Parathormone, vitamin D and the risk of atrial fibrillation in older adults: A prospective study.

BACKGROUND & AIMS: Vitamin D and parathormone (PTH) have been associated with cardiovascular outcomes, but their impact on atrial fibrillation (AF) onset is still unclear. We explored the influence of serum 25-hydroxyvitamin D (25[OH]D) and PTH on AF risk in older adults. METHODS AND RESULTS: Data come from 2418 participants enrolled in the Progetto Veneto Anziani study. Serum 25(OH)D and intact PTH were measured using radioimmunoassay and two-site immunoassay, respectively. The associations between 25(OH)D, PTH and adjudicated AF cases over 4-years were explored by Cox regression. Over the follow-up, 134 incident cases of AF were assessed. The incidence rate of the sample was 13.5 (95%CI 11.4-15.9) per 1000 person-years, and was higher among those with high PTH levels (high: 16.4 [95%CI 11.3-24.0] per 1000 person-years), especially when associated to low 25(OH)D (20.3 [95%CI 12.9-32.3] per 1000 person-years). At Cox regression, only high PTH was significantly associated to an increased risk of AF (HR = 1.90, 95%CI 1.27-2.84). A marginal significant interaction (p = 0.06) was found between 25[OH]D and PTH concentrations in influencing AF risk. When exploring the risk of AF for combined categories of 25(OH)D and PTH, we found that those with high PTH and low 25(OH)D levels had an AF risk twice as high as that of people with normal values (HR = 2.09, 95%CI 1.28-3.42). CONCLUSION: The risk of AF may be increased by high PTH levels, especially when associated with 25(OH)D deficiency. The identification and treatment of high PTH or vitamin D deficiency may thus contribute to lower the risk of AF.

Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison's disease on glucocorticoid and mineralocorticoid replacement therapy.

PURPOSE: to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids. METHODS: A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification. RESULTS: Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine. CONCLUSIONS: Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.

Extranodal extension of lymph node metastasis influences recurrence in prostate cancer: a systematic review and meta-analysis.

The extranodal extension (ENE) of nodal metastasis involves the extension of neoplastic cells through the lymph node capsule into the perinodal adipose tissue. This morphological feature has recently been indicated as an important prognostic factor in various cancer types, but its role in prostate cancer is still unclear. We aimed to clarify it, performing the first meta-analysis on this issue, comparing prognostic parameters in surgically treated, node-positive prostate cancer patients with (ENE+) vs. without (ENE-) ENE. Data were summarized using risk ratios (RRs) for number of deaths/recurrences and hazard ratios (HRs), with 95% confidence intervals (CI), for the time-dependent risk related to ENE positivity. Six studies followed-up 1,113 patients with N1 prostate cancer (658 ENE+ vs. 455 ENE-) for a median of 83 months. The presence of ENE was associated with a significantly higher risk of biochemical recurrence (RR = 1.15; 95%CI: 1.03-1.28; I2 = 0%; HR = 1.40, 95%CI: 1.12-1.74; I2 = 0%) and "global" (biochemical recurrence and distant metastasis) recurrence (RR = 1.15; 95%CI: 1.04-1.28; I2 = 0%; HR = 1.41, 95%CI: 1.14-1.74; I2 = 0%). ENE emerged as a potential prognostic moderator, earmarking a subgroup of patients at higher risk of recurrence. It may be considered for the prognostic stratification of metastatic patients. New possible therapeutic approaches may explore more in depth this prognostic parameter.

Low vitamin D levels increase the risk of type 2 diabetes in older adults: A systematic review and meta-analysis.

Low serum levels of 25 hydroxyvitamin D (25OHD) (hypovitaminosis D) is common in older adults and associated with several negative outcomes. The association between hypovitaminosis D and diabetes in older adults is equivocal, however. We conducted a meta-analysis investigating if hypovitaminosis D is associated with diabetes in prospective studies among older participants. Two investigators systematically searched major electronic databases, from inception until 10/07/2016. The cumulative incidence of diabetes among groups was estimated according to baseline serum 25OHD levels. Random effect models were used to assess the association between hypovitaminosis D and diabetes at follow-up. From 4268 non-duplicate hits, 9 studies were included; these followed 28,258 participants with a mean age of 67.7 years for a median of 7.7 years. Compared with higher levels of 25OHD, lower levels of 25OHD were associated with a higher risk of developing diabetes (6 studies; n=13,563; RR=1.31; 95% CI: 1.11-1.54; I2=37%). The findings remained significant after adjusting for a median of 11 potential confounders in all the studies available (9 studies; n=28,258; RR=1.17; 95% CI: 1.03-1.33; p=0.02; I2=0%). In conclusion, our data suggest that hypovitaminosis D is associated with an elevated risk of future diabetes in older people. Future longitudinal studies are required and should seek to confirm these findings and explore potential pathophysiological underpinnings.

Inflammation and frailty in the elderly: A systematic review and meta-analysis.

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Imaging of sarcopenia.

Sarcopenia is currently considered a geriatric syndrome increasing in older people. The consequences of sarcopenia - in terms of impaired mobility, limited self-sufficiency and disability - have been amply demonstrated, increasing the need to develop methods to identify muscle mass loss as early as possible. Although sarcopenia involves a reduction in both muscle mass and function, loss of muscle mass remains the essential criterion for diagnosing this condition in daily practice. Computed tomography and magnetic resonance imaging represent the gold standard for studying body composition, and can identify quantitative and qualitative changes in muscle mass. These techniques are costly, time-consuming and complex, however, so their applicability is limited to the research field. Sonography, on the other hand, has the advantage of being a relatively quick and inexpensive method for detecting loss of muscle fibers and fat infiltration by analyzing muscle thickness and echo intensity. To the best of our knowledge, however, only few studies have compared the results of ultrasound with those obtained by other methods in order to establish its reliability in this setting. Dual X-ray absorptiometry thus remains the most often used technology for studying body composition, detecting quantitative changes in muscle mass with the advantages of a low radiation dose, a simple technology and a rapid assessment.