differences between males and females and a clear impact of school education with apprentices being at risk for non-ideal CVH behaviors. CLINICAL TRIAL REGISTRATION NUMBER: NCT03929692, clinicaltrials.gov.

Impact of lifestyle and cardiovascular risk factors on early atherosclerosis in a large cohort of healthy adolescents: The Early Vascular Ageing (EVA)-Tyrol Study.

BACKGROUND AND AIMS: Atherosclerosis starts early in life. We aimed to assess the dimension and progression of the intima-media thickness, a surrogate marker for early vascular aging, and its association with a broad palette of cardiovascular risk and lifestyle factors in a large cohort of healthy adolescents. METHODS: The EVA-Tyrol cohort study enrolled 1573 adolescents with a mean age of 16.0 years (SD 0.9). 1000 participants had a prospective follow-up after 22.1 months on average (SD 3.4). Cardiovascular risk and lifestyle factors were evaluated by standardized interviews, physical examination, and fasting blood analyses. Carotid intima-media thickness (cIMT) was measured at baseline and follow-up by high-resolution ultrasound. Aortic intima-media thickness (aIMT) was assessed during follow-up only. RESULTS: Several vascular risk factors like elevated blood pressure (4.7% > 95th percentile), overweight (9.2% > 95th percentile) and smoking (29.7%) were already prevalent at this age. Maximum cIMT progressed by 2.78 µm (95% CI, 0.39-5.17) per year. In multivariable linear regression analysis, sex, body weight, systolic blood pressure, LDL-cholesterol and physical activity were independent predictors of cIMT both at baseline and follow-up. In addition, alanine-aminotransferase, a laboratory surrogate of non-alcoholic fatty liver disease, was independently associated with cIMT at follow-up and pack-years of smoking with aIMT. CONCLUSIONS: Unfavourable lifestyle and vascular risk factors were prevalent in adolescents and several of them were associated with vessel wall thickness, even though effect sizes were modest and cIMT variability was limited. These data suggest adolescence as a prime age range for early vascular prevention.

The Impact of Being Born Preterm or Small for Gestational Age on Early Vascular Aging in Adolescents.

OBJECTIVE: To assess the impact of being born preterm or small for gestational age (SGA) on early vascular aging (EVA) in a cohort of healthy Tyrolean adolescents. STUDY DESIGN: This study is part of an ongoing clinical trial, EVA Tyrol, a regional cohort study being conducted in western Austria. EVA was assessed in adolescents (mean age, 16 years) by means of carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (cIMT), and blood pressure measurements. Adolescents were grouped as either term or preterm. Subsequently, being born SGA was taken into consideration in subgroup analysis. Complete data on gestational age and birth weight were available for 930 adolescents. RESULTS: Systolic blood pressure and diastolic blood pressure were significantly higher in the preterm (mean gestational age, 34.8 ± 2.3 weeks) and appropriate for gestational age (AGA) group than in the term and AGA group (P < .05). This finding remained significant in linear regression analysis after adjustment for covariables in all models. PWV was significantly higher in the term-SGA group than in the term-AGA group (6.67 ± 1.73 m/s vs 6.07 ± 1.09 m/s; P < .05). In the linear regression analysis, this finding remained significant in all models. There were no differences in cIMT between study groups. CONCLUSION: Being born preterm or SGA might render persons susceptible to EVA. Long-term follow-up of preterm and SGA individuals is warranted to confirm these results.