Effectiveness and Satisfaction with Telemedicine in Geriatric Patients at High Risk of Fragility Fractures.

Background: Telemedicine has increasingly widespread to improve the monitoring of patients with chronic diseases. Secondary prevention of fragility fractures is an urgent matter to be addressed by means of available technology, although supported by little evidence so far. We investigated the feasibility, efficacy, and satisfaction of managing older adults at high risk of fragility fractures during the COVID-19 lockdown. Methods: During the period January to July 2021, a prospective observational study for safety and adherence purposes was conducted among older adults (n = 407) with ongoing treatments for secondary prevention of fragility fractures. The study procedures comply with national and regional resolutions related to telemedicine service (TS), including equipment, staff behaviors, and patient reports. Results: A majority (86.48% [n = 352]) of the eligible patients joined the remote visits, mainly women (88.2%), 81.4 ± 8.8 years of age, 49.6% independent in 5 out of 6 BADL, despite high comorbidity (4.9 ± 1.5), and polypharmacy (4.9 ± 3.1). Almost all were on second-line antifracture treatments (95.58%) due to previous major (84.03%) and minor (42.5%) fragility fractures. About 58% reported good and very good reliability of the internet network, allowing easy access to the TS platform, and 54% declared the degree of satisfaction with TS as good and very good. About 75% of clinicians acknowledged the efficacy of TS and expressed willingness to recommend the use of TS to colleagues. Ultimately, 68% of specialists defined the time allocated for patients' remote visits as acceptable. Conclusion: TS may be an opportunity to improve the availability of appropriate health care services to satisfy patients' needs and optimize health care resource allocation.

Bone Health Care Pathway for Non-metastatic Prostate Cancer Patients on Radiation and Androgen Deprivation Therapy.

BACKGROUND/AIM: Survival rates of prostate cancer (PCa) patients have improved considerably as a result of earlier diagnosis and therapies, including radiotherapy (RT) and androgen deprivation therapy (ADT). Patients on ADT develop cancer treatment-induced bone loss (CTIBL) and a high risk of fragility fractures. Bone health (BH) assessment is strongly recommended, together with timely initiation of treatments, to counteract CTIBL and preserve bone strength. Therefore, we decided to develop an interdisciplinary pathway of care (IPC) dedicated to non-metastatic PCa patients on long-term ADT and RT. PATIENTS AND METHODS: An interdisciplinary team allocated resources to support an IPC to manage patients' CTIBL and prevent fragility fractures. The team provided a diagnostic and therapeutic workflow according to patients' and professional perspectives, consistent with recommendations and healthcare policies. The hospital's quality department certified the IPC, the Ethical Committee approved procedures over the workflow. The Fracture Liaison Service (FLS) standards inspired services and professionals' activities and interactions. RESULTS: Preliminary data support the feasibility of the IPC from professionals' and patients' perspectives. Median age of the enrolled patients was 75 years, more than a half (58.9%) had low grade osteopenia or normal BMD (T-score ≥-1.5 standard deviation, SD), while 23.5% and 17.6% had osteoporosis and osteopenia, respectively. The IPC meets the requirements of a FLS concerning crucial indicators. CONCLUSION: Our IPC was a suitable approach to assure timely identification, assessment, initiation, and monitoring of adherence to anti-fracture treatments among non-metastatic PCa patients on long-term ADT and RT. Further data are required to show its effectiveness on fragility fracture prevention.

Obesity and Bone: A Complex Relationship.

There is a large literature on the relationship between obesity and bone. What we can conclude from this review is that the increase in body weight causes an increase in BMD, both for a mechanical effect and for the greater amount of estrogens present in the adipose tissue. Nevertheless, despite an apparent strengthening of the bone witnessed by the increased BMD, the risk of fracture is higher. The greater risk of fracture in the obese subject is due to various factors, which are carefully analyzed by the Authors. These factors can be divided into metabolic factors and increased risk of falls. Fractures have an atypical distribution in the obese, with a lower incidence of typical osteoporotic fractures, such as those of hip, spine and wrist, and an increase in fractures of the ankle, upper leg, and humerus. In children, the distribution is different, but it is not the same in obese and normal-weight children. Specifically, the fractures of the lower limb are much more frequent in obese children. Sarcopenic obesity plays an important role. The authors also review the available literature regarding the effects of high-fat diet, weight loss and bariatric surgery.

Effects of Weekly Supplementation of Cholecalciferol and Calcifediol Among the Oldest-Old People: Findings From a Randomized Pragmatic Clinical Trial.

Vitamin D inadequacy is pervasive in the oldest-old. Many vitamin D metabolites are available for supplementation, their effects on the recovery of adequate serum levels remain unknown. We investigate the effects of supplementation with cholecalciferol (D3) and calcifediol (25D3) on serum levels of 25(OH)D, 1-25(OH)D, bone and inflammatory markers, ultimately identifying clinical predictors of successful treatment. Sixty-seven oldest-old individuals were randomized to weekly administration of 150 mcg of 25D3 or D3, from hospital admission to 7 months after discharge. Supplementation of 25D3 and D3 were associated with increasing serum levels of 25(OH)D (p < 0.001) and 1-25(OH)D (p = 0.01). Participants on 25D3 experienced a steeper rise than those on D3 (group*time interaction p = 0.01), after adjustment for intact parathyroid hormone (iPTH) levels the differences disappeared (intervention*iPTH interaction p = 0.04). Vitamin D supplementation was associated with a decreasing trend of iPTH and C-reactive protein (CRP) (p < 0.001). Polypharmacy and low handgrip strength were predictors of failure of intervention, independent of vitamin D metabolites. In conclusion, D3 and 25D3 supplementation significantly increase vitamin D serum levels in the oldest-old individuals, with a tendency of 25D3 to show a faster recovery of acceptable iPTH levels than D3. Polypharmacy and low muscle strength weaken the recovery of adequate vitamin D serum levels.

Effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients discharged from acute care hospitals.

AIM: To comparatively investigate the effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients after hospital discharge. METHODS: Our series consisted of 733 patients aged ≥65 consecutively enrolled in a multicenter observational longitudinal study. PIMs were defined on the basis of updated versions of Beers and STOPP criteria. The occurrence of functional decline was defined as the loss of independency in at least 1 basic activity of daily living (BADL) from discharge through 3-month follow-up visit. RESULTS: After adjusting for several potential confounders, hyperpolypharmacy (OR = 2.20; 95%CI = 1.11-4.37) and Beers violations (OR = 1.99; 95%CI = 1.17-3.49) were significantly associated with functional decline, while STOPP (OR = 1.10; 95%CI = 0.64-1.88) and combined Beers + STOPP violations (OR = 1.72; 95%CI = 0.97-3.05) were not. In logistic regression models simultaneously including both hyperpolypharmacy and PIMs, hyperpolypharmacy was always associated with functional decline (OR = 1.98; 95%CI = 1.0-3.97 in the model including Beers violations; OR = 2.19; 95%CI = 1.11-4.35 in the model including STOPP violations; OR = 2.04; 95%CI = 1.02-4.06 in the model including combined Beers and STOPP violations). Beers violations (OR = 1.89; 95%CI = 1.09-3.28) also remained significantly associated with the outcome in this latter analysis, but not STOPP or combined Beers and STOPP violations. CONCLUSIONS: Hyperpolypharmacy, and to a lesser extent Beers violations predict functional decline in older patients discharged from acute care hospitals, whilst STOPP criteria are no longer associated with the outcome after adjusting for potential confounders. Hyperpolypharmacy is associated with functional decline independent of PIMs.

Tranexamic Acid in Pertrochanteric Femoral Fracture: Is it a Safe Drug or Not?

BACKGROUND: There is a high incidence of blood transfusion following hip fractures in elderly patients. AIM: The aim of this study is to evaluate the effectiveness and complications of use of tranexamic acid in proximal femur nailing surgery. MATERIALS AND METHODS: Our sample group consisted of 90 patients suffering from pertrochanteric fractures surgically treated with osteosynthesis with SupernailGT(LimaCorporate). The classification system AO/OTA was used to divide the fractures into 31A1 (n=45) and 31A2 (n=45). The patients were divided into two groups: 47 patients were administered 15 mg of tranexamic acid per kg (group A) and 43 patients were administered placebo (group B). Blood counts were monitored daily to evaluate the rate of anemia. As a safety criterion, we monitored the possible occurrence of vascular events, symptomatic or not, over the 8 weeks post-surgery. Markers predicting mortality and deep venous thrombosis (DVE) were also monitored (fibrinogen D-dimer). RESULTS: Blood loss occurring post-surgery can be influenced by numerous factors that are not linked to the use or non-use of tranexamic acid. While closely monitoring hemoglobin levels daily, we observed that 42% of the patients in group A required blood transfusion as opposed to 60% in group B. The results of the markers predicting mortality (alpha1-acid glycoprotein; albumin LDL) and those of DVE were not statistically significant between the two groups in this study (p>0.05). CONCLUSION: Based on this study, the use of tranexamic acid was statistically significant in reducing post-surgery blood loss.

The Relationship Between Urinary Total Polyphenols and the Frailty Phenotype in a Community-Dwelling Older Population: The InCHIANTI Study.

BACKGROUND: Frailty, an age-related state of increased vulnerability, is associated with a higher risk of multiple adverse events. Studies have suggested that the quality of dietary intake may affect the development of frailty. We hypothesized that frailty in older subjects would be associated with dietary total polyphenols (DTP) intake and its biomarker, urinary total polyphenols (UTP). METHODS: The Invecchiare in Chianti (InCHIANTI) Study is a prospective cohort study set in the Chianti area (Italy). We used data at baseline from 811 participants aged 65 years and older. UTP was determined using the Folin-Ciocalteu assay after solid-phase extraction. DTP was estimated using a validated Food Frequency Questionnaire and our own polyphenol database. The frailty, prefrailty, and nonfrailty states were defined according to the Fried and colleagues' criteria. Multinomial logistic regressions adjusted for potential confounders were used to assess the relationship between polyphenols and frailty. RESULTS: Both DTP and UTP concentrations progressively decrease from nonfrail to frail participants. Participants in the highest UTP tertile compared to those in the lowest tertile were significantly less likely to be both frail (odds ratio [OR] = 0.36 [0.14-0.88], p = .025) and prefrail (OR = 0.64 [0.42-0.98], p = .038). Exhaustion and slowness were the only individual frailty criteria significantly associated with UTP tertiles. No significant association was observed between frailty and DTP, after adjustment for covariates. CONCLUSIONS: High concentrations of UTP were associated with lower prevalence of frailty and prefrailty in an older community-dwelling population. A polyphenol-rich diet may protect against frailty in older persons. Our findings should be confirmed in longitudinal studies.

Polypharmacy and health outcomes among older adults discharged from hospital: results from the CRIME study.

AIM: To investigate if older adults using multiple drugs have an increased risk of rehospitalization and mortality after hospital discharge. METHODS: This was a prospective cohort study carried out in acute care hospitals. The primary outcomes of the study were rehospitalization and mortality within 1 year after discharge from acute care hospitals. The study population was categorized in two groups according to the number of drugs prescribed at hospital discharge: no polypharmacy (<8 drugs) and polypharmacy (≥8 drugs). RESULTS: The mean age of 480 participants was 78.6±6.8 years ,and half of them (n=238; 49.6%) were using multiple drugs (≥8 drugs). Overall, 65 out of 242 participants (26.9%) in the no polypharmacy group and 92/238 (39.1%) in the polypharmacy group were rehospitalized (P=0.004), and 15 out of 242 (6.2%) in the no polypharmacy and 23 out of 238 (9.7%) in the polypharmacy group died during the 1 year follow up (P=0.16). After adjusting for potential confounders, participants in the polypharmacy group had an increased risk of 1-year rehospitalization as compared with those in the no polypharmacy group (RR=1.81, 95% CI=1.18-2.75). No significant association was observed between mortality and polypharmacy. CONCLUSIONS: Older persons using multiple drugs are at increased risk of rehospitalization. Further studies are required to assess the impact of programs aimed at reducing polypharmacy on health outcomes.

Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease.

Alzheimer disease (AD) is an age-related neurodegenerative condition. AD is histopathologically characterized by the presence of three main hallmarks: senile plaques (rich in amyloid-ß peptide), neuronal fibrillary tangles (rich in phosphorylated tau protein), and synapse loss. However, definitive biomarkers for this devastating disease in living people are still lacking. In this study, we show that levels of oxidative stress markers are significantly increased in the mitochondria isolated from lymphocytes of subjects with mild cognitive impairment (MCI) compared to cognitively normal individuals. Further, an increase in mitochondrial oxidative stress in MCI is associated with MMSE score, vitamin E components, and ß-carotene. Further, a proteomics approach showed that alterations in the levels of thioredoxin-dependent peroxide reductase, myosin light polypeptide 6, and ATP synthase subunit ß might be important in the progression and pathogenesis of AD. Increased understanding of oxidative stress and protein alterations in easily obtainable peripheral tissues will be helpful in developing biomarkers to combat this devastating disorder.

Predictors of hospitalization in Italian nursing home residents: the U.L.I.S.S.E. project.

OBJECTIVE: To examine resident and facility characteristics associated with hospitalization in a cohort of Italian older nursing home residents. DESIGN: A longitudinal observational study. SETTING: The nursing homes participating in the U.L.I.S.S.E. study, a project evaluating the quality of care for older persons in Italy. SETTING PARTICIPANTS: Nursing home residents in 31 Italian nursing homes. MEASUREMENT: Each resident underwent a comprehensive geriatric assessment at baseline, and after 6 months and 1 year by means of the RAI MDS 2.0. Facility characteristics were collected using an ad hoc designed questionnaire. Hospitalizations were self-reported by facilities. RESULTS: A total of 170 (11.6%) of 1466 nursing home residents were admitted to the hospital at least once during the study period. Female gender and higher physician, nurse, and nursing assistant hours per resident were predictive of a lower probability to be admitted to the hospital, whereas a diagnosis of arrhythmia, a previous urinary tract infection, and polypharmacy were associated with a higher probability of being hospitalized. CONCLUSION: These findings suggest that a reduction of hospitalization of nursing home residents could be achieved by providing an adequate amount of care and optimizing the management of chronic diseases and polypharmacy. This hypothesis should be tested in future clinical trials.

Prior antiplatelet drug use and short-term mortality in older patients with acute ischemic stroke (AIS).

Some studies suggest that previous treatment with antiplatelet agents (AA) might reduce ischemic stroke severity and improve outcomes in terms of clinical deficits or mortality. We evaluated the effect of the prior chronic use of AA on short-term (30 days) mortality in a sample of consecutive patients with AIS. Four hundred thirty-nine older patients (>65 years) with "major" AIS (modified Rankin scale ≥ 3) consecutively admitted to the University ward of Internal Medicine or Geriatrics were enrolled. Stroke was classified according to Oxfordshire Community Stroke Project (OCSP). Data recorded included: (1) clinical features; (2) medical history including home therapies, and vascular risk factors; (3) routine clinical chemistry analyzes (verb)/analyses (noun). Short-term (30 days) mortality was 27.6%. One hundred fifteen subjects (26.2%) were taking AA before admission. Compared with subjects not treated, subjects taking AA were characterized by higher prevalence of recurrent stroke (35% vs. 22%). In this group, a trend toward a higher prevalence of congestive heart failure (CHF), smoking, and altered levels of consciousness (ALC) was noted. Stroke type and short-term mortality (33% vs. 26.2%; odds ratio=OR=1.25; 95% confidence interval=CI=0.75-2.10, age and gender adjusted) were not different between the two groups. Adjustment for glucose, CHF, previous stroke, smoking, and ALC did not change mortality risk (OR=0.83; 95%CI=0.40-1.72). We conclude that in older patients hospitalized for "major" AIS, prior use of AA was not associated with any benefit in terms of short-term mortality both in patients with first, as well as in those with recurrent ischemic stroke.

The prevention of adverse drug reactions in older subjects.

Adverse drug reactions (ADRs) are a public health problem in older subjects, being responsible for a significant morbidity, disability and mortality. Older subjects are more susceptible to develop ADRs mainly due to polypharmacy, multimorbidity and inappropriate prescribing. The prevention of these drug related negative events represents an important aim for physicians treating older patients. Several strategies could potentially be employed, including state of the art education of medical students and physicians concerning principles of geriatric medicine and appropriate prescription in older subjects, reduction of inappropriate drug use by means of computerized decision support systems, pharmacist involvement and comprehensive geriatric assessment, and finally the identification of at risk older patients. However, there is currently a lack of scientific evidence demonstrating that these strategies can achieve a reduction in ADRs and therefore future intervention studies should be performed to evaluate the best intervention to decrease the burden of drug related problems in the older population.

Potentially inappropriate drug prescriptions and risk of hospitalization among older, Italian, nursing home residents: the ULISSE project.

BACKGROUND: Potentially inappropriate medications in older patients increase the risk of adverse drug events, which are an important cause of hospital admission and death among hospitalized patients. Little information is available about the prevalence of potentially inappropriate drug prescriptions (PIDPs) and the related health adverse outcomes among nursing home (NH) residents. OBJECTIVE: To estimate the prevalence of PIDPs and the association with adverse outcomes in NH residents. METHODS: A total of 1716 long-term residents aged >or=65 years participating in the ULISSE (Un Link Informatico sui Servizi Sanitari Esistenti per l'anziano [A Computerized Network on Health Care Services for Older People]) project were evaluated using a standardized comprehensive geriatric assessment instrument, i.e. the interResident Assessment Instrument Minimum Data Set. A thorough evaluation of residents' drug use, medical diagnoses and healthcare resource utilization was performed. A PIDP was defined according to the most recent update of the Beers criteria. RESULTS: Almost one out of two persons (48%) had at least one PIDP and almost one out of five had two or more PIDPs (18%). Residents with a higher number of PIDPs had a higher likelihood of being hospitalized. Compared with residents without PIDPs, those with two or more PIDPs at baseline had a higher probability of being hospitalized (hazard ratio 1.73; 95% CI 1.14, 2.60) during the following 12 months. Risk of PIDP was positively associated with the total number of drugs and diseases, but negatively with age. PIDPs defined according to specific conditions (n = 780; 55%) were slightly more frequent than PIDPs based on single medications irrespective of specific indication (n = 639; 45%). CONCLUSIONS: PIDP is a significant problem among Italian NH residents. There is an urgent need for intervention trials to test strategies to reduce inappropriate drug use and its associated adverse health outcomes.

Relationship between higher estradiol levels and 9-year mortality in older women: the Invecchiare in Chianti study.

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT). DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy). SETTING: Community. PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2. MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA). RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01-1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03-1.13, P=.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02-1.18, P<.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03-1.17, P<.001). Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01-1.91, P=.04) and not predictive of death for less than 5 years (P=.78). CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.

Uric acid and dementia in community-dwelling older persons.

BACKGROUND: The biological action of uric acid (UA) in humans is controversial. UA is considered an antioxidant compound, but preclinical evidence suggests a proinflammatory action. Epidemiological studies found that hyperuricemia is associated with conditions leading to dementia. Our aim is to investigate the relationship between UA levels and dementia in older persons. METHODS: Cross-sectional study performed in 1,016 community-dwelling older persons participating in the InCHIANTI study. Participants underwent determination of circulating UA levels and neuropsychological evaluation. A multivariate logistic regression model was used to estimate the probability of participants belonging to the highest and middle UA tertile to be affected by dementia compared to those in the lowest tertile. RESULTS: Demented persons had higher UA levels (p = 0.001) and the prevalence of persons affected by dementia increased across UA tertiles (p < 0.0001). Independent of several confounders, persons belonging to the highest UA tertile had a threefold (OR = 3.32; 95% CI: 1.06-10.42) higher probability to suffer from a dementia syndrome while those in the middle UA tertile tended to have a higher probability of being demented compared to those in the lowest tertile. CONCLUSION: In a population-based sample, high circulating UA levels are associated with an increased likelihood to be affected by a dementia syndrome.

Estradiol and inflammatory markers in older men.

BACKGROUND: Aging is characterized by a mild proinflammatory state. In older men, low testosterone levels have been associated with increasing levels of proinflammatory cytokines. It is still unclear whether estradiol (E2), which generally has biological activities complementary to testosterone, affects inflammation. METHODS: We analyzed data obtained from 399 men aged 65-95 yr enrolled in the Invecchiare in Chianti study with complete data on body mass index (BMI), serum E2, testosterone, IL-6, soluble IL-6 receptor, TNF-alpha, IL-1 receptor antagonist, and C-reactive protein. The relationship between E2 and inflammatory markers was examined using multivariate linear models adjusted for age, BMI, smoking, physical activity, chronic disease, and total testosterone. RESULTS: In age-adjusted analysis, log (E2) was positively associated with log (IL-6) (r = 0.19; P = 0.047), and the relationship was statistically significant (P = 0.032) after adjustments for age, BMI, smoking, physical activity, chronic disease, and serum testosterone levels. Log (E2) was not significantly associated with log (C-reactive protein), log (soluble IL-6 receptor), or log (TNF-alpha) in both age-adjusted and fully adjusted analyses. CONCLUSIONS: In older men, E2 is weakly positively associated with IL-6, independent of testosterone and other confounders including BMI.

High basal metabolic rate is a risk factor for mortality: the Baltimore Longitudinal Study of Aging.

BACKGROUND: Despite longstanding controversies from animal studies on the relationship between basal metabolic rate (BMR) and longevity, whether BMR is a risk factor for mortality has never been tested in humans. We evaluate the longitudinal changes in BMR and the relationship between BMR and mortality in the Baltimore Longitudinal Study of Aging (BLSA) participants. METHODS: BMR and medical information were collected at the study entry and approximately every 2 years in 1227 participants (972 men) over a 40-year follow-up. BMR, expressed as kcal/m(2)/h, was estimated from the basal O(2) consumption and CO(2) production measured by open-circuit method. Data on all-cause and specific-cause mortality were also obtained. RESULT: BMR declined with age at a rate that accelerated at older ages. Independent of age, participants who died had a higher BMR compared to those who survived. BMR was a significant risk factor for mortality independent of secular trends in mortality and other well-recognized risk factors for mortality, such as age, body mass index, smoking, white blood cell count, and diabetes. BMR was nonlinearly associated with mortality. The lowest mortality rate was found in the BMR range 31.3-33.9 kcal/m(2)/h. Participants with BMR in the range 33.9-36.4 kcal/m(2)/h and above the threshold of 36.4 kcal/m(2)/h experienced 28% (hazard ratio: 1.28; 95% confidence interval, 1.02-1.61) and 53% (hazard ratio: 1.53; 95% confidence interval, 1.19-1.96) higher mortality risk compared to participants with BMR 31.3-33.9 kcal/m(2)/h. CONCLUSION: We confirm previous findings of an age-related decline of BMR. In our study, a blunted age-related decline in BMR was associated with higher mortality, suggesting that such condition reflects poor health status.

Usefulness of uric acid to predict changes in C-reactive protein and interleukin-6 in 3-year period in Italians aged 21 to 98 years.

The role of uric acid (UA) in the process of atherothrombosis is controversial. Although serum UA has powerful antioxidant properties, epidemiological studies showed that UA was a risk factor for cardiovascular diseases and was positively associated with proinflammatory markers. Relations between baseline UA and changes in UA circulating levels with C-reactive protein (CRP) and interleukin-6 (IL-6) after 3 years of follow-up in a cohort of 892 Italian men and women aged 21 to 98 years was investigated. Subjects had complete baseline and follow-up data for UA, inflammatory markers, and covariates. An autoregressive approach was used to study such a relation. In adjusted analyses, baseline UA and changes in UA predicted a 3-year change in CRP (p = 0.028), but not IL-6 (p = 0.101). The relation between UA and CRP persisted after adjustment for baseline IL-6. Subjects with high UA at baseline had a progressively higher probability of developing clinically relevant increased IL-6 (>2.5 pg/ml) and CRP (>3 mg/L) during 3 years. In conclusion, our study suggests that in a population-based cohort, baseline UA and changes in circulating UA during 3 years of follow-up predict changes in circulating CRP independent of relevant confounders, including baseline IL-6.

White blood cell count and mortality in the Baltimore Longitudinal Study of Aging.

OBJECTIVES: We investigated the secular trend in white blood cell (WBC) count and the relationship between WBC count and mortality between 1958 and 2002. BACKGROUND: The WBC count is a clinical marker of inflammation and a strong predictor of mortality. Limited data exist on the WBC count secular trend and the relationship between WBC and mortality. METHODS: One thousand eighty-three women and 1,720 men were evaluated longitudinally in the Baltimore Longitudinal Study of Aging. Blood samples and medical information were collected at the study entry and every 2 years during follow-up visits. The WBC count and all-cause, cardiovascular, and cancer mortality were assessed. RESULTS: A downward trend in WBC count was observed from 1958 to 2002. The secular downward trend was independent of age, gender, race, smoking, body mass index, and physical activity. The WBC count was nonlinearly associated with all-cause mortality and almost linearly associated with cardiovascular mortality. Participants with baseline WBC <3,500 cells/mm3 and WBC >6,000 cells/mm3 had higher mortality than those with 3,500 to 6,000 WBC/mm3. Within each WBC group, age-adjusted mortality rates declined in successive cohorts from the 1960s to the 1990s. Participants who died had higher WBC than those who survived, and the difference was statistically significant within 5 years before death. CONCLUSIONS: Our study provides evidence for a secular downward trend in WBC count over the period from 1958 to 2002. Higher WBC counts are associated with higher mortality in successive cohorts. We found no evidence that the decline of age-specific mortality rates that occurred from 1960 to 2000 was attributable to a secular downward trend in WBC.

Unexplained anaemia in older persons is characterised by low erythropoietin and low levels of pro-inflammatory markers.

Epidemiological studies report that a third of the cases of anaemia in older persons is unexplained. We compared erythropoietin (EPO), inflammatory markers and major comorbidities between older subjects with normal haemoglobin levels and those with different aetiologic forms of anaemia, including unexplained anaemia. Participants were a representative sample of 964 persons aged > or =65 years, with no evidence of bleeding, complete blood tests, and a complete blood count within 6 h of phlebotomy. Anaemia was defined as haemoglobin <130 g/l in men and 120 g/l in women, and classified as a result of chronic kidney disease, iron deficiency, chronic disease and B12/folate deficiency anaemia, or unexplained anaemia based on standard criteria. Of the 124 anaemic participants, 42 (36.8%) had unexplained anaemia. Participants with anaemia of chronic diseases had significantly higher interleukin-6 (IL-6) and C-reactive protein (CRP) levels, while those with unexplained anaemia had significantly lower CRP than non-anaemic controls. Iron deficiency anaemia was characterised by significantly higher EPO levels compared with other types of anaemia and normal haemoglobin, B12 and/or folate deficiency. Unexplained anaemia was characterised by unexpectedly low EPO and low lymphocyte count. Unexplained anaemia is associated with reduced kidney EPO response, low levels of pro-inflammatory markers and low lymphocyte counts.