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.

[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.

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.