Socio-geographical disparities of obesity and excess weight in adults in Spain: insights from the ENE-COVID study

Background: In Spain, differences in the prevalence of obesity and excess weight according to sex and sociodemographic factors have been described at the national level, although current data do not allow to delve into geographical differences for these conditions. The aim was to estimate national and regional prevalences of adult obesity and excess weight in Spain by sex and sociodemographic characteristics, and to explore difference sources of inequalities in its distribution, as well as its geographical pattern. Method: ENE-COVID study was a nationwide representative seroepidemiological survey with 57,131 participants. Residents in 35,893 households were selected from municipal rolls using a two-stage random sampling stratified by province and municipality size (April-June 2020). Participants (77.0% of contacted individuals) answered a questionnaire which collected self-reported weight and height, as well as different socioeconomic variables, that allowed estimating crude and standardized prevalences of adult obesity and excess weight. Results: Crude prevalences of obesity and excess weight were higher in men (obesity: 19.3% vs. 18.0%; excess weight: 63.7% vs. 48.4%), while severe obesity was more prevalent in women (4.5% vs. 5.3%). These prevalences increased with age and disability, and decreased with education, census tract income and municipality size. Differences by educational level, relative census income, nationality or disability were clearly higher among women. Obesity by province ranged 13.3-27.4% in men and 11.4-28.1% in women; excess weight ranged 57.2-76.0% in men and 38.9-59.5% in women. The highest prevalences were located in the southern half of the country and some north-western provinces. Sociodemographic characteristics only explained a small part of the observed geographical variability (25.2% obesity). Conclusion: Obesity and overweight have a high prevalence in Spain, with notable geographical and sex differences. Socioeconomic inequalities are stronger among women. The observed geographical variability suggests the need to implement regional and local interventions to effectively address this public health problem.This study was supported by Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.S

Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy: Genotype-phenotype correlation.

AIMS Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM), there is little information about its frequency and distribution pattern according to underlying genetic substrate. We sought to describe LGE patterns according to genotype and to analyze the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS Cardiac magnetic resonance findings and LGE distribution according to genetics was performed in a cohort of 600 DCM patients followed at 20 Spanish centers. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, LVEF 36.9 ± 13.9%) conformed the final cohort. A causative genetic variant was identified in 219 (38%) patients and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20 and MYH7 (0%, 5% and 20%, respectively). Patients with variants in DMD, DSP and FLNC showed predominance of LGE subepicardial pattern (50%, 41% and 18%, respectively) whereas patients with variants in TTN, BAG3, LMNA and MYBPC3 showed unspecific LGE patterns. Genetic yield differed according to LGE pattern. Patients with subepicardial, lineal midwall, transmural, right ventricular insertion points or with combination of LGE patterns showed increased risk of MVA compared with patients without LGE. CONCLUSION LGE patterns in DCM has a specific distribution according to the affected gene. Certain LGE patterns are associated with increased risk of MVA and with increased yield of genetic testing.This study has been funded by Instituto Salud Carlos III (ISCIII) through the projects ‘PI18/0004, PI19/01283, and PI20/0320’ (co-funded by the European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro, the Hospital Universitario Vall Hebrón, the Hospital General Universitario Gregorio Marañón, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart). F.d.F. receives grant support from ISCIII (CM20/00101). R.B. receives funding from the Obra Social la Caixa Foundation. M.B. receives funding from ISCIII (PI19/01283). The CNIC is supported by the ISCIII, Ministerio de Ciencia e Innovación of the Spanish Government (MCIN), and Pro CNIC Foundation.S

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P&lt;0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF &gt;35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P&lt;0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.</p

Instrucciones para planificar la actividad docente de una asignatura: la guía docente y la programación temporal

La planificación de detalle que realiza el profesorado de una determinada asignatura se recoge en dos documentos distintos: la guía docente y la programación temporal. La información incluida en ellos será de utilidad para los estudiantes que cursen la asignatura pero no solo para ellos, ya que se empleará también como base para la coordinación docente y en los procesos de revisión y seguimiento de los títulos. Este libro está concebido para servir de apoyo al profesorado a la hora de planificar su docencia y cumplimentar los dos documentos citados

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

Miocardiopatía dilatada familiar : genética, características clínicas y respuesta al tratamiento en función del genotipo

Introducción: La miocardiopatía dilatada idiopática (MCD) es una enfermedad primaria del músculo cardiaco caracterizada por dilatación y disfunción sistólica del ventrículo izquierdo, en ausencia de condiciones de carga anormales. Está determinada genéticamente en un 20-50% de los pacientes. Dada su heterogeneidad genética resulta imprescindible la realización de estudios para establecer correlaciones genotipo-fenotipo. Además, la relación entre genotipos concretos y la respuesta al tratamiento médico óptimo (TMO) valorada mediante la detección de remodelado reverso del ventrículo izquierdo (RRVI) y el análisis de eventos en el seguimiento, sigue siendo bastante desconocida. Objetivos: 1) Describir el genotipo y del fenotipo de pacientes con MCD en nuestro medio.2) Estudiar la respuesta al TMO en función del genotipo en base a la aparición de RRVI y de los eventos clínicos en el seguimiento.3) Caracterizar dos nuevos genes implicados en el desarrollo de miocardiopatías: JPH2 y FHL1. Material y métodos: Estudio unicéntrico retrospectivo que incluyó 145 pacientes consecutivos genotipados con MCD atendidos en la consulta de cardiopatías familiares del Hospital Virgen de la Arrixaca. Se clasificaron en grupos de genes pertenecientes al mismo subcompartimento celular o con características compartidas diferenciales (citoesqueleto, desmosómicos, sarcoméricos, truncamientos en titina, lamina, otras mutaciones y estudio negativo). Los pacientes estaban bajo tratamiento médico máximo tolerado y tenían al menos dos estudios ecocardiográficos separados como mínimo 6 meses. Se analizó la aparición de RRVI y los eventos clínicos en el seguimiento. Por otro lado se incluyeron los miembros de las 2 familias con nuevas mutaciones identificadas en JPH2 y FHL1 para caracterizar el fenotipo específico asociado a las mismas. Conclusiones: 1. El espectro genético de la MCD en nuestro medio es heterogéneo e involucra múltiples genes, siendo los más frecuentes los sarcoméricos motores. 2. La tecnología NGS unida a una evaluación familiar detallada permite la identificación de la mutación causal en el 68% de los casos de MCD. 3. Las características clínicas de los pacientes con MCD determinada genéticamente incluyen: mayor prevalencia de varones, edad en torno a los 45 años, escasa comorbilidad, baja prevalencia de fibrilación auricular, baja prevalencia de arritmias ventriculares, baja prevalencia de alteraciones de la conducción y escaso porcentaje de afectación neuromuscular. 4. El 37,9% de pacientes con MCD determinada genéticamente, presenta RRVI bajo TMO. 5. El genotipo no se asoció significativamente a la aparición de RRVI. 6. Las mutaciones en TTN se asociaron a un fenotipo con afectación más severa basal pero con elevada proporción de pacientes con RRVI y mayor supervivencia libre de muerte, trasplante e ingresos por insuficiencia cardiaca que el resto de grupos genéticos. 7. La agrupación de genes desmosómicos, lamina y fosfolambano se asoció significativamente a una menor supervivencia libre de muerte súbita cardiaca, parada cardiaca recuperada taquicardia ventricular sostenida y descarga apropiada del DAI, con un aumento del riesgo del evento combinado de casi 6 veces. 8. La mutación p. Glu85Lys en JPH2 supone la primera descripción de una mutación en este gen asociada a MCD. El fenotipo se caracteriza por una MCD asociada a hipertrabeculación, alteraciones de la conducción y escasa prevalencia de arritmias auriculares y ventriculares. 9. La mutación p.Cys255Ser en el gen FHL1 causa una miocardiopatía no clasificable caracterizada por hipertrofia ventricular izquierda leve no obstructiva y no compactación del ventrículo izquierdo que coexiste con afectación musculoesquelética. La miocardiopatía por FHL1 muestra además características histopatológicas de miocardiopatía arritmogénica biventricular. El pronóstico es malo, con disfunción sistólica y arritmias que con frecuencia requieren implante de DAI y trasplante a edad temprana. La presencia de trombopenia y elevación de CK asociadas a miocardiopatía con herencia ligada al X debería suscitar la sospecha de la existencia de una mutación en FHL1.Introduction: Idiopathic dilated cardiomyopathy (DCM) is a primary disease of the heart muscle characterized by left ventricular dilatation and systolic dysfunction, in the absence of abnormal loading conditions. It is genetically determined in 20-50% of patients. Given its genetic heterogeneity, it is essential to carry out studies to establish genotype-phenotype correlations. Furthermore, the relationship between specific genotypes and the response to optimal medical treatment (OMT) assessed in terms of left ventricular reverse remodeling (LVRR) and the analysis of events at follow-up, remains quite unknown. Objectives: 1) To describe the genotype and phenotype of patients with DCM in our environment. 2) To study the response to OMT depending on the genotype based on the appearance of LVRR and clinical events in the follow-up. 3) To characterize two new genes involved in the development of cardiomyopathies: JPH2 and FHL1. Material and Methods: Retrospective single-center study that included 145 consecutive genotyped patients with DCM seen at the Virgen de la Arrixaca Hospital. They were classified into clusters of genes belonging to the same cellular subcompartment or with differential shared characteristics (cytoskeleton, desmosomal, sarcomeric, titin truncations, lamin, other mutations and negative study). The patients were under maximum tolerated medical treatment and had at least two separate echocardiographic studies in 6 months. The appearance of LVRR and clinical events were analyzed at follow-up. On the other hand, members of the 2 families with new mutations identified in JPH2 and FHL1 genes were included in order to characterize the specific phenotype associated with them. Conclusions: 1. The genetic spectrum of DCM in our environment is heterogeneous and involves multiple genes, the most common being motor sarcomeric. 2. NGS technology coupled with a detailed family assessment allows identification of the causal mutation in 68% of DCM cases. 3. The clinical characteristics of patients with genetically determined DCM include: higher prevalence of males, age around 45 years, low comorbidity, low prevalence of atrial fibrillation, low prevalence of ventricular arrhythmias, low prevalence of conduction disturbances, and low percentage of neuromuscular involvement. 4. 37.9% of patients with genetically determined DCM have RRVI under OMT. 5. The genotype was not significantly associated with the appearance of LVRR. 6. Titin mutations were associated with a phenotype with more severe baseline involvement but with a high proportion of patients with LVRR and greater survival free of death, transplantation, and admissions for heart failure than the rest of the genetic groups. 7. Clustering of desmosomal genes, lamin, and phospholamban was significantly associated with decreased survival free of sudden cardiac death, recovered cardiac arrest, sustained ventricular tachycardia, and appropriate ICD shock, with an almost 6-fold increased risk of the combined event. 8. The mutation p. Glu85Lys in JPH2 represents the first description of a mutation in this gene related to DCM. The phenotype is characterized by DCM associated with hypertrabeculation, conduction disturbances, and low prevalence of atrial and ventricular arrhythmias. 9. The p.Cys255Ser mutation in the FHL1 gene causes an unclassifiable cardiomyopathy characterized by mild non-obstructive left ventricular hypertrophy and left ventricular non-compaction that coexists with musculoskeletal involvement. FHL1 cardiomyopathy also shows histopathological characteristics of biventricular arrhythmogenic cardiomyopathy. The prognosis is poor, with systolic dysfunction and arrhythmias that often require ICD implantation and transplantation at an early age. The presence of thrombopenia and CK elevation associated with X-linked inherited cardiomyopathy should raise the suspicion of a FHL1 mutation

Tourism, cultural activities and sustainability in the Spanish Mediterranean regions: A probit approach

Culture is the preferred activity of sun & sand tourists visiting the Spanish Mediterranean regions. Improving our knowledge on the factors surrounding this type of demand appears to be pivotal for the continuous renewal of those mature destinations. With this objective we apply probit models to a data set of more than 200,000 questionnaires accounting for the socio-economic characteristics of the tourists, their trip behaviour, and destination and time fixed effects. Results allow us to identify interesting characteristics of tourism of cultural activities making this product a good candidate to contribute to the sustainability of destinations.La cultura es la actividad preferida de los turistas de sol y playa que visitan las regiones del Mediterráneo español. Aumentar el conocimiento de los factores asociados a este tipo de demanda resulta clave para la renovación de estos destinos maduros. Con este objetivo aplicamos modelos probit a una muestra de datos de más de 200,000 cuestionarios, que recogen información sobre las características socio-económicas del turista, su patrón de viaje, y los propios efectos regionales y temporales del análisis. Los resultados de la investigación nos ayudan a identificar características propias del turismo de actividades culturales que lo convierten en un buen candidato para contribuir a mejorar la sostenibilidad de los destinos

Genetic Factors Involved in Cardiomyopathies and in Cancer

Cancer therapy-induced cardiomyopathy (CCM) manifests as left ventricular (LV) dysfunction and heart failure (HF). It is associated withparticular pharmacological agents and it is typically dose dependent, but significant individual variability has been observed. History of prior cardiac disease, abuse of toxics, cardiac overload conditions, age, and genetic predisposing factors modulate the degree of the cardiac reserve and the response to the injury. Genetic/familial cardiomyopathies (CMY) are increasingly recognized in general populations with an estimated prevalence of 1:250. Association between cardiac and oncologic diseases regarding genetics involves not only the toxicity process, but pathogenicity. Genetic variants in germinal cells that cause CMY (LMNA, RAS/MAPK) can increase susceptibility for certain types of cancer. The study of mutations found in cancer cells (somatic) has revealed the implication of genes commonly associated with the development of CMY. In particular, desmosomal mutations have been related to increased undifferentiation and invasiveness of cancer. In this article, the authors review the knowledge on the relevance of environmental and genetic background in CCM and give insights into the shared genetic role in the pathogenicity of the cancer process and development of CMY

Combination of late gadolinium enhancement and genotype improves prediction of prognosis in non-ischaemic dilated cardiomyopathy

Aims: Genotype and left ventricular scar on cardiac magnetic resonance (CMR) are increasingly recognized as risk markers for adverse outcomes in non-ischaemic dilated cardiomyopathy (DCM). We investigated the combined influence of genotype and late gadolinium enhancement (LGE) in assessing prognosis in a large cohort of patients with DCM. Methods and results: Outcomes of 600 patients with DCM (53.3 ± 14.1 years, 66% male) who underwent clinical CMR and genetic testing were retrospectively analysed. The primary endpoints were end-stage heart failure (ESHF) and malignant ventricular arrhythmias (MVA). During a median follow-up of 2.7 years (interquartile range 1.3–4.9), 24 (4.00%) and 48 (8.00%) patients had ESHF and MVA, respectively. In total, 242 (40.3%) patients had pathogenic/likely pathogenic variants (positive genotype) and 151 (25.2%) had LGE. In survival analysis, positive LGE was associated with MVA and ESHF (both, p < 0.001) while positive genotype was associated with ESHF (p = 0.034) but not with MVA (p = 0.102). Classification of patients according to genotype (G+/G−) and LGE presence (L+/L−) revealed progressively increasing events across L−/G−, L−/G+, L+/G− and L+/G+ groups and resulted in optimized MVA and ESHF prediction (p < 0.001 and p = 0.001, respectively). Hazard ratios for MVA and ESHF in patients with either L+ or G+ compared with those with L−/G− were 4.71 (95% confidence interval: 2.11–10.50, p < 0.001) and 7.92 (95% confidence interval: 1.86–33.78, p < 0.001), respectively. Conclusion: Classification of patients with DCM according to genotype and LGE improves MVA and ESHF prediction. Scar assessment with CMR and genotyping should be considered to select patients for primary prevention implantable cardioverter-defibrillator placementThis work was supported by grants from the Instituto de Salud Carlos III (ISCIII) (PI18/0004, PI19/01283, PI20/0320). (Co-funded by European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro Majadahonda, the Hospital Clinic, the Hospital Vall d’Hebron, the Hospital General Universitario Gregorio Marañón and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for rare, low-prevalence, and complex diseases of the heart (ERN GUARD-Heart). The CNIC is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). Conflict of interest: none declare