B‐type Natriuretic Peptide and Amino‐terminal Pro‐B‐type Natriuretic Peptide in Pediatric Patients with Pulmonary Arterial Hypertension

Objectives. B‐type natriuretic peptide (BNP) and the amino‐terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. Design. We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years old. Two hundred sixty‐three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. Results. There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean systemic arterial pressure ratio (r= 0.40, P < .01; r= 0.45, P < .01; respectively), mean right atrial pressure (r= 0.48, P < .01; r= 0.48, P < .01), and tricuspid regurgitant velocity (r= 0.36, P < .01; r= 0.41, P < .01). BNP and NTproBNP are associated with 6‐minute walk distance, mean pulmonary arterial pressure, mean pulmonary arterial pressure/mean systemic arterial pressure ratio, mean right atrial pressure, pulmonary vascular resistance index, and tricuspid regurgitant velocity when investigated longitudinally. On the average, a 1‐unit increase in log BNP or NTproBNP was associated with 4.5 units × m² or 3.4 units × m² increase in pulmonary vascular resistance index, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r= 0.87, P < .01). Conclusion. In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross‐sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time; therefore, NTproBNP can add additional information toward predicting these clinical measurements.     

Clinical and echocardiographic correlates of plasma B-type natriuretic peptide levels in patients with aortic valve stenosis and normal left ventricular ejection fraction

Background: Several studies suggest that BNP testing may help define the timing of aortic valve surgery in patients with aortic valve stenosis (AVS) prior onset of overt LV systolic dysfunction. The aim of this study was to identify clinical and echocardiographic correlates of plasma BNP levels in a large cohort of patients with AVS and preserved LV ejection fraction. Method and results: One hundred thirty‐five consecutive patients were prospectively included in the present study (Mean age 73 ± 13 years old, 66 (49%) male). Eighty‐nine patients (66%) had severe AVS (aortic valve area <0.6 cm²/m² BSA). Plasma BNP levels, clinical and comprehensive Doppler echocardiography evaluation was performed in all patients. Independent clinical correlates of plasma BNP levels (R²= 0.19) were older age (P < 0.0001) and presence of AVS symptoms (P = 0.004). Independent echocardiographic correlates of plasma BNP levels (R²= 0.38) were E/Ea ratio (P = 0.01), LV mass index (P = 0.018), left atrial surface (P < 0.0001) and systolic pulmonary artery pressure (sPAP; P = 0.004). Overall, independent correlates of plasma BNP levels (R²= 0.47) were older age (P = 0.001), known coronary artery disease (P = 0.047), increased LV mass index (P = 0.001), left atrial enlargement (P = 0.002), and increased sPAP (P = 0.003). Conclusions: In patients with AVS and normal LV ejection fraction, plasma BNP predominantly reflects the clinical and echocardiographic consequences of afterload burden imposed on the left ventricle rather than the severity of valve stenosis, per se. (Echocardiography 2011;28:695‐702)     

Blood pressure means rather than nocturnal dipping pattern are related to complications in Type 2 diabetic patients

Aim To determine whether systolic and diastolic blood pressure (BP) means, during ambulatory BP monitoring (ABPM), are more strongly correlated with microvascular complications and echocardiographic structural alterations than night‐time/daytime (N/D) BP ratio. Methods A cross‐sectional study was conducted in 270 Type 2 diabetes mellitus (DM) outpatients who underwent clinical and laboratory investigations, urinary albumin excretion rate (UAER) determination, echocardiography, office and 24‐h ABPM (Spacelabs 90207). Results UAER, after multivariate adjustments, was associated with office BP (systolic: R²_a 0.162, P < 0.001; diastolic: R²_a 0.124, P < 0.001) and ABPM (24‐h systolic: R²_a 0.195, P < 0.001; 24‐h diastolic: R²_a 0.197, P < 0.001) but not with N/D BP ratios (systolic: R²_a 0.062, P = 0.080; diastolic: R²_a 0.063, P = 0.069). Similar results were observed for echocardiographic parameters. The presence of retinopathy was associated only with night‐time BP values [systolic means: odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03–1.24 and diastolic means: OR 1.21, CI 1.04–1.40 and N/D diastolic BP ratio > 0.90, OR 3.21, CI 1.65–6.25]. Conclusions UAER and echocardiographic structural alterations had more consistent correlations of a greater magnitude with systolic BP means than with N/D BP ratios. The nocturnal BP values appear to be more relevant for diabetic retinopathy. BP measurement in patients with Type 2 DM should take into account the 24‐h period rather than focusing on a specific time span of BP homeostasis.     

B‐type natriuretic peptide is related to cardiac function and prognosis in hospitalized patients with decompensated cirrhosis

Background: B‐type natriuretic peptide (BNP) concentrations are high in cirrhosis, possibly related to volume status and cirrhotic cardiomyopathy. The prognostic significance of BNP in cirrhosis is unknown. Aims: We aimed to evaluate (i) the influence of haemodynamic parameters and volaemia, assessed by impedance cardiography (ICG), in BNP levels, (ii) the performance of BNP as a prognostic marker, in a cohort of cirrhotic patients. Methods: Patients consecutively hospitalized with decompensated cirrhosis during 1 year were evaluated. At admission, ICG and BNP measurements were performed in 83 patients (median age 56 years; median Child–Pugh score=10). The 70 patients discharged were followed for the occurrence of death within 6 months. Results: Median BNP levels were 130.3 (65.2–363.3) pg/ml. Independent BNP predictors in multivariate linear regression analysis were cardiac output, age and haemoglobin (R²=36.7%). The 24 patients with cardiac systolic dysfunction, defined by low cardiac output, had higher BNP concentrations than the other patients (230.8 vs 98.5 pg/ml, P=0.003). BNP levels above median were associated with an increased occurrence of death within 6 months of discharge (log rank P=0.023). Cardiac output and BNP were predictors of survival in univariate Cox regression analysis. Only BNP remained independently related to the outcome in multivariate analysis [hazard ratio=2.86 (1.11–7.38), P=0.03]. Conclusions: BNP levels in cirrhosis reflect cardiac systolic function and non‐cardiac variables that should be considered in their interpretation. BNP is an independent predictor of medium‐term survival in advanced cirrhosis, suggesting its utility in risk stratification of decompensated cirrhotic patients.     

Plasma brain natriuretic peptide and systemic ventricular function in asymptomatic patients late after the Fontan procedure

While increased plasma brain natriuretic peptide (BNP) levels have been documented late after the Fontan procedure, its significance remains unclear. We sought to test the hypothesis that plasma BNP levels reflect systemic ventricular function after the Fontan procedure by interrogating the relationship between plasma BNP level and indices of ventricular function. The plasma BNP levels and systemic ventricular function, as determined by conventional and tissue Doppler assessments, acoustic quantification (AQ), and myocardial performance index (MPI), of 35 asymptomatic Fontan patients were compared to those of 34 control subjects who had previous repair of ventricular septal defect. When compared with controls, Fontan patients had significantly higher plasma BNP levels (median 21 pg/ml, range 5–397 vs median 15 pg/ml, range 5–62, P = 0.04). Their systolic and diastolic ventricular function was impaired as evidenced by reduced systemic ventricular early diastolic (E) inflow velocity, early to late (A) diastolic inflow velocity ratio, left and right annular early diastolic (e), late diastolic (a), and systolic (s) velocities, AQ-derived ventricular fractional area change, peak emptying rate, and peak filling rate, and increased AQ-derived atrial filling fraction and MPI (all P < 0.05). Plasma BNP levels correlated negatively with E and A velocities, left-sided annular a velocity, and right-sided annular e, a, and s velocities, and positively with AQ-derived atrial filling fraction (all P < 0.05). In conclusion, our findings suggest that plasma BNP levels reflect primarily the diastolic function of the systemic ventricle in asymptomatic Fontan patients.     

B‐type natriuretic peptide and C‐terminal‐pro‐endothelin‐1 for the prediction of severely impaired peak oxygen consumption

Objective. To assess the utility of B‐type natriuretic peptide (BNP) and C‐terminal‐pro‐endothelin‐1 (CT‐proET‐1) to predict a severely impaired peak oxygen consumption (peak VO₂, < 14 mL kg^?1 min^?1) in patients referred for cardiopulmonary exercise testing. Design. Cross‐sectional study. Setting. Tertiary care center. Methods. Peak VO₂, BNP and CT‐proET‐1 were assessed in 141 consecutive patients referred for cardiopulmonary exercise testing. Results. B‐type natriuretic peptide [median (interquartile range) 48 (38–319) vs. 33 (15–86) pg mL^?1; P = 0.002] and CT‐proET‐1 [87 (76–95) vs. 60 (52–74) pmol L^?1; P < 0.001] were higher in patients with a peak VO₂ < 14 mL kg^?1 min^?1 (n = 30) than in those with a peak VO₂ ≥ 14 mL kg^?1 min^?1 (n = 111). CT‐pro‐ET‐1 had a higher area under the receiver‐operator‐characteristics curve (AUC) to predict a peak VO₂ < 14 mL kg^?1 min^?1 than BNP (0.79 vs. 0.68; P = 0.04). The optimal BNP cut‐off of 37.2 pg mL^?1 had a sensitivity of 80% and a specificity of 56%. The optimal CT‐proET‐1 cut‐off of 74.4 pmol L^?1 had a sensitivity of 80% and specificity of 76%. A five‐item score composed of body mass index, diabetes, forced expiratory volume within the first second, alveolo–arterial oxygen pressure difference, and BNP had an AUC of 0.88 to predict a peak VO₂ < 14 mL kg^?1 min^?1. Adding CT‐proET‐1 to the score resulted in an AUC of 0.92. Conclusions. C‐terminal‐pro‐endothelin‐1 is superior to BNP for the prediction of a peak VO₂ < 14 mL kg^?1 min^?1 in patients referred for CPET. A score incorporating body mass index, diabetes status, spirometry, blood gases, BNP and CT‐proET‐1 improves the prediction of a peak VO₂ < 14 mL kg^?1 min^?1 based on single biomarkers.     

Sildenafil Increases Systemic Saturation and Reduces Pulmonary Artery Pressure in Patients with Failing Fontan Physiology

Objective. The purpose of this study was to investigate the effect of sildenafil in patients with failing Fontan physiology. Design. A retrospective chart review was performed to compare history and available data in patients with Fontan circulations before and after starting sildenafil. The paired and unpaired Student's t‐tests were used for statistical analyses. Patients. Six patients at our institution with Fontan physiology, persistent symptoms of cyanosis or effusion, and poor hemodynamics as measured in the catheterization laboratory were placed on sildenafil. One patient was not included in the analysis because of insufficient length of treatment. All patients had symptoms of failing Fontan hemodynamics with either persistent cyanosis or effusions. In this group, the mean pulmonary artery pressure was greater than 15 mm Hg (17.4 ± 1.5 mm Hg) with mean estimated pulmonary vascular resistance of 3.5 ± 1.0 Wood units × m² prior to starting sildenafil. Results. Sildenafil significantly increased the systemic arterial oxyhemoglobin saturation in this group (82.8 ± 7.3% pre‐treatment vs. 91.0 ± 5.5% post‐treatment, P = .017). In the four out of five patients who have had follow‐up catheterizations, there was a significant decrease in pulmonary artery pressure (17.4 ± 1.5 mm Hg pre‐treatment vs. 13.8 ± 2.1 mm Hg post‐treatment, P = .018) and in estimated pulmonary vascular resistance pre‐ and post‐sildenafil treatment (3.5 ± 1.0 Wood units × m² pre‐treatment vs. 2.0 ± 0.4 Wood units × m² post‐treatment, P = .031). Conclusions. Sildenafil may be a useful adjunct to therapy in patients with failing Fontan physiology likely through its function as a pulmonary vasodilator.     

Quality of life and sexual well‐being in patients with a Fontan circulation: An explorative pilot study with a mixed method design

Objective

To get an impression of the quality of life (QOL) and sexual well‐being in the Fontan population, and to generate hypotheses for future research.

Methods

For this cross‐sectional pilot study, questionnaires regarding health‐related QOL, sexual function and fertility/pregnancy were completed by 21 patients with a Fontan circulation >16 years old, followed at the University Medical Center Groningen, the Netherlands. Semi‐structured qualitative interviews were conducted in 8 patients.

Results

Fontan patients scored significantly lower on general health than their healthy peers (t(19)=‐3.0, P = .008), whereas their scores on other QOL domains and sexual well‐being were comparable to normal values. During childhood, most patients experienced physical limitations and the feeling of being an outsider, and frequently faced bullying. Regarding sexual well‐being, large interindividual differences were noted. Four interviewed patients (25‐30 years) reported a good sexual well‐being, whereas the other interviewed patients (33‐47 years) reported erectile dysfunction, low self‐esteem and avoidance of sexual intercourse. Both the QOL domains mental health and role restrictions due to emotional problems were associated with female avoidance (P = .083, respectively, P = .089) and dyspareunia (P = ns respectively P = .094). In males, role restrictions due to physical problems and health change were related to sexual dissatisfaction (P = .056) respectively nonsensuality (P = .025).

Conclusions

Overall, Fontan patients have a relatively preserved quality of life and sexual wellbeing but face more social isolation and bullying during childhood/adolescence than their healthy peers. Sexual problems were mainly associated with physical limitations in males and with psychosocial limitations in females. Finally, sexual dysfunction was more common in older Fontan patients, and future research has to clarify whether progressive attrition of the Fontan circulation affects the patients' QOL and sexual well‐being.     

Anti–Jo‐1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy

Objective

Previous case series have examined the relationship between anti–Jo‐1 antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme‐linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti–Jo‐1 antibody levels and various disease manifestations of myositis.

Methods

Serum anti–Jo‐1 antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention‐to‐Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti–Jo‐1 antibody levels and organ‐specific disease activity in cross‐sectional and longitudinal analyses, respectively.

Results

Cross‐sectional assessment of 81 patients with anti–Jo‐1 antibody revealed a modest correlation between the anti–Jo‐1 antibody level and the serum creatine kinase (CK) level, as well as muscle and joint disease activity. Correlation coefficients were similar for CK levels (r_s = 0.38, P = 0.002), myositis VAS (r_s = 0.36, P = 0.002), and arthritis VAS (r_s = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti–Jo‐1 antibody levels correlated significantly with CK levels (R² = 0.65, P = 0.0002), myositis VAS (R² = 0.53, P = 0.0008), arthritis VAS (R² = 0.53, P = 0.006), pulmonary VAS (R² = 0.69, P = 0.005), global VAS (R² = 0.63, P = 0.002), and global MITAX (R² = 0.64, P = 0.0003).

Conclusion

In this large series of patients with idiopathic inflammatory myopathy, anti–Jo‐1 antibody levels correlated modestly with muscle and joint disease, an association confirmed by a custom ELISA using recombinant human Jo‐1. More striking associations emerged in a smaller longitudinal subset of patients that link anti–Jo‐1 antibody levels to muscle, joint, lung, and global disease activity.

     

Correlation between markers of peripheral nerve function and structure in type 1 diabetes

Background

Clinical and experimental studies in patients with type 1 and type 2 diabetes have demonstrated changes in ion channel function and nerve structure. In this study, we investigated the relationship between axonal dysfunction and morphological change in diabetic polyneuropathy by using neuromuscular ultrasound and nerve excitability techniques. We also explored possible differences in this relationship between type 1 and type 2 diabetes.

Methods

Nerve ultrasound and corresponding motor excitability studies were undertaken in 110 diabetes patients (50 type 1; 60 type 2) and 60 age‐matched controls (30 for each group). Neuropathy severity was assessed by using total neuropathy score. Median and tibial nerve cross‐sectional areas were measured at nonentrapment sites by using high‐resolution linear probe.

Results

Median and tibial nerve cross‐sectional areas were significantly higher in diabetes patients compared with controls: type 1 (median = 7.6 ± 0.2 mm² vs 6.3 ± 0.1 mm²; tibial = 14.5 ± 0.7 mm² vs 10.8 ± 0.3 mm², P < .05) and type 2 (median = 9.1 ± 0.3 mm² vs 7.2 ± 0.1 mm²; tibial = 18.5 ± 1.0 mm² vs 12.8 ± 0.5 mm², P < .05). In the type 1 cohort, significant correlations were found between nerve cross‐sectional area and excitability parameters including resting current‐threshold slope (median: r = 0.523, P < .0001; tibial: r = ?0.571, P = .004) and depolarizing threshold electrotonus at 90 to 100 ms (median: 0.424, P < .01; tibial: r = 0.435, P = .030). In contrast, there was no relationship between excitability values and nerve cross‐sectional area in the type 2 cohort.

Conclusions

This study has identified correlation between markers of axonal membrane function and structural abnormalities in peripheral nerves of type 1 diabetes patients. The differential relationship in nerve function and structure between type 1 and type 2 diabetes provides clinical evidence that different pathophysiological mechanisms underlie the development of neuropathy in these patient groups.     

Use of B-type natriuretic peptide as a screening tool for left ventricular diastolic dysfunction in rheumatoid arthritis patients without clinical cardiovascular disease

Objective

Patients with rheumatoid arthritis (RA) are at an increased risk for heart failure and left ventricular diastolic dysfunction (LVDD). B‐type natriuretic peptide (BNP) may be useful to screen for LVDD in the general population. We compared the effectiveness of BNP as a screening tool for LVDD in RA and non‐RA subjects without cardiovascular disease (CVD).

Methods

Study subjects were recruited from population‐based samples with and without RA, excluding subjects with CVD. LVDD was assessed by 2‐dimensional and Doppler echocardiography and categorized as none, mild, moderate/severe, or indeterminate. Linear regression and proportional odds models evaluated the association between LVDD and BNP, adjusting for age, sex, and body mass index.

Results

Among 231 RA and 1,730 non‐RA subjects without CVD, BNP was significantly higher in subjects with moderate/severe LVDD compared to those with no or mild LVDD (P = 0.02 for RA and P < 0.001 for non‐RA subjects). More RA subjects had elevated BNP than non‐RA subjects (16% versus 9%; P < 0.001). Positive predictive value (25% in RA and 18% in non‐RA subjects) and sensitivity (40% in RA and 26% in non‐RA subjects) were similarly low in both cohorts, but specificity was significantly lower in RA than in non‐RA subjects (89% versus 94%; P = 0.02).

Conclusion

While RA subjects were more likely to have elevated BNP, few RA patients with elevated BNP actually have LVDD. Also, normal BNP levels are less likely to rule out LVDD in RA than in non‐RA subjects. Therefore, BNP may be less effective for screening in RA subjects compared to the general population.     

Comparison of midregional pro‐atrial natriuretic peptide with N‐terminal pro‐B‐type natriuretic peptide in the diagnosis of heart failure

Objectives. The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10‐ to 50‐ fold higher than B‐type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro‐atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N‐terminal pro‐B‐type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. Design. The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. Results. Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L^?1, P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL^?1. Conclusion. Midregional pro‐atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT‐proBNP in some subgroups and should be further investigated in other studies.     

Renal iron load in sickle cell disease is influenced by severity of haemolysis

Spin density projection‐assisted R2‐magnetic resonance imaging (R2‐MRI; FerriScan^®) scans from 40 chelation‐naïve sickle cell patients were used to assess renal iron load by measuring renal R2 (R‐R2). Clinical data were collected retrospectively for the 2‐year period preceding the scan. R‐R2 showed no significant correlation with transfusional iron load (assessed by liver iron concentration), but correlated significantly with serum bilirubin (R = 0·61, P < 0·0001) and lactate dehydrogenase (R = 0·58, P < 0·0001). Mean (±standard deviation) R‐R2 was higher (P = 0·02) in patients with renal hyperfiltration (29·8 ± 10·3/s) than those without (23·11 ± 6·6/s). Five patients had significantly lower signal intensity in the renal cortex, as compared to the medulla. These patients had a significantly higher (P < 0·0001) mean R‐R2 than those showing no cortico‐medullary difference. We postulate that the increased R‐R2 is associated with haemolysis rather than transfusional iron load in sickle cell disease.     

Triceps Skinfold Thickness Is Associated With Lumbar Bone Mineral Density in Peritoneal Dialysis Patients

Anthropometric measurements, including body mass index (BMI), body weight and total fat mass are associated with the bone mineral density (BMD) in the general population. Compared to that in the general population, BMD was lower in dialysis patients. However, the association between anthropometric measurements and BMD is not well‐established among peritoneal dialysis (PD) patients. To study this, we conducted a cross‐sectional study in 48 chronic PD patients. Anthropometric parameters, biochemical data, and BMD measured by dual energy X‐ray absorptiometry in lumbar vertebrae (L2–L4) were collected. Among these PD patients, eight patients (16.7%) had osteoporosis and 22 patients (45.8%) osteopenia, while 18 patients were normal. Older age, decreased height, lower body weight, BMI, triceps skinfold thickness (TSF), mid‐arm fat area (MAFA), and higher adiponectin levels were observed in our patients with lower lumbar T‐scores. Height, body weight, waist circumference, BMI, body fat mass, TSF, mid‐arm circumference, MAFA, and serum phosphorus levels were positively, while age, adiponectin levels were negatively correlated with lumbar BMD levels. According to our multivariate forward stepwise linear regression analysis, TSF (R² change = 0.080, P = 0.017) and body weight (R² change = 0.333, P = 0.002) were both correlated with low lumbar BMD. In conclusion, either TSF or body weight in our chronic PD patients was proved to be an independent predictor for osteolytic bone lesions.     

Evaluation of left ventricular performance in hypertensive patients by speckle tracking echocardiography: Correlation with brain natriuretic peptide

BackgroundHypertension results in hemodynamic changes ranging from maladaptive left ventricular hypertrophy (LVH) to heart failure. Two-dimensional speckle tracking echocardiography (2D-STE) allows rapid and accurate analysis of regional and global left ventricular (LV) systolic and diastolic functions.ObjectiveAssessments of LV function in hypertensive patients with apparently preserved LV systolic function using 2D-STE in correlation with plasma brain natriuretic peptide (BNP) levels.Patients and MethodsEighty hypertensive patients were enrolled, they were classified into LVH group (group III) and non-LVH group (group II). Twenty sex and age-matched healthy individuals were recruited as controls (group I). 2D-STE was done to all subjects to assess LV longitudinal strain, and strain rate (SR). Plasma BNP levels were measured in all subjects.ResultsGlobal longitudinal systolic strain was significantly reduced in group III compared with group II (P = 0.037) and group I (P = 0.000). Furthermore, group III showed significantly reduced global LV longitudinal systolic SR and early diastolic strain rate compared with group II (P = 0.023 and 0.008 respectively), and group I (P = 0.01 and 0.0001 respectively). On the other hand, the mean values of global SRa s⁻¹ were significantly higher in both group II and group III compared to group I (P = 0.0001). A negative correlation was found between BNP level and global peak systolic strain, global systolic strain rate, early diastolic strain rate and late diastolic strain rate in hypertensive patients (groups II & III) in whom BNP level was significantly higher than controls (group I) (P = 0.000).ConclusionA substantial impairment of LV systolic and diastolic functions is detected in hypertensive patients with apparently preserved LV systolic function, especially if associated with LVH, as evidenced by two-dimensional speckle tracking echocardiography. Plasma BNP level is elevated in hypertensive patients and shows a significant negative correlation with strain and strain rate values.     

Diagnosis of different liver fibrosis characteristics by blood tests in non‐alcoholic fatty liver disease

Aims: Our aim was to develop an accurate, non‐invasive, blood‐test‐based method for identifying the main characteristics of liver fibrosis in non‐alcoholic fatty liver disease (NAFLD). Methods: Fibrosis was staged according to NASH‐CRN and Metavir systems in 226 patients with NAFLD. A fully automated algorithm measured the fractal dimension (FD) and the area of fibrosis (AOF). Independent predictors of diagnostic targets were determined using bootstrap methods. Results: (i) Development. Significant fibrosis defined by NASH‐CRN F≥2 was diagnosed by weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin index [area under the receiver operating characteristic (AUROC)=0.867]; significant fibrosis defined by Metavir F≥2 was diagnosed by weight, age, glycaemia, AST, ALT, ferritin and platelets (FibroMeter AUROC=0.941, P<0.005). AOF was estimated by the combination of hyaluronic acid, glycaemia, AST, ALT, platelets and prothrombin index (_aR²=0.530), while FD was estimated by hyaluronic acid, glycaemia, AST/ALT, weight and platelets (_aR²=0.529). (ii) Evaluation. Although NASH‐CRN was a better system for fibrosis staging, Metavir staging was a better reference for blood test. Thus, the patient rate with predictive values≥90% by tests was 97.3% with Metavir reference vs. 66.5% with NASH‐CRN reference (P<10^?3). FibroMeter showed a significantly higher AUROC than the NAFLD fibrosis score for significant fibrosis, but not for severe fibrosis or cirrhosis, with both staging systems. Relationships between fibrosis lesions were well reflected by blood tests, e.g., the correlation between histological area and FD of fibrosis (r_s=0.971, P<10^?3) was well reflected by the relationship between respective blood tests (r_s=0.852, P<10^?3). Conclusions: Different characteristics of fibrosis in NAFLD can be diagnosed and quantified by blood tests with excellent accuracy.     

Interleukin family member ST2 and mortality in acute dyspnoea

Abstract. Socrates T, deFilippi C, Reichlin T, Twerenbold R, Breidhardt T, Noveanu M, Potocki M, Reiter M, Arenja N, Heinisch C, Meissner J, Jaeger C, Christenson R, Mueller C. (Department of Internal Medicine, University Hospital Basel, Basel, Switzerland; University of Maryland, School of Medicine, Baltimore, MD, USA). Interleukin family member ST2 and mortality in acute dyspnoea. J Intern Med 2010; 268 : 493–500. Objectives. The study objective was to investigate the prognostic utility and patient‐specific characteristics of ST2 (suppression of tumorigenicity 2), assessed with a novel sensitive assay. Background. Suppression of tumorigenicity 2 signalling has been shown to be associated with death in cardiac and pulmonary diseases. Design/Subjects. In an international multicentre cohort design, we prospectively enrolled 1091 patients presenting with acute dyspnoea to the emergency department (ED). ST2 was measured in a blinded fashion using a novel assay and compared to B‐type natriuretic peptide (BNP) and NT‐proBNP. The primary end‐point was mortality within 30 days and 1 year. The prognostic value of ST2 was evaluated in comparison and in addition to BNP and NT‐proBNP. Results. Suppression of tumorigenicity 2 concentrations was higher amongst decedents than among survivors (median 85 vs. 43 U mL^?1, P < 0.001) and also higher in patients with impaired left ventricular ejection fraction (LVEF) when compared with preserved LVEF (P < 0.001). In receiver operator characteristics analysis, the area under the curve (AUC) for ST2, BNP and NT‐proBNP to predict 30‐day and 1‐year mortality were 0.76, 0.63 and 0.71, and 0.72, 0.71 and 0.73, respectively. The combinations of ST2 with BNP or NT‐proBNP improved prediction of mortality provided by BNP or NT‐proBNP alone. After multivariable adjustment, ST2 values above the median (50 U mL^?1) significantly predicted 1‐year mortality (HR 2.3, P < 0.001). Conclusion. In patients presenting to the ED with acute dyspnoea, ST2 is a strong and independent predictor of 30‐day and 1‐year mortality and might improve risk stratification already provided by BNP or NT‐proBNP.     

Liver complications of haemoglobin H disease in adults

Haemoglobin H (HbH) disease is a type of non‐transfusion‐dependent thalassaemia. This cross‐sectional study aimed at determining the prevalence and severity of liver iron overload and liver fibrosis in patients with HbH disease. Risk factors for advanced liver fibrosis were also identified. A total of 80 patients were evaluated [median (range) age 53 (24–79) years, male 34%, non‐deletional HbH disease 24%]. Patients underwent ‘observed’ T2‐weighted magnetic resonance imaging examination for liver iron concentration (LIC) quantification, and transient elastography for liver stiffness measurement (LSM) and fibrosis staging. In all, 25 patients (31%) had moderate‐to‐severe liver iron overload (LIC ≥7 mg/g dry weight). The median LIC was higher in non‐deletional than in deletional HbH disease (7·8 vs. 2.9 mg/g dry weight, P = 0·002). In all, 16 patients (20%) had advanced liver fibrosis (LSM >7.9 kPa) and seven (9%) out of them had probable cirrhosis (LSM >11.9 kPa). LSM positively correlated with age (R = 0·24, P = 0·03), serum ferritin (R = 0·36, P = 0·001) and LIC (R = 0·28, P = 0·01). In multivariable regression, age ≥65 years [odds ratio (OR) 4·97, 95% confidence interval (CI) 1·52–17·50; P = 0·047] and moderate‐to‐severe liver iron overload (OR 3·47, 95% CI 1·01–12·14; P = 0·01) were independently associated with advanced liver fibrosis. The findings suggest that regular screening for liver complications should be considered in the management of HbH disease.     

Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia

Background. Community‐acquired pneumonia (CAP) is the leading infectious cause of death in developed countries. Risk stratification has previously been difficult. Methods. Markers of cardiac stress (B‐type natriuretic peptide, BNP) and inflammation (C‐reactive protein, white blood cell count, procalcitonin) as well as the pneumonia severity index (PSI) were determined in 302 consecutive patients presenting to the emergency department (ED) with CAP. The accuracy of these parameters to predict death was evaluated as the primary endpoint. Prediction of treatment failure was considered as the secondary endpoint. Results. B‐type natriuretic peptide levels increased with rising disease severity as classified by the PSI (P = 0.015). BNP levels were significantly higher in nonsurvivors compared to survivors [median 439.2 (IQR 137.1–1384.6) vs. 114.3 (51.3–359.6) pg mL^?1, P < 0.001]. In a receiver operating characteristic analysis for the prediction of survival the area under the curve (AUC) for BNP was comparable to the AUC of the PSI (0.75 vs. 0.71, P = 0.52). Importantly, the combination of BNP and the PSI significantly improved the prognostic accuracy of the PSI alone (AUC 0.78 vs. 0.71; P = 0.02). The optimal cut‐off for BNP was 279 pg mL^?1. The accuracy of BNP to predict treatment failure was identical to the accuracy to predict death (AUC 0.75). Conclusions. In patients with CAP, BNP levels are powerful and independent predictors of death and treatment failure. When used in conjunction with the PSI, BNP levels significantly improve the risk prediction when compared with the PSI alone.     

Hepatitis C virus antibody-positive patients with HIV infection have a high risk of insulin resistance: a cross-sectional study

Objective

The aim of the study was to characterize and compare insulin resistance (IR) in hepatitis C virus (HCV)‐antibody (Ab)‐positive and HCV‐Ab‐negative patients with HIV infection.

Methods

This was a single‐centre cross‐sectional study of 1041 HIV‐infected patients (373 HCV‐Ab‐positive; 167 with detectable plasma HCV RNA). Metabolic and anthropometric assessments were performed, including measurement of IR using the homeostasis model for assessment of insulin resistance (HOMA‐IR).

Results

The prevalence of IR (i.e. a HOMA‐IR score ≥3.8) was significantly higher in HCV‐Ab‐positive than in HCV‐Ab‐negative patients (47.7 vs. 32.7%; P<0.0001). On multivariable linear regression analysis, the following variables were associated with HOMA‐IR score, expressed as an estimate of the percentage variation (Est.): high‐density lipoprotein cholesterol (per 0.3 mmol/L increase: Est.–4.1; P=0.01), triglycerides (per 0.1 mmol/L increase: Est. 0.6; P<0.001), alcohol intake (Est. ?12.4; P=0.002), sedentary lifestyle (Est. 14.7; P<0.001), CD4 T‐cell count in the highest quartile, i.e. ≥690 cells/μL (Est. 20.7; P=0.002), body mass index in the highest quartiles, i.e. ≥22.54 kg/m² (Est. 30.5–44.7; P<0.001), waist‐to‐hip ratio in the highest quartile, i.e. >1 (Est. 30.2; P<0.001) and HCV‐Ab positivity (Est. 24.4; P<0.001).

Conclusions

Our data confirm that HCV‐Ab positivity is an independent risk factor for IR. Management aimed at correcting known risk factors for IR should be implemented.