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

Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population

Depto. de Química FísicaFac. de Ciencias QuímicasTRUEpu

Metabolically Healthy Obesity: Presence of Arterial Stiffness in the Prepubescent Population

Aim: Arteriosclerotic cardiovascular disease, one of the world’s leading causes of death, first manifests itself at an early age. The identification of children who may have increased cardiovascular risk in the future could be an important prevention strategy. Our aim was to assess the clinical, analytical, and dietary variables associated with arterial stiffness (AS), measured by carotid-femoral pulse wave velocity (cfPWV) in a prepubescent population with metabolically healthy obesity (MHO). Subjects and Methods: A cross-sectional study in prepubescent subjects with obesity who had ≤1 metabolic syndrome criteria (abdominal perimeter and blood pressure ≥90th percentile, triglycerides >150 mg/dL, HDL-cholesterol < 0.0001), BMI (r = 0.44; p < 0.0001), WHtR (r = 0.26; p = 0.02), fasting insulin levels (r = 0.28; p = 0.02), and insulin resistance (Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index) (r = 0.25; p = 0.04). Multiple linear regression analysis identified BMI and HOMA-IR as independent parameters associated with cfPWV. Conclusions: Prepubescent children with obesity who were shown to be metabolically healthy presented with arterial stiffness, which is closely related to BMI and the state of insulin resistance.This work was supported by grants from the Instituto de Salud Carlos III, cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER (“Centros de Investigación En Red” (CIBER, CB06/03/0018)). M Rosa Bernal-Lopez was supported by the “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER.Ye

Epigenetic approach in obesity: DNA methylation in a prepubertal population which underwent a lifestyle modification

Background: Metabolically healthy obesity (MHO) is a considerably controversial concept as it is considered a transitory condition towards the development of different pathologies (type 2 diabetes, insulin resistance, or cardiovascular disease). MHO is closely related to lifestyle and environmental factors. Epigenetics has become an essential biological tool to analyze the link between obesity and metabolic status. The aim of this study was to determine whether MHO status is conditioned by the DNA methylation (DNAm) of several genes related to lipid metabolism (lipoprotein lipase, retinoid X receptor alpha, liver X receptor, stearoyl-CoA desaturase, sterol regulatory element binding factor 1), and inflammation (LEP) in peripheral blood mononuclear cells (PBMCs) from 131 prepubertal subjects with MHO phenotype after lifestyle modifications with personalized Mediterranean diet (MedDiet) combined with a physical activity (PA) program. Results: The DNAm of all studied genes were significantly modified in the population after 12 months of lifestyle modifications (MedDiet and PA). In addition, associations were found between the DNAm studies and BMI, homeostatic model assessment of insulin resistance, monounsaturated fatty acid and polyunsaturated fatty acid, moderate-vigorous PA, fat mass, and adherence to MedDiet. Conclusions: It was found that DNAm of genes related to lipid metabolism and inflammation are also present in childhood and that this methylation profile can be modified by interventions based on MedDiet and PA.This work was supported by grants from the Instituto de Salud Carlos III, cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER (“Centros de Investigación En Red” (CIBER, CB06/03/0018)). M Rosa Bernal-Lopez was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER.Ye

Metabolically healthy obesity: Inflammatory biomarkers and adipokines in elderly population.

Obesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain). Subjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C 166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p Healthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders

Comparison between the CO-Synch and J-Synch protocols for follicular dynamics, interval to ovulation, progesterone concentration, and pregnancy in beef heifers

Protocolos que combinan estradiol, GnRH, prostaglandina y progesterona son utilizados para realizar inseminación artificial a tiempo fijo (IATF). Se comparó la dinámica folicular, la progesterona plasmática y la ovulación entre vaquillonas británicas (Experimento 1, n = 46), la preñez entre vaquillonas británicas (Experimento 2, n = 130) y la preñez entre cruzas índicas (Experimento 3, n = 499) sincronizadas con JSynch o CO-Synch. J-Synch inició el día 0 con benzoato de estradiol y dispositivo intravaginal de progesterona (DIP), retiro del DIP y prostaglandina el día 6 e IATF y GnRH el día 9. CO-Synch inició con DIP el día 1, retiro del DIP y prostaglandina el día 6 e IATF y GnRH el día 9. El tamaño del folículo dominante (P = 0,01) y la progesterona plasmática al retiro del DIP (P = 0,02) fueron mayores para CO-Synch. No hubo diferencias en el intervalo a la ovulación (P = 0,70). Vaquillonas británicas se preñaron un 52,38 % con J-Synch y 46,27 % con CO-Synch (P = 0,50) y vaquillonas cruzas índicas 37,80 % con J-Synch y 40,41 % con CO-Synch (P = 0,60). En conclusión, no observamos diferencias de fertilidad en vaquillonas para carne sincronizadas con J-Synch o CO-Synch.Protocols using estradiol, GnRH, prostaglandin, and progesterone are used to conduct timed-artificial insemination (TAI). Follicular development, progesterone, and ovulation in Bos taurus (Experiment 1, n = 46) and pregnancy in Bos taurus (Experiment 2, n = 130) and Bos taurus x Bos indicus crossbred (Experiment 3, n = 499) heifers was compared between protocols J-Synch and COSynch. J-Synch protocol consisted in estradiol benzoate and an intravaginal progesterone device (IPD) on day 0, removal of IPD and prostaglandin on day 6, and GnRH/TAI on day 9. CO-Synch protocol consisted in a IPD on day 1, removal of IPD and prostaglandin on day 6, and GnRH/TAI on day 9. The size of the dominant follicle (P = 0,01) and plasmatic progesterone at IPD removal (P = 0,02) was greater for CO-Synch. There was no difference in time of ovulation (P = 0,70). Pregnancy per TAI was 52,38 % for J-Synch and 46,27 % for CO-Synch in Bos taurus heifers (P = 0,50) and 37,80 % for J-Synch and 40,41 % for COSynch (P = 0,60) in Bos taurus x Bos indicus crossbred heifers. In conclusion, no differences in fertility were detected in beef heifers synchronized with a J-Synch or CO-Synch protocol.Fil: Troncoso, Maria Cristina. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Bilbao, María Guillermina. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; ArgentinaFil: Zapata, Luis Oscar. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Gelid, Lucas Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional La Pampa-San Luis. Estación Experimental Agropecuaria Anguil; ArgentinaFil: Farcey, Maria Florencia. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Moran, Karen Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; Argentina. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Romero Harry, Hernán. Instituto Nacional de Tecnología Agropecuaria. Centro Regional La Pampa-San Luis. Estación Experimental Agropecuaria Anguil; ArgentinaFil: Perez, Wallace S.. Syntex. S.a.; ArgentinaFil: Ludueña, Martín. Actividad Privada; ArgentinaFil: Vilches, Alejandro. Actividad Privada; ArgentinaFil: Franco, Gabriel. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Calvo, C.. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; ArgentinaFil: Bartolomé, Julián Alberto. Universidad Nacional de La Pampa. Facultad de Ciencias Veterinarias; Argentin

Lifestyle Modification Program on a Metabolically Healthy Elderly Population with Overweight/Obesity, Young-Old vs. Old-Old. CONSEQUENCES of COVID-19 Lockdown in This Program

The SARS-CoV-2 pandemic led to lockdowns, which affected the elderly, a high-risk group. Lockdown may lead to weight gain due to increased food intake and reduced physical activity (PA). Our study aimed to analyze the impact of a 12-month lifestyle intervention on a metabolically healthy overweight/obese elderly (MHOe) population and how the lockdown by COVID-19 affected this program. Methods: MHOe participants (65-87 years) were recruited to participate in a lifestyle modification intervention based on the Mediterranean diet (MedDiet) and regular PA. Participants were classified into two groups: young-old (<75 years) or old-old (≥75 years). Anthropometric and clinical characteristics, energy intake, and energy expenditure were analyzed at baseline and after 12 months of intervention. Results: The final sample included 158 MHOe participants of both sexes (age: 72.21 ± 5.04 years, BMI: 31.56 ± 3.82 kg/m2): 109 young-old (age: 69.26 ± 2.83 years, BMI: 32.0 ± 3.85 kg/m2) and 49 old-old (age: 78.06 ± 2.88 years, BMI: 30.67 ± 3.64 kg/m2). After 12 months of intervention and despite lockdown, the young-old group increased MedDiet adherence (+1 point), but both groups drastically decreased daily PA, especially old-old participants. Fat mass significantly declined in the total population and the young-old. Depression significantly increased (26.9% vs. 21.0%, p < 0.0001), especially in the old-old (36.7% vs. 22.0%, p < 0.0001). No significant changes were found in the glycemic or lipid profile. Conclusions: This study indicates that ongoing MedDiet intake and regular PA can be considered preventative treatment for metabolic diseases in MHOe subjects. However, mental health worsened during the study and should be addressed in elderly individuals.This work was supported by grants from the Instituto de Salud Carlos III, co-funded by the Fondo Europeo de Desarrollo Regional-FEDER “Centros de Investigación En Red” (CIBER, CB06/03/0018) and PI18/00766. M Rosa Bernal-Lopez was supported by the “Miguel Servet Type II” program (CPII/00014) and the “Nicolas Monardes” program (C1-0005-2020). Lidia Cobos Pala cios and Jaime Sanz Cánovas were supported by the “Rio Hortega” program (CM20/00125 and CM20/00212, respectively) from the ISCIII-Madrid (Spain), co-funded by the Fondo Europeo de Desarrollo Regional-FEDER. Monica Muñoz Ubeda was supported by Consejeria de Salud, Junta de Andalucía (RH-0100-2020).Ye

A healthy lifestyle is associated with lower arterial stiffness in a metabolically healthy elderly population with overweight or obesity

Depto. de Química FísicaFac. de Ciencias QuímicasTRUEpu