Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

On the Role of Personality in Successful Aging: A Scoping Review.

BACKGROUND AND OBJECTIVES: This study aimed to critically examine current knowledge on the role of personality in successful aging, considering Hooker and McAdams' 3-level, 6-foci model of personality. The aim was also to pinpoint knowledge gaps that research should address in the future. RESEARCH DESIGN AND METHODS: We carried out a scoping review of the literature on successful aging and personality, following the 5-step framework proposed by Arksey and O'Malley and further expanded by Levac et al. RESULTS: Research into the role of personality in successful aging has grown significantly over the last 20 years. However, the increasing number of publications on the topic was primarily accounted for by studies focused on Layer 1 and particularly Layer 2 of McAdams' model of personality, with Layer 3 being scarcely addressed. Research that included more than 1 layer of personality was rare. DISCUSSION AND IMPLICATIONS: Our study pinpointed gaps that should be considered in future research in this area. These gaps were related to advancing toward agreed-upon definitions of successful aging and personality, broadening the scope of research on this topic, and integrating personality dimensions on research on successful aging.

Development and Validation of a Risk Score for Predicting Non-Adherence to Antiretroviral Therapy.

Several patient-related factors that influence adherence to antiretroviral therapy (ART) have been described. However, studies that propose a practical and simple tool to predict nonadherence after ART initiation are still scarce. In this study, we develop and validate a score to predict the risk of nonadherence in people starting ART. The model/score was developed and validated using a cohort of people living with HIV starting ART at the Hospital del Mar, Barcelona, between 2012 and 2015 (derivation cohort) and between 2016 and 2018 (validation cohort),. Adherence was evaluated every 2 months using both pharmacy refills and patient self-reports. Nonadherence was defined as taking <90% of the prescribed dose and/or ART interruption for more than 1 week. Predictive factors for nonadherence were identified by logistic regression. Beta coefficients were used to develop a predictive score. Optimal cutoffs were identified using the bootstrapping methodology, and performance was evaluated with the C statistic. Our study is based on 574 patients: 349 in the derivation cohort and 225 in the validation cohort. A total of 104 patients (29.8%) of the derivation cohort were nonadherent. Nonadherence predictors were patient prejudgment; previous medical appointment failures; cultural and/or idiomatic barriers; heavy alcohol use; substance abuse; unstable housing; and severe mental illness. The cutoff point (receiver operating characteristic curve) for nonadherence was 26.3 (sensitivity 0.87 and specificity 0.86). The C statistic (95% confidence interval) was 0.91 (0.87-0.94). These results were consistent with those predicted by the score in the validation cohort. This easy-to-use, highly sensitive, and specific tool could be easily used to identify patients at highest risk for nonadherence, thus allowing resource optimization and achieving optimal treatment goals.

[Influence of gender and place of residence differences on the evolution and mortality of ischemic cardiopathy in Catalonia: a population-based study.] / Influencia del género y el lugar de residencia sobre la evolución y mortalidad de la cardiopatía isquémica en Cataluña: un estudio de base poblacional.

OBJECTIVE: Some bibliography supports a diagnostic and therapeutic delay in women with high cardiovascular risk. The objective of this paper was to know the incidence of cardiovascular disease (CVD) and mortality in a cohort with Metabolic Syndrome (MetS); analyze possible differences in gender and place of residence, regarding the performance of primary angioplasties in patients with ischemic heart disease (IHD). METHODS: Population cohort study, with SIDIAP database (Sistema de Información para la Investigación en Atención Primaria), in primary care in Catalonia. We selected people of both sexes, between 35-75 years old, exempt from CVD at the beginning (2009), fulfilling MetS criteria (NCEP-ATPIII-National Cholesterol Education Program-Adult Treatment Panel III- criteria diagnoses). We performed descriptive statistics, and ANOVA and Chi-square test to evaluate differences between variables. RESULTS: 167,673 people met MetS criteria (5.2% of the population), 105,969 men (63.2%). 22% of the population belonged to rural areas. Those urban areas with the most socioeconomic differences (urban-1 and urban-5) exhibited the highest incidences of CVD and IHD. We registered 51,129 CVD (30.7%) of which 8,889 were acute myocardial infarctions (AMI) (5,3%) and 24,284 were IHD (14,5%). 1.758 primary angioplasties procedures were performed, 1,467 in men and 291 in women, representing, respectively, 4.4% and 0.9% (p<0.005). CONCLUSIONS: The incidence of IHD and AMI in subjects with MetS is high in Catalonia. There is a difference in the angioplasties performed, according to sex and place of residence. Probably a practical implication would be to detect IHD in time in women with MetS, so that they can benefit from revascularization therapy in the same way as men.

OBJETIVO: Existe bibliografía que apoya un retraso diagnóstico y terapéutico en mujeres con alto riesgo cardiovascular. El objetivo de este trabajo fue conocer la incidencia de la enfermedad cardiovascular (ECV) y la mortalidad en una cohorte con Síndrome Metabólico (SM), así como analizar posibles diferencias de género y lugar de residencia, respecto a la realización de angioplastias primarias en pacientes con cardiopatía isquémica (CI). METODOS: Se realizó un estudio de cohorte poblacional apoyándonos en la base de datos SIDIAP (Sistema de Información para la Investigación en Atención Primaria), en Atención Primaria de Cataluña. Seleccionamos personas de ambos sexos, entre 35-75 años, exentos de ECV al inicio (2009), cumpliendo criterios de SM (diagnósticos NCEP-ATPIII [National Cholesterol Education Program-Adult Treatment Panel III]). La variable resultado fue la incidencia a 10 años de ECV y la mortalidad global por toda causa. Registramos variables sociodemográficas (edad, sexo, fenotipo SM, índice socioeconómico MEDEA) y reperfusión coronaria. Se realizó estadística descriptiva, ANOVA y prueba de chi-cuadrado para verificar la diferencia entre variables. RESULTADOS: 167.673 personas cumplieron criterios de SM (5,2% de la población), de las cuales había 105.969 hombres (63,2%). El 22% de población pertenecía a áreas rurales. Aquellas áreas urbanas más dispares socioeconómicamente (urbana-1 y urbana-5), exhibieron las mayores incidencias de ECV y CI. Registramos 51.129 ECV (30,7%) de los cuales 8.889 fueron infartos agudos de miocardio (IAM; 5,3%) y 24.284 fueron CI (14,5%). Se realizaron 1.758 procedimientos de angioplastia primaria, 1.467 en hombres y 291 en mujeres, representando respectivamente un 4,4% y un 0,9% (p<0.005). CONCLUSIONES: La incidencia de IAM y CI en sujetos con SM es alta en Cataluña. Existe diferencia estadísticamente significativa en las angioplastias realizadas, según sexo y lugar de residencia. Probablemente una implicación práctica sería detectar a tiempo la CI en mujeres con SM, para que puedan beneficiarse de la terapia revascularizadora igual que los hombres.

Influencia del género y el lugar de residencia sobre la evolución y mortalidad de la cardiopatía isquémica en Cataluña: un estudio de base poblacional / Influence of gender and place of residence differences on the evolution and mortality of ischemic cardiopathy in Catalonia: a population-based study

FUNDAMENTOS: Existe bibliografía que apoya un retraso diagnóstico y terapéutico en mujeres con alto riesgo cardiovascular. El objetivo de este trabajo fue conocer la incidencia de la enfermedad cardiovascular (ECV) y la mortalidad en una cohorte con Síndrome Metabólico (SM), así como analizar posibles diferencias de género y lugar de residencia, respecto a la realización de angioplastias primarias en pacientes con cardiopatía isquémica (CI). MÉTODOS: Información para la Investigación en Atención Primaria), en Atención Primaria de Cataluña. Seleccionamos personas de ambos sexos, entre 35-75 años, exentos de ECV al inicio (2009), cumpliendo criterios de SM (diagnósticos NCEP-ATPIII [National Cholesterol Education Program-Adult Treatment Panel III]). La variable resultado fue la incidencia a 10 años de ECV y la mortalidad global por toda causa. Registramos variables sociodemográficas (edad, sexo, fenotipo SM, índice socioeconómico MEDEA) y reperfusión coronaria. Se realizó estadística descriptiva, ANOVA y prueba de chi-cuadrado para verificar la diferencia entre variables. RESULTADOS: 167.673 personas cumplieron criterios de SM (5,2% de la población), de las cuales había 105.969 hombres (63,2%). El 22% de población pertenecía a áreas rurales. Aquellas áreas urbanas más dispares socioeconómicamente (urbana-1 y urbana-5), exhibieron las mayores incidencias de ECV y CI. Registramos 51.129 ECV (30,7%) de los cuales 8.889 fueron infartos agudos de miocardio (IAM; 5,3%) y 24.284 fueron CI (14,5%). Se realizaron 1.758 procedimientos de angioplastia primaria, 1.467 en hombres y 291 en mujeres, representando respectivamente un 4,4% y un 0,9% (p<0.005). CONCLUSIONES: La incidencia de IAM y CI en sujetos con SM es alta en Cataluña. Existe diferencia estadísticamente significativa en las angioplastias realizadas, según sexo y lugar de residencia...(AU)

BACKGROUND: Some bibliography supports a diagnostic and therapeutic delay in women with high cardiovascular risk. The objective of this paper was to know the incidence of cardiovascular disease (CVD) and mortality in a cohort with Metabolic Syndrome (MetS); analyze possible differences in gender and place of residence, regarding the performance of primary angioplasties in patients with ischemic heart disease (IHD). METHODS: Population cohort study, with SIDIAP database (Sistema de Información para la Investigación en Atención Primaria), in primary care in Catalonia. We selected people of both sexes, between 35-75 years old, exempt from CVD at the beginning (2009), fulfilling MetS criteria (NCEP-ATPIII-National Cholesterol Education Program-Adult Treatment Panel III- criteria diagnoses). We performed descriptive statistics, and ANOVA and Chi-square test to evaluate differences between variables. RESULTS: 167,673 people met MetS criteria (5.2% of the population), 105,969 men (63.2%). 22% of the population belonged to rural areas. Those urban areas with the most socioeconomic differences (urban-1 and urban-5) exhibited the highest incidences of CVD and IHD. We registered 51,129 CVD (30.7%) of which 8,889 were acute myocardial infarctions (AMI) (5,3%) and 24,284 were IHD (14,5%). 1.758 primary angioplasties procedures were performed, 1,467 in men and 291 in women, representing, respectively, 4.4% and 0.9% (p<0.005). CONCLUSIONS: The incidence of IHD and AMI in subjects with MetS is high in Catalonia. There is a difference in the angioplasties performed, according to sex and place of residence. Probably a practical implication would be to detect IHD in time in women with MetS, so that they can benefit from revascularization therapy in the same way as men.

Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada / Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction

Antecedentes:El antígeno carbohidrato 125 (CA125) ha emergido como un nuevo biomarcador en insuficiencia cardiaca. El objetivo del estudio es determinar si los niveles séricos de CA125 predicen la mortalidad y reingresos totales a un año en pacientes mayores de 70 años e insuficiencia cardiaca aguda (ICA) con fracción de eyección preservada (FEP).Métodos:Estudio observacional prospectivo multicéntrico, que incluyó a 359 pacientes (edad media 81,5 años). La variable de valoración principal fue la mortalidad total por todas las causas y lo reingresos totales por ICA a un año. El análisis de regresión binomial negativa se utilizó para evaluar la asociación entre los valores de CA125 y el pronóstico.Resultados:Al año de seguimiento, se registraron 87 muertes (24,2%). Los pacientes del cuartil inferior de CA125 presentaron una tasa bruta de mortalidad menor (14,4%, 26,7, 26,7 y 29,2; p=0,090). Tras un análisis multivariado, el valor de CA125 se asoció de forma casi lineal y positiva a un mayor riesgo de mortalidad (p=0,009). Dicha asociación fue también positiva pero estadísticamente límite en el caso de los reingresos totales por ICA (p=0,089).Conclusiones:En población mayor de 70 años hospitalizada por ICA con FEP, los niveles elevados de CA125 se asocian a un aumento del riesgo de muerte a un año de seguimiento. La asociación con los reingresos fue más incierta. Los niveles bajos de CA125 identifica un subgrupo de pacientes de bajo riesgo. (AU)

Background:Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF).Methods:Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints.Results:At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089).Conclusions:In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk. (AU)

Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension.

AIMS: Prior studies have not fully characterized the haemodynamic effects of the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF-PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS-HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF-PH treated with sacubitril/valsartan. METHODS AND RESULTS: This single-arm, investigator-initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF-PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre-ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods. CONCLUSIONS: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH.

Carbohydrate antigen 125 (CA125) as a prognostic marker in the elderly with acute heart failure and preserved ejection fraction. / Antígeno carbohidrato 125 (CA125) como marcador pronóstico en ancianos con insuficiencia cardiaca aguda y fracción de eyección preservada.

BACKGROUND: Carbohydrate antigen 125 (CA125) has emerged as a new biomarker in heart failure. The objective of the study is to determine whether serum CA125 levels predict total mortality and readmissions at one year in patients >70 years old with acute heart failure (AHF) and preserved ejection fraction (PEF). METHODS: Multicenter prospective observational study, which included 359 patients (mean age 81.5 years). The primary endpoint was total all-cause mortality and total readmissions for AHF at 1 year. A negative binomial regression technique was used to evaluate the association between CA125 and both endpoints. RESULTS: At one year of follow-up, 87 deaths (24.2%) were registered. The patients in the lower quartile of CA125 had a lower crude mortality rate (14.4%, 26.7, 26.7, 29.2; p=0.09). After multivariate analysis, the CA125 value was positively associated with a higher risk (p=0.009). Such association was also positive but borderline significant for the risk of readmissions (p=0.089). CONCLUSIONS: In a population older than 70 years hospitalized for AHF with PEF, elevated levels of CA125 are associated with an increased risk of death at one year of follow-up. The association with readmission for AHF was more uncertain. Low levels of CA125 identifies a subgroup at low-risk.

Community Risk Factors in the COVID-19 Incidence and Mortality in Catalonia (Spain). A Population-Based Study.

The heterogenous distribution of both COVID-19 incidence and mortality in Catalonia (Spain) during the firsts moths of the pandemic suggests that differences in baseline risk factors across regions might play a relevant role in modulating the outcome of the pandemic. This paper investigates the associations between both COVID-19 incidence and mortality and air pollutant concentration levels, and screens the potential effect of the type of agri-food industry and the overall land use and cover (LULC) at area level. We used a main model with demographic, socioeconomic and comorbidity covariates highlighted in previous research as important predictors. This allowed us to take a glimpse of the independent effect of the explanatory variables when controlled for the main model covariates. Our findings are aligned with previous research showing that the baseline features of the regions in terms of general health status, pollutant concentration levels (here NO2 and PM10), type of agri-food industry, and type of land use and land cover have modulated the impact of COVID-19 at a regional scale. This study is among the first to explore the associations between COVID-19 and the type of agri-food industry and LULC data using a population-based approach. The results of this paper might serve as the basis to develop new research hypotheses using a more comprehensive approach, highlighting the inequalities of regions in terms of risk factors and their response to COVID-19, as well as fostering public policies towards more resilient and safer environments.

[Markers of myocardial injury in the prediction of short-term COVID-19 prognosis]. / Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT > 14 ng/L, the upper 99th percentile. Levels of NT-proBNP > 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

Markers of myocardial injury in the prediction of short-term COVID-19 prognosis.

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT> 14ng/L, the upper 99th percentile. Levels of NT-proBNP> 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT.

Trends in Short- and Long-Term ST-Segment-Elevation Myocardial Infarction Prognosis Over 3 Decades: A Mediterranean Population-Based ST-Segment-Elevation Myocardial Infarction Registry.

Background Coronary artery disease remains a major cause of death despite better outcomes of ST-segment-elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti-STEMI registry of in-hospital, 28-day, and 1-year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis. Methods and Results Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28-day and 1-year STEMI mortality and in-hospital complication trends across these periods. Mean patient age was 61.6±12.6 years, and 79.3% were men. The 28-day all-cause mortality declined from period 1 to period 5 (10.4% versus 6.0%; P<0.001), with a 40% reduction after multivariable adjustment (hazard ratio [HR], 0.6; 95% CI, 0.46-0.80; P<0.001). One-year all-cause mortality declined from period 1 to period 5 (11.7% versus 9.0%; P=0.001), with a 24% reduction after multivariable adjustment (HR, 0.76; 95% CI, 0.60-0.98; P=0.036). A significant temporal reduction was observed for in-hospital complications including postinfarct angina (-78%), ventricular tachycardia (-57%), right ventricular dysfunction (-48%), atrioventricular block (-45%), pericarditis (-63%), and free wall rupture (-53%). Primary ventricular fibrillation showed no significant downslope trend. Conclusions In-hospital STEMI complications and 28-day and 1-year mortality rates have dropped markedly in the past 30 years. Reducing ischemia-driven primary ventricular fibrillation remains a major challenge.

Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction.

OBJECTIVE: Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. METHODS: We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. RESULTS: Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). CONCLUSIONS: Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older.

Short- and Long-Term Mortality Trends in STEMI-Cardiogenic Shock over Three Decades (1989-2018): The Ruti-STEMI-Shock Registry.

AIMS: Cardiogenic shock (CS) is an ominous complication of ST-elevation myocardial infarction (STEMI), despite the recent widespread use of reperfusion and invasive management. The Ruti-STEMI-Shock registry analysed the prevalence of and 30-day and 1-year mortality rates in ST-elevation myocardial infarction (STEMI) complicated by CS (STEMI-CS) over the last three decades. METHODS AND RESULTS: From February 1989 to December 2018, 493 STEMI-CS patients were consecutively admitted in a well-defined geographical area of ~850,000 inhabitants. Patients were classified into six five-year periods based on their year of admission. STEMI-CS mortality trends were analysed at 30 days and 1 year across the six strata. Cox regression analyses were performed for comparisons. Mean age was 67.5 ± 11.7 years; 69.4% were men. STEMI-CS prevalence did not decline from period 1 to 6 (7.1 vs. 6.2%, p = 0.218). Reperfusion therapy increased from 22.5% in 1989-1993 to 85.4% in 2014-2018. Thirty-day all-cause mortality declined from period 1 to 6 (65% vs. 50.5%, p < 0.001), with a 9% reduction after multivariable adjustment (HR: 0.91; 95% CI: 0.84-0.99; p = 0.024). One-year all-cause mortality declined from period 1 to 6 (67.5% vs. 57.3%, p = 0.001), with an 8% reduction after multivariable adjustment (HR: 0.92; 95% CI: 0.85-0.99; p = 0.030). Short- and long-term mortality trends in patients aged ≥ 75 years remained ~75%. CONCLUSIONS: Short- and long-term STEMI-CS-related mortality declined over the last 30 years, to ~50% of all patients. We have failed to achieve any mortality benefit in STEMI-CS patients over 75 years of age.

Association of Circulating microRNAs with Coronary Artery Disease and Usefulness for Reclassification of Healthy Individuals: The REGICOR Study.

Risk prediction tools cannot identify most individuals at high coronary artery disease (CAD) risk. Oxidized low-density lipoproteins (oxLDLs) and microRNAs are actively involved in atherosclerosis. Our aim was to examine the association of CAD and oxLDLs-induced microRNAs, and to assess the microRNAs predictive capacity of future CAD events. Human endothelial and vascular smooth muscle cells were treated with oxidized/native low-density lipoproteins, and microRNA expression was analyzed. Differentially expressed and CAD-related miRNAs were examined in serum samples from (1) a case-control study with 476 myocardial infarction (MI) patients and 487 controls, and (2) a case-cohort study with 105 incident CAD cases and 455 randomly-selected cohort participants. MicroRNA expression was analyzed with custom OpenArray plates, log rank tests and Cox regression models. Twenty-one microRNAs, two previously undescribed (hsa-miR-193b-5p and hsa-miR-1229-5p), were up- or down-regulated upon cell treatment with oxLDLs. One of the 21, hsa-miR-122-5p, was also upregulated in MI cases (fold change = 4.85). Of the 28 CAD-related microRNAs tested, 11 were upregulated in MI cases -1 previously undescribed (hsa-miR-16-5p)-, and 1/11 was also associated with CAD incidence (adjusted hazard ratio = 0.55 (0.35-0.88)) and improved CAD risk reclassification, hsa-miR-143-3p. We identified 2 novel microRNAs modulated by oxLDLs in endothelial cells, 1 novel microRNA upregulated in AMI cases compared to controls, and one circulating microRNA that improved CAD risk classification.

Impact of Preoperative Measurement of Right Heart Chambers in the Evaluation of Pulmonary Hypertension Following Aortic Valve Replacement.

BACKGROUND: Severe pulmonary hypertension (PH) in patients with aortic stenosis is related to poor prognosis following aortic valve replacement (AVR). Current European PH guidelines recommend adding two different echocardiographic signs to tricuspid regurgitation velocity (TRV) in PH estimation, classifying its probability as low (TRV ≤ 2.8 m/s), intermediate (TRV 2.9-3.4 m/s), and high (TRV > 3.4 m/s). The right ventricle is an important determinant of prognosis in PH. The goal of this study was to analyze the value of right atrial area > 18 cm2 and right ventricular/left ventricular ratio > 1 in the long-term prognosis following AVR, mainly in the intermediate probability group. METHODS: This study included 429 consecutive patients (mean age, 73 ± 8 years; 55% male) with a median follow-up of 4.25 years (completed in 98%). Patients were divided into low (n = 247), intermediate (n = 117), and high probability groups (n = 65). The intermediate probability group was divided into two subgroups: subgroup 2a (n = 27; TRV nonmeasurable or ≤ 2.8 m/s and two signs present) and subgroup 2b (n = 90; TRV 2.9-3.4 m/s, and none or only one sign present). RESULTS: Overall mortality rates during follow-up of the low, intermediate, and high probability groups were 24%, 32%, and 42%, respectively. High PH probability was an independent predictor of all-cause mortality (hazard ratio [HR], 1.82; 95% CI, 1.11-3.00), but the intermediate probability group did not reach significance following multivariate analysis (HR, 1.40; 95% CI, 0.91-2.16). When the intermediate probability group was divided into subgroups, the subgroup 2a mortality rate (56%) was higher than that of both subgroup 2b (24%; P = .002) and the low probability group (24%; P < .001). Following multivariate analysis, subgroup 2a showed a significantly higher mortality (HR, 2.13; 95% CI, 1.11-4.10) in contrast to subgroup 2b (HR, 1.24; 95% CI, 0.75-2.05), both compared with the low probability group. CONCLUSIONS: Incorporating measurement of the right cavities into the PH probability model in the assessment of long-term prognosis following AVR allowed better risk discrimination, especially in the intermediate probability group.

Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients.

Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV-specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D-R-) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell-associated markers (ie, NKG2A, CD57, Immunoglobulin-like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan-Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV-specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.

Marcadores de daño miocárdico en la predicción del pronóstico a corto plazo de los pacientes con COVID-19 / Markers of myocardial injury in the prediction of short-term COVID-19 prognosis

INTRODUCCIÓN Y OBJETIVOS: La información sobre el daño miocárdico en la población con COVID-19 es muy escasa. Nuestro objetivo fue evaluar el daño cardiaco en pacientes con COVID-19 y determinar la correlación entre las concentraciones de troponina T ultrasensible (TnT-us) y fracción aminoterminal del propéptido natriurético cerebral (NT-proBNP) con la gravedad del COVID-19. MÉTODOS: Se incluyó a 872 pacientes consecutivos con COVID-19 confirmada desde febrero a abril de 2020. Se determinó al ingreso la TnT-us a 651 pacientes y la NT-proBNP a 506. El daño miocárdico se definió como una TnT-us> 14 ng/l,> percentil 99. La cifras de NT-proBNP> 300 pg/ml se consideraron relacionadas con daño miocárdico. El objetivo primario es muerte o ventilación mecánica (VM) a 30 días. RESULTADOS: Se observó daño miocárdico según la TnT-us en el 34,6%. Las tasas del evento muerte o VM fue superior en los pacientes con daño miocárdico (el 39,1 frente al 9,1%). Los valores de TnT-us y NT-proBNP fueron predictores independientes de muerte o VM (HR=2,18; IC95%, 1,23-3,83, y HR=1,87; IC95%, 1,05-3,36), y de mortalidad total (HR=2,91; IC95%, 1,211-7,04, y HR=5,47; IC95%, 2,10-14,26). Se observó que la NT-proBNP mejoró de manera significativa el modelo predictivo de la troponina para muerte o VM (estadístico C, 0,83-0,84) y mortalidad total (estadístico C, 0,85-0,87). CONCLUSIONES: El daño miocárdico analizado al ingreso se observó con frecuencia entre los pacientes con COVID-19 y es un potente predictor de muerte y necesidad de VM. La NT-proBNP mejoró la precisión pronóstica de la determinación de troponina

INTRODUCTION AND OBJECTIVES: COVID-19 is currently causing high mortality and morbidity worldwide. Information on cardiac injury is scarce. We aimed to evaluate cardiovascular damage in patients with COVID-19 and determine the correlation of high-sensitivity cardiac-specific troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) with the severity of COVID-19. METHODS: We included 872 consecutive patients with confirmed COVID-19 from February to April 2020. We tested 651 patients for high-sensitivity troponin T (hs-TnT) and 506 for NT-proBNP on admission. Cardiac injury was defined as hs-TnT> 14 ng/L, the upper 99th percentile. Levels of NT-proBNP> 300 pg/mL were considered related to some extent of cardiac injury. The primary composite endpoint was 30-day mortality or mechanical ventilation (MV). RESULTS: Cardiac injury by hs-TnT was observed in 34.6% of our COVID-19 patients. Mortality or MV were higher in cardiac injury than noncardiac injury patients (39.1% vs 9.1%). Hs-TnT and NT-proBNP levels were independent predictors of death or MV (HR, 2.18; 95%CI, 1.23-3.83 and 1.87 (95%CI, 1.05-3.36), respectively) and of mortality alone (HR, 2.91; 95%CI, 1.211-7.04 and 5.47; 95%CI, 2.10-14.26, respectively). NT-ProBNP significantly improved the troponin model discrimination of mortality or MV (C-index 0.83 to 0.84), and of mortality alone (C-index 0.85 to 0.87). CONCLUSIONS: Myocardial injury measured at admission was a common finding in patients with COVID-19. It reliably predicted the occurrence of mortality and need of MV, the most severe complications of the disease. NT-proBNP improved the prognostic accuracy of hs-TnT

Exceso de peso en España: situación actual, proyecciones para 2030 y sobrecoste directo estimado para el Sistema Nacional de Salud / Excess weight in Spain: current situation, projections for 2030, and estimated direct extra cost for the Spanish Health System

Introducción y objetivos: El exceso de peso potencia algunas enfermedades crónicas y reduce la calidad de vida, y su prevalencia crece en todo el mundo. El objetivo es estimar la evolución del exceso de peso entre 1987 y 2014 en población española adulta, calcular los casos de exceso de peso y sus sobrecostes médicos directos en 2006 y 2016, y proyectar su tendencia a 2030. Métodos: Se seleccionaron 47 artículos en una búsqueda bibliográfica sistemática para determinar la progresión de las prevalencias de sobrepeso, obesidad y obesidad mórbida y del índice de masa corporal promedio entre 1987 y 2014. Con estos datos, se estimó el número de casos en adultos españoles en 2006, 2016 y 2030 y sus sobrecostes directos. Resultados: Entre 1987 y 2014, las prevalencias de sobrepeso, obesidad y obesidad mórbida aumentaron el 0,28%/año (p=0,004), el 0,50%/año (p<0,001) y el 0,030%/año (p=0,006) en los varones y el 0,10%/año (p=0,123), el 0,25%/año (p=0,078) y el 0,042%/año (p=0,251) en las mujeres. El índice de masa corporal aumentó 0,10 puntos/año en varones (p<0,001) y 0,26 en mujeres (significativamente solo entre 1987-2002, p <0,001). Se estimaron 23.500.000 casos de exceso de peso en 2016, cuyo sobrecoste médico directo supuso 1.950.000.000 euros/año. De mantenerse la tendencia, entre 2016 y 2030 aparecerán 3.100.000 nuevos casos de exceso de peso, y se alcanzará en 2030 un sobrecoste médico directo de unos 3.000.000.000 euros/año. Conclusiones: El exceso de peso en los adultos en España aumenta desde que existen registros, y en 2016 supuso un sobrecoste directo del 2% del presupuesto sanitario. Con esta tendencia, en 2030 se habrá incrementado un 16% el número de casos y un 58% su sobrecoste sanitario directo

Introduction and objectives: Excess weight promotes the development of several chronic diseases and decreases quality of life. Its prevalence is increasing globally. Our aim was to estimate the trend in excess weight between 1987 and 2014 in Spanish adults, calculate cases of excess weight and its direct extra costs in 2006 and 2016, and project its trend to 2030. Methods: We selected 47 articles in a systematic literature search to determine the progression of the prevalence of overweight, nonmorbid obesity, and morbid obesity and average body mass index between 1987 and 2014. We projected the expected number of cases in 2006, 2016, and 2030 and the associated direct extra medical costs. Results: Between 1987 and 2014, the prevalence of overweight, obesity, and morbid obesity increased by 0.28%/y (P=.004), 0.50%/y (P <.001) and 0.030%/y (P=.006) in men, and by 0.10%/y (P=.123), 0.25%/y (P=.078), and 0.042%/y (P=.251) in women. The mean body mass index increased by 0.10 kg/m2/y in men (P <.001) and 0.26 kg/m2/y in women (significantly only between 1987 and 2002, P <.001). We estimated 23 500 000 patients with excess weight in 2016, generating 1.95 billion ⚬/y in direct extra medical costs. If the current trend continues, between 2016 and 2030, there will be 3 100 000 new cases of excess weight, leading to 3.0 billion ⚬/y of direct extra medical costs in 2030. Conclusions: Excess weight in Spanish adults has risen since the creation of population registries, generating direct extra medical costs that represent 2% of the 2016 health budget. If this trend continues, we expect 16% more cases in 2030 and 58% more direct extra medical costs