Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension

BACKGROUND: Rare mutations of the epithelial sodium channel (ENaC) result in the monogenic hypertension form of Liddle's syndrome. We decided to screen for common variants in the ENaC βand γ subunits in patients with essential hypertension and to relate their occurrence to the activity of circulating renin-angiotensin-aldosterone system. METHODS: Initially, DNA samples from 27 patients with low renin/low aldosterone hypertension were examined. The DNA variants were subsequently screened for in 347 patients with treatment-resistant hypertension, 175 male subjects with documented long-lasting normotension and 301 healthy Plasma renin and aldosterone levels were measured under baseline conditions and during postural and captopril challenge tests. RESULTS: Two commonly occurring βENaC variants (G589S and a novel intronic i12-17CT substitution) and one novel γENaC variant (V546I) were detected. One of these variants occurred in a heterozygous form in 32 patients, a prevalence (9.2%) significantly higher than that in normotensive males (2.9%, p = 0.007) and blood donors (3.0%, p = 0.001). βENaC i12-17CT was significantly more prevalent in the hypertension group than in the two control groups combined (4.6% vs. 1.1%, p = 0.001). When expressed in Xenopus oocytes, neither of the two ENaC amino acid-changing variants showed a significant difference in activity compared with ENaC wild-type. No direct evidence for a mRNA splicing defect could be obtained for the βENaC intronic variant. The ratio of daily urinary potassium excretion to upright and mean (of supine and upright values) plasma renin activity was higher in variant allele carriers than in non-carriers (p = 0.034 and p = 0.048). CONCLUSIONS: At least 9% of Finnish patients with hypertension admitted to a specialized center carry genetic variants of β and γENaC, a three times higher prevalence than in the normotensive individuals or in random healthy controls. Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Validity and Reliability of Spanish Version of the EQ-i: YV[S] in Colombian Children and Youth

Objective: To examine the psychometric properties of EQ-i:YV[S] with a Colombian’ sample. Method: We randomly selected a sample of 1355 children and adolescents between 8 and 14 years old (Mage = 10.80;SD = 1.41). We conducted exploratory (n1 = 416) and confirmatory (n2 = 939) factor analyses (EFA, CFA), reliability, internal consistency, and predictive validity. Results: The EFA explained 27.6% of the variance. The AFC indicated a multidimensional structure with four factors and 21 items obtained the best fit (χ 2 = 334.358; df = 183; RMSEA=0.030; CFI=.951; TLI=944; NFI=.899) with acceptable internal consistency (ω = .57,.75). EQ-i: YV[S] factors explain 18.5% of the observed variance in problem-centered coping scores. Conclusions: The psychometric fit of the inventory supports evidence of its usefulness for screening processes in clinical or educational assessment

Efficacy and safety of valsartan compared with enalapril at different altitudes

To compare the safety, tolerability, and antihypertensive efficacy of valsartan with enalapril at different altitudes. A total of 142 adult Colombian outpatients with mild to moderate essential hypertension were recruited in 3 cities at different altitudes (Bogotá at 2600 m, Medellı́n at 1538 m and Barranquilla at 100 m) and randomized in an open label fashion to receive either valsartan 80 mg once daily or enalapril 20 mg once daily for 8 weeks. Those patients not responding at 4 weeks received additional 1.25 mg indapamide daily during the remaining trial period. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to 4 weeks. Secondary efficacy variables included the change in mean sitting systolic blood pressure (SSBP). The primary criterion for tolerability was the incidence of adverse experiences. Both valsartan and enalapril reduced mean SDBP and SSBP with similar efficacy, independent of altitude. Adverse events irrespective of relationship to trial drug were reported by 12 patients (18.8%) on valsartan and by 15 (23.4%) patients on enalapril. Enalapril was associated with a significantly (P<0.05) higher rate of dry cough and more cases of headache than valsartan. Valsartan 80 mg once daily is as effective as enalapril 20 mg once daily in reducing blood pressure, with tolerability profile at least as good as enalapril’s

Agreement between cranial and facial classification through clinical observation and anthropometric measurement among envigado school children

Background: To evaluate the agreement between cranial and facial classification obtained by clinical observation and anthropometric measurements among school children from the municipality of Envigado, Colombia.Methods: This cross-sectional study was carried out among 8-15-year-old children. Initially, an indirect clinical observation was made to determine the skull pattern (dolichocephalic, mesocephalic or brachycephalic), based on visual equivalence of right eurion- left eurion and glabella-opisthocranion anthropometric points, as well as the facial type (leptoprosopic, mesoprosopic and euryprosopic), according to the left and right zygomatic, nasion and gnation points. Following, a direct measurement was conducted with an anthropometer using the same landmarks for cranial width and length, as well as for facial width and height. Subsequently, both the facial index [euryprosopic (=80.9%), mesoprosopic (between 81% - 93%) and leptoprosopic (=93.1%)] and the cranial index [dolichocephalic (index = 75.9%), mesocephalic (between 76% - 81%), and brachycephalic (=81.1%)] were determined. Concordance between the indices obtained was calculated by direct and indirect measurement using the Kappa statistic.Results: A total of 313 students were enrolled; 172 (55%) were female and 141 (45%) male. The agreement between the direct and indirect facial index measurements was 0.189 (95% CI 0.117-0261), and the cranial index was 0.388 (95% CI 0.304-0.473), indicating poor concordance.Conclusions: No agreement was observed between direct measurements conducted with an anthropometer and indirect measurements via visual evaluation. Therefore, the indirect visual classification method is not appropriate to calculate the cranial and facial indices. © 2014 Torres-Restrepo et al.; licensee BioMed Central [email protected]