Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

Evaluation of a new homogenous method for detection of small dense LDL cholesterol: Comparison with the LDL cholesterol profile obtained by density gradient ultracentrifugation

BackgroundSmall, dense LDL (sdLDL) are highly atherogenic, and evidence indicates that sdLDL are useful predictors of cardiovascular disease. We evaluated a homogeneous method for the quantitative determination of sdLDL cholesterol (sdLDL-C) and compared it to the LDL-cholesterol profile obtained by density gradient ultracentrifugation (DGUC).MethodssdLDL-C was measured in plasma and in lipoprotein fractions obtained by DGUC using the sdLDL-EX “Seiken” kit.ResultssdLDL-C was only present in dense or intermediate LDL fractions obtained by DGUC. Plasma sdLDL-C levels were inversely corelated to the LDL relative floatation rate. The proportion of LDL-C that is sdLDL-C increases as a function of LDL density from a median of 19% for very buoyant LDL to 91% for very dense LDL particles. Plasma sdLDL-C level was significantly correlated with plasma triglyceride (TG) (n = 840, r_s = 0.710, p < 0.001). Among subjects with plasma TG > 150 mg/dl, 75% had sdLDL-C > 30 mg/dl, whereas among those with TG ≤ 150 mg/dl, only 17% had sdLDL-C > 30 mg/dl.ConclusionsThis precise and fully automated method for measuring plasma levels of sdLDL-C will allow the analysis of large number of samples in routine laboratories which will facilitate the evaluation of the clinical usefulness of sdLDL as a risk factor for CHD.     

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

BackgroundThe measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity.MethodsIn order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease.ResultsThe linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r² = 0.9512 ± 0.0202 (n = 5) for urine and r² = 0.9709 ± 0.0291 (n = 5) for serum [r² = mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2–4 h and 4–8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points.ConclusionsWe have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.     

Validation of the Taiwanese version of the Athens Insomnia Scale and assessment of insomnia in Taiwanese cancer patients

ContextIt is well known that insomnia is highly prevalent in cancer patients. Although various studies have used the Athens Insomnia Scale (AIS) for insomnia assessment, it has never been applied to cancer patients with insomnia.ObjectivesThe purpose of this study was to establish the reliability and validity of the Taiwanese AIS version (AIS-T) and evaluate the severity of insomnia among cancer patients in Taiwan.MethodsUsing a cross-sectional research design, 195 cancer patients (n = 195) were recruited from outpatient oncology clinics.ResultsCronbach’s alpha for internal consistency was 0.83, and the test-retest reliability was 0.94 over an interval of three days, based on a sample of 30 patients. Moreover, concurrent validity could be evaluated by significant correlations of the AIS-T with the Pittsburgh Sleep Quality Index-Taiwan form (PSQI-T) (r = 0.82, P < 0.001) and sleep efficiency measured by Actiwatch parameters (r = ?0.54, P < 0.001). Construct validity could be established by the Brief Fatigue Inventory-Taiwan form (r = 0.56, P < 0.001) and Medical Outcomes Study Short Form-36-Taiwanese version (physical component summary: r = ?0.52, P < 0.001; mental component summary: r = ?0.53, P < 0.001). The AIS-T could detect significant known-group validity from sleep quality (PSQI-T ≥5 or <5, respectively). The Actiwatch parameters are consistent with the results of the AIS-T, and both data sets indicate that patients experienced sleep disturbances. The prevalence of insomnia, as defined by the criteria of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th ed., was 22.56%; 49.2% subjects had significant insomnia at the score ≥6 at AIS-T.ConclusionThis study concludes that the AIS-T is a reliable and valid instrument for assessing insomnia among cancer patients in Taiwan.     

Association between indices of body mass and antibody titers to heat-shock protein-27 in healthy subjects

ObjectivesWe have assessed the relationship between indices of adiposity and antibody titers to Hsp-27 in healthy subjects.DesignTwo-hundred and fifty subjects were studied, including 50 normal-weight subjects (body-mass-index (BMI) ?25 kg/m²), 100 overweight subjects (BMI 25 to ?30 kg/m²) (n = 100) and 100 obese subjects (BMI ≥ 30 kg/m²).ResultsAnti-Hsp27-antibody levels in obese subjects were [0.34 (0.20–0.39) absorbency unit], being significantly higher than overweight and normal-weight groups (P < 0.05). Anti-Hsp27-antibody levels in overweight subjects [0.29 (0.15–0.34) absorbency unit] were statistically higher than controls [0.18 (0.10–0.23) absorbency unit] (P < 0.05).ConclusionHigh anti-Hsp-27-antibody levels in obese-subjects without established coronary disease may be related to a heightened state of immunoactivation associated with obesity.     

Effect of obesity on the association between ATF3 gene haplotypes and C-reactive protein level in Taiwanese

ObjectiveATF3 has traditionally been related to various inflammatory processes. Our aim was to test the statistical association between variations in the ATF3 gene and levels of nine serum inflammatory markers, including C reactive protein (CRP), in a Taiwanese population using interaction analysis.MethodsA sample population of 604 Taiwanese subjects was enrolled. Five tagging single nucleotide polymorphisms of the ATF3 gene from the Han Chinese HapMap Database were selected and genotyped.ResultsWith or without adjustment for clinical covariates, ATF3 genotypes were found to be associated with CRP levels but not with other inflammatory marker levels. Minor alleles of 2 of the 5 ATF3 SNPs were associated with decreased CRP levels predominantly in non-obese subjects (Bonferoni P = 0.018, and P = 0.002 for rs11571530, and rs10475, respectively). Two haplotypes inferred from the 5 SNPs, GATTA and TACCA, were also associated with increased or decreased CRP levels, respectively, in non-obese subjects (Bonferoni P = 0.012 and P = 0.01, respectively) but not in obese subjects. Interaction analysis revealed interaction of obesity with an ATF3 genotype associated with a high CRP level (interaction P = 0.006 for SNP rs10475). An effect of obesity on CRP level was also noted in haplotype interaction analysis (interaction P = 0.019 for haplotype TACCA).ConclusionsATF3 polymorphisms are independently associated with CRP levels in Taiwanese subjects. Further, ATF3 genotypes/haplotypes interact with obesity to set CRP levels. These findings may have implications for the prediction of atherosclerotic disease.     

Carotid intima media thickness is related positively to plasma pre ß-high density lipoproteins in non-diabetic subjects

BackgroundLipid-poor or lipid-free high density lipoprotein (HDL) particles, designated pre ß-HDL, stimulate removal of cell-derived cholesterol to the extracellular compartment, which is an initial step in the reverse cholesterol transport pathway. Pre ß-HDL levels may be elevated in subjects with established cardiovascular disease. We determined the relationship of carotid intima media thickness (IMT), a marker of subclinical atherosclerosis, with pre ß-HDL in subjects without clinically manifest cardiovascular disease.MethodsIMT and plasma pre ß-HDL, assayed by crossed immuno-electrophoresis, were determined in 70 non-diabetic subjects (aged 56 ± 9 years; non-smokers only; 27 women).ResultsIMT was correlated positively with pre ß-HDL, both expressed as plasma apolipoprotein (apo) A-I concentration (r = 0.271, p = 0.023) and as% of apo A-I (r = 0.341, p = 0.004). In contrast, IMT was correlated inversely with HDL cholesterol (r = ? 0.253, p = 0.035). IMT was also related positively to pre ß-HDL after adjustment for age, sex, systolic blood pressure (in apoA-I concentration, ß = 0.203, p = 0.043; in% of plasma apoA-I, ß = 0.235, p = 0.023). IMT remained associated with pre ß-HDL after additional adjustment for either body mass index, plasma glucose, cholesterol, triglycerides, HDL cholesterol, apoA-I and apoB.ConclusionSubclinical atherosclerosis may relate to higher plasma pre ß-HDL independently of apoA-I and HDL cholesterol levels.     

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

BackgroundPlasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers.MethodsWe included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2 years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004 who had drank < 1/week. In the follow-up study in 2005–2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension.ResultsRaised plasma ALT (OR = 1.22 per SD of log-transformed level, P = 0.045) and GGT (OR = 1.38 per SD of log-transformed level, P = 0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P < 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P = 0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P = 0.004) after adjusting for covariates.ConclusionsAmong the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese.     

Looking beyond polypharmacy: quantification of medication regimen complexity in the elderly

BackgroundPolypharmacy has been shown to influence outcomes in elderly patients. However, the impact of medication regimen complexity, quantified by the Medication Regimen Complexity Index (MRCI), on health outcomes after discharge of elderly patients has not been studied.ObjectiveOur aim was to test the convergent, discriminant, and predictive validity of the MRCI in older hospitalized patients with varying functional and cognitive levels.MethodsWe retrospectively applied the MRCI to the medication regimen of 212 hospitalized patients and assessed its validity.ResultsThe mean (SD) MRCI scores for medication regimens and number of medications at discharge were 30.27 (13.95) and 5.95 (2.40), respectively. The MRCI scores were strongly correlated with the number of medications (r = 0.94, P < 0.001) and the number of daily doses (r = 0.87, P < 0.001) and increased as the number of medications taken ≥3 times daily increased (27.35, 34.45, and 43.00 for none, 1, and 2 drugs, respectively; P < 0.001). Positive correlations were observed between the Cumulative Illness Rating Scale–Geriatrics score and both the number of medications and the MRCI score (r = 0.40, r = 0.46, P < 0.001, respectively). No relationship was found between MRCI scores and the number of medications and age, sex, and postdischarge medication modifications. Patients nonadherent to at least 1 drug were discharged with a higher MRCI score and higher number of medications compared with medication-compliant patients (33.3 and 7.0 vs 27 and 5.8, respectively; P < 0.01). An inverse correlation was found between overall adherence 1 month after discharge and the MRCI score (r = ?0.188, P = 0.028); however, no such correlation was found regarding the number of medications at discharge.ConclusionsThe MRCI showed satisfactory validity and good evidence of classifying regimen complexity over a simple medication count. The MRCI demonstrated application in clinical research and practice in the elderly. However, more studies are needed to investigate its advantage over the number of medications for identifying patients with complex medication regimens and directing interventions to simplify their medication regimen complexity.     

Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach

ObjectivesThis study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques.Design and methodsComparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI < 25 kg/m²) and obese (n = 32, BMI ≥ 25 kg/m²) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation.ResultsAmong six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7 mg/dL, p < 0.001) and positively correlated with age (r = 0.253, p < 0.005), BMI (r = 0.265, p < 0.001) and hsCRP (r = 0.385, p < 0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient = 0.266, p < 0.01).ConclusionElevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

Exploring generalizability in a study of costs for community-based palliative care

ContextPalliative care researchers face challenges recruiting and retaining study subjects.ObjectivesThis article investigates selection, study site, and participation biases to assess generalizability of a cost analysis of palliative care program (PCP) clients receiving care at home.MethodsStudy subjects’ sociodemographic, geographic, survival, disease, and treatment characteristics were compared for the same year and region with those of three populations. Comparison I was with nonstudy subjects enrolled in the PCP to assess selection bias. Comparison II was with adults who died of cancer to assess study site bias. Comparison III was with study-eligible persons who declined to participate in order to assess participation bias.ResultsComparison I: When compared with the other 1010 PCP clients, the 50 study subjects were on average 3.6 years younger (P = 0.03), enrolled 70 days longer in the PCP (P < 0.001), lived 6.7 km closer to the PCP (P < 0.0001), and were more likely to have cancer (96.0% vs. 86.4%, P = 0.05). Comparison II: Compared with all cancer decedents, the 45 study subjects who died of cancer were on average 7.0 years younger (P < 0.001), lived 2.7 km closer to the PCP (P < 0.001), and were more likely to have had radiotherapy (62.2% vs. 33.8%, P < 0.0001) and medical oncology (28.9% vs. 14.8%, P = 0.01) consultations. Comparison III: The 50 study subjects lived on average 42 days longer after their diagnosis (P = 0.03) and 2.6 km closer to the PCP (P = 0.01) than the 110 eligible persons who declined to participate.ConclusionIf the study findings are applied to populations that differ from the study subjects, inaccurate conclusions are possible.     

Association between self-reported sleep disturbance and other symptoms in patients with advanced cancer

ContextSleep disturbance (SD) is a significant source of distress for patients with cancer. Studies of patients with advanced cancer receiving palliative care to identify symptoms associated with the severity of SD are limited.ObjectivesIn this study, we sought to identify the symptoms measured by the Edmonton Symptom Assessment Scale (ESAS) that are associated with SD, as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary aims of the study were to determine the association between occurrences of SD with occurrences of other symptoms and screening performance of the ESAS-Sleep item against the PSQI.MethodsWe reviewed the completed ESAS and PSQI assessments of 101 patients with advanced cancer who were receiving palliative care and had been admitted to prospective clinical trials previously initiated by us. Patients with a PSQI score of ≥5 were considered to have an SD. The frequency and severity of the ESAS symptoms items, their correlation with each other, the PSQI score, and the screening performance of the ESAS-Sleep item were calculated.ResultsThe median age of patients was 60 years. Most were white non-Hispanic (73%), had lung or breast cancer (41%), and were diagnosed with SD (85%). The PSQI score was correlated with the ESAS items of pain (r = 0.27, P = 0.006), dyspnea (r = 0.25, P < 0.001), well-being (r = 0.35, P < 0.0001), and sleep (r = 0.44, P < 0.0001). Compared with patients without SD, those with SD were more likely to report pain (P = 0.0132), depression (P = 0.019), anxiety (P = 0.01), and a poorer sense of well-being (P = 0.035). An ESAS-Sleep item cutoff score of ≥3 (of 10) resulted in a sensitivity of 74% and a specificity of 73%.ConclusionSD is associated with increased frequency of pain, depression, anxiety, and a worse sense of well-being. These four symptoms should be assessed in all patients with advanced cancer with a complaint of SD. The ideal cutoff point of the ESAS-Sleep item for screening for SD is a score of ≥3. More research is needed to better characterize this frequent and distressing syndrome.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Comparative analysis of serum proteomes of patients with cardiovascular disease

ObjectivesTo monitor increases or decreases in cardiovascular disease (CVD)-related proteins that will be released from the deposits or plaque on the inner wall of blood vessels.Design and methodsProtein profiles of sera from healthy subjects and CVD patients were determined via 2-DE. Differentially expressed spots in CVD patients were identified by ESI-Q-TOF MS/MS. Retinol binding protein 4 (RBP4), ceruloplasmin, and hemopexin were confirmed by Western blotting and RBP4 was further verified by ELISA.ResultsApproximately, 400 spots were detected in each gel via comparisons of the serum proteome. Among these spots, 19 spots were selected and identified by ESI-Q-TOF MS/MS (P < 0.05). The expression levels of RBP4 and ceruloplasmin were higher in CVD patients by Western blotting. The level of immunoreactive RBP4 in CVD patients was higher than that in healthy subjects.ConclusionsThe three proteins identified in the present study may constitute potential biomarkers for the diagnosis of CVD in patients.     

Serum retinol binding protein 4 in patients with familial partial lipodystrophy

ObjectiveTo determine Retinol Binding Protein 4 (RBP4) levels in patients with Familial Partial Lipodystrophy (FPLD).MethodsTen patients with FPLD and a control group (9 patients) were selected to participate in the study.ResultsRBP4-log levels were lower in patients with FPLD in comparison to control group (1.52  ±  0.32 vs 1.84 ± 0.25, p = 0.029). A statistical trend was observed between Waist-to-Hip Ratio and RBP4-log (r = - 0.44, p = 0.054).ConclusionRBP4 levels are decreased in FPLD.     

A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese

BackgroundAdrenomedullin, a vasodilatory peptide, facilitates the differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese population.MethodsFour SNPs were genotyped in 1391 subjects without dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included impaired fasting glucose, impaired glucose tolerance, and diabetes according to the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia.ResultsIn stepwise logistic regression, the SNP rs11042725 was a significant independent predictor of the development of dysglycemia (OR = 1.31, P = 0.012), together with baseline age (P < 0.001), plasma triglycerides (P < 0.001), body mass index (P = 0.004), 2-h glucose after oral glucose tolerance test (P < 0.001), homeostasis model assessment of insulin resistance index (P = 0.045), and follow-up duration (P = 0.009). The association was more significant in women (P = 0.002) and in subjects without regular exercise (P = 0.001).ConclusionsOur study suggests a potential role of genetic variants in the ADM gene in the development of dysglycemia in our local Chinese population.     

Fetuin-A serum levels are not correlated to kidney function in long-lived subjects

ObjectivesSerum Fetuin A has been identified as an inhibitor of ectopic calcification. It is reduced in subjects with chronic kidney disease (CKD) and it has been proposed as a potential link between CKD and the higher prevalence of arterial calcification observed in these patients. During aging both the stiffening of arterial wall due to calcification and a decline in kidney function are frequent. The aim of the study is to investigate if Fetuin A serum levels are associated with aging and with AHSG T256S polymorphism. Moreover, we aim at investigate whether serum Fetuin A is correlated to kidney function in this setting of senescence.Design and methods256 health long-lived subjects (age 92 [81–100]) were recruited for the study. Serum Fetuin A was evaluated by ELISA, Cystatin C by immune-nephelometry. AHSG T256S was determinated by PCR-RFLP.ResultsSerum Fetuin A shows a significant correlation with age (r = 0.20; P = 0.0048). AHSG TS and SS genotypes are associated to lower levels of serum protein (0.27 [0.19–0.29] g/L vs 0.42 [0.32–0.49] g/L; P < 0.027 and 0.34 [0.25–0.41] g/L vs 0.42 [0.32–0.49] g/L; P < 0.001, respectively). No significant correlation between Fetuin A and Cystatin C was observed.ConclusionsSerum Fetuin A increases with age in elder individuals and subjects with the TS or SS AHSG polymorphism have lower levels of the circulating protein. No correlation with kidney function decline was observed. Other mechanisms should be investigated to explain the increase of Fetuin A with age.     

Serum vascular adhesion protein-1 is higher in subjects with early stages of chronic kidney disease

ObjectivesAn increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD).Design and methodsWe included 262 subjects aged 30 and above with fasting plasma glucose level < 7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratio ≥ 30 μg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay.ResultsSerum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio ( r = 0.29, p < 0.0001) and negatively associated with estimated GFR (r = ?0.24, p =  0.0001). Subjects with CKD stage 2 (N =  51) and stage 3 (N =  91) had significantly higher levels of serum VAP-1 than those without CKD (p =  0.0003 and p =  0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p =  0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD.ConclusionsSerum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.     

Serum pigment epithelium-derived factor levels are increased in patients with biopsy-proven nonalcoholic fatty liver disease and independently associated with liver steatosis

BackgroundIncreased serum concentrations of pigment epithelium-derived factor (PEDF) have been linked to the metabolic syndrome in the general population. However, the relationship between serum PEDF and nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome, remains unknown.MethodsWe assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD and 103 nonsteatotic control subjects who were matched for age and sex. The association between levels of PEDF and clinical, biochemical, and histological phenotypes was examined.ResultsNAFLD patients had significantly higher serum PEDF levels (1.97 ± 0.50 μg/mL) than control subjects (1.51 ± 0.49 μg/mL, Student's t test, P < 0.001). Multivariable-adjusted stepwise regression analysis showed that PEDF ([beta] = 0.32, t = 3.13, P = 0.002) and triglycerides ([beta] = 0.22, t = 2.23, P = 0.02) were, in the order they entered into the model, the main independent predictors of steatosis scores in our patients with NAFLD.ConclusionsSerum PEDF levels are significantly increased in patients with biopsy-proven NAFLD and are associated with liver steatosis independently of traditional risk factors.