Left ventricular dysfunction and arrhythmias in asymptomatic patients with systemic sclerosis / Disfunción ventricular izquierda y arritmias en pacientes asintomáticos con esclerosis sistémica

Introduction and aims Cardiac involvement in systemic sclerosis (SS) is frequently silent and a major cause of mortality in these patients. This work aims to study the prevalence and associations of left ventricular dysfunction (LVD) and arrhythmias in SS. Methods and results Prospective study of SS patients (n=36), excluding those with symptoms of (or) cardiac disease, pulmonary arterial hypertension or cardiovascular risk factors (CVRF). A clinical, analytical, electrocardiogram (EKG), Holter, and echocardiogram with global longitudinal strain (GLS) assessment were performed. Arrhythmias were classified into clinically significant arrhythmias (CSA) and non-significant.Twenty-eight percent had left ventricular diastolic dysfunction (LVDD), 22% LV systolic dysfunction (LVSD) according to the GLS, 11.1% both, and 16.7% cardiac dysautonomia. Fifty percent presented alterations by EKG (44% CSA), 55.6% by Holter (75% CSA) and 8.3% CSA by both. An association was found between the elevation of troponin T (TnTc) and CSA and between the elevation of both NT-proBNP and TnTc with LVDD. Conclusions We found a higher prevalence of LVSD than in the literature, detected by GLS and being 10 times higher than that detected by LVEF, which justifies the need to incorporate this technique in the routine evaluation of these patients. The association of TnTc and NT-proBNP with LVDD suggests that they can be used as minimally invasive biomarkers of this affectation. The absence of correlation between LVD and CSA indicates that the arrhythmias could be due, not only to a supposed structural alteration of the myocardium, but to an independent and early cardiac involvement, which should be actively investigated even in asymptomatic patients without CVRF. (AU)

Introducción y objetivosLa afectación cardiaca en la esclerosis sistémica (ES) es frecuentemente asintomática y se asocia con una mortalidad importante. Este trabajo tiene como objetivo estudiar la prevalencia y las asociaciones de la disfunción ventricular izquierda (DVI) y las arritmias en la ES. Métodos y resultados Estudio prospectivo de pacientes con ES (n = 36), excluyendo aquellos con síntomas o enfermedad cardiaca, hipertensión arterial pulmonar o factores de riesgo cardiovascular (FRCV). Se les realizó una evaluación clínica, analítica, con electrocardiograma (ECG), Holter y ecocardiograma con strain longitudinal global (SLG). Las arritmias se clasificaron en arritmias clínicamente significativas (ACS) y no significativas.De los pacientes estudiados, 27,8% presentaba disfunción diastólica del ventrículo izquierdo (DDVI), 22% disfunción sistólica del VI (DSVI) según el SLG, 11,1% ambas y 16,7% disautonomía cardiaca; 50% presentó alteraciones por ECG (44% ACS), 55,6% por Holter (75% ACS) y 8,3% ACS por ambos. Se encontró una asociación entre la elevación de troponina T (TnTc) y ACS y entre la elevación NT-proBNP y TnTc con la DDVI. Conclusiones Encontramos una prevalencia de DSVI mayor que en la literatura, detectada por SLG y siendo 10 veces superior a la detectada por FEVI, lo que justifica la necesidad de incorporar esta técnica en la evaluación rutinaria de estos pacientes. La asociación de TnTc y NT-proBNP con DDVI sugiere que pueden ser utilizados como biomarcadores mínimamente invasivos de esta afectación. La ausencia de correlación entre DVI y ACS indica que las arritmias podrían deberse, no solo a una supuesta alteración estructural del miocardio, sino a un compromiso cardiaco independiente y temprano, que debe investigarse activamente incluso en pacientes asintomáticos sin FRCV. (AU)

Left ventricular dysfunction and arrhythmias in asymptomatic patients with systemic sclerosis.

INTRODUCTION AND AIMS: Cardiac involvement in systemic sclerosis (SS) is frequently silent and a major cause of mortality in these patients. This work aims to study the prevalence and associations of left ventricular dysfunction (LVD) and arrhythmias in SS. METHODS AND RESULTS: Prospective study of SS patients (n=36), excluding those with symptoms of (or) cardiac disease, pulmonary arterial hypertension or cardiovascular risk factors (CVRF). A clinical, analytical, electrocardiogram (EKG), Holter, and echocardiogram with global longitudinal strain (GLS) assessment were performed. Arrhythmias were classified into clinically significant arrhythmias (CSA) and non-significant. Twenty-eight percent had left ventricular diastolic dysfunction (LVDD), 22% LV systolic dysfunction (LVSD) according to the GLS, 11.1% both, and 16.7% cardiac dysautonomia. Fifty percent presented alterations by EKG (44% CSA), 55.6% by Holter (75% CSA) and 8.3% CSA by both. An association was found between the elevation of troponin T (TnTc) and CSA and between the elevation of both NT-proBNP and TnTc with LVDD. CONCLUSIONS: We found a higher prevalence of LVSD than in the literature, detected by GLS and being 10 times higher than that detected by LVEF, which justifies the need to incorporate this technique in the routine evaluation of these patients. The association of TnTc and NT-proBNP with LVDD suggests that they can be used as minimally invasive biomarkers of this affectation. The absence of correlation between LVD and CSA indicates that the arrhythmias could be due, not only to a supposed structural alteration of the myocardium, but to an independent and early cardiac involvement, which should be actively investigated even in asymptomatic patients without CVRF.

Fracturas de fatiga de repetición en pies en un paciente tratado con antirretrovirales / Recurrent stress fractures in the feet of a patient treated with antiretrovirals

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Actualización 2011 del consenso Sociedad Española de Reumatología de osteoporosis / 2011 Up-date of the consensus statement of the Spanish Society of Rheumatology on osteoporosis

Objetivo. Dado el creciente avance en el diagnóstico como evaluación y tratamiento de la osteoporosis, y la incorporación de nuevas herramientas y medicamentos, desde la Sociedad Española de Reumatología (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatólogos y otros profesionales de la salud implicados en el tratamiento de pacientes con osteoporosis. Métodos. Las recomendaciones se emitieron siguiendo la metodología de grupos nominales. El nivel de evidencia y el grado de recomendación se clasificaron según el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por técnica Delphi. Se utilizó toda la información de consensos previos y guías de práctica clínica disponibles. Resultados. Se realizan recomendaciones sobre el diagnóstico, la evaluación y el tratamiento en pacientes con osteoporosis. Estas recomendaciones incluyen la osteoporosis secundaria a glucocorticoides, la osteoporosis premenopáusica y la del varón. Conclusiones. Se presentan las recomendaciones SER sobre el diagnóstico, la evaluación y el manejo de pacientes con osteoporosis (AU)

Objective. Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. Methods. Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Evidence from previous consensus and available clinical guidelines was used. Results. We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. Conclusions. We present the SER recommendations related to the biologic therapy risk management (AU)

[2011 Up-date of the consensus statement of the Spanish Society of Rheumatology on osteoporosis]. / Actualización 2011 del consenso Sociedad Española de Reumatología de osteoporosis.

OBJECTIVE: Due to increasing improvement in the diagnosis, evaluation and management of osteoporosis and the development of new tools and drugs, the Spanish Society of Rheumatology (SER) has promoted the development of recommendations based on the best evidence available. These recommendations should be a reference to rheumatologists and other health professionals involved in the treatment of patients with osteoporosis. METHODS: Recommendations were developed following a nominal group methodology and based on a systematic review. The level of evidence and degree of recommendation were classified according to the model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through Delphi technique. Evidence from previous consensus and available clinical guidelines was used. RESULTS: We have produced recommendations on diagnosis, evaluation and management of osteoporosis. These recommendations include the glucocorticoid-induced osteoporosis, premenopausal and male osteoporosis. CONCLUSIONS: We present the SER recommendations related to the biologic therapy risk management.

Factores predictivos de nueva fractura tras vertebroplastia / Risk factors of new fractures after vertebroplasty

Objetivo: determinar los factores de riesgo de nueva fractura tras vertebroplastia. Pacientes y método: estudio prospectivo no controlado. Criterios de inclusión: pacientes con vertebroplastia por fracturas osteoporóticas. Visita previa (día 0), se incluyen datos clínicos y densitométricos. Visitas a los 30, 90 y 180 días, se recogen variables clínicas y efectos adversos, como extravasación de cemento y nuevas fracturas vertebrales. Para determinar factores de riesgo de nueva fractura se evaluaron las diferencias entre el grupo con nuevas fracturas (R1) y el grupo que no tenía fracturas (R0). Resultados: se realizó vertebroplastia a 43 pacientes (82 vértebras). En 11 (11,5%) casos se evidenció extravasación de cemento a disco y 9 pacientes presentaron 12 nuevas fracturas vertebrales (20,9%). Entre los grupos R1 y R0 no se observaron diferencias estadísticamente significativas en las variables: sexo, edad, T-score, vitamina D, grado de cifosis, osteoporosis primaria/secundaria, fracturas previas, número de vértebras cementadas y cantidad de cemento inyectado. Se estableció una relación positiva entre extravasación de cemento a disco y aparición de fracturas adyacentes (p<0,001). Conclusiones: la extravasación de cemento a disco aumenta el riesgo de fractura en una vértebra adyacente tras vertebroplastia (AU)

Purpose: To evaluate the risk factors of new fractures after vertebroplasty (VP). Patients and method: Prospective, non-randomized study including patients with acute osteoporotic fractures treated with VP. Baseline visit included clinical and densitometric data. At 30, 90 and 180 days, changes in clinical data and side effects (cement leakage and new fractures) were recorded. To establish the predictive factors of a new fracture, differences between the group of patients with new fractures (R1) and those without fractures (R0) were evaluated. Results: Vertebroplasty was performed in 43 patients (82 vertebrae). Cement leakage into a disc appeared in 11 cases (11,5%) and 12 new fractures occurred in 9 patients. No statistical differences were detected between groups R1 and R0 in the following variables: sex, age, vitamin D levels, T-score, kyphosis angle, primary/secondary osteoporosis, preexisting fractures, number of treated vertebrae and amount of cement injected. A positive, statistical significant correlation, was established between cement leakage into a disk and incidence of adjacent new fractures (p<0.001). Conclusions: Cement leakage into a disc increases the risk of adjacent new fractures after vertebroplasty (AU)

[Risk factors of new fractures after vertebroplasty]. / Factores predictivos de nueva fractura tras vertebroplastia.

PURPOSE: To evaluate the risk factors of new fractures after vertebroplasty (VP). PATIENTS AND METHOD: Prospective, non-randomized study including patients with acute osteoporotic fractures treated with VP. Baseline visit included clinical and densitometric data. At 30, 90 and 180 days, changes in clinical data and side effects (cement leakage and new fractures) were recorded. To establish the predictive factors of a new fracture, differences between the group of patients with new fractures (R1) and those without fractures (R0) were evaluated. RESULTS: Vertebroplasty was performed in 43 patients (82 vertebrae). Cement leakage into a disc appeared in 11 cases (11,5%) and 12 new fractures occurred in 9 patients. No statistical differences were detected between groups R1 and R0 in the following variables: sex, age, vitamin D levels, T-score, kyphosis angle, primary/secondary osteoporosis, preexisting fractures, number of treated vertebrae and amount of cement injected. A positive, statistical significant correlation, was established between cement leakage into a disk and incidence of adjacent new fractures (p<0.001). CONCLUSIONS: Cement leakage into a disc increases the risk of adjacent new fractures after vertebroplasty.

A haplotype-based analysis of the LRP5 gene in relation to osteoporosis phenotypes in Spanish postmenopausal women.

LRP5 encodes the low-density lipoprotein receptor-related protein 5, a transmembrane protein involved in Wnt signaling. LRP5 is an important regulator of osteoblast growth and differentiation, affecting bone mass in vertebrates. Whether common variations in LRP5 are associated with normal BMD variation or osteoporotic phenotypes is of great relevance. We used a haplotype-based approach to search for common disease-associated variants in LRP5 in a cohort of 964 Spanish postmenopausal women. Twenty-four SNPs were selected, covering the LRP5 region, including the missense changes p.V667M and p.A1330V. The SNPs were genotyped and evaluated for association with BMD at the lumbar spine (LS) or femoral neck (FN) and with osteoporotic fracture, at single SNP and haplotype levels, by regression methods. Association with LS BMD was found for SNP 1, rs312009, located in the 5'-flanking region (p = 0.011, recessive model). SNP 6, rs2508836, in intron 1, was also associated with BMD, both at LS (p = 0.025, additive model) and FN (p = 0.031, recessive model). Two polymorphisms were associated with fracture: SNP 11, rs729635, in intron 1, and SNP 15, rs643892, in intron 5 (p = 0.007 additive model and p = 0.019 recessive model, respectively). Haplotype analyses did not provide additional information, except for haplotype "GC" of the block located at the 3'end of the gene. This haplotype spans intron 22 and the 3' untranslated region and was associated with FN BMD (p = 0.029, one copy of the haplotype versus none). In silico analyses showed that SNP 1 (rs312009) lies in a putative RUNX2 binding site. Electro-mobility shift assays confirmed RUNX2 binding to this site.

Promoter 2 -1025 T/C polymorphism in the RUNX2 gene is associated with femoral neck bmd in Spanish postmenopausal women.

Stimulation of bone formation is a key therapeutic target in osteoporosis. Runx2 is a runt domain transcription factor essential to osteoblast differentiation, bone remodeling, and fracture healing. Runx2 knockout mice exhibit a complete lack of ossification, while overexpression of this gene in transgenic mice results in an osteoporotic phenotype. Thus, RUNX2 is a good candidate for the genetic determination of osteoporosis. In this association study, the effects of the -330 G/T polymorphism in promoter 1 and the -1025 T/C polymorphism (rs7771980) in promoter 2 of RUNX2 were tested in relation to lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) in a cohort of 821 Spanish postmenopausal women. The minor allele frequencies for the two polymorphisms were 0.15 and 0.07, respectively. The two polymorphisms, located more than 90 kb apart, were not in linkage disequilibrium (D' = 0.27, r (2) = 0.028). In an ANCOVA test adjusting by weight, height, age, and years since menopause, the -330 G/T polymorphism was not associated with any of the phenotypes analyzed, while we found the -1025 T/C polymorphism to be associated with FN BMD (p = 0.001). In particular, individuals carrying the TC genotype had higher mean adjusted FN BMD values than those bearing the TT genotype. Our results highlight the importance of this RUNX2 promoter 2 polymorphism in FN BMD determination.