The national burden of frailty and disproportionate distribution of its components-the predominance of slow gait speed: a 2018-19 face-to-face epidemiologic assessment representative of population of older Poles.

BACKGROUND: The prevalence of frailty and its components may be affected by age, diseases and geriatric deficits. However, the current operational definition of frailty assigns equal weight to the five components of frailty. AIMS: To perform a population-based assessment of physical frailty, its prevalence, and distribution of its components across different age, disease and deficit spectrum. METHODS: From 2018 to 2019, we conducted a face-to-face cross-sectional assessment of a representative sample of older Poles. We obtained data on frailty components, chronic disease burden, and prevalence of particular diseases and geriatric deficits. We calculated weighted population estimates, representative of 8.5 million older Poles, of prevalence of frailty and its components across the disease burden, associated with the particular diseases and the geriatric deficits present. RESULTS: Of 10,635 screened persons ≥ 60 years, 5987 entered the face-to-face assessment. Data of 5410 have been used for the present analysis. Seventy-two percent of the population are burdened with at least one frailty component. The estimated weighted population prevalence (95% CI) of frailty was 15.9% (14.6-17.1%), and of pre-frailty 55.8% (53.3-58.2%). Slow gait speed predominated across disease burden, specific diseases, geriatric deficits and the age spectrum. Overall, the prevalence of slow gait speed was 56.3% (52.7-60.0%), followed by weakness 26.9% (25.4-28.4%), exhaustion 19.2% (17.6-20.8%), low physical activity 16.5% (14.8-18.3%), and weight loss 9.4% (8.4-10.3%). CONCLUSIONS: Slow gait speed predominates among the components of frailty in older Poles. This may affect the component-tailored preventive and therapeutic actions to tackle frailty.

Disparate effects of ankle-brachial index on mortality in the 'very old' and 'younger old' populations-the PolSenior survey.

To assess the relationship between ankle-brachial index (ABI) and up to 10-year mortality in older individuals below and above the age of 80 years. In a multicenter survey of health status in the community dwelling subjects aged 55-59 and 65 + years in Poland, we assessed baseline medical history including risk-factors. We measured ABI, and serum creatinine, cholesterol, NT-proBNP, and interleukin-6 (IL-6) concentrations. We assessed mortality based on public registry. Between 2009 and 2019, 27.3% of 561 participants < 80 years, and 79.4% of 291 participants ≥ 80 years, died (p < 0.001); 67.8, 41.5, and 40.3% in the ABI groups < 0.9, 0.9-1.4, and > 1.4, respectively (p < 0.01). In the unadjusted Cox models, ABI was associated with mortality in the entire group, and < 80 years. In the entire group, analysis adjusted for age and sex showed mortality risk increased by 11% per year, and 50% with male sex. Mortality decreased by 37% per 1 unit ABI increase. In the group of people ≥ 80 years, only age was significantly associated with mortality (p < 0.001). In stepwise regression ABI < 0.9, male sex, active smoking, and NT-proBNP level were associated with risk of death < 80 years. In the ≥ 80 years old, mortality risk was associated with older age, and higher levels of IL-6, but not ABI. The ABI < 0.9 is associated with higher mortality in older people, but not among the oldest-old. In the oldest age group, age is the strongest predictor of death. In this age group, inflammageing is of importance.

Mortality of older persons with and without abnormalities in the physical examination of arterial system.

BACKGROUND: Ankle-brachial index (ABI) is a screening tool for peripheral arterial disease (PAD). However, persons with normal ABI may still exhibit abnormalities in the physical examination of arterial system (PHEA). OBJECTIVE: In older persons from the PolSenior study, we aimed to assess the risk of total mortality associated with abnormalities in PHEA in the context of dichotomised ABI. METHODS: We used data from the PolSenior survey and matched them with mortality information from the Polish Census Bureau. We obtained sociodemographic, medical history, and lifestyle data. The PHEA by a geriatrician included carotid, femoral, popliteal, posterior tibial and the dorsalis pedis arterial pulses, and auscultation of aorta, carotid, femoral, and renal arteries. Ankle-brachial index was tibial to brachial SBP ratio. We plotted the stratified Kaplan-Meier curves and used Cox's regression to assess the unadjusted and adjusted influence of PHEA result on time to death. RESULTS: The mean (standard deviation, SD) age of 852 persons (46.7% women) was 74.7 (10.6) years. In the ABI < 0.9 group, the PHEA was not associated with mortality. However, in the ABI ≥ 0.9 group, both in unadjusted and adjusted (RHR; 95% CI: 1.08; 1.02-1.16, p = 0.01) Cox regression, PHEA greater by 1 score was associated with mortality. Presence of 4 or more PHEA abnormalities was raising the risk in the ABI ≥ 0.9 group to the level associated with ABI < 0.9. CONCLUSIONS: In the older persons with normal ABI, the greater number of abnormalities during physical examination of arteries may be indicative of higher risk of death.

Productivity Loss Among Parents of Children With Inflammatory Bowel Diseases in Relation to Disease Activity and Patient's Quality of Life.

OBJECTIVES: To assess the productivity losses among the parents of children with inflammatory bowel diseases (IBDs) in Poland and their relationship with disease activity and the patient's quality of life. METHODS: A questionnaire-based self-reported Internet survey was conducted among the parents of patients (0--17 years old) with a diagnosis of ulcerative colitis (UC) or Crohn disease (CD). Data on indirect and direct costs, general patient characteristics, disease activity, pharmacological treatment, and children's quality of life measured with the Pediatric Quality of Life Inventory (PedsQL) were collected. RESULTS: A total of 113 completed questionnaires were obtained. Remission was reported in 58.6% of cases. Severe disease was more common in patients with UC (7.3% vs 2.9%). The mean reduction in parents' daily activities was 40% (range: 0%-100%). The mean (SD) reduction of parents' work productivity because of absenteeism was 21% (0.27), and the mean cost was &OV0556;902.77 (1136.90) per year per parent. The mean (SD) productivity loss at paid work of a working parent (presenteeism) was 35% (0.31) and the mean (SD) cost was &OV0556;1125.13 (1121.16) per year per parent. The PedsQL score was significantly higher among patients with inactive than with active disease. CONCLUSIONS: A significant difference between patients with inactive and active disease was observed for the total reduction of parent's work productivity and the PedsQL score. A negative correlation was observed for indirect costs and the PedsQL score for the whole study population; better health-related quality of life among patients in remission was revealed.

First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects - a cohort study.

Obesity is a risk factor for several aging-related diseases such as type 2 diabetes, cardiovascular disease, and cancer. Especially, cardiovascular disease is triggered by obesity by inducing vascular senescence and chronic low-grade systemic inflammation, also known as inflamm-aging. Released molecules from damaged cells and their recognition by the innate immune system is one of the mechanisms driving inflamm-aging. Obesity results in mitochondrial damage, leading to endothelial inflammation triggered by cytosolic mtDNA via the cGAS/STING pathway. Recently, we have shown STING SNP R293Q to be associated with a decreased risk for aging-related diseases in current smokers. Since current smoking triggers DNA damage that, similar to obesity, may result in the release of DNA into the cytoplasm, we hypothesized that the cGAS/STING pathway can modify the phenotype of aging also in obese subjects. Therefore, the objective of our study was to investigate whether STING R293Q is associated with aging-related diseases in obese individuals. We indeed show that STING 293Q is associated with protection from combined aging-related diseases (P = 0.014) and, in particular, cardiovascular disease in these subjects (P = 0.010). Therefore, we provide the first evidence that stratification for obesity may reveal new genetic loci determining the risk for aging-related diseases.

STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases.

BACKGROUND: Aging is a multifactorial process driven by several conditions. Among them, inflamm-aging is characterized by chronic low-grade inflammation driving aging-related diseases. The aged immune system is characterized by the senescence-associated secretory phenotype, resulting in the release of proinflammatory cytokines contributing to inflamm-aging. Another possible mechanism resulting in inflamm-aging could be the increased release of danger- associated molecular patterns (DAMPs) by increased cell death in the elderly, leading to a chronic low-grade inflammatory response. Several pattern recognition receptors of the innate immune system are involved in recognition of DAMPs. The DNA-sensing cGAS-STING pathway plays a pivotal role in combating viral and bacterial infections and recognizes DNA released by cell death during the process of aging, which in turn may result in increased inflamm-aging. OBJECTIVE: The aim of this study was to investigate whether a variation within the STING gene with known impaired function may be associated with protection from aging-related diseases by decreasing the process of inflamm-aging. METHODS: STING (Tmem173) R293Q was genotyped in a cohort of 3,397 aged subjects (65-103 years). The distribution of the variant allele in healthy subjects and subjects suffering from aging-associated diseases was compared by logistic regression analysis. RESULTS: We show here that STING 293Q allele carriers were protected from aging-associated diseases (OR = 0.823, p = 0.038). This effect was much stronger in the subgroup of subjects suffering from chronic lung diseases (OR = 0.730, p = 0.009). CONCLUSION: Our results indicate that decreased sensitivity of the innate immune receptors is associated with healthy aging, most likely due to a decreased process of inflamm-aging.

Use of renal risk drugs in a nation-wide Polish older adult population: an analysis of PolSenior database.

BACKGROUND: Numerous medications should be avoided, or require dose adjustment in subjects with impaired kidney function. We aimed to assess the prevalence of potentially inappropriate use of renal risk drugs in a nation-wide, community-dwelling Polish older adult population. METHODS: We analysed regular intake of 38 medications that should be avoided, requiring dose modification, increase the risk of pre-renal kidney injury, or may cause potassium retention in subjects with moderately to severely impaired renal function in the PolSenior data base (N = 4514, mean age 76 ± 11 yrs). Kidney function was assessed with short Modification of Diet in Renal Disease formula estimated glomerular filtration rate (sMDRD) and Cockcroft-Gault creatinine clearance (CC). RESULTS: There were 855 (19%) individuals with sMDRD < 60 ml/min/1.73m2, and 1734 (38%) with CC <  60 ml/min. Among drugs that should be avoided, spironolactone (20.4% of patients as classified by sMDRD and 17.5% by CC), non-steroidal anti-inflammatory drugs (13.4 and 11.3%), hydrochlorothiazide (11.1 and 11.0%), and metformin (6.9 and 8.2%) were most frequently used. The most frequently used drugs requiring dose modification were piracetam (13.9% by sMDRD, and 11.9% by CC), digoxin (8.3 and 8.8%), and gliclazide (6.8 and 5.9%). Classification of a drug use as 'appropriate' or 'inappropriate' was discordant depending on the method of kidney function assessment (sMDRD or CC) in up to 30%. Subgroups with sMDRD < 60 ml/min/1.73m2 and with CC <  60 ml/min were taking ≥2 drugs increasing the risk of pre-renal kidney injury more frequently than individuals with better kidney function (46.6 vs. 23.1 and 33.0% vs. 24.4%, respectively). There were 24.7% of individuals with sMDRD < 60 ml/min/1.73m2 and 18.0% with CC <  60 ml/min taking 2 or more drugs increasing serum potassium level. The proportion of subjects with hyperkalaemia increased with the number of such drugs. CONCLUSIONS: Use of drugs that should be avoided or require dose adjustment due to renal impairment, and potentially inappropriate drug combinations is a common problem in older adults in Poland. Assessment of kidney function with sMDRD may result in overlooking of requirements for dose adjustment formulated based on creatinine clearance. TRIAL REGISTRATION: Not applicable.

Clinical examination of peripheral arterial disease and ankle-brachial index in a nationwide cohort of older subjects: practical implications.

BACKGROUND: Prevalence of peripheral arterial disease increases with age and is related to increased morbidity and mortality. The clinical diagnosis includes the measurement of ankle-brachial index (ABI). AIMS: To check the prevalence of abnormal ABI, and the value of physical examination of arterial system in detection of ABI < 0.9. METHODS: We performed subgroup analysis of patients included in the PolSenior survey. We measured ABI, performed physical examination of arterial system, assessed laboratory and questionnaire factors related to atherosclerosis. Participants were divided according to ABI strata of < 0.9, 0.9-1.4 and > 1.4. Clinical score of abnormalities on physical examination was proposed. Using logistic regression, we obtained areas under the curve (AUC). RESULTS: The mean age of 844 participants (53.3% men) was 74.7 (10.6) years. ABI < 0.9 was found in 20.3% participants and it was linked to history of myocardial infarction, hypertension and renal failure. In the entire group, 72.4% of subjects declared, that they were able to walk a distance of 200 m without interruption. Higher clinical score was associated with lower ABI. Full physical examination (AUC = 0.67) followed by examination of lower extremities (AUC = 0.65) showed strongest diagnostic value for PAD based on ABI. Neither ABI nor clinical examination was a good predictor of the inability to walk 200 meters without difficulties. DISCUSSION/CONCLUSIONS: Full clinical examination, only moderately, adds to detection of PAD. The ability to walk 200 m is not a good measure of PAD in older subjects.

Socio-economic determinants of vitamin D deficiency in the older Polish population: results from the PolSenior study.

OBJECTIVE: Numerous studies have reported an association between vitamin D (25-hydroxyvitamin D; 25(OH)D) deficiency and low economic status, lower educational level, drugs exposure, smoking and reduced physical activity. Our study analysed the association between sociodemographic factors and 25(OH)D status in Polish (Caucasian) seniors. DESIGN: Cross-sectional study (part of the PolSenior study). Serum 25(OH)D concentration was measured by a solid-phase ELISA method; a standardized questionnaire evaluated educational level, economic status, alcohol consumption, current or past cigarette smoking, physical activity, activities of daily living (ADL) and instrumental activities of daily living. SETTING: Community-dwelling randomly selected individuals aged 65 years or older, selected using three-stage stratified, proportional draw. SUBJECTS: Seniors (n 3472; 1658 women and 1814 men). RESULTS: Mean serum 25(OH)D concentration was 20·5 (sd 9·6) ng/ml. Values below the recommended level (30 ng/ml) were detected in 82·8 % of men and 90·4 % of women. Regression analysis revealed that the difference between sexes was associated with decreased walking activity in women, probably resulting in less sunlight exposure. There was a positive association between any disability in ADL and the presence of vitamin D deficiency/insufficiency. In the sex-adjusted analysis, older age, alcohol abstinence and lack of cycling and long-distance walking were explanatory variables for vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency/insufficiency is frequent in the older Polish population and associated with functional disability and impaired mobility of seniors.

Dental status in the Polish senior population and its correlates-Results of the national survey PolSenior.

OBJECTIVE: The aim of the study was to assess dental status of Polish seniors having and wearing dentures in relation to demographic, socioeconomic and lifestyle factors. BACKGROUND: Tooth loss is associated with deterioration of general health status. The epidemiological data on dental status in Poland, including Polish seniors, are fragmented. MATERIALS AND METHODS: The study cohort consisted of 4524 randomly selected participants, aged 65 years and over, representative for Polish seniors. Demographic, socioeconomic, lifestyle factors and dental status were collected using standardised questionnaires. RESULTS: The prevalence of partial and complete edentulism in the Polish senior population was estimated at 45.7% and 47.1%, respectively. Fourteen point four per cent (14.4%) of complete edentulous participants and 31.1% with partial edentulism (1-19 natural teeth) did not have dentures, and one-twelfth of respondents having dentures were not wearing them. The independent correlates of complete edentulism were: female sex, advanced age, rural dwelling, lower education level, physical work in the past, smoking and diabetes. Male sex, age 90+, rural dwelling, type of work, dependence in activities of daily living and partial edentulism were independent correlates of not having dentures and denture disuse. Lower than average personal income was only significant for not having dentures. CONCLUSIONS: Complete edentulism is frequent among older Poles and affects almost 50% of them. It is associated with female sex, age, rural dwelling, poor economic status, smoking and diabetes. Rural dwelling and dependence of daily living are significant correlates of not having dentures and denture disuse.

Pharmacological stroke prevention in the elderly with atrial fibrillation in Poland - Results of PolSenior study.

INTRODUCTION: Atrial fibrillation (AF) is the most frequent clinically significant arrhythmia, especially common in the elderly. As it is known, AF is associated with increased risk of stroke. Little is known about pharmacological cardiovascular prevention in the elderly with AF in Poland. OBJECTIVES: The purpose of the study was to evaluate the frequency of pharmacological stroke prevention among the elderly with AF in Poland and its association with clinical characteristics and concomitant cardiovascular risk factors. PATIENTS AND METHODS: The analysis included elderly (≥65 years) participants of the PolSenior study performed in years 2008-2012. RESULTS: The study group consisted of 4979 people (mean age: 79.3±8.7 years). Among them, there were 875 patients (18.7%) with documented history of AF. Pharmacological prevention with the use of vitamin K antagonists (VKA) was applied by 117 (13.4%) of the elderly with AF, including 15 (1.7%) on dual therapy. Additionally, 386 (45.3%) subjects with AF were using oral antiplatelet therapy (OAPs), mostly aspirin. Acenocoumarol was much more often used than warfarin. New oral anticoagulant drugs (NOACs) were not used at all. Only personal income was associated with the use of VKA. No significant correlation was found for the age, sex, place of residence and level of education. CONCLUSIONS: The study was unique to determine the frequency of pharmacological stroke prevention among elderly people with AF in Poland. It occurred that oral anticoagulant drugs were applied too rarely in this group of patients. Educational programs should be developed among general practitioners concerning current recommendations for patients with AF.

TLR-6 SNP P249S is associated with healthy aging in nonsmoking Eastern European Caucasians - A cohort study.

BACKGROUND: To investigate mechanisms that determine healthy aging is of major interest in the modern world marked by longer life expectancies. In addition to lifestyle and environmental factors genetic factors also play an important role in aging phenotypes. The aged immune system is characterized by a chronic micro-inflammation, known as inflamm-aging, that is suspected to trigger the onset of age-related diseases such as cardiovascular disease, Alzheimer's disease, cancer, and Diabetes Mellitus Type 2 (DMT2). We have recently shown that a Toll-like receptor 6 variant (P249S) is associated with susceptibility to cardiovascular disease and speculated that this variant may also be associated with healthy aging in general by decreasing the process of inflamm-aging. RESULTS: Analyzing the PolSenior cohort we show here that nonsmoking S allele carriers are significantly protected from age-related diseases (P = 0.008, OR: 0.654). This association depends not only on the association with cardiovascular diseases (P = 0.018, OR: 0.483) for homozygous S allele carriers, but is also driven by a protection from Diabetes Mellitus type 2 (P = 0.010, OR: 0.486) for S allele carriers. In addition we detect a trend but no significant association of this allele with inflamm-aging in terms of baseline IL-6 levels. CONCLUSION: We confirm our previous finding of the TLR-6 249S variant to be protective regarding cardiovascular diseases. Furthermore, we present first evidence of TLR-6 249S being involved in DMT2 susceptibility and may be in general associated with healthy aging possibly by reducing the process of inflamm-aging.

Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study.

BACKGROUND: In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. RESULTS: IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015-1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001). CONCLUSIONS: Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling.

BACKGROUND: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. MATERIALS AND METHODS: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR. RESULTS: The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3 mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for 'latent inflammation' proved to be hs-CRP and IL-6 serum levels. In the case of 'nutritional status', important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant. CONCLUSION: The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.

Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a hormone involved in calcium-phosphate homoeostasis. The data of recently published studies suggest that FGF-23 may also play a role in some metabolic processes beyond mineral metabolism, such as insulin resistance or energy homoeostasis. The aim of the study was to attempt the relationships between plasma cFGF-23 (C-terminal) and iFGF-23 (intact) concentrations and the occurrence of obesity, insulin resistance and inflammation in elderly population. MATERIALS AND METHODS: The analysis included 3115 elderly subjects (1485 women). During three visits, a questionnaire survey, comprehensive geriatric assessment and anthropometric measurements were performed as well as blood and urine samples were collected by trained nurses. Serum phosphorus, calcium, intact parathormone (iPTH), 25(OH)D3 , iFGF-23 and cFGF-23, insulin, glucose, albumin (also in urine), creatinine, hs-CRP, interleukin-6 and NT-proBNP concentrations were assessed. HOMA-IR was calculated according to the standard formula. RESULTS: Both forms of FGF23, iPTH and 25-OH-D3 levels were not related to the occurrence of obesity and insulin resistance. Increase in phosphorus, iPTH and NT-proBNP concentrations is associated with rise in plasma iFGF23 and cFGF23 levels. Additionally, increase in hs-CRP explained the elevated plasma iFGF23 levels. In multiple regression models, circulating iFGF23 and cFGF23 level's variability in elderly population were explained by changes in serum phosphorus, iPTH, eGFR, hs-CRP and NT-proBNP levels but not by BMI and HOMA-IR values. CONCLUSION: In conclusion, our study shows that increased levels of both circulating Fibroblast growth factor 23 forms in elderly subjects are associated with inflammation but not obesity or insulin resistance per se.

Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration is not related to kidney function in elderly subjects.

BACKGROUND: Studies assessing plasma visfatin/nicotinamide phosphoribosyltransferase (NAMPT) concentrations in chronic kidney disease with the ELISA method are restricted mainly to subjects with end-stage kidney disease. Therefore, little is known about to what extent glomerular filtration rate (GFR) affects the plasma levels of visfatin/NAMPT. The aim of this study was to assess the relations between circulating visfatin/NAMPT levels and estimated GFR (eGFR), independently of potential confounders such as inflammation, nutritional status, and insulin resistance in the elderly population. METHODS: The analysis included 3023 elderly subjects (1076 with impaired kidney excretory function - eGFR <60 mL/min/1.73 m2) who were participants of the PolSenior study. Serum insulin, glucose, creatinine, C-reactive protein, interleukin-6, and plasma visfatin/NAMPT concentrations were measured by a highly specific ELISA method. Insulin resistance was assessed on the basis of homeostasis model assessment for insulin resistance, and kidney excretory function was assessed using the full MDRD formula. RESULTS: Similar plasma visfatin/NAMPT levels were found in subjects with eGFR ≥60 and <60 mL/min/1.73 m2 (0.96 ng/mL in both groups), and even in those subjects with eGFR 15-30 mL/min/1.73 m2 (0.83 ng/mL). Additionally, there was no association between plasma visfatin/NAMPT concentrations and eGFR values in models of regression analysis including confounding factors. CONCLUSIONS: The results of our study suggest that plasma visfatin/NAMPT levels are not affected by impaired kidney excretory function in elderly subjects.

A common copy number variation polymorphism in the CNTNAP2 gene: sexual dimorphism in association with healthy aging and disease.

BACKGROUND: New therapeutic targets are needed to fight aging-related diseases and increase life span. A new female-specific association with diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the CNTNAP4 gene from the neurexin superfamily. OBJECTIVE: We asked whether there are CNVs that are associated with aging phenotypes within other genes from the neurexin superfamily and whether this association is sex specific. METHODS: Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR assays. RESULTS: A case/control study, in which a group of 81- to 90-year-old community-dwelling Caucasians with no chronic diseases (case) was compared to a similar control group of 65- to 75-year-olds, revealed a negative association with healthy aging for the ins allele of common esv11910 CNV in the CNTNAP2 gene (n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95% CI: 0.42-1.57, p = 0.625 for females). This male-specific association was validated in a study of an independent group of 76- to 80-year-olds. To look for a corresponding positive association of the allele with aging-related diseases, two case subgroups of 81- to 90-year-olds, one composed of individuals with cognitive impairment and the other with various diseases not directly related to the nervous system, such as cardiovascular diseases, etc., were compared to a healthy control subgroup of the same age. A positive male-specific association was found for both cases (OR = 2.75, p = 0.008 for association with cognitive impairment, and OR = 3.18, p = 0.002 for other diseases combined). CONCLUSIONS: A new male-specific association with aging is reported for a CNV in the CNTNAP2 gene. The polymorphism might be useful for diagnosing individual genetic predispositions to healthy aging versus aging complicated by chronic diseases.

Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the elderly.

BACKGROUND: Better biomarkers of CKD reflecting responses to decreased glomerular filtration rate (GFR) are needed. We determined the value of estimated GFR (eGFR) as a threshold for the increase of plasma cFGF23 (C-terminal) and intact fibroblast growth factor-23 (iFGF23) (intact) concentrations in the course of chronic kidney disease (CKD) and compared this eGFR value with values related to increased serum intact parathyroid hormone (iPTH) or phosphorus concentrations in an elderly population. METHODS: We measured plasma iFGF23, cFGF23, serum phosphorus, calcium, albumin, creatinine, urea, cystatin C, iPTH and vitamin 25-OH-D3 in 3780 population-based study participants aged ≥ 65 years. RESULTS: Serum phosphorus concentrations hardly increased until mean eGFR reached 47.3 ± 4.7 mL/min/1.73 m(2) but then increased exponentially. Similarly, both iPTH and iFGF23 increased slightly in early CKD but then increased exponentially when eGFR reached 55.0 ± 4.2 mL/min/1.73 m(2) for iPTH and 51.6 ± 5.7 mL/min/1.73 m(2) for iFGF23. The departure point for exponential increases in cFGF23 preceded those for iPTH and iFGF23 and occurred at a mean eGFR of 57.7 ± 7.8 mL/min/1.73 m(2). The prevalence of increased iFGF23 occurred at a remarkably higher eGFR value than that of cFGF23 across the CKD stages. CONCLUSIONS: The increase in cFGF23 preceded both the increase in iPTH and iFGF23 as eGFR declined. Increased plasma iFGF23 level did not precede the rise in serum iPTH concentrations and did not occur before stage-3 CKD in elderly persons. However, cFGF23 was not an early marker of CKD in the elderly subjects.

Secondary prevention of stroke in elderly people in Poland--results of PolSenior study.

BACKGROUND AND PURPOSE: The purpose of the study was to evaluate the frequency of use of oral antiplatelet (OAP) and anticoagulant (OAC) drugs as secondary stroke prevention among older people in Poland and its association with sociodemographic factors, place of residence, and concomitant cardiovascular risk factors. MATERIAL AND METHODS: The study group consisted of 426 subjects with a history of a previous stroke (mean age of 81.5±8.2 years), participants of multicentre, population-based PolSenior study. RESULTS: Among the study group, 261 people (61.3%) used at least one drug as a secondary prevention. OAPs were regularly used by 237 people (55.6%), and OACs-by 25 people (5.9%). The most often used drug was acetylsalicylic acid. Ticlopidine was more frequently used than clopidogrel, and acenocoumarol was used more often than warfarin. Among all of the concomitant cardiovascular risk factors, congestive heart failure was mostly associated with OAP treatment, and a history of atrial fibrillation-with OAC treatment. Use of drugs did not depend on age, sex, place of residence (rural or urban), level of education and personal income, but it was associated with the region where the respondents lived. CONCLUSIONS: Secondary cardiovascular preventive therapy in Poland is used too rarely in older people after stroke, and it especially concerns anticoagulant therapy in those with a history of atrial fibrillation. Structured educational programmes should be developed in Poland to improve usage of secondary preventive therapy in the elderly.

Frailty and Survivability of Polish Caucasian Nonagenarians and Centenarians.

Frailty is a major geriatric problem leading to an increased risk of disability and death. Prevention, identification, and treatment of frailty are important challenges in gerontology and public health. The study aimed to estimate the prevalence of the frailty phenotype (FP) among the oldest-old Polish Caucasians and investigate the relationship between the FP and mortality. Baseline data were collected from 289 long-lived individuals, including 87 centenarians and 202 subjects aged 94-99. Mortality was obtained from population registers over the following 5 years. Sixty percent of subjects were classified as frail, 33% as prefrail, and 7% as robust. Frailty was more common in women than men and among centenarians than nonagenarians. During the 5-year observation period, 92.6% of the frail women and all frail men died, while mortality rates were lower among prefrail, 78.8% and 66.7%, and robust individuals, 60% and 54.5%, respectively. In the survival analysis, frailty was the strongest negative risk factor: HR = 0.328 (95% CI: 0.200-0.539). The inability to perform handgrip strength measurement was an additional predictor of short survival. In conclusion, the FP is prevalent in nonagenarians and centenarians and correlates with lower survivability. Future studies should address differences between unavoidable age-associated frailty and reversible disability in long-lived individuals.