Plasma Inflammatory Biomarkers and Anorexia of Ageing among Community-Dwelling Older Adults: An Exploratory Analysis of the MAPT Study.

Anorexia of aging and biological aging might share physiological underpinnings. The aim of this secondary analysis was to investigate the associations between circulating inflammation-related markers and anorexia of aging in community-dwelling older adults. C-reactive protein (CRP), tumor necrosis factor receptor-1 (TNFR-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and growth/differentiation factor-15 (GDF-15) were measured in plasma. Anorexia of aging was defined by the response "severe/moderate decrease in food intake" to the first item of the Mini-Nutritional Assessment. We included 463 subjects (median age=74y, IQR=71-78; 63.1% women). 33 subjects (7.1%) presented with anorexia at baseline, whereas 25 out of 363 (6.9%) developed it along 1-year follow-up. We found that TNFR1 (OR=1.74, 95%CI=1.27-2.39) and GDF-15 (OR=1.38, 95%CI=1.01-1.89) were associated with a significant increase in the odds of presenting with anorexia of aging cross-sectionally. No further significant associations were found. Biological aging mechanisms might be involved in the pathogenesis of anorexia of aging.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study.

BACKGROUND: Frailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses - disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different. OBJECTIVES: The aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults. MATERIAL AND METHODS: We performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET). RESULTS: Although not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [ß = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [ß = -2.42 (-4.76, -0.08)], Omega 3 Index [ß = -0.50 (-0.95, -0.06)] and hippocampal volume [ß = -0.22 (-0.42,-0.02)]. They also had higher values of GDF15 [ß = 246.1 (88.9, 403.4)] and TNFR1 [ß = 157.5 (7.8, 307.2)]. CONCLUSION: Age-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

Frequency of Conditions Associated with Declines in Intrinsic Capacity According to a Screening Tool in the Context of Integrated Care for Older People.

BACKGROUND: The screening tool of the Integrated Care for Older People (ICOPE Step 1), designed to detect declines in the domains of intrinsic capacity, has been incipiently investigated in older adult populations. OBJECTIVES: To retrospectively estimate the frequency of priority conditions associated with declines in intrinsic capacity according to an adaptation of the screening tool ICOPE Step 1 among participants of the Multidomain Alzheimer Preventive Trial (MAPT). DESIGN: A cross-sectional retrospective analysis from the baseline assessment of the MAPT. SETTING: The data was gathered during a preventive consultation for cardiovascular risk factors in memory clinics in France. PARTICIPANTS: Seven hundred fifty-nine older adults aged 70-89 years with memory complaints, allocated to the multidomain groups of the MAPT study. MEASUREMENTS: Five domains of intrinsic capacity (cognition, locomotion, nutrition, sensorial, and psychological) were assessed using a screening tool similar to the ICOPE Step 1 (MAPT Step 1). The frequency of six conditions associated with declines in intrinsic capacity (cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms) was obtained for older adults with memory complaints participating in the MAPT study. RESULTS: Overall, 89.3% of the participants had one or more conditions associated with declines in intrinsic capacity. The overall frequency of each condition was: 52.2% for cognitive decline, 20.2% for limited mobility, 6.6% for malnutrition, 18.1% for visual impairment, 56.2% for hearing loss, and 39% for depressive symptoms. CONCLUSION: After being screened with an adaptation of the ICOPE step 1 (MAPT step 1) tool, 9/10 older adults had one or more conditions associated with declines in intrinsic capacity. The relative frequency differs across conditions and could probably be lower in a population without memory complaints. The frequency of screened conditions associated with declines in IC highlights how relevant it is to develop function-centered care modalities to promote healthy aging.

The INSPIRE Bio-Resource Research Platform for Healthy Aging and Geroscience: Focus on the Human Translational Research Cohort (The INSPIRE-T Cohort).

BACKGROUND: The Geroscience field focuses on the core biological mechanisms of aging, which are involved in the onset of age-related diseases, as well as declines in intrinsic capacity (IC) (body functions) leading to dependency. A better understanding on how to measure the true age of an individual or biological aging is an essential step that may lead to the definition of putative markers capable of predicting healthy aging. OBJECTIVES: The main objective of the INStitute for Prevention healthy agIng and medicine Rejuvenative (INSPIRE) Platform initiative is to build a program for Geroscience and healthy aging research going from animal models to humans and the health care system. The specific aim of the INSPIRE human translational cohort (INSPIRE-T cohort) is to gather clinical, digital and imaging data, and perform relevant and extensive biobanking to allow basic and translational research on humans. METHODS: The INSPIRE-T cohort consists in a population study comprising 1000 individuals in Toulouse and surrounding areas (France) of different ages (20 years or over - no upper limit for age) and functional capacity levels (from robustness to frailty, and even dependency) with follow-up over 10 years. Diversified data are collected annually in research facilities or at home according to standardized procedures. Between two annual visits, IC domains are monitored every 4-month by using the ICOPE Monitor app developed in collaboration with WHO. Once IC decline is confirmed, participants will have a clinical assessment and blood sampling to investigate markers of aging at the time IC declines are detected. Biospecimens include blood, urine, saliva, and dental plaque that are collected from all subjects at baseline and then, annually. Nasopharyngeal swabs and cutaneous surface samples are collected in a large subgroup of subjects every two years. Feces, hair bulb and skin biopsy are collected optionally at the baseline visit and will be performed again during the longitudinal follow up. EXPECTED RESULTS: Recruitment started on October 2019 and is expected to last for two years. Bio-resources collected and explored in the INSPIRE-T cohort will be available for academic and industry partners aiming to identify robust (set of) markers of aging, age-related diseases and IC evolution that could be pharmacologically or non-pharmacologically targetable. The INSPIRE-T will also aim to develop an integrative approach to explore the use of innovative technologies and a new, function and person-centered health care pathway that will promote a healthy aging.

Osteoporosis in Frail Older Adults: Recommendations for Research from the ICFSR Task Force 2020.

Interactions among physiological pathways associated with osteoporosis and sarcopenia are thought to contribute to the onset of frailty. The International Conference on Frailty and Sarcopenia Research Task Force thus met in March 2020 to explore how emerging interventions to manage fracture and osteoporosis in older adults may reduce frailty, disability, morbidity, and mortality in the older population. Both pharmacological and non-pharmacological interventions (including nutritional intervention, exercise, and other lifestyle changes) were discussed, including nutritional intervention, exercise, and other lifestyle changes. Pharmacological treatments for osteoporosis include bone-forming and antiresorptive agents, which may optimally be used in sequential or combination regimens. Since similar mechanisms related to resorption underlie physiological changes in muscle and bone, these interventions may provide benefits beyond treating osteoporosis. Clinical trials to test these interventions, however, often exclude frail older persons because of comorbidities (such as mobility disability and cognitive impairment) or polypharmacy. The Task Force recommended that future clinical trials use harmonized protocols, including harmonized inclusion criteria and similar outcome measures; and that they test a range of multidomain therapies. They further advocated more high-quality research to develop interventions specifically for people who are frail and old. The ICOPE program recommended by WHO appears to be highly recommended to frail older adults with osteoporosis.

Texture-Modified Diet for Improving the Management of Oropharyngeal Dysphagia in Nursing Home Residents: An Expert Review.

OBJECTIVES: This paper provides evidence-based and, when appropriate, expert reviewed recommendations for long-stay residents who are prescribed texture-modified diets (TMDs), with the consideration that these residents are at high risk of worsening oropharyngeal dysphagia (OD), malnutrition, dehydration, aspiration pneumonia, and OD-associated mortality, poorer quality of life and high costs. DESIGN: Nestlé Health Science funded an initial virtual meeting attended by all authors, in which the unmet needs and subsequent recommendations for OD management were discussed. The opinions, results, and recommendations detailed in this paper are those of the authors, and are independent of funding sources. SETTING: OD is common in nursing home (NH) residents, and is defined as the inability to initiate and perform safe swallowing. The long-stay NH resident population has specific characteristics marked by a shorter life expectancy relative to community-dwelling older adults, high prevalence of multimorbidity with a high rate of complications, dementia, frailty, disability, and often polypharmacy. As a result, OD is associated with malnutrition, dehydration, aspiration pneumonia, functional decline, and death. Complications of OD can potentially be prevented with the use of TMDs. RESULTS: This report presents expert opinion and evidence-informed recommendations for best practice on the nutritional management of OD. It aims to highlight the practice gaps between the evidence-based management of OD and real-world patterns, including inadequate dietary provision and insufficient staff training. In addition, the unmet need for OD screening and improvements in therapeutic diets are explored and discussed. CONCLUSION: There is currently limited empirical evidence to guide practice in OD management. Given the complex and heterogeneous population of long-stay NH residents, some 'best practice' approaches and interventions require extensive efficacy testing before further changes in policy can be implemented.

No Difference in the Phenotypic Expression of Frailty among Elderly Patients Recently Diagnosed with Cancer Vs Cancer Free Patients.

OBJECTIVES: To examine frailty determinants differences in patients with a recent diagnosis of cancer compared to non-cancer patients among older adult. Revealing those differences will allow us to individualize the exact frailty management in those patients diagnosed with cancer. DESIGN: This is an observational cross-sectional, monocentric study. SETTING: Patients were evaluated at the Geriatric Frailty Clinic (GFC), in the Toulouse University Hospital, France, between October 2011 and February 2016. PARTICIPANTS: 1996 patients aged 65 and older were included (1578 patients without cancer and 418 patients with solid and hematological cancer recently diagnosed). MEASUREMENTS: Frailty was established according to the frailty phenotype. The frailty phenotype measures five components of frailty: weight loss, exhaustion, low physical activity, weakness and slow gait. Frailty phenotype was categorized as robust, pre-frail and frail. RESULTS: In a multinomial logistic regression, cancer, compared to the non-cancer group, is not associated with an increased likelihood of being classified as pre frail (RRR 0.9, 95% CI [0.5 ; 1.6 ], p 0.9) or frail (RRR 1.2, 95% CI [0.7 ; 2.0], p 0.4) rather than robust. When considering each Fried criterion, a significant higher odd of weight loss was observed in older patients with cancer compared to the non-cancer patients (OR 2.3, 95% CI [1.8; 3.0], p <0.001) but no statistically significant differences was found among the four other Fried criteria. Sensitivity analysis on the frailty index showed that cancer was not associated with a higher FI score compared to non-cancer (ß 0.002, 95%CI [-0.009; 0.01], p 0.6). CONCLUSION: In this real-life study evaluating elderly patients with and without cancer, we didn't confirm our hypothesis, in fact we found that cancer was not associated with frailty severity using both a phenotypic model and a deficit accumulation approach. Cancer may contribute, at least additively, to the development of frailty, like any other comorbidity, rather than a global underlying condition of vulnerability.

Associations Between Multidomain Lifestyle Interventions and Intrinsic Capacity Domains During Aging: A Narrative Review.

Background: Recently, the World Health Organization defined five domains of intrinsic capacity (IC), composed of physical and mental capacities linked to body functions, and that contribute to healthy aging: locomotion, cognition, psychological, vitality and sensorial. In the past decade, studies investigating the effects of concomitant lifestyle interventions (also called multidomain interventions) on one or several IC domains have been developed. The aim of this study is to synthetize the scientific literature about the associations between multidomain lifestyle interventions and IC domains. Methods: We conducted a narrative review of randomized controlled trials examining the effects of multidomain lifestyle interventions on at least one IC domain among older people. Multidomain intervention was defined as the presence of at least two of the following lifestyle interventions: physical activity/exercise, nutrition, cognitive stimulation, and management of cardiovascular risk factors (eg, smoking, alcohol consumption). Results: Multidomain interventions were associated with improvements on locomotion (as measured by performance-based tests of lower-limb function) and vitality (as measured by handgrip strength); benefits on cognitive function were also found, in particular among populations at increased risk of dementia and when operationalizing strong multidomain interventions (eg, using regular exercise training instead of physical activity advices). No study investigated the effects of multidomain lifestyle interventions on the sensorial domain (hearing and/or vision). The modalities composing the multidomain interventions and intervention length, as well as study population, substantially varied across studies; the most common combination of interventions was physical activity- and nutritional-related interventions. Conclusion: Available evidence is still limited, but literature suggests a positive effect of multidomain lifestyle interventions on IC domains, in particular locomotion. Further studies are still needed on this topic, in particular, studies exploring the effects of multidomain lifestyle interventions on the sensorial domain, as well as on a composite measurement of all IC domains.

Potentially modifiable determinants of malnutrition in older adults: A systematic review.

BACKGROUND & AIMS: Malnutrition in older adults results in significant personal, social, and economic burden. To combat this complex, multifactorial issue, evidence-based knowledge is needed on the modifiable determinants of malnutrition. Systematic reviews of prospective studies are lacking in this area; therefore, the aim of this systematic review was to investigate the modifiable determinants of malnutrition in older adults. METHODS: A systematic approach was taken to conduct this review. Eight databases were searched. Prospective cohort studies with participants of a mean age of 65 years or over were included. Studies were required to measure at least one determinant at baseline and malnutrition as outcome at follow-up. Study quality was assessed using a modified version of the Quality in Prognosis Studies (QUIPS) tool. Pooling of data in a meta-analysis was not possible therefore the findings of each study were synthesized narratively. A descriptive synthesis of studies was used to present results due the heterogeneity of population source and setting, definitions of determinants and outcomes. Consistency of findings was assessed using the schema: strong evidence, moderate evidence, low evidence, and conflicting evidence. RESULTS: Twenty-three studies were included in the final review. Thirty potentially modifiable determinants across seven domains (oral, psychosocial, medication and care, health, physical function, lifestyle, eating) were included. The majority of studies had a high risk of bias and were of a low quality. There is moderate evidence that hospitalisation, eating dependency, poor self-perceived health, poor physical function and poor appetite are determinants of malnutrition. Moderate evidence suggests that chewing difficulties, mouth pain, gum issues co-morbidity, visual and hearing impairments, smoking status, alcohol consumption and physical activity levels, complaints about taste of food and specific nutrient intake are not determinants of malnutrition. There is low evidence that loss of interest in life, access to meals and wheels, and modified texture diets are determinants of malnutrition. Furthermore, there is low evidence that psychological distress, anxiety, loneliness, access to transport and wellbeing, hunger and thirst are not determinants of malnutrition. There appears to be conflicting evidence that dental status, swallowing, cognitive function, depression, residential status, medication intake and/or polypharmacy, constipation, periodontal disease are determinants of malnutrition. CONCLUSION: There are multiple potentially modifiable determinants of malnutrition however strong robust evidence is lacking for the majority of determinants. Better prospective cohort studies are required. With an increasingly ageing population, targeting modifiable factors will be crucial to the effective treatment and prevention of malnutrition.

[Characteristics of non-pharmacological interventions in the elderly with COPD. Smoking cessation, pulmonary rehabilitation, nutritional management and patient education]. / Particularités de la prise en charge non médicamenteuse de la BPCO chez les sujets âgés. Réhabilitation, sevrage tabagique, nutrition et éducation thérapeutique.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder responsible for a high mortality and disability. People older than 65 years are more commonly affected than younger people and tend to present with more symptoms and a greater level of disability. Non-pharmacological interventions play an important role in the management of all patients with COPD and this is particularly true in the elderly. Given the improvement in quality of life and risk of hospitalization, smoking cessation should be promoted to patients of all ages. Increased physical activity is associated with reduced respiratory symptoms. Tests such as the "Short Physical Performance Battery" can be useful in frailer older people with COPD, while walking tests such as the 6-minute walk test are used as an assessment before pulmonary rehabilitation. Increased physical activity should be combined with nutritional management. Screening for undernutrition by questionnaire, body mass index and albumin quantification is recommended in the elderly. In case of undernutrition, oral supplementation seems to reduce the risk of re-admission. All these measures must be included in an education program adapted to the elderly comorbidities (hearing loss, isolation…).

Phosphorylation of SOS1 on tyrosine 1196 promotes its RAC GEF activity and contributes to BCR-ABL leukemogenesis.

Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. Although the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro and for platelet-derived growth factor (PDGF) activation of RAC- and RAC-dependent actin remodeling and cell migration. SOS1 is also phosphorylated on Y1196 by BCR-ABL in chronic myelogenous leukemic cells. Importantly, in these cells, SOS1 is required for BCR-ABL-mediated activation of RAC, cell proliferation and transformation in vitro and in a xenograft mouse model. Finally, genetic removal of Sos1 in the bone marrow-derived cells (BMDCs) from Sos1fl/fl mice and infected with BCR-ABL causes a significant delay in the onset of leukemogenesis once BMDCs are injected into recipient, lethally irradiated mice. Thus, SOS1 is required for full transformation and critically contribute to the leukemogenic potential of BCR-ABL.

[MRI-based radiotherapy planning]. / Planification à partir d'imagerie par résonance magnétique en radiothérapie.

MRI-based radiotherapy planning is a topical subject due to the introduction of a new generation of treatment machines combining a linear accelerator and a MRI. One of the issues for introducing MRI in this task is the lack of information to provide tissue density information required for dose calculation. To cope with this issue, two strategies may be distinguished from the literature. Either a synthetic CT scan is generated from the MRI to plan the dose, or a dose is generated from the MRI based on physical underpinnings. Within the first group, three approaches appear: bulk density mapping assign a homogeneous density to different volumes of interest manually defined on a patient MRI; machine learning-based approaches model local relationship between CT and MRI image intensities from multiple data, then applying the model to a new MRI; atlas-based approaches use a co-registered training data set (CT-MRI) which are registered to a new MRI to create a pseudo CT from spatial correspondences in a final fusion step. Within the second group, physics-based approaches aim at computing the dose directly from the hydrogen contained within the tissues, quantified by MRI. Excepting the physics approach, all these methods generate a synthetic CT called "pseudo CT", on which radiotherapy planning will be finally realized. This literature review shows that atlas- and machine learning-based approaches appear more accurate dosimetrically. Bulk density approaches are not appropriate for bone localization. The fastest methods are machine learning and the slowest are atlas-based approaches. The less automatized are bulk density assignation methods. The physical approaches appear very promising methods. Finally, the validation of these methods is crucial for a clinical practice, in particular in the perspective of adaptive radiotherapy delivered by a linear accelerator combined with an MRI scanner.

Body Composition and Anti-Neoplastic Treatment in Adult and Older Subjects - A Systematic Review.

BACKGROUND: The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy. METHOD: We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition. RESULTS: Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients. CONCLUSIONS: Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.

Physical Activity and ß-Amyloid Brain Levels in Humans: A Systematic Review.

Physical activity (PA) contributes to brain health and plasticity, which suggests that PA would protect against the development of Alzheimer's disease (AD). However, research on PA and AD biomarkers is very scarce. The objective of the present study was to perform a systematic review of studies that investigated the associations between PA and ß-amyloid brain deposition in humans. Electronic searches were performed in PubMed, Cochrane Library, SportDiscus, PEDro, and PsychInfo databases. Articles were eligible if they have assessed both PA and ß-amyloid brain deposition in humans. Five articles, published between 2010 and 2013, met eligibility criteria (study population varied across studies from 54 to 515, according with the ß-amyloid measure. All five studies assessed both PA and PET-amyloid; among them, two studies also assessed CSF Aß42 levels). All studies were based on cross-sectional data, from non-demented populations. Among the five included studies, three found significant associations between PA and ß-amyloid brain deposition, and the other two did not find any significant association; limited evidence suggests that PA-amyloid plaques associations would be APOE ε4 allele-specific. In sum, no solid conclusions can be drawn on the associations between PA and human ß-amyloid brain deposition currently. Future research on this topic should particularly pay attention to the operationalisation of clinically relevant and valid PA variables and should include important confounders in multivariate analysis. More information is needed on the potential interactions between PA and other AD risk factors (e.g., cognitive activities, APOE ε4 status, nutrition, smoking) and their combined effects on AD biomarkers.

Association of calcium concentration with pulse pressure in older women: data from a large population-based multicentric study.

OBJECTIVE: High arterial pulse pressure is a predictor of cardiovascular morbimortality. Mineral metabolism has been associated with blood pressure regulation. Our objective was to determine which variable among serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations, was associated with pulse pressure among older adults. DESIGN: Cross-sectional study corresponding to the baseline assessment of the EPIDOS study. SETTING: Five French cities including Amiens, Lyon, Montpellier, Paris and Toulouse. PARTICIPANTS: Randomized sample of 610 community-dwelling older women (mean age 80.2±3.5years) using no antihypertensive drugs. MEASUREMENTS: Serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations; supine pulse pressure after 15 minutes of rest (hypertension defined as pulse pressure >50mmHg). Age, body mass index, the number of morbidities and of drugs daily taken, diabetes mellitus, dysthyroidy, the use of estrogenic drugs, smoking, alcohol consumption, practice of a regular physical activity, creatinine clearance, and the effects of season and study centers were used as potential confounders. RESULTS: Hypertensive participants (n=539) had higher calcium concentrations than normotensive ones (94.33±4.12mg/L versus 93.28±3.36mg/L respectively, P=0.040). There were no between-group differences for serum parathyroid hormone and 25-hydroxyvitamin D concentrations. The multiple logistic regressions examining the serum calcium, parathyroid hormone and 25-hydroxyvitamin D concentrations as predictors of hypertension found an association only with calcium (adjusted odds ratio=1.19, P=0.015), but not with parathyroid hormone (adjusted OR=1.01, P=0.349) or 25-hydroxyvitamin D concentration (adjusted OR=0.99, P=0.971). CONCLUSION: Increased serum calcium concentration was independently and positively associated with high pulse pressure in our study, possibly due to increased arterial stiffness. Interventions aimed at normalizing calcaemia may be attractive to prevent hypertension and cardiovascular risk in older adults.

Vitamin D deficiency is associated with orthostatic hypotension in oldest-old women.

OBJECTIVES: Orthostatic hypotension, a condition that mostly affects 'oldest-old' (i.e. ≥80 years) adults, is primarily explained by age-related dysfunction of blood pressure control. Vitamin D may contribute to blood pressure control. The aim of this study was to determine whether vitamin D deficiency is associated with orthostatic hypotension in oldest-old adults. DESIGN: Cross-sectional analysis at baseline of the EPIDOS study. SETTING: Five French areas. PARTICIPANTS: A total of 329 community-dwelling oldest-old women (mean age 83.3 ± 0.2 years). MAIN OUTCOMES MEASURES: Orthostatic hypotension was defined as a systolic blood pressure drop of ≥20 mmHg and/or a diastolic blood pressure drop of ≥10 mmHg within 3 min of standing. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25OHD) concentration ≤10 ng mL(-1) . Covariates included in the models were age, body mass index, diabetes mellitus, supine mean arterial pressure, number of drugs taken per day, use of antihypertensive or psychoactive drugs, cognition, quadriceps strength, current smoking, alcohol consumption, serum concentrations of parathyroid hormone, calcium and creatinine and season of testing. RESULTS: Diastolic orthostatic hypotension was observed more often among women with vitamin D deficiency (19.2%) compared to those without (10.0%; P = 0.03). There was an inverse linear association between 25OHD concentration and change in diastolic blood pressure after 3 min of standing (adjusted ß = -0.07, P = 0.046). Similarly, 25OHD deficiency was associated with orthostatic hypotension [adjusted odds ratio (OR) 3.36, P = 0.004], specifically with diastolic orthostatic hypotension (adjusted OR 3.81, P = 0.003). CONCLUSIONS: 25OHD deficiency was associated with orthostatic hypotension in oldest-old women, due to a greater drop in diastolic blood pressure on standing. This finding may lead to better understanding of the pathophysiology of falls in oldest-old adults with vitamin D deficiency.