A Validated Highly Sensitive Microsatellite Instability Assay Accurately Identifies Individuals Harboring Biallelic Germline PMS2 Pathogenic Variants in Constitutional Mismatch Repair Deficiency.

BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) is a rare and extraordinarily penetrant childhood-onset cancer predisposition syndrome. Genetic diagnosis is often hampered by the identification of mismatch repair (MMR) variants of unknown significance and difficulties in PMS2 analysis, the most frequently mutated gene in CMMRD. We present the validation of a robust functional tool for CMMRD diagnosis and the characterization of microsatellite instability (MSI) patterns in blood and tumors. METHODS: The highly sensitive assessment of MSI (hs-MSI) was tested on a blinded cohort of 66 blood samples and 24 CMMRD tumor samples. Hs-MSI scores were compared with low-pass genomic instability scores (LOGIC/MMRDness). The correlation of hs-MSI scores in blood with age of cancer onset and the distribution of insertion-deletion (indel) variants in microsatellites were analyzed in a series of 169 individuals (n = 68 CMMRD, n = 124 non-CMMRD). RESULTS: Hs-MSI achieved high accuracy in the identification of CMMRD in blood (sensitivity 98.5% and specificity 100%) and detected MSI in CMMRD-associated tumors. Hs-MSI had a strong positive correlation with whole low-pass genomic instability LOGIC scores (r = 0.89, P = 2.2e-15 in blood and r = 0.82, P = 7e-3 in tumors). Indel distribution identified PMS2 pathogenic variant (PV) carriers from other biallelic MMR gene PV carriers with an accuracy of 0.997. Higher hs-MSI scores correlated with younger age at diagnosis of the first tumor (r = -0.43, P = 0.011). CONCLUSIONS: Our study confirms the accuracy of the hs-MSI assay as ancillary testing for CMMRD diagnosis, which can also characterize MSI patterns in CMMRD-associated cancers. Hs-MSI is a powerful tool to pinpoint PMS2 as the affected germline gene and thus potentially personalize cancer risk.

Emotional Problems in Spanish Children and Adolescents during the COVID-19 Pandemic: A Systematic Review / Los problemas emocionales de los niños y adolescentes españoles durante la pandemia del COVID-19: una revisión sistemática

The COVID-19 pandemic has particularly affected the mental health of children and adolescents. In Spain, numerous studies have been carried out about the emotional impact on this population. The objective of this paper is to examine, through a systematic review, the most immediate psychological effects of the pandemic on Spanish children and adolescents and the related variables. A search was conducted, obtaining 356 articles of which 27 met the inclusion criteria. The studies reviewed address emotional problems, emotion-regulation problems, anxiety, depression, and stress in Spanish children and adolescents. An increase in emotional problems during confinement was observed. Differences were found in emotional problems, being generally more common in girls and older children and adolescents. Related variables of a family nature and referred to the pandemic, coping styles, and other psychological problems were examined. These results are relevant to design interventions that can prevent the impact of other similar situations.

La pandemia del COVID-19 ha afectado de forma particular a la salud mental infanto-juvenil. En España se han llevado a cabo numerosos estudios acerca de las repercusiones emocionales en esta población. El objetivo de este trabajo es examinar, mediante una revisión sistemática, los efectos psicológicos más inmediatos de la pandemia en niños y adolescentes españoles y las variables relacionadas. Se realizó una búsqueda, obteniéndose 356 artículos de los que 27 cumplieron los criterios de inclusión. Los estudios revisados abordan problemas emocionales, de regulación emocional, ansiedad, depresión y estrés en niños y adolescentes españoles. Se encontraron diferencias en estos problemas emocionales, siendo generalmente más comunes en chicas y en niños mayores y adolescentes. Se revisaron variables relacionadas de carácter familiar, relativas a la pandemia, estilos de afrontamiento y otros problemas psicológicos. Estos resultados son relevantes para el diseño de intervenciones que puedan prevenir la repercusión de otras situaciones similares.

Hot money: Illuminating the financing of high-carbon infrastructure in the developing world.

Major infrastructure financiers will have to significantly decarbonize their investments to meet mounting promises to cut carbon emissions to "net-zero" by mid-century. We provide new details about those needed shifts. Using two World Bank databases of infrastructure projects throughout the developing world, and applying a methodology for imputing the projects' likely future carbon output, we assess the emissions profile of power-plant projects executed from 2018 through 2020 - the three years immediately preceding the spate of net-zero pledges. We find that approximately half the generation executed in those years is too carbon-intensive to align with keeping Earth's average temperature from exceeding 1.5°C above pre-industrial levels, largely because of the prevalence of new natural-gas-fired power plants. We also find new evidence of host countries' agency in shaping carbon trajectories: Much of the climate-misaligned financing is not foreign but domestic. And we find different institutions are financing infrastructure portfolios with significantly differing carbon intensities.

The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease.

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

Effect of part-time cardiac catheterization facilities in patients with acute myocardial infarction.

BACKGROUND: Although the easy availability of invasive cardiac care facilities is associated with an increase in their use, their influence on outcomes is not clear. We sought to investigate whether a newly available cardiac catheterization laboratory (CCL) performing percutaneous coronary intervention (PCI) on a part-time (PT) basis might improve outcomes in patients with acute myocardial infarction (AMI). METHODS: This was an observational cohort study that included all consecutive patients with AMI admitted to a secondary-level hospital in Spain before and after the PT-CCL opened in January 2006: during 1998-2005 and 2006-2014, respectively. All-cause in-hospital and long-term mortality were the co-primary endpoints. In-hospital complications and length of stay were secondary endpoints. For the analyses, patients were stratified according to propensity-score (PS) quintiles. RESULTS: A total of 5339 patients were recruited, and 50.3% were managed after the opening of the PT-CCL. The PT-CCL was associated with greater use of PCI (81.2 vs. 32.5%, p<0.001) and guidelines-recommended medication (all p<0.001), lower risk of recurrent angina (PS-adjusted RR=0.160, 95% CI 0.115-0.222) and shorter length of hospital stay (PS-adjusted RR for length of stay <8days=0.357, 95% CI 0.301-0.422). In patients with NSTEMI, PT-CCL was associated with improved long-term survival (PS-adjusted HR=0.764, 95% CI 0.602-0.970). CONCLUSIONS: In patients with AMI, a new PT-CCL was associated with greater use of PCI and guideline-recommended medication, lower risk of recurrent angina and shorter length of hospital stay. In a subset of patients with NSTEMI, PT-CCL was associated with improved long-term survival.

Nivel de estudios y mortalidad a largo plazo en pacientes con infarto agudo de miocardio / Educational level and long-term mortality in patients with acute myocardial infarction

Introducción y objetivos. Existe controversia acerca del valor del nivel socieconómico como marcador pronóstico en el infarto agudo de miocardio. El objetivo de este estudio fue evaluar el impacto del nivel de estudios, como marcador del estatus socioeconómico, sobre el pronóstico vital a largo plazo tras un infarto agudo de miocardio. Métodos. Estudio prospectivo y observacional de 5.797 pacientes hospitalizados por un infarto agudo de miocardio. Se estudió la mortalidad por todas las causas a largo plazo (mediana 8,5 años) mediante modelos de regresión ajustados. Resultados. Un 73,1% de los pacientes había cursado estudios primarios (n = 4.240), los segundos más frecuentes fueron los estudios medios (secundaria, bachiller) (n = 843; 14,5%). Un 7,0% (n = 407) era analfabeto y el 5,3% tenía estudios superiores (n = 307). Los pacientes con un nivel de estudios medio o superior fueron significativamente más jóvenes, en mayor proporción varones y presentaban menos factores de riesgo y comorbilidad. Eran pacientes que acudían antes al hospital y se presentaban con menor grado de insuficiencia cardiaca. Durante el ingreso recibieron con más frecuencia terapia de reperfusión y su mortalidad cruda fue inferior. El tratamiento hospitalario y al alta incluyó más fármacos recomendados por las guías. En un contexto multivariado, el nivel de estudios medio o superior se mostró como un predictor independiente y protector respecto de la mortalidad a largo plazo (hazard ratio = 0,85; intervalo de confianza del 95%, 0,74-0,98). Conclusiones. Este estudio muestra una relación inversa e independiente entre el nivel de estudios previos y la mortalidad a largo plazo en pacientes que han experimentado un infarto agudo de miocardio (AU)

Introduction and objectives: The value of socioeconomic status as a prognostic marker in acute myocardial infarction is controversial. The aim of this study was to evaluate the impact of educational level, as a marker of socioeconomic status, on the prognosis of long-term survival after acute myocardial infarction. Methods: We conducted a prospective, observational study of 5797 patients admitted to hospital with acute myocardial infarction. We studied long-term all-cause mortality (median 8.5 years) using adjusted regression models. Results: We found that 73.1% of patients had primary school education (n = 4240), 14.5% had secondary school education (including high school) (n = 843), 7.0% was illiterate (n = 407), and 5.3% had higher education (n = 307). Patients with secondary school or higher education were significantly younger, more were male, and they had fewer risk factors and comorbidity. These patients arrived sooner at hospital and had less severe heart failure. During admission they received more reperfusion therapy and their crude mortality was lower. Their drug treatment in hospital and at discharge followed guideline recommendations more closely. On multivariate analysis, secondary school or higher education was an independent predictor and protective factor for long-term mortality (hazard ratio = 0.85; 95% confidence interval, 0.74-0.98). Conclusions: Our study shows an inverse and independent relationship between educational level and long-term mortality in patients with acute myocardial infarction (AU)

Importancia de la presencia de cardiomegalia en el pronóstico de los pacientes con infarto agudo de miocardio / Prognostic importance of cardiomegaly in patients with acute myocardial infarction

Objetivos: Conocer el significado pronóstico intrahospitalario y a largo plazo de la presencia de cardiomegalia en la radiología simple inicial de los pacientes ingresados por infarto agudo de miocardio. Métodos: Estudio prospectivo de 7.644 pacientes ingresados por un infarto agudo de miocardio en dos hospitales. Se obtuvo información clínica detallada y se prestó especial atención a la presencia/ausencia de cardiomegalia en la radiografía de tórax. Realizamos modelos ajustados para predecir mortalidad (por cualquier causa) hospitalaria y tras el alta con una mediana de 6 años. Resultados: 1.351 (17,7%) pacientes presentaron cardiomegalia. La mortalidad hospitalaria global fue 11,2% y la densidad de incidencia de mortalidad a largo plazo fue de 5,7 por cada 100 pacientes-año. Los pacientes con cardiomegalia presentaron mayor edad y más factores de riesgo cardiovascular excepto tabaquismo activo, mayor comorbilidad, fueron menos revascularizados y tratados al alta de forma subóptima. Durante la hospitalización, la cardiomegalia se asoció a mayores tasas de complicaciones, especialmente insuficiencia cardiaca (70,8 vs 21,4%, p < 0,001) y mortalidad (27,8 vs 7,7%, p < 0,001). La cardiomegalia resultó predictor independiente sobre la mortalidad hospitalaria (odds ratio = 1,34; p = 0,02) y tras el alta (hazard ratio = 1,16, p < 0,01). Conclusiones: En pacientes con infarto agudo de miocardio la cardiomegalia resultó predictor independiente de mortalidad hospitalaria y a largo plazo tras el alta (AU)

Objectives: To assess the in-hospital and long-term prognostic importance of cardiomegaly demonstrated by a simple admission radiograph in patients hospitalized for acute myocardial infarction. Methods: Prospective study of 7644 patients admitted for acute myocardial infarction; 2 hospitals participated. We recorded detailed clinical data, especially noting the presence or absence of cardiomegaly in the chest radiograph. Adjusted predictive models for all-cause mortality in hospital or after discharge were constructed. The median follow-up was 6 years. Results: Cardiomegaly was detected in 1351 (17.7%) of the patients. Hospital mortality was 11.2% overall; the incidence of long-term mortality was 5.7 per 100 patient-years. Patients with cardiomegaly were older and had more cardiovascular risk factors other than current smoking; they also had more concomitant conditions, had undergone fewer revascularization procedures, and received suboptimal care after discharge. Cardiomegaly was associated with higher in-hospital rates of adverse events, especially heart failure (70.8% in patients with cardiomegaly vs 21.4% in others, P<.001) and death (27.8% vs 7.7%, P<.001). Cardiomegaly was also an independent predictor of hospital mortality (odds ratio, 1.34; P=.02) as well as mortality after discharge (hazard ratio, 1.16; P<.01). Conclusions: Cardiomegaly was an independent predictor of both hospital mortality and long-term mortality after discharge in this series (AU)

Relation of New Permanent Right or Left Bundle Branch Block on Short- and Long-Term Mortality in Acute Myocardial Infarction Bundle Branch Block and Myocardial Infarction.

The aim of this study was to investigate the prognosis associated with bundle branch block (BBB) depending on location, time of appearance, and duration in patients with myocardial infarction (MI). From January 1998 to January 2008, we recruited 5,570 patients with acute MI. Thirty-day and 7-year all-cause mortality, according to BBB location, time of appearance, and duration were analyzed by multivariable analyses. BBB was present in 964 patients (17.3%); right BBB (RBBB) 10.6% and left BBB (LBBB) 6.7%. Overall mortality rate at 30 days was 13.2% (n = 738) and 7 years was 6.34 deaths per 100 patient-year. Both RBBB and LBBB were more frequently previous, 42.9% and 58.8%. Compared with non-BBB, all BBB groups showed higher prevalence of co-morbidities, especially rates of diabetes (49.0% vs 34.3%, p <0.001) and more often heart failure during hospitalization (54.5% vs 26.6%, p <0.001). Compared with RBBB, patients with LBBB had a higher prevalence of co-morbidities and a higher mortality, especially the new BBB, 30 days: 52.5% versus 31.6% and 7 years (incident rate): 27.2 versus 13.3 per 100 patient-year. New transient BBB had lower heart failure on admission (42.6% vs 58.3%, p = 0.008) and 30-day mortality (20.3% vs 69.6%, p <0.001) compared with permanent in both locations. New permanent RBBB was independently associated with 30-day (hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.45 to 2.79) and 7-year mortality (HR 3.12, 95% CI 2.38 to 4.09). New-permanent LBBB was independently associated with 30-day (HR 2.15, 95% CI 1.47 to 3.15) and 7-year mortality (HR 2.91, 95% CI 2.08 to 4.08). In conclusion, in patients with acute MI, the appearance of a new BBB was independently associated with a higher 30-day and 7-year all-cause mortality.

Educational Level and Long-term Mortality in Patients With Acute Myocardial Infarction.

INTRODUCTION AND OBJECTIVES: The value of socioeconomic status as a prognostic marker in acute myocardial infarction is controversial. The aim of this study was to evaluate the impact of educational level, as a marker of socioeconomic status, on the prognosis of long-term survival after acute myocardial infarction. METHODS: We conducted a prospective, observational study of 5797 patients admitted to hospital with acute myocardial infarction. We studied long-term all-cause mortality (median 8.5 years) using adjusted regression models. RESULTS: We found that 73.1% of patients had primary school education (n=4240), 14.5% had secondary school education (including high school) (n=843), 7.0% was illiterate (n=407), and 5.3% had higher education (n=307). Patients with secondary school or higher education were significantly younger, more were male, and they had fewer risk factors and comorbidity. These patients arrived sooner at hospital and had less severe heart failure. During admission they received more reperfusion therapy and their crude mortality was lower. Their drug treatment in hospital and at discharge followed guideline recommendations more closely. On multivariate analysis, secondary school or higher education was an independent predictor and protective factor for long-term mortality (hazard ratio=0.85; 95% confidence interval, 0.74-0.98). CONCLUSIONS: Our study shows an inverse and independent relationship between educational level and long-term mortality in patients with acute myocardial infarction.

Pronóstico a corto y largo plazo de la fibrilación auricular previa y de novo en pacientes con infarto agudo de miocardio con elevación del segmento ST / Short- and long-term prognosis of previous and new-onset atrial fibrillation in ST-segment elevation acute myocardial infarction

Introducción y objetivos El impacto de la fibrilación auricular en el pronóstico del infarto de miocardio sigue siendo controvertido. Se analizó la importancia pronóstica de la fibrilación auricular previa y de nueva aparición (de novo) en el hospital y a largo plazo en el infarto agudo de miocardio. Métodos Estudio prospectivo de 4.284 pacientes con infarto agudo de miocardio con elevación del segmento ST. Se estudió la mortalidad por todas las causas hospitalaria y a largo plazo (mediana, 7,2 años) mediante modelos ajustados. Resultados El 3,2% de los pacientes tenían fibrilación auricular previa y el 9,8%, de novo. En general ambos grupos de pacientes tenían un perfil de mayor riesgo basal y mayor probabilidad de complicaciones intrahospitalarias. La mortalidad bruta hospitalaria fue mayor entre los pacientes con fibrilación auricular previa que en la de novo (el 22 frente al 12%; p < 0,001; 30 frente al 10%; p < 0,001). La densidad de incidencia de mortalidad a largo plazo fue de 11,11/100 pacientes-año en la fibrilación auricular previa y 5,35/100 pacientes-año en la de novo (ambos grupos, p < 0,001). Únicamente la fibrilación auricular de novo (odds ratio = 1,55; intervalo de confianza del 95%, 1,08-2,22) fue predictor independiente de mortalidad hospitalaria. La fibrilación auricular previa (hazard ratio = 1,24; intervalo de confianza del 95%, 0,94-1,64) y la de novo (hazard ratio = 0,98; intervalo de confianza del 95%, 0,80-1,21) no resultaron predictores independientes de mortalidad a largo plazo. Conclusiones La fibrilación auricular de novo durante el ingreso es un factor independiente de mortalidad hospitalaria en el infarto agudo de miocardio (AU)

Introduction and objectives The impact of atrial fibrillation on the prognosis of myocardial infarction is still the subject of debate. We analyzed the influence of previous and new-onset atrial fibrillation on in-hospital and long-term prognosis in patients with acute myocardial infarction. Methods Prospective study of 4284 patients with ST-segment elevation acute myocardial infarction. We studied all-cause in-hospital and long-term mortality (median, 7.2 years) using adjusted models. Results In total, 3.2% of patients had previous atrial fibrillation and 9.8% had new-onset atrial fibrillation. In general, both groups of patients had a high baseline risk profile and an increased likelihood of in-hospital complications. The crude in-hospital mortality rate was higher in patients with previous atrial fibrillation than in those with new-onset atrial fibrillation (22% vs 12%; P < .001; 30% vs 10%; P < .001). The long-term mortality rate was 11.11/100 patient-years in patients with previous atrial fibrillation and 5.35/100 patient years in those with new-onset atrial fibrillation (both groups, P < .001). New-onset fibrillation alone (odds ratio = 1.55; 95% confidence interval, 1.08-2.22) was an independent predictor of in-hospital mortality. Previous atrial fibrillation (hazard ratio = 1.24; 95% confidence interval, 0.94-1.64) and new-onset atrial fibrillation (hazard ratio = 0.98; 95% confidence interval, 0.80-1.21) were not independent predictors of long-term mortality. Conclusions New-onset atrial fibrillation during hospitalization is an independent risk factor for in-hospital mortality in acute myocardial infarction (AU)

[Prognostic importance of cardiomegaly in patients with acute myocardial infarction]. / Importancia de la presencia de cardiomegalia en el pronóstico de los pacientes con infarto agudo de miocardio.

OBJECTIVES: To assess the in-hospital and long-term prognostic importance of cardiomegaly demonstrated by a simple admission radiograph in patients hospitalized for acute myocardial infarction. MATERIAL AND METHODS: Prospective study of 7644 patients admitted for acute myocardial infarction; 2 hospitals participated. We recorded detailed clinical data, especially noting the presence or absence of cardiomegaly in the chest radiograph. Adjusted predictive models for all-cause mortality in hospital or after discharge were constructed. The median followup was 6 years. RESULTS: Cardiomegaly was detected in 1351 (17.7%) of the patients. Hospital mortality was 11.2% overall; the incidence of long-term mortality was 5.7 per 100 patient-years. Patients with cardiomegaly were older and had more cardiovascular risk factors other than current smoking; they also had more concomitant conditions, had undergone fewer revascularization procedures, and received suboptimal care after discharge. Cardiomegaly was associated with higher in-hospital rates of adverse events, especially heart failure (70.8% in patients with cardiomegaly vs 21.4% in others, P<.001) and death (27.8% vs 7.7%, P<.001). Cardiomegaly was also an independent predictor of hospital mortality (odds ratio, 1.34; P=.02) as well as mortality after discharge (hazard ratio, 1.16; P<.01). CONCLUSION: Cardiomegaly was an independent predictor of both hospital mortality and long-term mortality after discharge in this series.

OBJETIVO: Conocer el significado pronóstico intrahospitalario y a largo plazo de la presencia de cardiomegalia en la radiología simple inicial de los pacientes ingresados por infarto agudo de miocardio. METODO: Estudio prospectivo de 7.644 pacientes ingresados por un infarto agudo de miocardio en dos hospitales. Se obtuvo información clínica detallada y se prestó especial atención a la presencia/ausencia de cardiomegalia en la radiografía de tórax. Realizamos modelos ajustados para predecir mortalidad (por cualquier causa) hospitalaria y tras el alta con una mediana de 6 años. RESULTADOS: 1.351 (17,7%) pacientes presentaron cardiomegalia. La mortalidad hospitalaria global fue 11,2% y la densidad de incidencia de mortalidad a largo plazo fue de 5,7 por cada 100 pacientes-año. Los pacientes con cardiomegalia presentaron mayor edad y más factores de riesgo cardiovascular excepto tabaquismo activo, mayor comorbilidad, fueron menos revascularizados y tratados al alta de forma subóptima. Durante la hospitalización, la cardiomegalia se asoció a mayores tasas de complicaciones, especialmente insuficiencia cardiaca (70,8 vs 21,4%, p < 0,001) y mortalidad (27,8 vs 7,7%, p < 0,001). La cardiomegalia resultó predictor independiente sobre la mortalidad hospitalaria (odds ratio = 1,34; p = 0,02) y tras el alta (hazard ratio = 1,16, p < 0,01). CONCLUSIONES: En pacientes con infarto agudo de miocardio la cardiomegalia resultó predictor independiente de mortalidad hospitalaria y a largo plazo tras el alta.

Short- and long-term prognosis of previous and new-onset atrial fibrillation in ST-segment elevation acute myocardial infarction.

INTRODUCTION AND OBJECTIVES: The impact of atrial fibrillation on the prognosis of myocardial infarction is still the subject of debate. We analyzed the influence of previous and new-onset atrial fibrillation on in-hospital and long-term prognosis in patients with acute myocardial infarction. METHODS: Prospective study of 4284 patients with ST-segment elevation acute myocardial infarction. We studied all-cause in-hospital and long-term mortality (median, 7.2 years) using adjusted models. RESULTS: In total, 3.2% of patients had previous atrial fibrillation and 9.8% had new-onset atrial fibrillation. In general, both groups of patients had a high baseline risk profile and an increased likelihood of in-hospital complications. The crude in-hospital mortality rate was higher in patients with previous atrial fibrillation than in those with new-onset atrial fibrillation (22% vs 12%; P<.001; 30% vs 10%; P<.001). The long-term mortality rate was 11.11/100 patient-years in patients with previous atrial fibrillation and 5.35/100 patient years in those with new-onset atrial fibrillation (both groups, P<.001). New-onset fibrillation alone (odds ratio=1.55; 95% confidence interval, 1.08-2.22) was an independent predictor of in-hospital mortality. Previous atrial fibrillation (hazard ratio=1.24; 95% confidence interval, 0.94-1.64) and new-onset atrial fibrillation (hazard ratio=0.98; 95% confidence interval, 0.80-1.21) were not independent predictors of long-term mortality. CONCLUSIONS: New-onset atrial fibrillation during hospitalization is an independent risk factor for in-hospital mortality in acute myocardial infarction.

Importancia de la carga vascular previa en la mortalidad intrahospitalaria y a largo plazo de pacientes con infarto de miocardio y segmento ST elevado / Impact of Previous Vascular Burden on In-hospital and Long-term Mortality in Patients With ST-segment Elevation Myocardial Infarction

Introducción y objetivos El paciente con síndrome coronario agudo con antecedentes de cardiopatía isquémica, arteriopatía periférica y/o accidente cerebrovascular previos muestra un peor pronóstico. Sin embargo, la relación existente entre dichos antecedentes y el pronóstico a largo plazo no ha sido aclarada del todo. Métodos Estudio prospectivo de 4.247 pacientes con infarto agudo de miocardio y segmento ST elevado. Se obtuvo información clínica detallada que incluye los antecedentes de cardiopatía isquémica, arteriopatía periférica y accidente cerebrovascular. Estudiamos la mortalidad intrahospitalaria y a largo plazo (mediana, 7,2 años) mediante modelos ajustados. Resultados Se observó que 1.131 (26,6%) pacientes tenían un territorio enfermo y 221 (5,2%), ≥ 2 territorios. La mortalidad hospitalaria total fue del 12,3% y la densidad de incidencia de mortalidad a largo plazo fue de 3,5/100 pacientes-año. Los antecedentes de cardiopatía isquémica (odds ratio = 0,83; p = 0,35), arteriopatía periférica (odds ratio = 1,30; p = 0,34) y accidente cerebrovascular (odds ratio = 1,15; p = 0,59) no fueron predictores independientes de mortalidad hospitalaria. En un modelo ajustado, los dos últimos fueron predictores de mortalidad a largo plazo (hazard ratio = 1,57; p < 0,001; y hazard ratio = 1,34; p = 0,001, respectivamente). La afección de ≥ 2 territorios vasculares fue predictora de mortalidad a largo plazo (hazard ratio = 2,35; p < 0,001), aunque no de mortalidad intrahospitalaria (odds ratio= 1,07; p = 0,844).Conclusiones En el infarto de miocardio con segmento ST elevado, la carga vascular previa condiciona mayor mortalidad a largo plazo. Individualmente, la arteriopatía periférica y el accidente cerebrovascular previos son predictores de muerte tras el alta (AU)

Introduction and objectives Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. Methods Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease («vascular burden») were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. Results One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844).Conclusions In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge (AU)

Impact of previous vascular burden on in-hospital and long-term mortality in patients with ST-segment elevation myocardial infarction.

INTRODUCTION AND OBJECTIVES: Patients with a current acute coronary syndrome and previous ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease are reported to have a poorer outcome than those without these previous conditions. It is uncertain whether this association with outcome is observed at long-term follow-up. METHODS: Prospective observational study, including 4247 patients with ST-segment elevation myocardial infarction. Detailed clinical data and information on previous ischemic heart disease, peripheral arterial disease, and cerebrovascular disease ("vascular burden") were recorded. Multivariate models were performed for in-hospital and long-term (median, 7.2 years) all-cause mortality. RESULTS: One vascular territory was affected in 1131 (26.6%) patients and ≥ 2 territories in 221 (5.2%). The total in-hospital mortality rate was 12.3% and the long-term incidence density was 3.5 deaths per 100 patient-years. A background of previous ischemic heart disease (odds ratio = 0.83; P = .35), peripheral arterial disease (odds ratio = 1.30; P = .34), or cerebrovascular disease (stroke) (odds ratio = 1.15; P = .59) was not independently predictive of in-hospital death. In an adjusted model, previous cerebrovascular disease and previous peripheral arterial disease were both predictors of mortality at long-term follow-up (hazard ratio = 1.57; P < .001; and hazard ratio = 1.34; P = .001; respectively). Patients with ≥ 2 diseased vascular territories showed higher long-term mortality (hazard ratio = 2.35; P < .001), but not higher in-hospital mortality (odds ratio = 1.07; P = .844). CONCLUSIONS: In patients with a diagnosis of ST-segment elevation acute myocardial infarction, the previous vascular burden determines greater long-term mortality. Considered individually, previous cerebrovascular disease and peripheral arterial disease were predictors of mortality at long-term after hospital discharge.

Apo A-I promoter polymorphism influences basal HDL-cholesterol and its response to pravastatin therapy.

Statins decrease cardiovascular morbidity and mortality, essentially, by reducing LDL-cholesterol levels and, additionally, by increasing HDL-cholesterol concentrations. Environmental and genetic factors are known to affect LDL-C response to statins but less is known regarding HDL-C. We have evaluated the lipid and lipoprotein response to 20 mg/day of pravastatin for 16 weeks in relation to the G/A polymorphism in the promoter region of the apo A-I gene in 397 hypercholesterolaemic subjects followed-up on an out-patient basis. In the study population, 61.7% were homozygous for the G allele and 36% were heterozygous. The A allele carriers had an HDL-C 6.5% higher than the G allele homozygotes (P=0.021 in univariate analysis; P=0.009 in multivariate analysis). However, on segregation by gender and smoking status the effect was significant only in non-smoking males. The A allele carriers did not increase their HDL-C concentrations after treatment (-0.3, 95%CI -3.3 to 2.7%) while G allele homozygotes had a 4.9% increase (95%CI 2.5-7.3%). Differences in the response between both groups were significant before (P=0.008) and after adjustment for confounding variables such as age and baseline HDL-C concentration (P=0.046). We conclude that the G/A polymorphism of the apo A-I promoter region affects not only baseline HDL-C concentrations but also its response to pravastatin treatment.

Respuesta variable a la inhibición biológica de las plaquetas por abciximab en pacientes sometidos a revascularización coronaria percutánea / Variable Response to the Biological Inhibition of Platelets by Abciximab in Patients Subjected to Percutaneous Coronary Angioplasty

Introducción y objetivo. La utilización de abciximab ha demostrado reducir el riesgo de complicaciones trombóticas en el contexto de la angioplastia coronaria transluminal percutánea (ACTP). Sin embargo, todavía quedan aspectos por resolver. Se han estudiado varios aspectos biológicos de la acción del abciximab sobre las plaquetas en la ACTP. Métodos. Se determinó el grado de inhibición plaquetaria con adenosín difosfato (ADP) a concentraciones de 5 y 20 µmol/l, el tiempo de obturación que mide la capacidad hemostática de las plaquetas (PFA-100) y los marcadores de activación plaquetaria en 15 pacientes sometidos a angioplastia coronaria basalmente, a los 15 min, al finalizar la intervención y a las 24 h de ser tratados con abciximab. Resultados. Un total de 13 pacientes tuvieron más de un 80 por ciento de inhibición de la agregación plaquetaria durante el procedimiento, pero sólo dos la mantenían a las 24 h (p de 300 s en 13 pacientes durante el procedimiento, normalizándose a las 24 h en seis (p < 0,05). Hubo buena correlación (p = 0,02) entre estos 2 parámetros durante la intervención, pero no se mantuvo a las 24 h. En 2 pacientes no se produjo ningún grado de inhibición ni de cambios en el tiempo de obturación a lo largo del estudio. La expresión de P-selectina aumentó significativamente durante la intervención (p < 0,05).Conclusiones. La variabilidad en la inhibición de la función plaquetaria y la existencia de activación circulante durante la intervención hace considerar la necesidad de realizar un control analítico precoz tras la administración de abciximab, con objeto de poder modificar su pauta para optimizar su acción o asociarlo a otro agente antitrombótico (AU)

Polimorfismo de la apolipoproteína E y enfermedad coronaria / Apo E polymorphism and coronary heart disease

FUNDAMENTO: La apolipoproteína E (apo E) desempeña un importante papel en el desarrollo de la arteriosclerosis. Esta proteína es polimórfica, habiéndose descrito tres alelos codominantes, 2, 3 y 4. En el presente estudio hemos evaluado la asociación entre el alelo 4 y la presencia de enfermedad coronaria en una muestra de sujetos hipercolesterolémicos procedentes de toda la geografía nacional. SUJETOS Y MÉTODO: Se seleccionaron 389 personas (un 56 por ciento de mujeres, con una edad media de 57 años) con indicación de tratamiento hipolipemiante tras seguir una dieta pobre en grasas saturadas. La concentración de lípidos y lipoproteínas y la determinación del genotipo de apo E fueron realizadas de forma centralizada. RESULTADOS: La distribución por genotipos de la población fue la siguiente: 2/ 3, 3 por ciento; 3/ 3, 75 por ciento; 3/ 4, 20 por ciento; 4/ 4, 1 por ciento, y 2/ 4, 1 por ciento. Los sujetos fueron divididos según poseían (n = 83) o no (n = 303) el alelo 4, siendo excluidos los 2/ 4. No existieron diferencias entre ambos grupos en la edad, el sexo, la prevalencia de hipertensión arterial o el tabaquismo, ni en la concentración de lípidos. La prevalencia de enfermedad coronaria fue del 15,7 por ciento en los 4 y del 6,9 por ciento en los no 4 (OR, 2,49; IC del 95 por ciento, 1,19-5,22). En un análisis de regresión logística múltiple, la relación entre el alelo 4 y la presencia de enfermedad coronaria se mantuvo significativa tras corregir para la edad, el sexo, los factores de riesgo cardiovascular y la concentración de colesterol total, cHDL y triglicéridos (OR, 2,56; IC del 95 por ciento, 1,03-6,39). CONCLUSIÓN: En España, los portadores del alelo 4 presentan una prevalencia de enfermedad coronaria mayor que los no E4 (AU)

Valoración de la función de las plaquetas por el sistema PFA-100® en pacientes sometidos a revascularización coronaria percutánea tratados con abciximab / Assessment of platelet function by the PFA-100® system in patients undergoing percutaneous coronary revascularization treated with abciximab

Las variaciones interindividuales en la acción biológica de los antagonistas del receptor gpIIb/IIIa plaquetario hace necesaria la monitorización de sus efectos para optimizar su uso clínico. El objetivo de este trabajo ha sido valorar el sistema PFA-100®, diseñado para medir la adhesión y agregación plaquetaria en unas condiciones determinadas de flujo en sangre total en 15 pacientes tratados con abciximab y angioplastia. Métodos: se realizó el tiempo de oclusión-ADP y la agregación con ADP 5 y 20 µm antes y a los 15 y 60 m y 24 h de iniciado el procedimiento. Basalmente se determinó el tiempo de oclusión-epinefrina y la agregación con ácido araquidónico en los pacientes con aspirina como tratamiento habitual. Resultados: se produjo un alargamiento del tiempo de oclusión y una inhibición de la agregación con ADP con una variación significativa (p < 0,05) durante el estudio y una correlación entre ambas técnicas a los 15 minutos (p < 0,05). Dos de los pacientes no presentaron cambios en los valores en ninguna determinación. De los 13 pacientes tratados con aspirina, 10 presentaron alargamiento del tiempo de oclusión-epinefrina y disminuciones de la agregación con ácido araquidónico, significativos respecto a los valores de un grupo control. Cuatro sólo presentaron disminución de la agregación. Conclusiones: el PFA-100® detecta los niveles altos de inhibición funcional plaquetaria por abciximab y sus variaciones interindividuales. Discrimina el efecto de abciximab del producido por aspirina y las posibles 'resistencias' a éste. Se necesitaría mayor sensibilidad en dicho analizador para establecer los niveles de eficacia y seguridad según el proceso clínico (AU)