Biomarkers of left atrial overload in obese and nonobese patients with atrial fibrillation qualified for electrical cardioversion.

BACKGROUND: Biomarkers of left atrial (LA) overload are considered factors affecting the efficacy of atrial fibrillation (AF) treatment. Increasing obesity rates contribute to a growing number of obese patients qualified for electrical cardioversion (CVE).Biomarkers of left atrial (LA) overload are considered as factors influencing efficacy of atrial fibrillation (AF) treatment. The increasing rate of obesity contributes to obese patients constituting a significant group of subjects qualified to electrical cardioversion (CVE). AIMS: The aim of the study was to evaluate serum concentrations of biomarkers of LA overload and their impact on the efficacy of CVE. METHODS: A total of 82 patients with persistent AF who underwent successful CVE were prospectively enrolled in the study. The study population was divided into the obese group (OG) and the nonobese group (NOG). The serum levels of the following biomarkers were measured on the day of admission and at follow­up: high­sensitivity C­reactive protein (hs­CRP), N­terminal pro­B­type natriuretic peptide, copeptin, galectin 3, growth differentiation factor 15 (GDF­15), and renalase. RESULTS: Baseline and follow­up hs­CRP levels were increased in the OG compared with the NOG. Four­week CVE efficacy was 38.8% in the OG and 60.6% in the NOG. Time of the observation, allocation to the groups, and CVE outcomes showed no associations with most LA biomarkers during follow­up. Baseline concentrations of 2 biomarkers of LA overload were associated with clinical characteristics of the study group, that is, log10 serum GDF­15 and log10 serum renalase levels correlated positively with the CHA2DS2­VASc score. CONCLUSIONS: Although obesity modifies the long­term efficacy of CVE, the OG and NOG did not differ significantly in most biomarkers of LA overload, except hs­CRP. The efficacy of CVE seems to be independent of the levels of biomarkers. A favorable procedure outcome did not affect their blood concentrations.

Renal resistive index and long-term outcome in patients with coronary artery disease.

BACKGROUND: The study aimed to evaluate the application of intra-renal Doppler flow indices for the prediction of major adverse cardiac and cerebrovascular events (MACCE) during 24-month follow-up in patients with coronary artery disease (CAD) subject to coronary angiography (CA). METHODS: This prospective study comprised 111 consecutive patients with stable and unstable CAD (68.5% men; median age 65 years), referred for CA. Ultrasonographic parameters of intra-renal blood flow in arcuate/interlobular arteries, including renal resistive index (RRI) and pulsatility index (RPI), were acquired directly before and 1 h after the procedure. Endpoint of MACCE (cardiovascular death, myocardial infarction, myocardial revascularization or stroke) were recorded during 24-month follow-up. RESULTS: MACCE occurred in 14 patients (12.6%). Patients with MACCE had more diffuse CAD reflected by Syntax score (23.6 vs.14.4 pts., p = 0.02), higher platelet level (242.4 vs. 207.2 × 1000/µl, p = 0.01), higher rate of left main CAD (42.9% vs.5.2%, p < 0.001) and left ventricular ejection fraction < 50% (50% vs.23.7%,p = 0.045). Patients with MACCE had higher pre-procedural (0.68 ± 0.06 vs. 0.62 ± 0.06, p < 0.001) and post-procedural RRI (0.72 ± 0.06 vs.0.66 ± 0.06, p = 0.01), but comparable RPI (p = 0.63 and p = 0.36, respectively). Cox proportional hazards model revealed that pre-procedural RRI (OR = 1.11 per 0.01; p = 0.02) and left main CAD (OR = 5.75, p = 0.002) were the only independent predictors of MACCE occurrence. Receiver operator characteristic curve analysis revealed that preprocedural RRI > 0.645 accurately predicted the composite endpoint (AUC = 0.78, p = 0.001) and identified patients with impaired 24-month prognosis according to Kaplan-Meier curve (log-rank p < 0.001). CONCLUSIONS: Increased pre-procedural RRI, together with left main CAD, are associated with worse 24-month prognosis in patients with CAD referred for CA.

Circulating vaspin levels and nutritional status and insulin resistance in polycystic ovary syndrome.

OBJECTIVES: The study aimed to assess the associations between circulating vaspin levels and nutritional status (assessed on tha basis of BMI) as well as insulin resistance in PCOS. MATERIAL AND METHODS: Eighty-seven PCOS women, 48 obese and 39 normal weight, were enrolled in the cross-sectional study. Seventy-two Non-PCOS women, 41 obese and 31 normal weight, constituted a control group. Body mass, height and waist circumference as well as body composition by bioimpedance were measured. In the morning (16h after the last meal) we determined: serum glucose, insulin, androgens, gonadotropin (LH, FSH) and sex hormone-binding globulin (SHBG) as well as plasma vaspin levels. Standard HOMA-IR formula was used to assess insulin resistance (IR). RESULTS: Plasma vaspin levels were significantly lower in PCOS, both normal weight and obese, than in Non-PCOS groups. Vaspin levels were similar in normal weight and obese PCOS subgroups. There was no association between plasma vaspin levels and anthropometric parameters in PCOS group. While in Non-PCOS group a negative correlation between plasma vaspin levels and body mass (r = -0.26; p < 0.05) was found. We did not observe correlations between plasma vaspin levels and serum glucose and insulin concentrations as well as HOMA-IR values, however, in multivariable, stepwise backward regression waist circumference and HOMA-IR values explained 18.0% of plasma vaspin levels variability in the study subjects. CONCLUSIONS: PCOS occurrence is associated with decreased vaspin levels. The influence of nutritional status on vaspin level observed in Non-PCOS is abolished in PCOS women, possibly by more severe insulin resistance.

Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data.

D-Lactate is produced by the intestinal biota and later absorbed into circulation. Some patients with cystic fibrosis (CF) develop exocrine pancreatic insufficiency that may disturb the gut microbiome and enhance the production of D-lactate. However, this concept has not been studied yet. The aim of the study was to assess D-lactate concentration in relation to the occurrence of clinical features, activity of CF, and diet composition in paediatric patients. Patients and Method. Serum concentrations of D-lactate were measured in 38 CF patients (19 girls and 19 boys) from 6 months to 18 years of age. The analysis included age, sex, clinical symptoms, diet (the variety and calorie needs), the laboratory tests for pancreatic efficiency (serum levels of albumin and glucose, faecal elastase activity, and faecal fat index) and faecal calprotectin (the marker of intestinal inflammation), and parameters of liver damage and of cholestasis (the activity of aminotransferases, γ-glutamyltransferase, level of bilirubin, and international normalized ratio). Results. The median level of D-lactate was 0.86 µg/ml (1Q-3Q: 0.48-2.03) and correlated with the CF severity in the Schwachman-Kulczycki score, parameters of pancreatic insufficiency, and the presence of intestinal inflammation. An increased level of D-lactate was observed in the subgroup with pancreas insufficiency (1.05 versus 0.73; p < 0.05), parallel with an elevated level of calprotectin (0.948 versus 0.755; p = 0.08). There was no relationship between energy consumption and diet composition and serum D-lactates. Conclusion. Serum D-lactate concentration in CF patients is a promising new marker of exocrine pancreatic insufficiency probably related to intestinal flora dysbiosis/overgrowth.

Plasma concentration of Retinol Binding Protein 4 (RBP4) in relation to nutritional status and kidney function in older population of PolSenior Study.

PURPOSE: The aim of the study was to assess plasma RBP4 concentration in elderly subjects in relation to nutritional status and kidney function in the population of the PolSenior Study. MATERIAL AND METHODS: We assessed RBP4, glucose, insulin, albumin, lipid profile, C-reactive protein, (hsCRP) and creatinine concentrations in 2614 PolSenior Study participants (1235 women and 1379 men). The study group was divided based on BMI and HOMA-IR values, and the occurrence of diabetes. RESULTS: Plasma RBP4 concentration was similar in normal weight, overweight, and obese subgroups, both in women (40.4 vs 40.8 vs 41.8 ng/ml, respectively), and men (41.2 vs 40.3 vs 42.9 ng/ml, respectively). Similar values were found in subjects with HOMA-IR <2.5; ≥2.5 and diabetes, while those with decreased eGFR (<60 ml/min/1.73 m2) were characterized by increased RBP4 levels [46.0 (32.0-64.8) vs 39.4 (28.2-54.9) ng/ml; p < 0.001]. Plasma RBP4 level variability was explained by: age, waist circumference or BMI, and eGFR, but not HOMA-IR and/or hsCRP. The standardized coefficients ß (slopes) for BMI and waist circumference were similar. CONCLUSIONS: The results revealed that in older subjects, circulating RBP4 levels are mostly affected by kidney function and modestly by age, gender, and nutritional status, but not insulin resistance.

Plasma Level of Retinol-Binding Protein 4, N-Terminal proBNP and Renal Function in Older Patients Hospitalized for Heart Failure.

BACKGROUND/AIM: Elevated plasma concentration of retinol-binding protein 4 (RBP4) has recently emerged as a potential new risk factor for cardiovascular diseases, including hypertension (HT) and coronary artery disease (CAD). Limited data suggest that RBP4 promotes inflammatory damage to cardiomyocytes and participates in the development of heart failure (HF). This study aimed to analyze the relationship between concentrations of plasma RBP4 and serum N-terminal proBNP (NT-proBNP), a powerful biomarker of left ventricle dysfunction, in the older Polish population. METHODS: The study sample consisted of 2,826 (1,487 men) participants of the PolSenior study, aged 65 years and older, including a subgroup hospitalized for HF (n = 282). In all subjects, plasma concentrations of RBP4, interleukin-6 (IL-6), serum level of NT-proBNP, and hs-CRP were measured. Additionally, BMI, estimated glomerular filtration rate (eGFR), and HOMA-IR were calculated. The prevalence of HT, CAD, atrial fibrillation (AF), and medication were considered as potential confounders. RESULTS: Similar RBP4 levels were found in subjects with NT-proBNP < 125 and ≥125 ng/mL, with and without AF, and in the subgroups hospitalized for HF with and without AF. Regression analysis revealed no association between log10(NT-proBNP) and log10(RBP4). Plasma levels of RBP4 were increased by HT occurrence and diuretic therapy, while diminished with regard to female gender, age, eGFR values, AF, and IL-6 levels. CONCLUSION: Our results show that RBP4 is affected by GFR but cannot be considered as an independent biomarker of heart muscle dysfunction.

Urinary renalase concentration in patients with preserved kidney function undergoing coronary angiography.

AIM: The purpose of the study was to evaluate urinary renalase concentration before and after coronary angiography/percutaneous coronary interventions (CA/PCI) in patients with coronary artery disease (CAD) and preserved kidney function and verify its potential application as contrast-induced acute kidney injury (CI-AKI) diagnostic marker. METHODS: This prospective study comprised 95 consecutive patients (69.5% men; median age 65 years) with CAD submitted to elective or urgent CA/PCI. Data regarding 128 clinical variables were obtained. Urine samples were collected on admission and 6 h after CA/PCI and tested for urinary renalase using ELISA method, which was expressed as renalase-to-creatinine ratio. The CI-AKI diagnosis was based on ≥50% relative or ≥0.3 mg/dl absolute increase of serum creatinine concentration 48 h following the procedure. RESULTS: Nine patients developed CI-AKI (9.5%). In comparison to baseline values, urinary renalase-to-creatinine ratio significantly decreased 6 h following CA/PCI, (2843.6 vs.1540.7 ng/mg, P < 0.0001). Nine patients developed CI-AKI (9.5%).The reduction of renalase level was profound both in CI-AKI (2709.7 vs. 1585.7 ng/mg, P = 0.007) and non-CI-AKI group (2814.9 vs.1561.8 ng/mg, P < 0.0001). There was a trend towards a greater relative decrease of urinary renalase in CI-AKI group (-57.3 vs.-41.8%, P = 0.10). Univariate analysis revealed that both pre- and post-procedural urinary renalase did not predict CI-AKI onset; however, absolute decrease of renalase below 25 percentile was a predictor of CI-AKI (OR = 5.4, 95% CI:1.3-21.9, P = 0.027). CONCLUSION: Urinary renalase concentration is reduced in the aftermath of CA/PCI, which may be related to CI-AKI development. Further studies are warranted to elucidate the role of urinary renalase as a CI-AKI diagnostic marker.

Prediction of contrast-induced acute kidney injury by early post-procedural analysis of urinary biomarkers and intra-renal Doppler flow indices in patients undergoing coronary angiography.

BACKGROUND: The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra-renal Doppler flow indices for the prediction of contrast-induced acute kidney injury (CI-AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI). METHODS: This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra-renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin-18 (IL-18), liver-fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) using ELISA method. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post-procedurally. RESULTS: CI-AKI was confirmed in nine patients (9.5%). CI-AKI onset was associated with significantly higher urinary KIM-1 at 6 h (P = 0.003) and ΔKIM-1 concentrations (P = 0.001), and urinary IL-18 at 6 h (P = 0.014) and ΔIL-18 concentrations (P = 0.012), however, L-FABP and ΔL-FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post-procedural IL-18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM-1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI-AKI onset. Logistic regression analysis of postoperative predictors revealed that IL-18 and RRI were independent predictors of CI-AKI onset (AUC = 0.96; P < 0.0001). CONCLUSIONS: Joint assessment of early post-procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI-AKI in patients undergoing coronary interventions.

Serum levels of vascular endothelial growth factor and basic fibroblast growth factor in children with brain tumors.

BACKGROUND: Angiogenesis is the process of new vessel formation originating from the existing vascular network. It plays an important role in the growth and spread of malignancies, including brain tumors. The process of angiogenesis is characterized by increased expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and by the release of their soluble forms into circulation. OBJECTIVES: The aim of the study was to evaluate serum levels of VEGF and bFGF in children with malignant and benign brain tumors. MATERIAL AND METHODS: The study group (group N) included 106 children diagnosed with brain tumors. The children in group N were classified according to tumor pathology into 3 subgroups: N1 (n = 63): patients with malignant tumors, excluding anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM); N2 (n = 25): patients with benign tumors; and N3 (n = 18): patients with high grade gliomas (AA and GBM). VEGF and bFGF were determined by ELISA in blood samples before the initiation of chemotherapy. VEGF and bFGF levels were compared within the subgroups in relation to tumor grading and the extent of surgery. RESULTS: The median VEGF in patients with brain tumors was significantly higher than in the control group. The median levels of VEGF and bFGF in subgroup N1 were significantly higher than in the control group. The differences in VEGF and bFGF concentrations between the subgroups in relation to the extent of tumor resection were not significant. CONCLUSIONS: Significantly higher plasma VEGF levels in children with brain neoplasms may reflect enhanced angiogenesis in the tumors.

Increased plasma RBP4 concentration in older hypertensives is related to the decreased kidney function and the number of antihypertensive drugs-results from the PolSenior substudy.

Increased plasma retinol-binding protein 4 (RBP4), a novel adipokine, has been associated in previous studies with obesity, type 2 diabetes, dyslipidemia, hypertension (HT), atherosclerosis, and coronary artery disease. This study aimed to analyze the relationship between HT occurrence and its treatment, and plasma RBP4 concentrations in the older polish population. The study sample consisted of 1728 (890 men and 838 women) PolSenior study participants aged 65 years and older with available plasma samples and NT-proBNP values below 2000 pg/mL. The analysis included body mass index, waist circumference, blood pressure, antihypertensive medication, estimated glomerular filtration rate, serum glucose and insulin (and the homeostatic model assessment of insulin resistance), and plasma RBP4 levels. RBP4 plasma concentrations were higher in hypertensive (N = 645) than normotensive (N = 236) men (43.4 [30.4-64.8] vs. 38.1 [27.1-54.4] ng/mL, respectively; P < .01) but not in women (44.6 [29.6-63.5] vs. 40.7 [29.1-58.1] ng/mL, respectively; P = .21). In the subanalysis, higher plasma RBP4 levels were observed in women with treated than untreated HT and in subjects taking four of more antihypertensive drugs. The linear regression shown that estimated glomerular filtration rate (ß = -0.015), thiazide diuretics (ß = 0.041), and α-blockers (ß = 0.049) were explaining log10RBP4 plasma levels variability in the study group. Older male Caucasians with HT are characterized by elevated plasma RBP4 levels. This increase is proportional to the number of antihypertensive drugs and decreased glomerular filtration rate. Among the antihypertensive drugs, only thiazide diuretics and α-blockers had a significant influence on RBP4 levels.

Pre-procedural renal resistive index accurately predicts contrast-induced acute kidney injury in patients with preserved renal function submitted to coronary angiography.

The study aimed to evaluate the clinical utility of ultrasonographic intra-renal blood flow parameters, together with the wide range of different risk factors, for the prediction of contrast-induced acute kidney injury (CI-AKI) in patients with preserved renal function, referred for coronary angiography or percutaneous coronary interventions (CA/PCI). This prospective study covered 95 consecutive patients (69.5% men; median age 65 years) subject to elective or urgent CA/PCI. Data regarding 128 peri-procedural variables were collected. Ultrasonographic intra-renal blood flow parameters, including renal resistive index (RRI) and pulsatility index (RPI), were acquired directly before the procedure. CI-AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine 48 h after procedure. CI-AKI was confirmed in nine patients (9.5%). Patients with CI-AKI had higher SYNTAX score (p = 0.0002), higher rate of left main disease (p < 0.00001), peripheral artery disease (PAD; p = 0.02), coronary artery anomaly (p = 0.017), more frequently underwent surgical revascularization (p = 0.0003), 'had greater...' intima-(p = 0.004) and extra-medial thickness (p = 0.001), and received higher contrast media dose (p = 0.049), more often overused non-steroidal anti-inflammatory drugs (p = 0.001), and had substantially higher pre-procedural RRI (0.69 vs. 0.62; p = 0.005) and RPI values (1.54 vs. 1.36; p = 0.017). Logistic regression confirmed age, SYNTAX score, presence of PAD, diabetes mellitus, and pre-procedural RRI independently predicted CI-AKI onset (AUC = 0.95; p < 0.0001). Pre-procedural RRI > 0.69 had 78% sensitivity and 81% specificity in CI-AKI prediction. High pre-procedural RRI seems to be a useful novel risk factor for CI-AKI in patients with preserved renal function. Coronary, peripheral and renal vascular pathology contribute to the development of CI-AKI following CA/PCI.

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.

C-Terminal to Intact Fibroblast Growth Factor 23 Ratio in Relation to Estimated Glomerular Filtration Rate in Elderly Population.

BACKGROUND/AIMS: An analytical equivalence between intact fibroblasts growth factor(iFGF23) and C-terminal(cFGF23) assays is logically expected, however, numerous studies demonstrate lack of a strong association between them. Previously, we have demonstrated the increase in cFGF23 slightly precedes the increase of iFGF23 with the impairment of kidney excretory function; without actually analyzing the ratio between both assays, which are postulated to be affected by declining kidney function. Therefore, the aim of this study was to analyze the ratio between C and iFGF23 in relation to the estimated glomerular filtration rate (eGFR) in an elderly population. METHODS: We analysed the variability of c/iFGF23 ratio in the population of 3264 elderly PolSenior study participants (≥ 65years) in the relation to eGFR calculated according full Modification of Diet in Renal Disease, serum levels of C-reactive protein (hs-CRP), and iron. RESULTS: The log10(c/i FGF23 ratio) increased in the subsequent CKD stages. Serum iron and CRP levels reduced the log10 and increased it with age in multivariate regression analysis. CONCLUSIONS: Our results suggest impairment in the cleavage of the C-terminal FGF23 fragments with the deterioration of kidney excretory function and age in the elderly population. Inflammation and low serum iron level seems to diminish degradation capacity of FGF23 fragments.

Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration in elderly subjects with metabolic syndrome.

INTRODUCTION: Visceral adipose tissue is the main source of circulating proinflammatory adipokine, visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT), whose role in the pathogenesis of metabolic syndrome (MS) components such as hypertension and carbohydrate and lipid disturbances is still uncertain, due to commonly used low specific C-terminal immunoassays to determine visfatin/NAMPT levels. OBJECTIVES: The aim of the study was to assess the association between the occurrence of MS components and circulating visfatin/NAMPT levels in elderly popula tion. PATIENTS AND METHODS: The analysis included 2174 elderly participants of the PolSenior study without heart failure, severe chronic kidney disease, cancer, and malnutrition. MS was defined according to the modified International Diabetes Federation criteria. Plasma visfatin/NAMPT concentrations were measured by a highly specific enzyme-linked immunosorbent assay. Additionally, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and insulin levels were assessed, and the homeostasis model assessment for insulin resistance was calculated. RESULTS: Women were diagnosed with MS more often than men (71.2% vs 56.8%; P <0.001) and had a greater prevalence of all MS components except for type 2 diabetes. Women with MS had higher concentrations of hsCRP and IL-6 than those without MS. Visfatin/NAMPT concentrations were higher in women with MS than in those without MS (1.06 ng/ml [0.65-1.87] vs 0.85 ng/ml [0.54-1.40]; P <0.001), but no differences were observed in men (0.97 ng/ml [0.59-1.61] vs 0.90 ng/ml [0.56-1.60], respectively; P = 0.5). In women, there was a stronger association between the number of components of MS and increased plasma visfatin/NAMPT levels than in men. CONCLUSIONS: Plasma visfatin/NAMPT levels are increased only in elderly women with MS. It is difficult to distinguish the components of MS specifically associated wit h increased visfatin/NAMPT levels.

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 fibroblast growth factor 23 concentration and iron status. Does the relationship exist in the elderly population?

OBJECTIVE: Fibroblast growth factor 23 (FGF23) is a phosphaturic agent involved in calcium-phosphate homeostasis. Recent findings show that iron deficiency and inflammation regulate FGF23 release and/or biodegradation. Iron deficiency is frequently observed in the elderly, therefore the aim of this study was to find out if iron deficiency is independent from low grade inflammatory factors affecting both forms of FGF23 that are detectable in circulation in a large population-based study of elderly subjects. DESIGN AND METHODS: The analysis included 3780 elderly (1798 females) PolSenior study participants and assessed levels of phosphorus, calcium, iron, ferritin, interleukin 6, C-reactive protein (hs-CRP), intact (iFGF23), and c-terminal FGF (cFGF23). The analysis was performed for all subjects and terciles of serum iron levels in relation to hs-CRP were calculated. RESULTS: The highest plasma cFGF23 and iFGF23 concentrations were found in subjects with the lowest serum iron levels (p<0.001). The effect of low grade inflammation was markedly weaker and affected only iFGF23 levels. The adjusted serum levels of hs-CRP, iPTH, phosphorus, and 25-(OH)-D3 analysis revealed that plasma iFGF23 and cFGF23 levels were almost unchanged up to a serum iron level of 59.3 ng/mL and 57.3 ng/mL respectively and then were nearly linearly increasing by 0.285 pg/mL and 3.742 RU/mL for each unit of serum iron increase. CONCLUSIONS: Low iron levels are associated with increased levels of both cFGF23 and iFGF23, independent of low grade inflammation. A similar analysis of cFGF23 and iFGF23 does not suggest enhanced biodegradation of iFGF23 induced by iron deficiency.

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.

Plasma visfatin/nicotinamide phosphoribosyltransferase levels in hypertensive elderly - results from the PolSenior substudy.

Visfatin/nicotinamide phosphoribosyltransferase (NAMPT), is a 52 kDa adipokine with proinflammatory properties produced mostly by macrophages and adipocytes from visceral adipose tissue. It seems that visfatin/NAMPT plays a role in the pathogenesis of arterial hypertension. As this condition is frequently present in the elderly, the aim of the study was to assess the plasma visfatin/NAMPT levels in normotensive and hypertensive subjects from the Polish elderly population. Visfatin/NAMPT levels were measured by specific enzyme-linked immunosorbent assay method in plasma samples from 2789 elderly subjects (1338 females, 1451 males) without heart failure, the PolSenior study participants, in addition to previously estimated serum concentrations of insulin, glucose, creatinine, C-reactive protein, and interleukin-6. Homeostasis model assessment for insulin resistance was calculated and used as a marker of insulin resistance. In the study group, 591 subjects were normotensive, 449 had untreated hypertension, and 1749 had treated hypertension. Plasma visfatin/NAMPT levels were not related to the presence of hypertension or the use of antihypertensive drugs, including angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. The regression analysis revealed that plasma visfatin/NAMPT concentration variability is increased in subjects with high-sensitivity C-reactive protein concentration above 3 mg/L and with homeostasis model assessment for insulin resistance ≥2.5, and decreased in those aged over 80 years. Our study shows that the presence of hypertension is not associated with the plasma levels of visfatin/NAMPT in elderly subjects. Plasma visfatin/NAMPT concentrations positively correlate with inflammation and insulin resistance, and are decreased in the oldest.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy.

BACKGROUND: Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. MATERIALS AND METHODS: Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. RESULTS: The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. CONCLUSION: Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation.