Sun exposure influences the prognostic power of components of mineral metabolism in patients with coronary artery disease.

BACKGROUND AND AIM: Calcidiol (vitamin D metabolite) plasma levels vary with sun exposure (SE). However, it is not known if SE influences its prognostic ability. We have studied the effect of SE on plasma levels of the components of mineral metabolism (calcidiol, fibroblast growth factor-23 [FGF-23], parathormone [PTH], and phosphate [P]) and on their prognostic value in patients with coronary artery disease (CAD). METHODS AND RESULTS: We studied prospectively 704 patients with stable CAD. Clinical variables and baseline calcidiol, FGF-23, PTH, and P plasma levels were assessed. We divided the population in two subgroups, according to the period of plasma extraction: High SE (HSE) (April-September) and low SE (LSE) (October-March). The outcome was the development of acute ischemic events (acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Mean follow-up was 2.15 ± 0.99 years. Calcidiol and P levels were higher in HSE group. In the whole population, calcidiol (HR = 0.84 for each 5 ng/ml increase, 95% CI = 0.71-0.99; p = 0.038) and FGF-23 (HR = 1.14 for each 100 RU/ml increase, 95% CI = 1.05-1.23; p = 0.009) were predictors of the outcome, along with age, hypertension, body-mass index, peripheral artery disease, and P levels. In the LSE subgroup, calcidiol (HR = 0.75; 95% CI = 0.57-0.99; p = 0.034) and FGF-23 (HR = 1.34; 95% CI = 1.13-1.58; p = 0.003) remained as predictors of the outcome. In the HSE group calcidiol and FGF-23 had not independent prognostic value. CONCLUSIONS: In patients with stable CAD, low calcidiol and high FGF-23 plasma levels predict an adverse prognosis only when the sample is obtained during the months with LSE. SE should be taken into account in the clinical practice.

Parathormone Levels Are Independently Associated with the Presence of Left Ventricular Hypertrophy in Patients with Coronary Artery Disease.

BACKGROUND: Abnormalities of mineral metabolism and inflammation may affect the cardiovascular system. We have assessed the relationship of left ventricular hypertrophy (LVH) with inflammation and mineral metabolism. METHODS: LVH was measured in 146 outpatients with stable coronary artery disease (SCAD) using echocardiography. Calcidiol (a vitamin D metabolite), parathyroid hormone (PTH), fibroblast growth factor-23, high-sensitivity C-reactive protein, MCP-1 (monocyte chemoattractant protein-1), galectin-3, NGAL (neutrophil gelatinase-associated lipocalin), and sTWEAK (soluble TNF-related weak inducer of apoptosis) plasma levels were studied. RESULTS: LVH, defined as septal thickness ≥11 mm, was present in 19.9% of cases. These patients were older [75.0 (61.0-81.0) vs 64.0 (51.0-76.0) years; p=0.002], had higher prevalence of left ventricular ejection fraction (LVEF)>40%, and had higher PTH [84.7 (59.6-104.7) vs 63.2 (49.2-85.2) pg/ml; p=0.007], galectin-3 [9.6 (8.0-11.1) vs 8.3 (6.9-9.9) ng/ml; p=0.037], and NGAL (208.5±87.6 vs 173.9±73.4 ng/ml; p=0.031) plasma levels than those without LVH. Glomerular filtration rate was lower in patients with LVH than in those without it (65.1±20.0 vs 74.7±19.9 mL/min/1.73 m2; p=0.021). There were no significant differences in hypertension (79.3 vs 68.4%; p=0.363) or sex between both groups. Variables showing differences based on univariate analysis and hypertension were entered into a logistic regression analysis. Only age [odds ratio (OR) =1.052 (1.011-1.096); p=0.013], PTH plasma levels [OR=1.017 (1.003-1.031); p=0.021], and LVEF>40% [OR=7.595 (1.463-39.429); p=0.016] were independent predictors of LVH. CONCLUSIONS: In patients with SCAD, elevated PTH levels are independently associated with the presence of LVH. Further studies are needed to elucidate the role of PTH in the development of myocardial hypertrophy.

La menor proporción de parathormona circulante biológicamente activa en diálisis peritoneal no permite el ajuste intermétodo de parathormona establecida para hemodiálisis / A lower proportion of circulating active parathyroid hormone in peritoneal dialysis does not allow the pth inter-method adjustment proposed for haemodialysis

Introducción: la parathormona (PTH) presenta buena correlación con los parámetros histomorfométricos y bioquímicos de remodelado óseo, aunque su cuantificación presenta limitaciones por la variabilidad según el método empleado. La PTH circulante es una mezcla de péptidos, y solo la PTH 1-84 es responsable de su actividad. Los fragmentos carboxiterminales tienen acción antagónica y, al aclararse por el riñón, varía su proporción según el estadio de enfermedad renal crónica. Nos planteamos estudiar posibles diferencias en su proporción en función del tipo de diálisis: hemodiálisis (HD) o diálisis peritoneal (DP). Material y métodos: En 73 pacientes en DP (46 varones y 27 mujeres entre 22 y 82 años) se cuantificó calcio total (Ca) y iónico (Cai), fosforo (P), telopéptidos carboxiterminales del colágeno tipo I (BCTx) y PTH mediante seis métodos de segunda generación (uno isotópico (IRMA) y cinco inmunoquimioluminescentes (ECLIA) y por el único método PTH de tercera generación (IRMA) disponible en ese momento. Resultados: Las concentraciones medias de Ca, Cai, P y BCTx fueron respectivamente, 9.03, 4.76, 4.73 mg/dl y 1181 pmol/l. Se observaron diferencias significativas en la PTH dependiendo del método de segunda generación utilizado. Los valores de PTH ajustados al rango equivalente a 150-300 de la PTH Allegro de Nichols en los pacientes en DP fueron superiores a los obtenidos en el estudio previo de HD. El porcentaje de PTH 1-84 biológicamente activa y el ratio PTH 1-84/7-84 fueron significativamente menores, indicando que, a igualdad de valor de PTH intacta, el porcentaje de fragmentos 7-84 circulantes es mayor en los pacientes en DP. Conclusión: Los pacientes en DP tienen una mayor proporción de fragmentos 7-84 PTH. Por este motivo las fórmulas de corrección inter-método utilizadas en los pacientes en HD no son aplicables en DP. En este estudio sugerimos otras fórmulas para aplicar en DP (AU)

Introduction: Parathyroid hormone (PTH) shows a strong correlation with histomorphometric and biochemical parameters of bone turnover, however its measurement presents limitations due to inter-method variability. Circulating PTH is a mixture of peptides, but only on its whole form (1-84 PTH) is responsible of PTH biological activity. Carboxyl-terminal fragments exhibit antagonist actions and their proportion differs at each stage of chronic kidney disease, as consequence of differences on their renal clearance. The aim of this study is to evaluate possible differences in the proportion of these fragments according to dialysis type: haemodialysis (HD) or peritoneal dialysis (PD). Material and methods: Serum total (Ca) and ionized calcium (iCa), phosphate (P), carboxyl-terminal telopeptides of collagen type I (BCTx) were measured in 73 patients on PD (46 men and 27 women with an age between 22 and 82 years). PTH was quantified by six second generation assays (one isotopic and five chemiluminescence assays) and by one third generation PTH method. Results: Mean serum levels of Ca, iCa, P and BCTx were 9.03, 4.76, 4.73 mg/dl and 1181 pmol/l, respectively. Significant differences were observed in PTH values according to the method used. Adjustment of PTH results to PTH Allegro (Nichols) range of 150-300 nmol/l in PD patients showed higher values than those assessed previously for HD population. The percentage of biologically active 1-84 PTH as the 1-84 PTH/ 7-84 PTH ratio in PD were significantly lower than in HD patients, reflecting the higher proportion of 7-84 PTH circulating fragments for a given intact PTH result in PD. Conclusions: PD patients have a higher proportion of 7-84 PTH circulating fragments. Consequently, the inter-method adjustment algorithms proposed for HD patients are not useful for PD patients. This study proposes alternative algorithms for PTH inter-method adjustment to be applied in PD (AU)

A lower proportion of circulating active parathyroid hormone in peritoneal dialysis does not allow the pth inter-method adjustment proposed for haemodialysis.

INTRODUCTION: Parathyroid hormone (PTH) shows a strong correlation with histomorphometric and biochemical parameters of bone turnover, however its measurement presents limitations due to inter-method variability. Circulating PTH is a mixture of peptides, but only on its whole form (1-84 PTH) is responsible of PTH biological activity. Carboxyl-terminal fragments exhibit antagonist actions and their proportion differs at each stage of chronic kidney disease, as consequence of differences on their renal clearance. The aim of this study is to evaluate possible differences in the proportion of these fragments according to dialysis type: haemodialysis (HD) or peritoneal dialysis (PD). MATERIAL AND METHODS: Serum total (Ca) and ionized calcium (iCa), phosphate (P), carboxyl-terminal telopeptides of collagen type I (BCTx) were measured in 73 patients on PD (46 men and 27 women with an age between 22 and 82 years). PTH was quantified by six second generation assays (one isotopic and five chemiluminescence assays) and by one third generation PTH method. RESULTS: Mean serum levels of Ca, iCa, P and BCTx were 9.03, 4.76, 4.73 mg/dl and 1181 pmol/l, respectively. Significant differences were observed in PTH values according to the method used. Adjustment of PTH results to PTH Allegro (Nichols) range of 150-300 nmol/l in PD patients showed higher values than those assessed previously for HD population. The percentage of biologically active 1-84 PTH as the 1-84 PTH/ 7-84 PTH ratio in PD were significantly lower than in HD patients, reflecting the higher proportion of 7-84 PTH circulating fragments for a given intact PTH result in PD. CONCLUSIONS: PD patients have a higher proportion of 7-84 PTH circulating fragments. Consequently, the inter-method adjustment algorithms proposed for HD patients are not useful for PD patients. This study proposes alternative algorithms for PTH inter-method adjustment to be applied in PD.

Influence of colectomy on hydrogen excretion in breath.

INTRODUCTION: Hydrogen breath test is the most commonly used method to analyze carbohydrate absorption and diagnose carbohydrate malabsorption. The result of the H(2) breath test is influenced by different factors, which are mostly related to quantitative or qualitative aspects of colonic flora. A scarcely studied variable is the effect of colonic anatomical integrity on H(2) excretion in breath. PURPOSE: The present study aims to determine whether loss of colonic integrity reduces H(2) excretion capacity after an oral load of an unabsorbable carbohydrate. METHODS: An observational study was conducted in three patient groups: controls with preserved colon, patients with partial colectomy, and patients with complete colectomy and ileostomy. H(2) concentration in breath was measured by gas chromatography every 10 min for 3 h after oral lactulose administration. RESULTS: Twenty-two patients with partial colectomy, 18 controls with preserved colon, and seven patients with ileostomy were included. H(2) excretion after lactulose did not differ between patients with partial colectomy and controls (basal excretion = 8.5 vs 4 ppm; delta increase = 50.0 vs 47.5 ppm; area under the curve = 4,480.0 vs 4,710.5 ppm/min). In contrast, H(2) excretion was significantly lower in the ileostomy group. CONCLUSIONS: Partial colectomy does not influence the capacity for H(2) excretion after oral unabsorbable carbohydrate administration.

Development, validation, and applicability of a symptoms questionnaire for lactose malabsorption screening.

UNLABELLED: Lactase deficiency has a high prevalence worldwide. Thus, a valid symptom scale would be a useful tool for identifying patients with lactose malabsorption. OBJECTIVE: To develop, validate, and apply a symptoms questionnaire on lactose malabsorption to identify lactose malabsorbers diagnosed with the gold-standard hydrogen breath test. METHODS: In the first part of the study, 292 patients completed a questionnaire at the end of a 50-g lactose breath test. The questionnaire included five items (diarrhea, abdominal cramping, vomiting, audible bowel sounds, and flatulence or gas) scored on a 10-cm visual analogue scale. In the second part of the study, 171 patients completed the questionnaire twice: first, according to their opinion when consuming dairy products at home and second, after a 50-g lactose breath test. Patients were grouped as absorbers or malabsorbers according to the result of the breath test. RESULTS: Diarrhea, abdominal cramping, and flatulence were scored significantly higher in malabsorbers than in absorbers. Total score of the symptomatic questionnaire was significantly higher in malabsorbers (17.5 versus 3.0, P<0.01). According to receiver operator characteristics (ROC) analysis, the most discriminant cut-off of the total score to identify lactose malabsorption was 6.5 (sensitivity 0.75, specificity 0.67). In 58 malabsorbers the effect size of the questionnaire to determine sensitivity to change was 1.32. In the second part of the study, scoring of the home questionnaire was higher than after the lactose-breath test. The lactose malabsorbers rate was higher according to the home questionnaire than after the lactose breath test (72% versus 52%). The home questionnaire had excellent sensitivity (0.82) but low specificity (0.35). CONCLUSION: We developed and validated a five-item symptoms questionnaire for lactose malabsorption. This is a valid test that permits patients with a total score lower than 7 to be excluded from future studies.

[High prevalence of vitamin D deficiency in postmenopausal women at a rheumatology office in Madrid. Evaluation of 2 vitamin D prescription regimens]. / Alta prevalencia de deficiencia de vitamina D en mujeres posmenopáusicas de una consulta reumatológica en Madrid. Evaluación de dos pautas de prescripción de vitamina D.

BACKGROUND: Vitamin D deficiency has been frequently observed in the elderly population in Europe. However few information is available about the vitamin D status in postmenopausal women in the Mediterranean countries. The aim of this study was to evaluate the vitamin D status assessed by serum 25(OH)D3 (calcidiol) in postmenopausal women who attended a Rheumatology practice in Madrid area, and to evaluate calcidiol serum levels through one year after two forms of vitamin D administration. PATIENTS AND METHODS: Calcidiol serum levels were measured in 171 postmenopausal women (111 with osteoporosis and 60 without osteoporosis). 82 women with calcidiol serum levels < 10 ng/ml were distributed in two groups: Group I received 800 U/day of vitamin D3 associated with calcium (1 g/day) and group II, one dose of 80,000 U vitamin D orally as calcidiol and latter a daily dose of 800 U vitamin D3 plus 1 g calcium. Calcidiol serum levels were measured by RIA in both groups at basal condition and after three, six and twelve months under treatment. RESULTS: Three cut-offs were considered: 10, 15 and 20 ng/ml of calcidiol. Percentages of postmenopausal women with vitamin D deficiency for such cut-offs were: 35.3%, 64.1% and 87.1%, respectively. After three months of treatment, women from group II showed calcidiol serum levels higher than group I. At six and twelve months calcidiol serum levels were similar in both groups. CONCLUSIONS: A high prevalence of vitamin D deficiency was observed in a group of postmenopausal women who attended a rheumatology practice in Madrid area. Both forms of vitamin D administration seem not sufficient to maintain the adequate calcidiol serum levels in postmenopausal deficient women. A dose of 80,000 U of calcidiol twice a year should be considered.

Alta prevalencia de deficiencia de vitamina D en mujeres posmenopáusicas de una consulta reumatológica en Madrid. Evaluación de dos pautas de prescripción de vitamina D / High prevalence of vitamin D deficiency in postmenopausal women in a outpatient rheumatological clinic from Madrid area (Spain). Evaluation of two forms of vitamin D prescription

Fundamento: Se ha descrito una elevada frecuencia de deficiencia de vitamina D en la población senil en Europa, pero hay poca información sobre la prevalencia de deficiencia de esta vitamina en la población posmenopáusica en países mediterráneos. El objetivo de este estudio ha sido valorar su prevalencia en mujeres posmenopáusicas procedentes de una consulta reumatológica y evaluar la vitamina D durante un año tras dos pautas de tratamiento. Pacientes y métodos: Se valoró el 25(OH)D3 (calcidiol) sérico en 171 mujeres posmenopáusicas (111 con osteoporosis y 60 sin ella) procedentes de una consulta de reumatología en Madrid. Un grupo seleccionado de 83 mujeres con concentraciones de calcidiol inferiores a 10 ng/ml fue aleatorizado en dos grupos: al grupo I se le prescribieron 800 U/día de vitamina D3 y 1 g/día de calcio, y al grupo II una dosis de 80.000 U de vitamina D3 en forma de calcidiol, seguida de 800 U/día de vitamina D3 junto a 1 g/día de calcio. El calcidiol se cuantificó por RIA en situación basal y a los 3, 6 y 12 meses de tratamiento. Se establecieron tres puntos de corte: 10, 15 y 20 ng/ml de calcidiol para calcular la prevalencia de deficiencia. Resultados: Los porcentajes de mujeres con deficiencia de vitamina D considerada como calcidiol < 10, < 15 o < 20 ng/ml fueron: el 35,3, el 64,1 y el 87,1 por ciento, respectivamente. Tras el tratamiento el calcidiol en el grupo II fue mayor que en el grupo I a los 3 meses. El porcentaje de mujeres con concentraciones superiores a 10 y 15 ng/ml fue mayor en el grupo II que en el grupo I. Sin embargo, los valores de calcidiol se igualaron a los 6 y 12 meses. Conclusión: Se observa una elevada prevalencia de deficiencia de vitamina D en un grupo de mujeres posmenopáusicas que acudieron a una consulta reumatológica en Madrid. Ambas pautas de administración de vitamina D parecen ser insuficientes para mantener las concentraciones adecuadas de calcidiol sérico. Debería considerarse una pauta de 80.000 U dos veces al año. (AU)

Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density.

To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women (aged 47-66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37 nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above 37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin D supplementation should therefore be considered in this population during the winter season.

Effects of age, menopause and osteoporosis on free, peptide-bound and total pyridinium crosslink excretion.

We evaluated urinary excretion of free pyridinoline (PYD)-deoxypyridinoline (DPD) by an enzymelinked immunosorbent assay (ELISA) method, free and total PYD by high-performance liquid chromatography (HPLC), free DPD by ELISA, chemiluminiscent immunoassay (CLEIA) and HPLC, total DPD by HPLC, and N-telopeptides (NTX) and C-telopeptides (CTX) by ELISA in 234 women distributed into three groups: 43 healthy young women (aged 26.2 +/- 2.5 years), 56 control postmenopausal women (aged 55.9 +/- 4.5 years) and 133 untreated osteoporotic women (aged 55.1 +/- 4.0 years). The control postmenopausal women had increased values of all markers considered, except NTX, compared with healthy young women. The osteoporotic postmenopausal women had significantly increased values compared with control postmenopausal women for free DPD by HPLC and free DPD by ELISA or CLEIA. HPLC, ELISA and CLEIA showed adequate correlation to measure free PYD and DPD. Control postmenopausal women had significantly decreased values of the fraction of free PYD and DPD (48.4% and 32.0%, respectively), as did the osteoporotic postmenopausal women (48.0% and 46.1%), compared with healthy young women (55.3% and 57.0%). We found a significant negative correlation comparing age with fraction of free PYD and DPD, but a positive correlation with total PYD and DPD, considering or not the osteoporotic postmenopausal women. T-score and Z-score values derived from healthy young women and control postmenopausal women for PYD, DPD, NTX and CTX measured by immunoassays were calculated to detect changes in bone turnover, DPD by ELISA or CLEIA showing the highest Z-score. The sensitivity and specificity of the different assays were evaluated using a receiver operating characteristic (ROC) curve. With a specificity of 90% the sensitivity of the markers considered was low (from 33% for DPD by CLEIA to 11% for PYD-DPD by ELISA), but increased considerably with a specificity of 75%. In conclusion, urinary pyridinium crosslink derivatives increase with age and after the menopause, and rise slightly in women with osteoporosis, there being a negative correlation among age and the fraction of free PYD and DPD of the total urinary excretion. Among the resorption markers most often available in clinical laboratories, free DPD by ELISA or CLEIA was the best at discriminating osteoporotic postmenopausal women from aged-matched control postmenopausal women.

Cathepsin D in breast cancer tissue.

The cathepsin D concentration in 18 women with benign breast pathology has a cut-off value of 43 pmol/mg of protein. High values have been detected in two cases of chronic mastitis. These high values of cathepsin D were found in a study of 62 patients suffering from breast cancer and are independent of the hormone dependent state of the tumour. The cathepsin D concentration may have a prognostic function in breast cancer determination, as high concentrations are found in combination with other prognostic factors such as clinical stage, size of the tumour, state of the axillary lymph nodes and in the histological differentiation grade, where from a statistical point of view, the combination is important.