Association between B‐type natriuretic peptide and within‐visit blood pressure variability

Background

Blood pressure variability (BPV) has been shown to predict cardiovascular events. Within‐visit BPV is the simplest and easiest measure of BPV, but previous studies have shown conflicts as to whether within‐visit BPV correlates with target organ damage. We aimed to evaluate whether within‐visit BPV correlates with B‐type natriuretic peptide (BNP) in a general population.

Hypothesis

Within‐visit BPV correlates with BNP in a general population.

Methods

This was a cross‐sectional study that included 633 individuals, randomly selected, age 45 to 99 years, registered in the primary care program from an urban medium‐sized town. Patients were scheduled for a single‐day visit that consisted of clinical evaluation and laboratory tests. Three blood pressure (BP) readings, 1 minute apart, were done, and within‐visit BPV was determined as the coefficient of variation (CV) of the 3 BP measures. Our main outcome was to correlate BNP and within‐visit BPV. A multivariable model was estimated using a generalized linear model to evaluate the independent effects of different variables on BNP levels.

Results

The median age was 57 years. Median BNP was 16 pg/mL, and the median systolic and diastolic BP‐CV were, respectively, 3.9% and 3.5%. There was a weak but positive correlation between BNP and both systolic BP‐CV and diastolic BP‐CV (r = 0.107 and P = 0.007 and r = 0.092 and P = 0.019, respectively). In multiple regression equation, systolic BP, diastolic BP‐CV, body mass index, and estimated glomerular filtration rate were associated with BNP.

Conclusions

In the present study, there was a positive, albeit weak, correlation between within‐visit BPV and BNP. In addition, diastolic BPV was associated with BNP even after adjustment for multiple confounders.     

Effects of the Recombinant Form of the Natural Human B‐type Natriuretic Peptide and Levosimendan on Pulmonary Hyperventilation and Chemosensivity in Heart Failure

Background: The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored. Methods: We tested in a prospective, placebo‐controlled, three‐way cross‐over, double‐blind randomized study the effects of the recombinant form of the natural human B‐type natriuretic peptide (R‐BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise. Results: Eleven stable chronic HF patients were randomized to sessions of 6‐min treadmill‐walking tests during placebo, or levosimendan or R‐BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R‐BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R‐BNP effects. BNP blood levels remained unchanged. Conclusions: The novelty of the present findings is that R‐BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.     

Factors Associated with Serum Brain Natriuretic Peptide Levels after the Fontan Procedure

Objective. Although a useful marker of heart failure in adults, the utility of brain natriuretic peptide concentration (BNP) for children after the Fontan procedure is not well studied. Design. BNP was measured in 510 patients who were 6–18 years old in the Pediatric Heart Network Fontan cross‐sectional study at a median of 8.2 years after Fontan. Patients underwent echocardiography, exercise testing, magnetic resonance imaging (MRI) and functional health status questionnaires. Associations of BNP with baseline patient characteristics, medical history and cross‐sectional assessment were examined with multivariable linear regression analyses. Results. The distribution of BNP was highly skewed, median 13.0 pg/mL (interquartile range: 7.1, 25.9), and was normalized with logarithmic transformation (logBNP). Among medical history variables, logBNP was greater in females (P= .02) and older patients (P < .001). Presence of pre‐Fontan systolic ventricular dysfunction, greater number of post‐Fontan complications, and thrombosis after Fontan were independently associated with higher logBNP (R²= 0.16). Age‐adjusted logBNP was significantly related to Fontan connection type (lower with extracardiac conduits, higher with atriopulmonary connection; P < .001). Lower physical functioning health status (R²= 0.05), lower chronotropic index during exercise (R²= 0.17), indices of diastolic dysfunction measured by echocardiography (R²= 0.15), and higher total ventricular mass on MRI (R²= 0.33) were related to higher logBNP. Conclusions. Despite a markedly abnormal circulation, BNP was variable but within a normal range in the majority of Fontan patients in this large outpatient cohort. Higher BNP was associated with several markers of suboptimal outcome, although associations were weak. The routine use of BNP as an outpatient surveillance tool in asymptomatic Fontan patients is not warranted.     

B‐type natriuretic peptide is predictive of hospitalization in community‐dwelling elderly without heart diseases

Aim: To examine prospectively the relationship between plasma B‐type natriuretic peptide (BNP) levels in community‐dwelling elderly and their hospitalization. Methods: A total number of 644 subjects aged 65 years or older were recruited from the annual community health examinations. Those with a history of stroke or neurological findings were not included. After excluding those with old myocardial infarction, left ventricular dysfunction, moderate or severe valvular disorders, atrial fibrillation, renal insufficiency, and history of hospitalization within 1 year, 602 participants (226 men, 376 women; mean age, 80.3 ± 6.2 years) remained eligible for this study. Antihypertensive medications, activities of daily living (ADL) score and history of hospitalization were assessed by annual interview. Measurement of casual blood pressure, Mini‐Mental State Examination, electrocardiography and echocardiography were performed. Plasma BNP, serum creatinine, total cholesterol, albumin and hemoglobin A1c levels were also examined. A follow‐up survey was performed for the occurrence and reasons for hospitalization. Results: During a median follow up of 37 months, 112 subjects were hospitalized. After adjustment for conventional risk factors of hospitalization using the Cox proportional hazard model, each increment of 1 standard deviation in log BNP levels was associated with a 36% increase in the risk of hospitalization (P = 0.02). Plasma BNP levels were significantly higher in the hospitalized subjects due to stroke, heart diseases, dementia, pneumonia and also difficulty to live alone than those of the subjects without hospitalization. Conclusion: Plasma BNP level is a very useful biochemical marker predictive of future hospitalization in community‐dwelling independent elderly people without apparent heart diseases.     

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.     

血清骨保护素和脑利钠肽水平与非ST段抬高型急性冠状动脉综合征患者冠状动脉病变程度的相关性

目的 探讨血清骨保护素和脑利钠肽水平与非ST段抬高急性冠状动脉综合征患者冠状动脉病变程度之间的关系.方法 192例受试者分为三组:稳定型心绞痛患者58例,不稳定型心绞痛/非ST段抬高心肌梗死患者99例,对照者35例,入院时检测血清骨保护素和脑利钠肽水平,并进行冠状动脉造影.根据造影结果对冠状动脉病变进行Gensini评分,分析两种标志物与冠状动脉狭窄数及冠状动脉病变Gensini评分的相关性.结果所有冠心病患者骨保护素水平高于对照组(P<0.01),稳定型心绞痛组骨保护素水平低于不稳定型心绞痛/非ST段抬高心肌梗死组(P<0.01);稳定型心绞痛组脑利钠肽水平略高于对照组(P>0.05),不稳定型心绞痛/非ST段抬高心肌梗死组脑利钠肽水平明显高于稳定型心绞痛组(P<0.01);多支血管病变患者脑利钠肽水平显著高于单支血管病变患者(P<0.01),脑利钠肽与冠状动脉病变Gensini评分轻微相关(r=0.45,P<0.01),骨保护素与冠状动脉病变Gensini评分显著相关 (r=0.64,P<0.001),多元回归分析发现骨保护素和脑利钠肽与冠心病独立相关(P<0.01).结论血清骨保护素与不稳定型心绞痛/非ST段抬高心肌梗死患者冠状动脉狭窄程度及病变进展有关,提示骨保护素可能参与了冠状动脉疾病的进程.不稳定型心绞痛/非ST段抬高心肌梗死患者脑利钠肽水平也增高,表明脑利钠肽水平与缺血范围以及严重程度有较大的关联.     

Hepatitis B core‐related antigen monitoring during peginterferon alfa treatment for HBeAg‐negative chronic hepatitis B

Serum Hepatitis B core‐related antigen (HBcrAg) level moderately correlates with cccDNA. We examined whether HBcrAg can add value in monitoring the effect of peginterferon (PEG‐IFN) therapy for HBeAg‐negative chronic hepatitis B (CHB) infection. Thus, serum HBcrAg level was measured in 133 HBeAg‐negative, mainly Caucasian CHB patients, treated with 48 weeks of PEG‐IFN alfa‐2a. We assessed its association with response (ALT normalization & HBV DNA < 2000 IU/mL) at week 72. HBcrAg level strongly correlated with HBV DNA level (r = 0.8, P < 0.001) and weakly with qHBsAg and ALT (both r = 0.2, P = 0.01). At week 48, mean HBcrAg decline was ?3.3 log U/mL. Baseline levels were comparable for patients with and without response at week 72 (5.0 vs 4.9 log U/mL, P = 0.59). HBcrAg decline at week 72 differed between patients with and without response (?2.4 vs ?1.0 log U/mL, P = 0.001), but no cut‐off could be determined. The pattern of decline in responders resembled that of HBV DNA, but HBcrAg decline was weaker (HBcrAg ?2.5 log U/mL; HBV DNA: ?4.0 log IU/mL, P < 0.001). For early identification of nonresponse, diagnostic accuracy of HBV DNA and qHBsAg decline at week 12 (AUC 0.742, CI‐95% [0.0.629‐0.855], P < 0.001) did not improve by adding HBcrAg decline (AUC 0.747, CI‐95% [0.629‐0.855] P < 0.001), nor by replacing HBV DNA decline by HBcrAg decline (AUC 0.754, CI‐95% [0.641‐0.867], P < 0.001). In conclusion, in Caucasian patients with HBeAg‐negative CHB, decline of HBcrAg during PEG‐IFN treatment was stronger in patients with treatment response. However, HBcrAg was not superior to HBV DNA and qHBsAg in predicting response during PEG‐IFN treatment.     

B-type Natriuretic Peptide: Perioperative Patterns in Congenital Heart Disease

Objective. B-type natriuretic peptide (BNP) has diagnostic, prognostic, and therapeutic roles in adults with heart failure. BNP levels in children undergoing surgical repair of congenital heart disease (CHD) were characterized broadly, and distinguishable subgroup patterns delineated. Design. Prospective, blinded, observational case series. Setting. Academic, tertiary care, free-standing pediatric hospital. Patients. Children with CHD; controls without cardiopulmonary disease. Interventions. None. Measurements. Preoperative cardiac medications/doses, CHD lesion types, perioperative BNP levels, intraoperative variables (lengths of surgery, bypass, cross-clamp), postoperative outcomes (lengths of ventilation, hospitalization, open chest; averages of inotropic support, central venous pressure, perfusion, urine output; death, low cardiac output syndrome (LCOS), cardiac arrest; readmission; and discharge medications). Results. Median BNP levels for 102 neonatal and non-neonatal controls were 27 and 7 pg/mL, respectively. Serial BNP measures from 105 patients undergoing CHD repair demonstrated a median postoperative peak at 12 hours. The median and interquartile postoperative 24-hour average BNP levels for neonates were 1506 (782–3784) pg/mL vs. 286 (169–578) pg/mL for non-neonates (P < 0.001). Postoperative BNP correlated with inotropic requirement, durations of open chest, ventilation, intensive care unit stay, and hospitalization (r = 0.33–0.65, all P < 0.001). Compared with biventricular CHD, Fontan palliations demonstrated lower postoperative BNP (median 150 vs. 306 pg/mL, P < 0.001), a 3-fold higher incidence of LCOS (P < 0.01), and longer length of hospitalization (median 6.0 vs. 4.5 days, P= 0.01). Conclusions. Perioperative BNP correlates to severity of illness and lengths of therapy in the CHD population, overall. Substantial variation in BNP across time as well as within and between CHD lesions limits its practical utility as an isolated point-of-care measure. BNP commonly peaks 6–12 hours postoperatively, but the timing and magnitude of BNP elevation demonstrates notable age-dependency, peaking earlier and rising an order of magnitude higher in neonates. In spite of higher clinical acuity, non-neonatal univentricular CHD paradoxically demonstrates lower BNP levels compared with biventricular physiologies.     

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.     

B-Type Natriuretic Peptide and the Right Heart

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.     

Potential use of Brain Natriuretic Peptide in patients with asymptomatic significant mitral stenosis

ObjectiveTo evaluate the ability of BNP to identify a subset of patients with asymptomatic significant rheumatic MS, who get symptoms on stress exercise testing.MethodsSeventy asymptomatic patients with significant rheumatic MS (MVA ⩽1.5 cm²) were included in the study. All patients underwent resting echo-Doppler study, exercise echocardiography and BNP level assessment pre- and one week post-balloon dilatation (for group I patients who had PMC).Patients were divided into two groups. Group I included 33 patients who became symptomatic on exercise and had low exercise capacity. Group II included 37 patients who were asymptomatic on exercise and had reasonable exercise capacity.ResultsBNP level in group I was 92 ± 12 compared to 40 ± 10 pg/ml in group II, P < 0.001. Post PMC, BNP in group I significantly decreased (92 ± 12, compared to 31 ± 9 pg/dl, P < 0.001). LA dimension was significantly different between both groups (50 ± 2.9 in group I compared to 46 ± 3.1 mm in group II, P < 0.001). Post-exercise SPAP was 72 ± 12 in group I compared to 46 ± 13 mmHg in group II, P < 0.001. Post-exercise MV gradient was 28 ± 9 compared to 20 ± 12 mmHg, P = 0.002. BNP significantly correlated with post-exercise SPAP (r = 0.635; P < 0.001). Area under the ROC curve for BNP as a predictor of low exercise capacity and development of symptoms on exercise was 0.98 [CI 95% 0.96–1.0]. When using a cutoff value of 55 pg/mL for BNP, sensitivity was 93.9% and specificity was 91.9%.ConclusionBNP may be used to approach asymptomatic patients with significant MS. BNP may identify a subset of patients with exercise-induced clinical and echo-Doppler criteria that meet the contemporary guidelines for intervention.     

Genetic and Nongenetic Factors Influencing Pharmacokinetics of B-Type Natriuretic Peptide

BackgroundNatriuretic peptides (NPs) represent a critical pathway in heart failure (HF). However, there is wide individual variability in NP system activity, which could be partly genetic in origin. We explored genetic and nongenetic contributions to B-type natriuretic peptide (BNP) inactivation.MethodsChronic HF patients (n = 95) received recombinant human BNP (nesiritide) at standard doses, and BNP levels were measured at baseline, after 2 hours of infusion, and 30 minutes after discontinuation. Genomic DNA was genotyped for 91 single-nucleotide polymorphisms (SNP) in 2 candidate genes. We tested the association of patient characteristics and genotype with 5 pharmacokinetics (PK) parameters: elimination rate constant, ΔBNP, BNP clearance, adjusted BNP clearance, and half-life. Linear regression with pleiotropic analysis was used to test genotype associations with PK.ResultsParticipants’ mean age was 63 years, 44% were female, and 46% were African American. PK parameters varied widely, some >10-fold. HF type (preserved vs reduced) was associated with PK (P < .01), whereas renal function, demographics, and body mass index and were not. Two SNPs in MME (rs989692, rs6798179) and 2 in NPR3 (rs6880564, rs2062708) also had associations with PK (P < .05).ConclusionsThe pharmacokinetics of BNP varies greatly in HF patients, differs by HF type, and possibly by MME or NPR3 genotype. Additional study is warranted.     

Increase of B-type Natriuretic Peptide from Baseline Increases the Risk of Death or Retransplant in Pediatric Cardiac Transplant Patients,Midterm Results

Background. Several studies have demonstrated the utility of B-type natriuretic peptide (BNP) in the months following cardiac transplant. The purpose of this study was to analyze longitudinal BNP data in pediatric cardiac transplant patients and determine the efficacy of BNP in routine follow-up of transplant to help predict the adverse event of death or re-transplant. Methods. From October 2002 to July 2007, 53 pediatric cardiac transplant patients were treated in an unmatched case-control study. Along with routine studies, BNP values were obtained at regular intervals. Six patients were excluded due to recent transplant, and three patients were excluded due to poor compliance. A baseline BNP was established for each subject utilizing the mean of all BNP values during year 2 post-transplant, or the first year of measured BNP in those patients whose transplant preceded the study by more than 1 year (time from transplant to first BNP 7.0 ± 3.5 years). The median BNP of all data points since transplant was utilized as an additional surrogate baseline. Univariate logistic regression was used to evaluate BNP versus other covariates on cardiac death. Results. Forty-four patients provided 1254 BNP data points spanning 173 patient years. Nine (20.5%) had an adverse event. Patients who experienced an adverse event had a higher baseline BNP (mean 365 ± 290; median 375 ± 352)) when compared to patients without an event (mean 128 ± 78; median 121 ± 62; p = 0.04 and p = 0.06)). All subjects with adverse events had a BNP value ≥ 250 during the 90 days preceding the event compared to 32.4% of those who did not (odds ratio: 23.13, p < 0.01). A log fold increase in the BNP value compared to the baseline median BNP is a risk for cardiac death in the subsequent 90-day period (OR: 6.82, 95% confidence interval: 1.25–37.11, p = 0.03). Conclusion. Routine BNP monitoring in the post-cardiac transplant pediatric patient allows for the determination of a median BNP, which can be used as a baseline. A log fold increase from the median BNP, or a BNP value ≥ 250, increases the risk of death or re-transplant and suggests a 90-day period of heightened clinical surveillance, perhaps necessitating increased medication or re-listing for repeat transplant.     

B‐type natriuretic peptide in the evaluation and management of dyspnoea in primary care

Abstract. Burri E, Hochholzer K, Arenja N, Martin‐Braschler H, Kaestner L, Gekeler H, Hatziisaak T, Büttiker M, Fräulin A, Potocki M, Breidthardt T, Reichlin T, Socrates T, Twerenbold R, Mueller C (University Hospital Basel, Basel; University Hospital, Basel, Switzerland). B‐type natriuretic peptide in the evaluation and management of dyspnoea in primary care. J Intern Med 2012; 272: 504–513. Objectives. The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B‐type natriuretic peptide (BNP) levels. Design. A randomized controlled trial. Setting. Twenty‐nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. Subjects. A total of 323 consecutive patients presenting with dyspnoea. Interventions. Assignment in a 1 : 1 ratio to a diagnostic strategy including point‐of‐care measurement of BNP (n = 163) or standard assessment without BNP (n = 160). The total medical cost at 3 months was the primary end‐point. Secondary end‐points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. Results. Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3 months [median $1655, interquartile range (IQR), 850–3331 vs. $1541, IQR 859–2827; P = 0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work‐up (33% vs. 45%; P = 0.02) and accelerated the initiation of the appropriate treatment (13 days vs. 25 days; P = 0.01). The area under the receiver‐operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81–0.93). Conclusions. The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end‐points including diagnostic certainty and time to initiation of appropriate treatment.     

Subjects with chronic lymphocytic leukaemia‐like B‐cell clones with stereotyped B‐cell receptors frequently show MDS‐associated phenotypes on myeloid cells

An increasing body of evidence suggests the potential occurrence of antigen encounter by the cell of origin in chronic lymphocytic leukaemia (CLL) and CLL‐like monoclonal B‐cell lymphocytosis (MBL). However, the scenario in which this event might occur remains unknown. In order to gain insight into this scenario we investigated the molecular, cytogenetic and haematological features of 223 CLL‐like (n = 84) and CLL (n = 139) clones with stereotyped (n = 32) versus non‐stereotyped (n = 191) immunoglobulin heavy chain variable region (IGHV) amino acid sequences. Overall, stereotyped CLL‐like MBL and CLL clones showed a unique IGHV profile, associated with higher IGHV1 and lower IGHV3 gene family usage (P = 0·03), longer IGHV complementary determining region 3 (HCDR3) sequences (P = 0·007) and unmutated IGHV (P < 0·001) versus non‐stereotyped clones. Whilst the overall size of the stereotyped B‐cell clones in peripheral blood did not appear to be associated with the CLL‐related cytogenetic profile of B‐cells (P > 0·05), it did show a significant association with the presence of myelodysplastic syndrome (MDS)‐associated immunophenotypes on peripheral blood neutrophils and/or monocytes (P = 0·01). Altogether our results point to the potential involvement of different selection forces in the expansion of stereotyped vs. non‐stereotyped CLL and CLL‐like MBL clones, the former being potentially favoured by an underlying altered haematopoiesis.     

Steatosis correlates with hepatic expression of death receptors and activation of nuclear factor‐κB in chronic hepatitis C

Background: Steatosis is recognized as a predictor of the severity as well as the progression of fibrosis in chronic hepatitis C. The mechanisms that cause increased hepatocellular injury associated with steatosis remain largely unknown. Methods: We studied the correlation of hepatic expression of death receptors: Fas and tumour necrosis factor‐α receptor 1 (TNF‐R1), and downstream caspase (caspase‐3) with hepatic steatosis by immunohistochemical study in chronic hepatitis C and determined the role of nuclear factor‐κB (NF‐κB). Results: Ninety patients (49 males and 41 females, mean age of 50.5 ± 10.4 years, genotype 1 or 2) with chronic hepatitis C virus infection were recruited. The factors associated with steatosis grade were body mass index (P=0.004) and fibrosis stage (P=0.034). Moderate/severe steatosis was an independent variable associated with advanced fibrosis stage by stepwise logistic regression analysis. The expression of immunoreactivity for Fas, TNF‐R1 and active caspases‐3 in liver tissues was significantly correlated with the steatosis grade (P<0.001, P<0.001 and P<0.001 respectively). The extent of active caspases‐3 correlated significantly with the expression of Fas (r=0.659, P<0.001) and TNF‐R1 (r=0.617, P<0.001). NF‐κB p65 expression correlated significantly with the extent of Fas (r=0.405, P<0.001), TNF‐R1 (r=0.448, P=0.002) and active caspase‐3 (r=0.313, P=0.003), and correlated with steatosis grade (P<0.001) but not with inflammatory and fibrosis scores. Conclusion: Our observations suggest a mechanism whereby steatosis contributes to the progression of liver injury in chronic hepatitis C through upregulation of death receptors and activation of NF‐κB.     

From short‐term blood pressure variability to atherosclerosis: Relative roles of vascular stiffness and endothelial dysfunction

Both arterial blood pressure (BP) average levels and short‐term BP variability (BPV) relate to hypertension‐mediated organ damage, in particular increased carotid artery intima‐media thickness (IMT) and carotid‐femoral pulse wave velocity (PWV). Endothelial dysfunction possibly mediates such damage. The authors aimed at further investigating such role in hypertensive patients. In 189 recently diagnosed, untreated hypertensive patients the authors evaluated, in a cross‐sectional design, the relationships of BP average levels and short‐term systolic (S) BPV (standard deviation of awake SBP or of 24‐hour‐weighted SBP) with IMT and PWV, and how much these relationships are explained by endothelial function parameters—brachial artery flow‐mediated dilation (FMD) and digital reactive hyperemia index (RHI). Multivariable models assessed the strength of these relationships to derive a plausible pathogenetic sequence. Both average SBP values and our measures of SBPV were significantly related to IMT (24‐hour mean SBP: r = .156, P = .034; 24‐hour‐weighted SBPV: r = .157, P = .033) and to PWV (24‐hour mean SBP: r = .179, P = .015; 24‐hour‐weighted SBPV: r = .175; P = .018), but only poorly related to FMD or RHI (P > .05 for all). At univariable regression analysis, FMD and RHI were both related to IMT, (P < .001), but not to PWV. When FMD and RHI were added to average SBP and SBPV parameters in a multivariable model, both significantly (P < .005) contributed to predict IMT, but not PWV. Thus, endothelial dysfunction relates to IMT independently of BP parameters, but appears to play a minor role in the association between BP variability‐related variables and arterial stiffening.     

Knowledge regarding hepatitis B mother‐to‐child transmission among healthcare workers in South China

To determine the knowledge regarding hepatitis B virus (HBV) mother‐to‐child transmission (MTCT) and its prevention and treatment among healthcare workers (HCWs) in Guangdong Province, China, an HBV endemic area. An HBV knowledge questionnaire was administered to 900 HCWs from the 3rd Affiliated Hospital of Sun Yat‐Sen University and 2 rural hospitals in Guangdong Province. The 27 items in the questionnaire fell into 3 sections: HBV MTCT general knowledge, respondents’ practices of preventing HBV MTCT and awareness of the resources of preventing HBV MTCT. The data collected were coded and analysed using SPSS software version 20. In total, 503 of 900 HCWs responded to the survey (response rate: 55.9%). Eighty‐four individuals responded correctly to all of the knowledge questions: 58 were doctors, and 26 were nurses (P < .05). Doctors more often performed practices than nurses (t = 3.591, P < .01). Participants from the infectious disease department demonstrated a significantly higher proportion of correct answers and resource utilization than other specialties (χ² = 14.052, 7.998, P < .01). In terms of the average knowledge score, t test or ANOVA showed that there were significant differences between the specialty groups (t = 3.110, P < .01), hospital level groups (t = 2.337, P < .05) and age groups (F = 3.020, P < .05). Respondents’ initiative increased with hospital level and age (t = 2.993, 7.493, P < .01). A considerable percentage of HCWs has misconceptions about HBV MTCT. Healthcare workers, in particular nurses, those working in noninfectious disease departments or township hospitals and younger medical staff, lack systematic and comprehensive knowledge about HBV MTCT and are in urgent need of HBV‐related training.     

Effects of rituximab and dexamethasone on regulatory and proinflammatory B‐cell subsets in patients with primary immune thrombocytopenia

Objective

To investigate the cytokine production and surface marker composition of B cells in adult patients with newly diagnosed primary immune thrombocytopenia (ITP) before and 12 months after treatment with rituximab + dexamethasone (RTX+DXM) or dexamethasone (DXM).

Methods

Peripheral blood mononuclear cells were isolated from nine patients treated with RTX+DXM, seven patients treated with DXM, and seven healthy donors. Expression of the cell‐surface markers CD5, CD27, CD25, and CD19, and intracellular content of IL‐6 and IL‐10 were measured by flow cytometry.

Results

PBMCs from ITP patients at baseline contained a lower proportion of IL‐10⁺ B cells (P < .01) and IL‐6⁺ B cells (P < .01) than healthy controls. All patients responded to therapy and levels were normalized at 12 months. The proportion of CD5⁺ B cells increased (P < .01) and CD27⁺ memory B cells decreased (P < .05) 12 months after treatment with RTX+DXM compared to baseline, with an inverse correlation between platelet numbers and the proportion of CD27⁺ B cells (R = ?0.71; P < .05).

Conclusion

Both treatment regimens normalized the frequencies of cytokine‐producing B cells. The additional increase in CD5⁺ B cells after RTX+DXM is compatible with induction of Bregs.     

Serum N‐Terminal Brain Natriuretic Peptide Indicates Exercise Induced Augmentation of Pulmonary Artery Pressure in Patients with Mitral Stenosis

Introduction: To determine whether elevated N‐terminal pro‐BNP (NT pro‐BNP) predicts pulmonary artery systolic pressure increase on exercise stress echocardiography in asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis. Methods and Results: Forty‐one asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis and 21 age‐ and sex‐matched healthy subjects. Transthoracic echocardiography was performed in all patients to assess the severity of the valve disease and to measure pulmonary artery pressure before and immediately after treadmill exercise. Blood samples for NT pro‐BNP were also collected before and immediately after treadmill exercise at the time of echocardiographic examination. The plasma concentrations of NT pro‐BNP levels were significantly higher in patients with mitral stenosis than in control subjects before and after exercise (P < 0.001). Patients with atrial fibrillation had significantly higher NT pro‐BNP levels compared to those with sinus rhythm (P < 0.001). Pre‐ and postexercise NT pro‐BNP levels correlated statistically significantly with the left atrial (LA) dimension, right ventricle enddiastolic diameter, exercise duration, heart rate, rest, and exercise pulmonary artery systolic pressure, after exercise mitral valve mean gradient. Area under the receiver‐operating characteristic curve for NT pro‐BNP as an exercise induced augmentation of pulmonary artery pressure was 0.78. Using an optimized cutoff value of 251 pg/mL for NT pro‐BNP, sensitivity was 89.47%. The independent determinants of higher pulmonary artery pressure were LA diameter and pretest NT pro‐BNP levels in multivariante analysis. Conclusion: NT pro‐BNP levels correlate with functional class and echocardiographic findings in patients with mitral stenosis and indicate exercise induced augmentation of peak PAP > 60 mmHg. (Echocardiography 2011;28:8‐14)