Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Plasma advanced oxidation products as an additional tool in assessment of post-infarction heart failure.

OBJECTIVE: To define which oxidative stress markers could be used as diagnostic tools in the assessment of post-infarction heart failure (HF). METHODS: This observational study enrolled patients with HF that were divided into three subgroups (ejection fraction [EF] ≥ 50%; EF 40-49%; EF < 40%) and age- and sex-matched healthy control subjects. The plasma concentrations of advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances, catalase activity and free thiols were determined in all participants. RESULTS: The study enrolled 81 patients with HF and 68 healthy control subjects. There were significant differences in the values ​​of oxidative stress markers between patients and controls. Oxidative stress parameters did not differ between the subgroups of patients, except for AOPP, which was significantly higher in the EF < 40% group. Univariate and multivariate logistic regression analyses showed an association between AOPP and HF in the EF ≥ 50% group, while receiver operating characteristic (ROC) curve analysis identified a cut-off value of 60.89 µmol/l for AOPP. CONCLUSIONS: Based on the ROC curve analysis of AOPP and the higher significance in the multivariate analyses for patients with EF ≥ 50%, these current results suggest that AOPP could be a useful additional tool in the assessment of post-infarction HF.

Combined Effect of Inter- and Intrapatient Variability in Tacrolimus Exposure on Graft Impairment Within a 3-Year Period Following Kidney Transplantation: A Single-Center Experience.

BACKGROUND AND OBJECTIVE: Tacrolimus is a cornerstone of the most immunosuppressive protocols after kidney transplantation, but its use is complicated by notable interpatient and intrapatient variability (IPV). The goal of this study was to evaluate whether or not tacrolimus IPV, or average dose-adjusted trough concentration (C0/D), during 6-12 months post-transplantation might have contributed to graft function decline in a 3-year period following kidney transplantation. After primary evaluation of individual effects of tacrolimus IPV and C0/D, the study aimed to estimate the combined effect of tacrolimus IPV and C0/D on composite endpoint (consisting of graft failure, chronic allograft dysfunction, chronic rejection, and doubling of serum creatinine concentration) in the period between 13 and 36 months after kidney transplantation. In addition, the goal was to analyze the impact of genetics on interpatient variability in tacrolimus exposure in the early and late post-transplantation periods. METHODS: The study enrolled 104 Caucasian patients and included 2541 patient examinations up to 36 months after kidney transplantation. All patients were genotyped on CYP3A5 6986A>G and ABCB1 3435C>T gene polymorphism. Patients were divided into groups based on the tacrolimus IPV tertiles and the median value of average C0/D during 6-12 months post-transplantation. RESULTS: The results showed a more pronounced decline in estimated glomerular filtration rate values within the high IPV tertile group (p = 0.018), as well as within the low C0/D group (p = 0.013) in a 3-year period after kidney transplantation. The carriers of CYP3A5*1/*3 genotype had lower C0/D compared to the CYP3A5*3/*3 carriers during the entire study period, while the results for ABCB1 were inconsistent when considering tacrolimus C0/D. Patients with high IPV/low C0/D had significantly reduced graft survival compared to the other tacrolimus IPV/C0/D combination groups (i.e., high IPV/high C0/D, low IPV/low C0/D, low IPV/high C0/D) with the hazard ratio of 3.14 in Cox analysis for reaching the composite endpoint. CONCLUSION: The findings of this study suggest that combined assessment of tacrolimus IPV and tacrolimus C0/D may categorize patients towards risk of graft deterioration in the long-term post-transplantation period.

Associations of Cardiovascular and All-Cause Mortality with Metabolic Syndrome in Hemodialysis Patients: A Prospective Single-Center Study.

Background and objectives: Metabolic syndrome (MetS) is a cluster of risk factors, such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, that together increase the risk of cardiovascular disease. Chronic hemodialysis (HD) patients have multiple comorbidities and many metabolic disorders, causing the frequent occurrence of metabolic syndrome. The goal of this study was to assess the prevalence of MetS in HD patients, and its association with all-cause and cardiovascular (CV) mortality. Patients and methods: A total of 138 HD patients were included in this prospective study. We analyzed demographic, anthropometric and biochemical data. Outcome measures were all-cause and CV mortality during the three-year follow-up. Results: MetS was diagnosed in 57.24% of enrolled patients. During the 36 months of follow-up, 33 patients died. MetS patients showed a significantly higher mortality rate than non-MetS (30.4% versus 16.36%, p < 0.001). The association of different MetS components with cardiovascular mortality reached significance when a minimum of three components were present (1.81 (95% confidence interval CI = 1.21-2.33)), with a grouped increase in effect size for subjects with four or five MetS components. Subjects with MetS exhibited nearly twice as high risk for all-cause (hazard ratio HR = 1.99 (95%CI) = 1.42-2.97) and 2.5 times for CV (HR = 2.51 (95%CI) = 1.25-3.83) mortality compared with those without MetS, after adjustment for age, gender, and cardiovascular disease. Conclusions: The study demonstrates that MetS is widespread in HD patients. In future, the focus must be on an active screening approach, and treatment of cardiometabolic risk factors, aiming to reduce mortality.

The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients.

PURPOSE: Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral-bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme. MATERIALS AND METHODS: Patients (n = 142) were genotyped for G-395A Klotho gene. Components of mineral-bone metabolism, classical and non-classical (FGF23, Klotho and vitamin D) as well as echocardiographic examination were determined. Predictive models were designed to determine the significance of Klotho gene variations and mineral-bone metabolism components for left ventricle hypertrophy (LVH). RESULTS: A-allele carriers were longer on haemodialysis (p = 0.033), and had higher phosphorus levels (p = 0.016) while the level of Klotho protein was significantly lower (p = 0.001) compared to non-A-allele carriers. The best gains were achieved upon addition of allele A, and all three new markers; the AUC made significant improvement from 0.596 to 0.806 (p < 0.001), and improved net reclassification for 82.1% (95% CI 42.9-121.3%). CONCLUSIONS: The genetic background of A-allele carriers of the G-395A Klotho gene polymorphism increases the susceptibility patients to haemodialysis. A-allele carriers are at a higher risk for the development of cardiovascular complications. The addition of non-classical to classical mineral metabolism components improves prediction power to LVH.

The association of CAT-262C/T polymorphism with catalase activity and treatment response in juvenile idiopathic arthritis.

Oxidative stress is believed to be of great importance for both the etiology and the persistence of juvenile idiopathic arthritis (JIA). The aim of this study was to investigate the association of -262C/T polymorphism of the catalase (CAT) gene with JIA, as well as to evaluate whether this polymorphism can influence plasma CAT activity and outcome in JIA patients treated with etanercept. A total of 154 subjects (60 JIA patients and 94 healthy volunteers) were screened for CAT-262C/T gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma CAT activity was determined using the spectrophotometric method according to Goth, prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA ACR (American College of Rheumatology) response criteria. The genotype and allele frequency distributions of CAT-262C/T polymorphism in the patients were significantly different from those of the controls (p = 0.014, p = 0.006). The TT genotype (polymorphic homozygous) was associated with a 4.36-fold higher likelihood of having JIA (95% CI 1.545-12.323, p = 0.005) as compared to the CC genotype (wild-type). At month 12 of treatment, JIA patients, carriers of the CC genotype, showed significantly higher plasma CAT activity (p = 0.004) and achieved the JIA ACR 70 response more often (p = 0.003) than the patients, carriers of the CT/TT genotype. This is the first study implying the possible association of CAT-262C/T polymorphism with JIA. The results suggest the potential protective effect of the CC genotype, with regard to CAT activity and treatment outcome.

Vitamin D receptor gene polymorphism influences lipid profile in patients with juvenile idiopathic arthritis.

Vitamin D receptor (VDR) gene FokI (rs2228570) polymorphism was postulated to influence outcome of several inflammatory diseases. The aim of this study was to evaluate the influence of rs2228570 polymorphism on lipid profile and on outcome in patients with juvenile idiopathic arthritis (JIA) treated with etanercept. A total of 153 subjects (62 JIA patients and 91 controls) were screened for the rs2228570 using the PCR-RFLP method. Lipid profile (cholesterol, triacylglycerol, HDL-C, and LDL-C) was determined using standard biochemical analysis in controls, while in JIA patients, it was determined prior to and 12 months after anti-TNF (etanercept) therapy. Clinical outcome was assessed using the JIA-American College of Rheumatology (ACR) response criteria. There were significant differences in the distribution of genotypes (p = 0.024) and alleles (p = 0.006; OR = 2.222, 95% CI 1.136-4.348) of the rs2228570 between patients and controls. Etanercept treatment significantly increased HDL-C levels (p = 0.006) in JIA patients with FF genotype in comparison to baseline values. No significant differences were seen in JIA-ACR 30/50/70 responses at month 12 between FF and Ff/ff genotype carriers. This is the first study to demonstrate the protective effect of the VDR FokI FF genotype on lipid profile in JIA patients treated with etanercept. However, this has to be confirmed in a larger cohort of patients.