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.

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 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)