Atherogenic Ratios in Patients with Recurrent Acute Coronary Syndrome and Receiving Statin Therapy: Clinical Usefullness as Cardiovascular Predictors

Patients who have already suffered a vascular event require more and better control of cardiovascular risk factors. Different atherogenic indexes such as TC/HDLc, LDLc/HDLc, apoB/apoA-I, LDLc/apoB and non-HDLc/HDLc have been used to follow-up the patients because of their predictive capacity of the lipid profile. The aim of this study was to evaluate atherogenic ratios as a marker of the lipid residual risk in high-risk patients receiving statin therapy and to know the changes produced by previous lipid-lowering drugs treatment for a previous coronary event. The study including patients admitted to coronary care units of six Spanish tertiary hospitals for Acute Coronary Syndrome (ACS). A total of 633 ACS patients were included; of these, 478 (75.8%) had presented a myocardial infarction and 153 (24.2%) angina. A previous ACS had occurred in 43.1% of cases, and was the first episode in 56.9% of the studied patients. Among patients with known ischemic heart disease, 187 (52.2%) were receiving lipid-lowering drugs, mainlystatins (182 patients, 50.7%). Of those with a first ACS, 59 (21.7%) were on lipid-lowering drugs: 55 (20.1%) statins and 4 (1.7%) fibrates. Patients with recurrent ACS had similar triglyceride and HDLc levels, but significantly lower total cholesterol and LDLc concentrations compared with those presenting the first ACS. Patients with recurrent ACS had significantly lower non-HDLc levels, TC/HDLc and LDLc/HDLc, but higher HDLc/TC and HDLc/LDLc ratios compared with first ACS patients. In patients taking statins the lipid residual vascular risk was related with the persistence of cardiovascular risk factors, and related with lipid profile with dyslipemia no-LDL dependent. So, we can conclude that the correction of lipid profile by statin is not per se sufficient to control cardiovascular risk

Differential expression of circulating miRNAs as a novel tool to assess BAG3-associated familial dilated cardiomyopathy.

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in BAG3 gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy (DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant correlation with systolic and diastolic blood pressure, A wave, left atrium length, and left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination, suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show diagnostic value. Further studies will require long-term follow-up, and validation in larger populations.post-print729 K

Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify highrisk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value

Circulating circRNA as biomarkers for dilated cardiomyopathy etiology

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing - involving genetics, imaging, or cardiovascular techniques - makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed differentially among etiology-based DCM. The study was based on a case-control multicentric study. We enrolled 130 subjects: healthy controls (n = 20), idiopathic DCM (n = 30), ischemic DCM (n = 20), and familial DCM patients which included pathogen variants of (i) LMNA gene (n = 30) and (ii) BCL2-associated athanogene 3 (BAG3) gene (n = 30). Differentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and correlated to relevant systolic and diastolic parameters. The pathophysiological implications were explored through bioinformatics tools. Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confirm the discriminative capacity of circRNAs. The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker. Key messages The limitations of cardiac diagnostic imaging and the absence of a robust biomarker reveal the need for a diagnostic tool for dilated cardiomyopathy (DCM). The circular RNA (circRNA) expression pattern is paramount for categorizing the DCM etiologies. Our peripheral circRNAs fingerprint discriminates between various among etiology-based DCM and correlates with some echocardiographic parameters. We provide a potential non-invasive biomarker for the etiology-based diagnosis of LMNA-related DCM and ischemic DCM.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants in the framework of the European Regional Development Fund (ERDF) Integrated Territorial Initiative (ITI PI0048-2017 and ITI0033_2019), a clinical research grant from the Spanish Society of Cardiology for Basic Research in cardiology (PI0012_2019), COST (European Cooperation in Science and Technology) Action EUCardioRNA CA17129, and the Portuguese Foundation for Science and Technology (FCT) under the framework of the research grant PTDC-MED-GEN-29389-2017

Efecto de las variantes genéticas en apoa5 en la activación de la lipoproteina lipasa y su asociación al síndrome de quilomicronemia familiar

La lipoproteína Lipasa (LPL) tiene entre sus activadores a la APO-AV, aunque existe controversia sobre si esta resulta esencial en la activación de la enzima. Nuestro objetivo fue estudiar el efecto de determinadas variantes genéticas en APOA5 presentes en 4 pacientes con historia de Hipertrigliceridemia Grave (HTG) sobre la actividad de la Lipoproteína Lipasa post-heparina in vitro y su asociación con las manifestaciones clínicas del Síndrome de Quilomicronemia Familiar (SQF). Material y métodos: Para estudiar la capacidad de activación del suero cada paciente sobre la actividad Lipoproteína Lipasa, se añadieron cantidades crecientes del suero pre-heparina de cada paciente, como fuente de APO-AV, a la mezcla de reacción (10, 20 y 40 µL; pre-calentados a 56 °C durante 60 minutos con PMSF al 0.1% (m/v)). En cada ensayo enzimático a punto final se empleó LPL de un plasma post-heparina (100 U/Kg) procedente de un individuo sano. Por otro lado, se estableció el perfil apolipoproteico mediante turbidimetría, ELISA y ultracentrifugación secuencial, se estableció la presencia de HPLI mediante el cálculo del cociente de triglicéridos en quilomicrones entre triglicéridos en VLDL y se recogieron datos clínicos y antropométricos. Resultados: PACIENTE RESUMEN DE VARIANTES GENÉTICAS EN APOA5 1 Hom c.758T>C 2 het c.758T>C & c.326_327insC 3 Het c.990_993delAACA & c.289C>T 4 het c.289C>T & c.50-2ª>G Los pacientes 1, 2 y 3, presentaron HPLI, y hospitalizaciones por episodios de pancreatitis. Además, los sueros pre-heparina de estos pacientes no activaron significativamente la actividad LPL (p<0.05). En cambio, el paciente 4 no presentó HPLI, no tuvo episodios de pancreatitis y su plasma pre-heparina sí activó significativamente la actividad LPL (p<0.05). Conclusiones: En pacientes con historia clínica de HTG, determinadas variantes genéticas en APOA5 no activan a la LPL, asociándose además a la presencia de HPLI y a una clínica compatible con SQF.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Método para la identificación de pacientes con mayor riesgo de desarrollar miocardiopatías dilatada secundariaa mutaciones en el gen lamina A/C

[EN] The present invention relates to a signature of circulating miRNAs that allow patients with pathogenic mutations in the lamin A/C (LMNA) gene to be identified, said mutations being associated with dilated cardiomyopathy (DCM). This profile also allows differentiation between healthy subjects without pathogenic mutations and subjects who have pathogenic mutations but are still phenotypically negative for DCM, and between various aetiologies of the disease, idiopathic DCM and genetic DCM associated with mutations in the LMNA gene.[ES] La presente invención se refiere a firma de miRNA circulantes que permiten identificar pacientes con mutaciones patogénicas en el gen de LMNA asociadas a Miocardiopatía Dilatada (MCD). Este perfil también permite diferenciar entre sujetos sanos sin mutaciones patogénicas y aquellos sujetos portadores de mutaciones patogénicas pero aun fenotípicamente negativos para la MCD y entre diferentes etiología de la enfermedad, MCD idiopática y MCD genética asociada a mutaciones en el gen LMNA.[FR] La présente invention concerne une signature de miARM circulants permettant d'identifier des patients présentant des mutations pathogènes au niveau du gène de LMNA associées à une myocardiopathie dilatée (CMD). Ce profil permet également de distinguer des sujets sains sans mutation pathogène et des sujet poteurs de mutations pathogènes mais encore phénotypiquement négatifs à la CMD et différentes étiologies de la maladie, la CMD idiopathique et la CMD génétique associée à des mutations du gène LMNA.Peer reviewedUniversidad de Cádiz, Fundació Institut de Recerca - Hospital de la Santa Creu i Sant Pau,Consejo Superior de Investigaciones Científicas (España),Servicio andaluz de saludA1 Solicitud de patente con informe sobre el estado de la técnic

Marcadores para la miocardiopatía dilatada

Marcadores para la miocardiopatía dilatada. La presente invención se refiere a firma de miRNA circulantes que permiten identificar pacientes con mutaciones patogénicas en el gen de LMNA. Este perfil también permite diferenciar entre sujetos sanos sin mutaciones patogénicas y aquellos sujetos portadores de mutaciones patogénicas pero aun fenotípicamente negativos para la MCD. Además, dos de estos miRNAs, let-7a-5p y miR-145-5p, permiten discriminar entre diferentes etiología de la enfermedad, MCD idiopática y MCD familiar asociada a mutaciones en el gen LMNA. El potencial de estos miRNA como biomarcadores es superior al de marcadores establecidos en la práctica clínica como el NT-proBNP. Es una herramienta no invasiva y de fácil acceso para el cribado clínico de pacientes y familiares que carecen de una etiología clara.Peer reviewedUniversidad de Cádiz, Fundació Institut de Recerca - Hospital de la Santa Creu i Sant Pau,Consejo Superior de Investigaciones Científicas (España),Servicio andaluz de saludA1 Solicitud de patente con informe sobre el estado de la técnic

Impact of COVID-19 on Physical Activity and Lifestyles in Post-Confinement Sports Science Undergraduates

The aim of this study was to assess whether the infection by SARS-CoV-2 has significantly influenced physical activity, diet, alcohol, and drug consumption habits, as well as the quality of life of students of the bachelor&rsquo;s degree in Physical Activity and Sports Sciences. For this purpose, an online survey was conducted, which included socio-demographic questions related to the COVID-19 disease. Physical activity was analyzed using the International Physical Activity Questionnaire (IPAQ), adherence to the Mediterranean diet using the PREDIMED questionnaire, alcohol consumption using the AUDIT questionnaire, and drug consumption using the DAST-10 questionnaire. Health-related quality of life was analyzed with the SF-12 questionnaire. Our results reveal that those who engaged in either vigorous physical activity or, on the contrary, very low-intensity physical activity, were affected by the SARS-CoV-2 disease, which reduced the average weekly time they spent on their type of activity. However, those who previously performed moderate activities have managed to stay on the same fitness level despite having suffered from SARS-CoV-2 disease (p = 0.433). In conclusion, general health is affected by suffering from the COVID-19 disease, inadequate eating habits, substance use, and the performance of vigorous or very low-intensity of physical activity

Relationship between lipoprotein (a) and micro/macro complications in type 2 diabetes mellitus: a forgotten target.

OBJECTIVES: Increased lipoprotein (a) serum concentrations seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein (a) and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. METHODS: This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data (insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro- and macrovascular complications were collected. RESULTS: Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein (a) was 22.2 ± 17.3 mg/dL (22.1 ± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females). Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein (a). Similarly, the patients with hyperlipoprotein (a) (≥ 30 mg/dL) presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein (a) is positively correlated with coronary heart disease and diabetic nephropathy (P < 0.01 and P < 0.005, respectively). CONCLUSIONS: The elevation of plasma levels of lipoprotein (a) are associated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein (a) may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus