Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.

Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide. Materials and Methods: The data is taken from the stable systolic heart failure (EF < 50%) FAR NHL registry (FARmacology and NeuroHumoraL activation). The primary endpoint at two-year follow-up was death, heart transplantation, or LVAD implantation. Results: A total of 1088 patients were enrolled in the FAR NHL registry; MR-proADM levels were available for 569 of them. The mean age was 65 years, and 81% were male. The aetiology of HF was ischemic heart disease in 53% and dilated cardiomyopathy in 41% of patients. The mean EF was 31 ± 9%. Statistically significant differences (p < 0.001) were obtained in several parameters: patients with higher MR-proADM levels were older, rated higher in NYHA class, suffered more often from lower limb oedema, and had more comorbidities such as hypertension, atrial fibrillation, diabetes, and renal impairment. MR-proADM level was related to furosemide dose. Patients taking higher doses of diuretics had higher MR-proADM levels. The mean MR-proADM level without furosemide (n = 122) was 0.62 (±0.55) nmol/L, with low dose (n = 113) 1−39 mg/day was 0.67 (±0.30) nmol/L, with mid dose (n = 202) 40−79 mg/day was 0.72 (±0.34) nmol/L, with high dose (n = 58) 80−119 mg/day was 0.85 (±0.40) nmol/L, and with maximum dose (n = 74) ≥120 mg/day was 1.07 (±0.76) nmol/L, p < 0.001. Patients with higher MR-proADM levels were more likely to achieve the primary endpoint at a two-year follow-up (p < 0.001) according to multivariant analysis. Conclusions: Elevated plasma MR-proADM levels in patients with chronic heart failure are associated with an increased risk of death and hospitalization. Higher MR-proADM levels in combination with increased use of loop diuretics reflect residual congestion and are associated with a higher risk of severe disease progression.

Activation of the Nitric Oxide Pathway and Acute Myocardial Infarction Complicated by Acute Kidney Injury.

BACKGROUND/AIMS: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients. METHODS: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model. RESULTS: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p < 0.001). SOD, uric acid, NOx, neopterin, BNP and troponin were significantly associated with the development of AKI (area under curve [AUC]-receiver operating curve [ROC] ranging between 0.70 and 0.81). In multivariate analysis cardiogenic shock, neopterin, NOx and troponin were independent predictors of AKI. AUC-ROC of the association of multibiomarkers and clinical model was 0.90 and outperformed the predictive value of the clinical model alone. OR of NOx ≥45 µmol/L was 8.0 (95% CI 3.1-20.6) for AKI. CONCLUSION: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.

Renal Functions and Prognosis Stratification in Chronic Heart Failure Patients and the Importance of Neutrophil Gelatinase-Associated Lipocalin.

BACKGROUND/AIMS: The rate of incidence and prevalence of acute kidney injury is increasing due to an increased number of patients with heart failure. Therefore it is very pertinent to early detect the level of renal injuries and to make necessary heart failure predictions. Thus the aim of this study is to determine renal functions and prognosis stratification in chronic heart failure patients and importance of Neutrophil Gelatinase-Associated Lipocalin (NGAL), an early diagnostic marker of acute kidney injury, as well as stratification of cardiovascular risk in heart failure patients. METHODS: Data including age, gender, comorbidities and medical history of outpatients and hospitalized patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry comprising three Cardiological Centers in the Czech Republic were collected between 1st October 2014 and 30th November 2015. One-year follow-up data were collected in November 2016 in such a way that all patients had at least one-year data from the time of recruitment, but up to two years to the time of follow-up. One-year data were used for the whole set of patients while data up to 24 months were used with Kaplan-Meier's survival curves to analyse the patients' survival data. Blood samples were collected from the patients and basic parameters were evaluated in order to analyse Neutrophil gelatinase-associated lipocalin (NGAL) and plasma levels of N-terminal pro-brain natriuretic peptide (NT-ProBNP) using Lipocalin-2/NGAL Human ELISA kit (Bio Vendor, Czechia) and the Cobas E411 NT-proBNP Immunoassay kit (Roche Diagnostics, Indianapolis, IN, USA) respectively. Statistical analysis was further carried out to explain the level of significance of the evaluated parameters using Spearman Correlation, Mann Whitney or Kruskal-Wallis test and log-rank test. RESULTS: Out of 547 patients from Farmacology and NeuroHumoraL activation (FAR NHL) multicenter prospective registry with available data on hospitalizations, mortality, biomarkers and one-year follow-up that were recorded, there were 439 males (80.3%) with a median age of 66 years. At least one-month stable patients with left ventricle ejection fraction (LV EF) under 50% were recorded. The etiology of heart failure was ischemic heart disease in 54%, dilated cardiomyopathy in 40% and others in 6%. 69% patients were in New York Heart Association functional class II. There were 76 events (13.9%; all-cause mortality, acute heart failure hospitalization, left ventricle assist device implantation and orthotopic heart transplant) in the first 365 days of follow-up. The area under the receiver operating characteristic curve was higher for NT-proBNP (0.77) than the creatinine (0.57), NGAL (0.55) or creatinine clearance (0.54). In multivariable analyses, NT-proBNP (P= 0.001) and NGAL (P = 0.004) were significant predictors of events. Subjects with NT-proBNP and NGAL above the cut off value (NT-proBNP 1,121 pg/ml, NGAL 80 ng/ml) survived without any event in 55.7%, subjects with NT-proBNP and NGAL under the cut off value survived without any event in 90.5%, after two years (P = 0.001). CONCLUSION: The findings of the study showed that NGAL associated with NT-proBNP was a stronger predictor of the primary endpoint than NGAL or NT-proBNP alone. The level of NGAL was rising in hypertension, ischemia, anemia, hypoalbuminemia, diabetes or arrhythmias.

Allelic variants in vitamin D receptor gene are associated with adiposity measures in the central-European population.

BACKGROUND: There is an increasing body of evidence suggesting that vitamin D is involved in ethiopathogenesis of obesity and therefore the aim of the study was to investigate whether 5 selected SNPs in VDR (vitamin D receptor) gene are associated also with anthropometry in the obese and non-obese Central-European population. METHODS: A total of 882 Central European Caucasian individuals of Czech origin were recruited (n = 882, 232 M/650 F) and weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold thickness were measured. Univariate and multivariate models were constructed in order to investigate the relationship between anthropometry and VDR polymorphisms. RESULTS: In the univariate modeling, the CC genotype of FokI SNP was associated with reduced waist circumference (ß = -3.48; 95%CI:-7.11;0.15; p = 0.060), sum of skin fold thickness (ß = -6.53, 95% CI: -12.96;-0.11; p = 0.046) as well as total % of body fat (ß = -3.14, 95% CI: -5.18;-1.09; p = 0.003) compared to TT genotype. The AC genotype of ApaI SNP was associated with reduced waist circumference compared to AA genotype (ß = -4.37, 95% CI: -7.54;-1.20; p = 0.007). GG genotype of EcoRV SNP was associated with reduced sum of skin fold thickness compared to AA genotype (ß = -7.77, 95% CI: -14.34;-1.21; p = 0.020). In the multivariate modelling, multiple significant associations of VDR with investigated traits were observed, too. CONCLUSION: Our study suggests that genetic variability in the VDR region may be an important factor influencing anthropometric characteristics associated with obesity.

Association of circulating levels of RANTES and -403G/A promoter polymorphism to acute heart failure after STEMI and to cardiogenic shock.

Chemokines, including RANTES, play a crucial role in the processes of inflammation during cardiovascular disorders, including myocardial infarction, disease progression and complications. This study aimed to evaluate the role of RANTES -403G/A polymorphism and levels in circulation in processes of development and progression of myocardial infarction and cardiogenic shock. A total of 609 patients with ST-segment elevation myocardial infarction, 43 patients with cardiogenic shock and 130 control subjects were enrolled in the study. RANTES -403G/A promoter polymorphism and baseline serum RANTES levels were analyzed. In the present study, we associated RANTES -403G/A promoter polymorphism with acute heart failure in patients with myocardial infarction (p = 0.006) and ejection fraction 3 months after MI onset (p = 0.02). Further, a difference in circulating RANTES levels among controls and STEMI subjects, and a relation of serum levels with acute heart failure was observed (p = 0.03, p = 0.003, respectively). We found a significant difference when comparing cardiogenic shock patients and controls (p < 0.001), with the most significant difference between cardiogenic shock and AHF subgroup of STEMI patients (p < 0.001). We observed a decreasing tendency of serum RANTES levels with the severity of myocardial infarction and progression, with the lowest levels in patients with cardiogenic shock (cutoff level ≥80.4 ng/ml). Our results suggest the role of RANTES as a potential biomarker of cardiogenic shock and acute heart failure in the hospital phase after myocardial infarction.