Magnetic resonance imaging in patients with cardiac implantable electronic devices: A prospective study.

BACKGROUND: The number of patients with cardiac implantable electronic devices in whom magnetic resonance imaging (MRI) is indicated is constantly increasing. The potential risk of electromagnetic interference has limited its use and it is still contraindicated by the Food and Drug Administration in some cases. The aim of this study is to evaluate the safety and efficacy of MRI in these patients. METHODS: A prospective registry comprising patients with a pacemaker (PM) or implantable cardioverter-defibrillator (ICD), MRI-conditional or not, who were candidates for MRI (at 1.5 T) with no suitable alternative diagnostic technique. All devices were programmed before the procedure and patients were monitored throughout the test. Clinical, electrical, and technical parameters were evaluated before and after MRI. RESULTS: 147 MRI examinations (132 PM and 15 ICD) were performed. There were no clinical events or significant differences in the electrical parameters of the leads after MRI. A variation in the impedance of the ventricular leads was detected, although the difference was not clinically relevant. In one patient with a PM, a failure in release of the safety impulse was detected in the auto-threshold test, although the threshold was correctly determined. In 11 of the 17 thoracic MRIs, image artifacts were detected, preventing the diagnosis in two of them. CONCLUSIONS: In patients with cardiac implantable electronic devices, MRIs performed under a specific protocol has been shown to be safe in the short term even in the thoracic region, as well as interpretable in most cases.

Predictores de fibrilación auricular en pacientes con ictus embólico de origen indeterminado / Atrial fibrillation predictors in patients with embolic stroke of undetermined source

Antecedentes y objetivos: En el accidente cerebrovascular embólico de origen indeterminado (ESUS) la detección de fibrilación auricular (FA) conlleva un cambio de tratamiento y una reducción drástica en la incidencia de nuevos ictus. Es necesario determinar qué pacientes se benefician en mayor medida de una monitorización electrocardiográfica prolongada. Nuestro objetivo fue la búsqueda de predictores electrocardiográficos y ecocardiográficos de FA en pacientes con ESUS.Materiales y métodosSe diseñó un estudio observacional de cohortes en el que se incluyeron 95 pacientes consecutivos que ingresaron por ESUS en un hospital terciario. A todos se les realizó un electrocardiograma (ECG), un Holter electrocardiograma (Holter-ECG) de 24h y un ecocardiograma durante el ingreso. Se realizó un seguimiento presencial durante 2años mediante Holter-ECG de 24h, trimestral durante el primer año y semestral durante el segundo.ResultadosDurante el seguimiento se detectó FA en 11 pacientes (11,6%), siendo la tasa detección del 3,2% a los 6meses, del 7,4% a los 12meses y del 11,6% a los 18 y a los 24meses. Las variables que se relacionaron de forma independiente con el desarrollo de FA fueron la dilatación en grado moderado o severo de la aurícula izquierda (AI) (p=0,02), el bloqueo interauricular avanzado (BIA-A) (p=0,04) y la presencia de más de 1.000 extrasístoles auriculares (EA) en Holter-ECG de 24h (p=0,01).ConclusionesLa dilatación en un grado moderado o severo de AI, el BIA-A y la presencia de más de 1.000 EA en Holter-ECG de 24h se comportan como predictores independientes de FA en pacientes con ESUS. (AU)

Background and objectives: Atrial fibrillation (AF) detection in patients with embolic stroke of underdetermined source (ESUS) entails a change of medical treatment and a significant decrease in the incidence of new strokes. It is necessary to determine which patients would benefit more from prolonged electrocardiographic monitoring. Our aim was to find electrocardiographic and echocardiographic AF predictors in patients with ESUS.MethodsWe performed a cohort study that included 95 consecutive patients admitted to the hospital because of an ESUS. An electrocardiogram, each subject in the study underwent a 24-hour Holter-electrocardiogram (Holter-ECG) and an echocardiogram. A 2-year follow up was also conducted, with a 24-hour Holter-ECG every 3months for the first year, and every 6months during the second one.ResultsDuring the follow-up, AF was detected in 11 patients (11.6%), with a detection rate of 3.2% at 6months, 7.4% at 12months, and 11.6% at 18months as well as at 24months. The variables that were independently related to AF detection included moderate or severe left atrium dilation (P=.02), interatrial advanced block (P=.04) and more than 1000 premature atrial beats on 24-hour Holter-ECG (P=.01).ConclusionsModerate or severe atrial dilation, interatrial advanced block, and the presence of more than 1000 premature atrial beats on 24-hour Holter-ECG behave as AF predictors in patients with ESUS. (AU)

[Atrial fibrillation predictors in patients with embolic stroke of undetermined source]. / Predictores de fibrilación auricular en pacientes con ictus embólico de origen indeterminado.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) detection in patients with embolic stroke of underdetermined source (ESUS) entails a change of medical treatment and a significant decrease in the incidence of new strokes. It is necessary to determine which patients would benefit more from prolonged electrocardiographic monitoring. Our aim was to find electrocardiographic and echocardiographic AF predictors in patients with ESUS. METHODS: We performed a cohort study that included 95 consecutive patients admitted to the hospital because of an ESUS. An electrocardiogram, each subject in the study underwent a 24-hour Holter-electrocardiogram (Holter-ECG) and an echocardiogram. A 2-year follow up was also conducted, with a 24-hour Holter-ECG every 3months for the first year, and every 6months during the second one. RESULTS: During the follow-up, AF was detected in 11 patients (11.6%), with a detection rate of 3.2% at 6months, 7.4% at 12months, and 11.6% at 18months as well as at 24months. The variables that were independently related to AF detection included moderate or severe left atrium dilation (P=.02), interatrial advanced block (P=.04) and more than 1000 premature atrial beats on 24-hour Holter-ECG (P=.01). CONCLUSIONS: Moderate or severe atrial dilation, interatrial advanced block, and the presence of more than 1000 premature atrial beats on 24-hour Holter-ECG behave as AF predictors in patients with ESUS.

Proof of Concept on Functionality Improvement of Mesenchymal Stem-Cells, in Postmenopausal Osteoporotic Women Treated with Teriparatide (PTH1-34), After Suffering Atypical Fractures.

Osteoporosis long-term treatment with nitrogen-containing bisphosphonates, has been associated with uncommon adverse effects, as atypical femoral fractures (AFF). Thus, treatment with teriparatide (TPTD; fragment of human parathyroid hormone; PTH1-34) has been proposed for such patients. Besides its anabolizing effect on bone, TPTD may affect stem-cell mobilization and expansion. Bone marrow mononuclear cells (BMMNC) were isolated from five women that had suffered AFF associated to bisphosphonate treatment, before and after 6 months of TPTD therapy. The presence of mesenchymal stromal cells (CD73, CD90 and CD105 positive cells), gene expression of NANOG, SOX2 and OCT4, proliferation, senescence and capacity to differentiate into osteoblasts and adipocytes were analyzed. After TPTD treatment, BMMNC positive cells for CD73, CD90 and CD105 increased from 6.5 to 37.5% (p < 0.05); NANOG, SOX2 and OCT4 were upregulated, being statistically significant for NANOG (p < 0.05), and cells increased proliferative capacity more than 50% at day 7 (p < 0.05). Senescence was reduced 2.5-fold (p < 0.05), increasing differentiation capacity into osteoblasts and adipocytes, with more than twice mineralization capacity of extracellular matrix or fat-droplet formation (p < 0.05), respectively. Results show that TPTD treatment caused BMMNC "rejuvenation", increasing the number of cells in a more undifferentiated stage, with higher differentiation potency. This effect may favor TPTD anabolic action on bone in such patients with AFF, increasing osteoblast precursor cells. Such response could also arise in other osteoporotic patients treated with TPTD, without previous AFF. Furthermore, our data suggest that TPTD effect on stromal cells may have clinical implications for bone-regenerative medicine. Further studies may deepen on this potential.

Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo / Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization

Antecedentes y objetivos: El déficit de 25(OH)D se ha relacionado con un riesgo cardiovascular aumentado, aunque los estudios de intervención son contradictorios. El objetivo principal fue evaluar el efecto del tratamiento con calcifediol (25(OH)D3) sobre el sistema cardiovascular en pacientes con síndrome coronario agudo sin elevación de segmento ST. Pacientes y método: Estudio prospectivo que incluyó a 41 pacientes (70,6±6,3 años) ≥60 años con síndrome coronario agudo sin elevación de segmento ST y enfermedad coronaria revascularizada percutáneamente. Se aleatorizaron a recibir calcifediol+tratamiento habitual o tratamiento habitual exclusivo, con evaluación de major adverse cardiovascular events (MACE, «episodios cardiovasculares mayores adversos») a los 3 meses. Se estudió la 25(OH)D en relación con otras variables analíticas y con la extensión de la enfermedad coronaria. Resultados: Niveles basales de 25(OH)D≤50nmol/l se asociaron a enfermedad coronaria multivaso (RR: 2,6 [IC 95%: 1,1-7,1], p=0,027) y 25(OH)D≤50nmol/l+paratohormona≥65pg/ml identificaron a pacientes con mayor riesgo de MACE (RR: 4 [IC 95%: 1,1-21,8], p=0,04). Se registró un MACE en el grupo de pacientes suplementados y 5 en el de tratamiento convencional (p=0,66). Entre los pacientes con niveles séricos de 25(OH)D≤50nmol/l al final del estudio el 28,6% presentaron MACE frente al 0% si los niveles eran>50nmol/l (RR: 1,4; p=0,037). Conclusiones: El déficit de vitamina D que implica un hiperparatiroidismo secundario puede ser un buen predictor de MACE. En pacientes suplementados con calcifediol se observó una tendencia a la disminución de MACE en el seguimiento. Niveles finales de 25(OH)D≤50nmol/l se asociaron significativamente a un mayor número de MACE, por lo que la normalización de 25(OH)D, además de mejorar la salud ósea, puede mejorar la salud cardiovascular

Background and objectives: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. Patients and methods: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. Results: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). Conclusions: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health

Effect of calcifediol treatment on cardiovascular outcomes in patients with acute coronary syndrome and percutaneous revascularization. / Efecto del tratamiento con calcifediol, sobre los episodios cardiovasculares en pacientes revascularizados tras síndrome coronario agudo.

BACKGROUND AND OBJECTIVES: Vitamin D deficiency has been consistently linked with cardiovascular diseases. However, results of intervention studies are contradictory. The aim of this study was to evaluate the effect of treatment with calcifediol (25(OH)D3) on the cardiovascular system of patients with non-ST-elevation acute coronary syndrome after percutaneous coronary intervention. PATIENTS AND METHODS: A prospective study assessing≥60-year-old patients with non-ST-elevation acute coronary syndrome, coronary artery disease and percutaneous revascularisation. We randomly assigned 41 patients (70.6±6.3 years) into 2 groups: Standard treatment+25(OH)D3 supplementation or standard treatment alone. Major adverse cardiovascular events (MACE) were evaluated at the conclusion of the 3-month follow-up period. 25(OH)D levels were analysed with regard to other relevant analytical variables and coronary disease extent. RESULTS: Basal levels of 25(OH)D≤50nmol/L were associated with multivessel coronary artery disease (RR: 2.6 [CI 95%:1.1-7.1], P=.027) and 25(OH)D≤50nmol/L+parathormone ≥65pg/mL levels correlated with increased risk for MACE (RR: 4 [CI 95%: 1.1-21.8], P=.04]. One MACE was detected in the supplemented group versus five in the control group (P=.66). Among patients with 25(OH)D levels≤50nmol/L at the end of the study, 28.6% had MACE versus 0% among patients with 25(OH)D>50nmol/L (RR: 1,4; P=.037). CONCLUSIONS: Vitamin D deficiency plus secondary hyperparathyroidism may be an effective predictor of MACE. A trend throughout the follow up period towards a reduction in MACE among patients supplemented with 25(OH)D3 was detected. 25(OH)D levels≤50nmol/L at the end of the intervention period were significantly associated with an increased number of MACE, hence, 25(OH)D level normalisation could improve cardiovascular health in addition to bone health.

High Serum Retinol as a Relevant Contributor to Low Bone Mineral Density in Postmenopausal Osteoporotic Women.

There is controversial information about the impact of vitamin A on bone. Some epidemiological studies show that excessive intake of vitamin A, or an excess of serum vitamin A, has related with adverse impact on bone mass; however, other studies did not find these links, and some authors have proposed that this vitamin might promote a better bone health. The present work aims to contribute to clarify the real role of vitamin A in bone tissue. For this purpose, a cross-sectional study of 154 osteoporotic non-treated postmenopausal women (> 65 years old) was carried out. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. We assessed concentrations of serum retinol, osteocalcin, parathyroid hormone, alkaline phosphatase, calcium, and phosphorus. We also studied demographic and anthropometric parameters. Spearman's correlations between retinol levels and other variables found negative correlations with BMD in both lumbar spine (R = - 0.162, P < 0.01) and femoral neck (R = - 0.182, P < 0.01), as well as alkaline phosphatase (R = - 0.110; P < 0.05) and phosphorus (R = - 0.110; P < 0.05). A positive correlation between retinol and fertile window was observed (R = 0.158; P < 0.01). After multivariable adjustment, we still found a negative correlation between serum retinol and BMD, both at the lumbar spine (R = - 0.210; P < 0.01) and at the femoral neck (R = - 0.324, P < 0.001). It is concluded that elevated serum-retinol levels are associated with an increased risk of low bone mass and thus with osteoporotic fractures. Therefore, osteoporosis-risk assessment should include quantification of serum metabolite of vitamin A.

Serum from postmenopausal women treated with a by-product of olive-oil extraction process stimulates osteoblastogenesis and inhibits adipogenesis in human mesenchymal stem-cells (MSC).

Aging may enhance both oxidative stress and bone-marrow mesenchymal stem-cell (MSC) differentiation into adipocytes. That reduces osteoblastogenesis, thus favoring bone-mass loss and fracture, representing an important worldwide health-issue, mainly in countries with aging populations. Intake of antioxidant products may help to retain bone-mass density. Interestingly, a novel olive-pomace physical treatment to generate olive oil also yields by-products rich in functional antioxidants. Thus, diet of postmenopausal women was supplemented for two months with one of such by-products (distillate 6; D6), being rich in squalene. After treatment, serum from such women showed reduced both lipidic peroxidation and oxidized low-density lipoprotein (LDL). Besides, vitamin E and coenzyme Q10 levels increased. Furthermore, culture medium containing 10% of such serum both increased osteoblastogenesis and reduced adipogenesis in human MSC from bone marrow. Therefore, highly antioxidant by-products like D6 may represent a relevant source for development of functional products, for both prevention and treatment of degenerative pathologies associated with aging, like osteoporosis.

Vitamin D3 and calcidiol are not equipotent.

Despite the discussion on the optimal threshold of 25-hydroxyvitamin D serum level continues, there is now consensus on the fact that post-menopausal and elderly populations have inadequate Vitamin D serum levels worldwide. The adjustment of these levels is necessary to improve both bone and general health, as it is to optimize bone response to antiresortive treatments. It is recommended, as endorsed by international clinical guides, to use Vitamin D3, the physiological form of Vitamin D, in a dose range between 600-2000IU. It should be administered on a daily basis or on its weekly or monthly equivalents. In Spain, the use of calcidiol (25(OH)D3) at the same dose than Vitamin D3 is the most extended prescription, notwithstanding the available evidence stating that they are not equipotent. This may lead to over-dosage. In order to provide evidence on this circumstance, a convenience study was performed. Four groups of ten post-menopausal osteoporotic women each (average age 67), deficient in Vitamin D ((25(OH)D 37.5±10 nmol/L)) were enrolled. Each group followed a different treatment regimen: (G1) vitamin D3 20µg/day [800IU/day]; (G2) 25 (OH)D3 20µg/day; (G3) 25(OH)D3 266µg/week and (G4) 25(OH)D3 0.266mg every two weeks. 25(OH)D levels were measured for each group at 0, 6 and 12 months, with the following results: G1 (40.5±4.7;80.0±2; 86.2±23.7), G2 (37,2±4.2; 161±21.7;188.0±24.0), G3 (38±3.7;213.5±80.0; 233.0±81.2), G4 (39.5±4;164.5±41,7;210.5±22.2). These data reveal that both metabolites are not equipotent. Calcidiol is faster and 3-6 times more potent to obtain serum levels of 25(OH)D in the medium to long term. This circumstance must be assessed and included in the therapeutic prescription guides for Osteoporosis, since it should be of concern when planning and prescribing treatments to normalize serum levels of 25(OH)D3 and avoid potential adverse impacts.

[Vitamin D, determinant of bone and extrabone health. Importance of vitamin D supplementation in milk and dairy products]. / Vitamina D, determinante de la salud ósea y extra ósea; importancia de su suplementación en la leche y derivados.

Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a proper supplementation of milk with vitamin D is an attractive chance and a challenge for Public Health of Spain and the European Union. It has provided excellent results in the US, Canada, Northern Europe Countries, etc.

La vitamina D se obtiene fundamentalmente a partir de la irradiación ultravioleta en la piel del 7-dehidrocolesterol para formar colecalciferol (vitamina D3) y mínimamente por la dieta, salvo que se tomen alimentos fortificados en vitamina D, fundamentalmente leche; en algunos países se emplea ergocalciferol (vitamina D2). En el hígado la vitamina D3 se hidroxila para formar 25-hidroxivitamina D3 (marcador del estatus nutricional corporal en vitamina D). La 25OHD3, se hidroxila para formar 1,25-dihidroxivitamina D3 (1,25OH)2D3 en el riñón, para controlar la homeostasis del calcio y la salud del hueso y en otras células o tejidos, mediante el estímulo del VDR, incluyendo piel, músculo, los sistemas cardiovascular e inmune, homeostasis de la glucosa, y proliferación celular en general; de tal manera, que alrededor del 3% del genoma humano está regulado por la hormona 1,25(OH)2 vitamina D3. Estudios de asociación describen acciones beneficiosas a nivel cardiovascular, hipertensión arterial, cáncer colorectal, de mama, esclerosis múltiple, función inmune e inflamación etc. Un objetivo mínimo irrenunciable, para la salud pública, debe ser conseguir niveles séricos de 25OHD superiores a 20 ng/ml, para asegurar un estatus óptimo para la salud ósea y preferiblemente mayor de 30 ng/ml, si nos proponemos alcanzar otros objetivos. "Paradójicamente" en España se da una elevada prevalencia de insuficiencia o incluso franca deficiencia de vitamina D en niños y jóvenes, persiste en adultos, en mujeres postmenopáusicas (osteoporóticas o no), o ancianos que viven en sus casas, y que es mayor si viven en residencias, con una variación estacional que apenas llega a normalizar los niveles séricos de 25OHD después del verano-otoño. También se ha demostrado una elevada prevalencia de niveles inadecuados de vitamina D en mujeres posmenopáusicas en tratamiento por osteoporosis con niveles de 25-hidroxivitamina D menores de 30 ng/ml y 20 ng/ml en el 63 y 30% respectivamente, lo que constituye un importante factor contribuyente a falta respuesta ósea al tratamiento. Una adecuación de niveles séricos de vitamina D, permitiría que la dieta proporcionara el calcio necesario para conseguir una buena salud ósea. Dada la dificultad para conseguir niveles adecuados de vitamina D por irradiación UV y por dieta, la suplementación adecuada de leche y derivados con vitamina D supone una atractiva posibilidad y un reto, para la Salud Pública de España y la Unión Europea, que ha dado excelentes resultados en EEUU, Canadá, Países de Norte de Europa, etc.

Vitamina D, determinante de la salud ósea y extra ósea; importancia de su suplementación en la leche y derivados / Vitamin D, determinant of bone and extrabone health. Importance of Vitamin D supplementation in milk and dairy products

La vitamina D se obtiene fundamentalmente a partir de la irradiación ultravioleta en la piel del 7-dehidrocolesterol para formar colecalciferol (vitamina D3) y mínimamente por la dieta, salvo que se tomen alimentos fortificados en vitamina D, fundamentalmente leche; en algunos países se emplea ergocalciferol (vitamina D2). En el hígado la vitamina D3 se hidroxila para formar 25-hidroxivitamina D3 (marcador del estatus nutricional corporal en vitamina D). La 25OHD3, se hidroxila para formar 1,25-dihidroxivitamina D3 (1,25OH)2D3 en el riñón, para controlar la homeostasis del calcio y la salud del hueso y en otras células o tejidos, mediante el estímulo del VDR, incluyendo piel, músculo, los sistemas cardiovascular e inmune, homeostasis de la glucosa, y proliferación celular en general; de tal manera, que alrededor del 3% del genoma humano está regulado por la hormona 1,25(OH)2 vitamina D3. Estudios de asociación describen acciones beneficiosas a nivel cardiovascular, hipertensión arterial, cáncer colorectal, de mama, esclerosis múltiple, función inmune e inflamación etc. Un objetivo mínimo irrenunciable, para la salud pública, debe ser conseguir niveles séricos de 25OHD superiores a 20 ng/ml, para asegurar un estatus óptimo para la salud ósea y preferiblemente mayor de 30 ng/ml, si nos proponemos alcanzar otros objetivos. 'Paradójicamente' en España se da una elevada prevalencia de insuficiencia o incluso franca deficiencia de vitamina D en niños y jóvenes, persiste en adultos, en mujeres postmenopáusicas (osteoporóticas o no), o ancianos que viven en sus casas, y que es mayor si viven en residencias, con una variación estacional que apenas llega a normalizar los niveles séricos de 25OHD después del verano-otoño. También se ha demostrado una elevada prevalencia de niveles inadecuados de vitamina D en mujeres posmenopáusicas en tratamiento por osteoporosis con niveles de 25-hidroxivitamina D menores de 30 ng/ml y 20 ng/ml en el 63 y 30% respectivamente, lo que constituye un importante factor contribuyente a falta respuesta ósea al tratamiento. Una adecuación de niveles séricos de vitamina D, permitiría que la dieta proporcionara el calcio necesario para conseguir una buena salud ósea. Dada la dificultad para conseguir niveles adecuados de vitamina D por irradiación UV y por dieta, la suplementación adecuada de leche y derivados con vitamina D supone una atractiva posibilidad y un reto, para la Salud Pública de España y la Unión Europea, que ha dado excelentes resultados en EEUU, Canadá, Países de Norte de Europa, etc (AU)

Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a proper supplementation of milk with vitamin D is an attractive chance and a challenge for Public Health of Spain and the European Union. It has provided excellent results in the US, Canada, Northern Europe Countries, etc (AU)

Stimulation of in-vitro angiogenesis by low concentrations of risedronate is mitigated by 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3.

The nitrogen-containing or nitrogenous bisphosphonates (N-BF) are currently the main class of drugs used for the treatment of diseases characterized by an increased bone resorption. Preliminary data suggest that N-BF have also direct or indirect anti-tumoral effects, and recent evidence suggests that part of the anti-tumoral activity of N-BF may be attributed to their anti-angiogenic capacity when they are used at high concentrations. On the other hand, an optimal vitamin-D status seems to be necessary to maximize the bone response to N-BF. Our aim has been to evaluate the effect of risedronate, alone or in combination with either 1,25(OH)2D3 or 24,25(OH)2D3 (two main vitamin-D metabolites) on parameters related to the angiogenic capacity of human umbilical-vein endothelial cells (HUVEC). The studies of tube formation through in-vitro angiogenesis assays with Matrigel, chemotaxis and migration in a scratch assay showed that low concentrations of risedronate (0.01 to 1µM) stimulated angiogenesis and cellular migration in vitro. The presence of 1,25(OH)2D3 in the medium inhibited tubular-structure formation and cellular migration. In addition, the presence of 1,25 or 24,25(OH)2D3 in the culture medium also decreased the pro-angiogenic effects of low-concentrations of risedronate. These data show the differential effects of different concentrations of vitamin-D metabolites and risedronate on angiogenesis, thus stressing the importance of an adequate vitamin D status during medical treatment with risedronate. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Síndrome coronario agudo y coronariografía sin lesiones significativas: ¿lo sabemos todo? / Acute coronary syndrome and coronariography without significant lesions: do we know everything?

Hasta en un 14% de los pacientes que presentan un síndrome coronario agudo (SCA) no se detectan obstrucciones coronarias. Frecuentemente el diagnóstico de la causa subyacente no se establece y existe controversia en cuanto al pronóstico. Los pacientes con SCA y coronarias normales o sin lesiones angiográficamente significativas son más frecuentemente mujeres, de edad joven y con menor incidencia de factores de riesgo cardiovascular (FRCV). Clásicamente el pronóstico ha sido excelente, aunque en los últimos años diferentes resultados demuestran una evolución no tan benigna. Esto podría explicarse por los diferentes grados de lesiones coronarias, la presentación clínica, la movilización de biomarcadores o los FRCV. Es necesario establecer la causa del SCA y estratificar el riesgo de estos pacientes para instaurar un tratamiento adecuado, especialmente en los casos de enfermedad coronaria no detectada por angiografía, donde la ausencia de tratamiento específico puede condicionar un peor pronóstico (AU)

Obstructive coronary artery disease is not detected in up to 14% of patients who present with acute coronary syndrome (ACS). Diagnosis of the underlying cause is usually not made and there is much controversy regarding prognosis. Those patients who develop ACS while having normal or near normal coronary arteries are more frequently young women and have fewer cardiovascular risk factors (CVRF). Its prognosis has typically been excellent. However, different results published in recent years show that these conditions are not always so benign. This might be explained by the different degrees of coronary obstruction, varied clinical presentation, biomarkers’ mobilization or CVRF. It is necessary to determine the cause of ACS and stratify the risk of these patients in order to establish the appropriate treatment. This is especially relevant in those cases of coronary disease not detected by angiography, in which the absence of specific treatment can lead to poorer prognosis (AU)

Vitamin D status and the Cdx-2 polymorphism of the vitamin D receptor gene are determining factors of bone mineral density in young healthy postmenopausal women.

UNLABELLED: Bone mineral density (BMD) is a main determinant of osteoporotic fractures. A cross-sectional study was conducted in 229 young, healthy postmenopausal women (PMW) to evaluate the contribution of the vitamin D endocrine system and other clinical, biochemical and genetic parameters. Clinical risk factors for osteoporosis were obtained by a questionnaire. Serum concentrations of 25OHD, 1,25(OH)2D, PTH, and bone turnover markers were measured. The BsmI, FokI and Cdx-2 polymorphisms of the vitamin D receptor (VDR) gene were determined. DXA and the WHO criteria were applied for the diagnosis of osteoporosis. Univariate logistic and multivariate logistic regression analyses were carried out. RESULTS: The prevalence of vitamin D deficiency (<50nmol/l) was 50%. Age increased osteoporosis risk; whereas body mass index (BMI), number of reproductive years, 25OHD level and the Cdx-2 polymorphism in the VDR gene (when allele A is present) were found to be protective. Therefore, both serum 25OHD and VDR polymorphism should be taken into account in the evaluation and implementation of therapeutic strategies concerning PMW, especially as the prevalence of vitamin D deficiency is still alarmingly high even at Southern latitudes. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

[Acute coronary syndrome and coronariography without significant lesions: do we know everything?]. / Síndrome coronario agudo y coronariografía sin lesiones significativas: ¿lo sabemos todo?

Obstructive coronary artery disease is not detected in up to 14% of patients who present with acute coronary syndrome (ACS). Diagnosis of the underlying cause is usually not made and there is much controversy regarding prognosis. Those patients who develop ACS while having normal or near normal coronary arteries are more frequently young women and have fewer cardiovascular risk factors (CVRF). Its prognosis has typically been excellent. However, different results published in recent years show that these conditions are not always so benign. This might be explained by the different degrees of coronary obstruction, varied clinical presentation, biomarkers' mobilization or CVRF. It is necessary to determine the cause of ACS and stratify the risk of these patients in order to establish the appropriate treatment. This is especially relevant in those cases of coronary disease not detected by angiography, in which the absence of specific treatment can lead to poorer prognosis.