Subclinical Atherosclerosis in Young, Socioeconomically Vulnerable Hispanic and Non-Hispanic Black Adults.

BACKGROUND Non-Hispanic Black persons are at greater risk of cardiovascular (CV) events than other racial/ethnic groups; however, their differential vulnerability to early subclinical atherosclerosis is poorly understood. OBJECTIVES This work aims to study the impact of race/ethnicity on early subclinical atherosclerosis in young socioeconomically disadvantaged adults. METHODS Bilateral carotid and femoral 3-dimensional vascular ultrasound examinations were performed on 436 adults (parents/caregivers and staff) with a mean age of 38.0 ± 11.1 years, 82.3% female, 66% self-reported as Hispanic, 34% self-reported as non-Hispanic Black, and no history of CV disease recruited in the FAMILIA (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health) trial from 15 Head Start preschools in Harlem (neighborhood in New York, New York, USA). The 10-year Framingham CV risk score was calculated, and the relationship between race/ethnicity and the presence and extent of subclinical atherosclerosis was analyzed with multivariable logistic and linear regression models. RESULTS The mean 10-year Framingham CV risk was 4.0%, with no differences by racial/ethnic category. The overall prevalence of subclinical atherosclerosis was significantly higher in the non-Hispanic Black (12.9%) than in the Hispanic subpopulation (6.6%). After adjusting for 10-year Framingham CV risk score, body mass index, fruit and vegetable consumption, physical activity, and employment status, non-Hispanic Black individuals were more likely than Hispanic individuals to have subclinical atherosclerosis (OR: 3.45; 95% CI: 1.44-8.29; P = 0.006) and multiterritorial disease (P = 0.026). CONCLUSIONS After adjustment for classic CV risk, lifestyle, and socioeconomic factors, non-Hispanic Black younger adults seem more vulnerable to early subclinical atherosclerosis than their Hispanic peers, suggesting that the existence of emerging or undiscovered CV factors underlying the residual excess risk (Family-Based Approach in a Minority Community Integrating Systems-Biology for Promotion of Health [FAMILIA (Project 2)]; NCT02481401).This study was funded by the American Heart Association under grant No 14SFRN20490315 and the Stephen Gellman Children’s Outreach Program. Dr Fernandez-Jimenez is recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria- Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund/European Social Fund "A way to make Europe"/"Investing in your future." Dr Santos-Beneit is recipient of grant LCF/PR/MS19/ 12220001 funded by “la Caixa” Foundation (ID 100010434). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/ 501100011033). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

The challenge of sustainability: Long-term results from the Fifty-Fifty peer group-based intervention in cardiovascular risk factors.

The Fifty-Fifty trial demonstrated that a peer-group-based intervention was able to improve healthy behaviors in individuals with cardiovascular (CV) risk factors immediately post-intervention. To determine the long-term sustainability of a one-year peer-group-based intervention focused on CV health and behavior. A total of 543 adults aged 25 to 50 years with at least 1 CV risk factor were screened and recruited, received initial training through workshops, and were then randomized 1:1 to a peer-group-based intervention group (IG) or a self-management control group (CG) for 12 months. At a median of 52 months from baseline, 321 participants were re-assessed (~60% retention). The primary outcome was the mean change in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco use (Fuster-BEWAT score [FBS], range 0-15). Intervention effects were assessed using linear-mixed effects models. The mean age of retained participants was 48.0 years (SD: 5.4), and 73% were female. Consistent with previous results, the change of overall FBS was significantly greater in the IG than in the CG at 12-month follow-up (between-group difference, 0.60 points; 95% CI, 0.08-1.12; P = .025). Assessment of long-term sustainability (52-month follow-up) showed that there were no between-group differences in the mean overall FBS (IG mean score, 8.52; 95% CI, 7.97-9.07 vs CG mean score, 8.51; 95% CI, 7.93-9.10; P = .972) or in the change of overall FBS from screening (IG mean change, 0.64; 95% CI, 0.00-1.28; CG mean change, 0.46; 95% CI, -0.20-1.12; P = .497). A one-year peer-group-based intervention showed favorable results at immediate post-intervention but did not demonstrate significant differences between the IG and CG at 52 months. Combination of an initial training period (workshops) with the maintenance of peer-support groups or other re-intervention strategies may be required to achieve sustained effects on healthy behaviors. ClinicalTrials.gov identifier NCT02367963. Registered (https://clinicaltrials.gov/show/NCT02367963).This study was co-funded by the SHE Foundation -“la Caixa” Foundation (LCF/PR/CE16/10700001 and LCF/PR/MS19/12220001) and the Ministry of Health, Social Services and Equality. R.F-J is recipient of funding from the Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria (PI19/01704) co-funded by the European Regional Development Fund/European Social Fund (“A way to make Europe”/“Investing in your future”). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministry of Science and Innovation, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Magnetic resonance imaging reference values for cardiac morphology, function and tissue composition in adolescents.

BACKGROUND Cardiovascular magnetic resonance (CMR) is a precise tool for the assessment of cardiac anatomy, function, and tissue composition. However, studies providing CMR reference values in adolescence are scarce. We aim to provide sex-specific CMR reference values for biventricular and atrial dimensions and function and myocardial relaxation times in this population. METHODS Adolescents aged 15-18 years with no known cardiovascular disease underwent a non-contrast 3-T CMR scan between March 2021 and October 2021. The imaging protocol included a cine steady-state free-precession sequence for the analysis of chamber size and function, as well as T2-GraSE and native MOLLI T1-mapping for the characterization of myocardial tissue. FINDINGS CMR scans were performed in 123 adolescents (mean age 16 ± 0.5 years, 52% girls). Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.7 ± 11.6 vs 78.1 ± 8.3 ml/m2, p < 0.001; and 101.3 ± 14.1 vs 84.1 ± 10.5 ml/m2, p < 0.001), as was the indexed left ventricular mass (48.5 ± 9.6 vs 36.6 ± 6.0 g/m2, p < 0.001). Left ventricular ejection fraction showed no significant difference by sex (62.2 ± 4.1 vs 62.8 ± 4.2%, p = 0.412), whereas right ventricular ejection fraction trended slightly lower in boys (55.4 ± 4.7 vs. 56.8 ± 4.4%, p = 0.085). Indexed atrial size and function parameters did not differ significantly between sexes. Global myocardial native T1 relaxation time was lower in boys than in girls (1215 ± 23 vs 1252 ± 28 ms, p < 0.001), whereas global myocardial T2 relaxation time did not differ by sex (44.4 ± 2.0 vs 44.1 ± 2.4 ms, p = 0.384). Sex-stratified comprehensive percentile tables are provided for most relevant cardiac parameters. INTERPRETATION This cross-sectional study provides overall and sex-stratified CMR reference values for cardiac dimensions and function, and myocardial tissue properties, in adolescents. This information is useful for clinical practice and may help in the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in this population. FUNDING Instituto de Salud Carlos III (PI19/01704).Instituto de Salud Carlos III (PI19/01704). The authors are indebted to the adolescents who participated in this study. Rodrigo Fernández-Jiménez is recipient of grant PI19/01704 by the Instituto de Salud Carlos III (ISCIII) - Fondo de Investigación Sanitaria and the European Regional Development Fund/European Social Fund (A way to make Europe/Investing in your future), which funded the EnIGMA (Early ImaGing Markers of unhealthy lifestyles in Adolescents) study. Jesús Martínez-Gómez was a postgraduate fellow of the Ministerio de Ciencia e Innovación at the Residencia de Estudiantes (2020–2022) and is a recipient of grant FPU21/04891 (Ayudas para la formación de profesorado universitario, FPU-2021) from the Ministerio de Educación, Cultura y Deporte Gloria Santos-Beneit is recipient of grant LCF/PR/MS19/12220001 funded by ““la Caixa” Foundation (ID 100010434). The SHE Foundation is supported by “la Caixa” Foundation (LCF/PR/CE16/10700001). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). Simon Bartlett (CNIC) provided English editing.S

Rationale and design of the SI! Program for health promotion in elementary students aged 6 to 11 years: A cluster randomized trial

Unhealthy habits in children are increasing at an alarming rate. The school provides a promising setting for effective preventive strategies to improve children's lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based educational intervention aimed at all stages of compulsory education in Spain. Here, we present the design of the SI! Program for Elementary School cluster-randomized controlled trial, targeting children aged 6 to 11 years. This trial aims to study the impact of different timings and intensities of exposure to SI! Program activities on elementary school children and their immediate environment (parents/caregivers, teachers, and school). The trial includes 1770 children from 48 public elementary schools in Madrid (Spain), together with their parents and teachers. Schools and their children were randomly assigned to the intervention group (the SI! curriculum-based educational program over 3 or 6 academic years) or to the control group (standard curriculum). The primary outcomes are the change from baseline at 3-year and 6-year follow-up in children's scores for knowledge, attitudes, and habits (KAH) and health factors (blood pressure, height, weight, waist circumference, and skinfold thickness). Secondary outcomes include 3-year and 6-year changes from baseline in lifestyle questionnaire scores for parents/caregivers and teachers, and in the school environment questionnaire. The overarching goal of the SI! Program is to provide an effective and sustainable health promotion program for the adoption of healthy behaviors in children. The present trial will address the impact and the optimal timing and duration of this educational intervention in the elementary school setting. (Am Heart J 2019;210:9-17.)This study is partly funded by the Daniel & Nina Carasso Foundation and the la Caixa Foundation (LCF/PR/CE16/ 10700001). This study forms part of a project that has received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska- Curie grant agreement No. 707642 and from the American Heart Association under grant No. 14SFRN2049031

Prevalence and correlates of cardiovascular health among early adolescents enrolled in the SI! Program in Spain: a cross-sectional analysis.

The Instituto de Salud Carlos III-Fondo de Investigacion Sanitaria (PI19/01704) and the European Regional Development Fund/European Social Fund ("A way to make Europe"/"Investing in your future"), the Fundació la Marató de TV3 (369/C/2016), the ‘la Caixa’ Foundation (LCF/PR/CE16/10700001 and LCF/PR/MS19/12220001), the Ministerio de Ciencia e Innovación (AGL2016–75329-R), the Generalitat de Catalunya, and the SHE Foundation. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Urinary Nitric Oxide Levels Are Associated with Blood Pressure, Fruit and Vegetable Intake and Total Polyphenol Excretion in Adolescents from the SI! Program.

Nitric oxide (NO) is important to cardiovascular health (CVH), and its bioavailability could be regulated by the antioxidant effect of polyphenols, improving endothelial function and consequently blood pressure (BP). However, scant research has been carried out on NO and CVH correlates in adolescent populations. Therefore, our aim was to investigate the association between NO and the CVH status and other health factors in adolescents. NO, total polyphenol excretion (TPE), anthropometric measurements, BP, blood lipid profile, blood glucose, diet, physical activity, and smoking status were recorded, while CVH score was classified as ideal, intermediate, and poor. Negative associations were observed between NO and body mass index, body fat percentage, BP, and triglycerides; and positive associations between NO and skeletal muscle percentage, HDL-cholesterol, fruit and vegetable intake, and TPE was observed. To capture more complex interactions among different factors, multiple linear regression was performed, obtaining a significant association between NO and fruit and vegetable intake (β = 0.175), TPE (β = 0.225), and systolic BP (β = -0.235). We conclude that urinary NO levels are positively associated with the consumption of fruits and vegetables rich in antioxidants such as polyphenols and negatively associated with systolic BP.The SI! Program for Secondary Schools trial was supported by the SHE Foundation, the la Caixa Foundation (LCF/PR/CE16/10700001), the Fundació la Marató de TV3 (grant number 369/C/2016). Support was also provided by the Ministerio de Ciencia, Innovación y Universidades (PID2020-114022RB-I00), CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades (AEI/FEDER, UE), and Generalitat de Catalunya. RF-J is a recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria- Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund/European Social Fund a way to make Europe/Investing in your future. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). GS-B was the recipient of grant LCF/PR/MS19/12220001 funded by la Caixa Foundation (ID 100010434). AT-R is a Serra Húnter fellow. EL-S was a FI-SDUR (EMC/3345/2020) fellowship from the Generalitat de Catalunya. JM-G was a postgraduate fellow of the Ministerio de Ciencia e Innovación of Spain at the Residencia de Estudiantes (2020–ongoing).S

Total urinary polyphenols and ideal cardiovascular health metrics in Spanish adolescents enrolled in the SI Program: a cross-sectional study

To study the relationship between urinary total polyphenol excretion (TPE) in adolescents and ideal cardiovascular (CVH) metrics. 1151 adolescents aged 12.04 (0.46) years participating in the SI! Program for Secondary Schools were selected based on the availability of urine samples and information required to assess CVH metrics. Data on health behaviours (smoking status, body mass index, physical activity, and healthy diet) and health factors (blood pressure, total cholesterol, and blood glucose) were used to calculate the CVH metrics. TPE in urine was analysed by a Folin-Ciocalteu method after solid-phase extraction. Associations between TPE (categorized into tertiles) and CVH metrics (total and separate scores) were assessed using multilevel mixed-effect regression models. Higher TPE levels were associated with higher (healthier) CVH scores and ideal smoking status (OR 1.54, 95% CI 1.10; 1.87, p value = 0.007), physical activity (OR 1.12, 95% CI 1.02; 1.23, p value = 0.022) and total cholesterol (OR 1.78, 95% CI 1.16; 2.73, p value = 0.009) after multivariate adjustment. An association between TPE and total CVH scores was observed only in boys. Girls with higher TPE had higher rates of ideal total cholesterol and blood pressure. According to our findings, higher urinary TPE is related to better CVH scores, with relevant differences in this association by gender

Lessons Learned From 10 Years of Preschool Intervention for Health Promotion: JACC State-of-the-Art Review.

Implementing a health promotion program for children is a complex endeavor. In this review, we outline the key lessons learned over 10 years of experience in implementing the SI! Program (Salud Integral-Comprehensive Health) for cardiovascular health promotion in preschool settings in 3 countries: Colombia (Bogotá), Spain (Madrid), and the United States (Harlem, New York). By matching rigorous efficacy studies with implementation science, we can help bridge the divide between science and educational practice. Achieving sustained lifestyle changes in preschool children through health promotion programs is likely to require the integration of several factors: 1) multidisciplinary teams; 2) multidimensional educational programs; 3) multilevel interventions; 4) local program coordination and community engagement; and 5) scientific evaluation through randomized controlled trials. Implementation of effective health promotion interventions early in life may induce long-lasting healthy behaviors that could help to curb the cardiovascular disease epidemic.This work is supported by the SHE Foundation and “la Caixa” Foundation (LCF/CE16/10700001). The project in Colombia was funded by Santo Domingo Foundation; the study in the United States (FAMILIA) was funded by the American Heart Association (grant no. 14SFRN20490315); and the study in Spain (SI! Program) was funded by the SHE Foundation, the research grant FIS-PI11/ 01885 (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III), and Fundació la Marató de TV3 (369/C/2016). Dr SantosBeneit is the recipient of grant LCF/PR/MS19/12220001 funded by “la Caixa” Foundation (ID 100010434). Dr Fernández-Jiménez is the recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III and co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future.” The Centro Nacional de Investigaciones Cardiovasculares is supported by the Instituto de Salud Carlos III, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Total urinary polyphenols and ideal cardiovascular health metrics in Spanish adolescents enrolled in the SI Program: a cross-sectional study.

To study the relationship between urinary total polyphenol excretion (TPE) in adolescents and ideal cardiovascular (CVH) metrics. 1151 adolescents aged 12.04 (0.46) years participating in the SI! Program for Secondary Schools were selected based on the availability of urine samples and information required to assess CVH metrics. Data on health behaviours (smoking status, body mass index, physical activity, and healthy diet) and health factors (blood pressure, total cholesterol, and blood glucose) were used to calculate the CVH metrics. TPE in urine was analysed by a Folin-Ciocalteu method after solid-phase extraction. Associations between TPE (categorized into tertiles) and CVH metrics (total and separate scores) were assessed using multilevel mixed-effect regression models. Higher TPE levels were associated with higher (healthier) CVH scores and ideal smoking status (OR 1.54, 95% CI 1.10; 1.87, p value = 0.007), physical activity (OR 1.12, 95% CI 1.02; 1.23, p value = 0.022) and total cholesterol (OR 1.78, 95% CI 1.16; 2.73, p value = 0.009) after multivariate adjustment. An association between TPE and total CVH scores was observed only in boys. Girls with higher TPE had higher rates of ideal total cholesterol and blood pressure. According to our findings, higher urinary TPE is related to better CVH scores, with relevant differences in this association by gender.The authors wish to thank all the volunteers and their families, teachers, and schools for their contribution to the SI! Program for Secondary Schools. The SI! Program for Secondary Schools trial was supported by the SHE Foundation, the “la Caixa” Foundation (grant numbers LCF/PR/CE16//10700001 and LCF/PR/MS19/12220001), and the Fundació la Marató de TV3 (grant number 369/C/2016). Support was also provided by the Ministerio de Ciencia, Innovación y Universidades (grant number AGL2016–75329-R), and Generalitat de Catalunya. Rodrigo Fernández-Jiménez is a recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria- Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund/European Social Fund "A way to make Europe"/"Investi ng in your future". The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). Anna Tresserra-Rimbau was supported by a Serra Húnter Fellowship. Emily P. Laveriano-Santos is thankful for the FI-SDUR (EMC/3345/2020) fellowship from the Generalitat de Catalunya. Isabella Parilli-Moser thanks the FI-SDUR (EMC/2703/2019) fellowship.S

Rationale and design of the school-based SI! Program to face obesity and promote health among Spanish adolescents: A cluster-randomized controlled trial

Unhealthy habits in adolescents are increasing at an alarming rate. The school offers a promising environment in which to implement effective preventive strategies to improve adolescents' lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based health-promotion intervention aimed at all stages of compulsory education in Spain. We present the study design of the SI! Program for Secondary Schools, targeting adolescents aged 12 to 16 years. Aim: The main goal of this study is to evaluate the impact of the SI! Program educational intervention on adolescent lifestyle behaviors and health parameters. Methods: The study was designed as a cluster-randomized controlled intervention trial and enrolled 1326 adolescents from 24 public secondary schools in Spain, together with their parents/caregivers. Schools and their students were randomly assigned to the intervention group (the SI! curriculum-based educational program over 2 or 4 academic years) or to the control group (usual curriculum). The primary endpoint will be the change from baseline at 2-year and 4-year follow-up in the composite Ideal Cardiovascular Health (ICH) score, consisting of four health behaviors (body mass index, dietary habits, physical activity, and smoking) and three health factors (blood pressure, total cholesterol, and glucose). Secondary endpoints will include 2-year and 4-year changes from baseline in ICH score subcomponents, the Fuster-BEWAT health scale, adiposity markers (waist circumference and body composition), polyphenol and carotenoid intake, and emotion management. Discussion: The overarching goal of the SI! Program is to instill healthy behaviors in children and adolescents that can be sustained into adulthood. The SI! Program for Secondary School is a comprehensive health-promotion intervention targeting 12-16-year-old adolescents and their immediate environment. The present study addresses the optimal timing and impact of the educational intervention on health in adolescence