B-type natriuretic peptide increases cortisol and catecholamine concentrations in healthy subjects

2017 ◽  
Vol 122 (5) ◽  
pp. 1249-1254 ◽  
Author(s):  
Gabriele Grimm ◽  
Michael Resl ◽  
Birgit B. Heinisch ◽  
Martin Hülsmann ◽  
Anton Luger ◽  
...  

B-type natriuretic peptide (BNP) is a hormone released by the heart in response to volume load and exerts natriuretic properties. It is clinically used as a diagnostic and prognostic biomarker and investigated as a pharmacological agent in the therapy of heart failure. Here we investigate the changes in pituitary, adrenal, and thyroid hormones in response to BNP administration in a randomized single-blinded crossover study conducted in ten healthy men aged 21–29 yr. Participants received in two study sessions a continuous intravenous infusion during 4 h (once placebo and once 3 pmol·kg−1·min−1 BNP) and remained in supine position throughout the study. Circulating concentrations of pituitary, adrenal, and thyroid hormones, heart rate, and blood pressure were measured at baseline and hourly afterwards. BNP prevented the physiological decrease in cortisol during the late morning hours leading to elevated serum cortisol levels ( P = 0.022) and increased circulating epinephrine and norepinephrine concentrations ( P = 0.018 and P = 0.036, respectively). These hormone changes were accompanied by an increase in heart rate ( P = 0.019) but no differences in blood pressure. Taken together, the impact of BNP on the endocrine system extends beyond the well-known inhibition of the renin-angiotensin-aldosterone system and includes increased adrenergic activity and cortisol concentrations. This neuroendocrine activation might impact the outcome of therapeutical BNP administrations and should be further investigated in conditions associated with increased BNP secretion. NEW & NOTEWORTHY The heart hormone B-type natriuretic peptide (BNP) is increased in patients with heart failure, where it is thought to have beneficial effects by reducing the preload. Here we report that intravenous administration of BNP in men leads to increases in adrenal hormones cortisol, epinephrine, and norepinephrine. Cortisol and catecholamine levels are independent predictors of increased cardiovascular mortality risk; therefore, drugs targeting the BNP system should be evaluated regarding their effects on the neuroendocrine activation accompanying heart failure.

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001425
Author(s):  
Marc Meller Søndergaard ◽  
Johannes Riis ◽  
Karoline Willum Bodker ◽  
Steen Møller Hansen ◽  
Jesper Nielsen ◽  
...  

AimLeft bundle branch block (LBBB) is associated with an increased risk of heart failure (HF). We assessed the impact of common ECG parameters on this association using large-scale data.Methods and resultsUsing ECGs recorded in a large primary care population from 2001 to 2011, we identified HF-naive patients with a first-time LBBB ECG. We obtained information on sex, age, emigration, medication, diseases and death from Danish registries. We investigated the association between the PR interval, QRS duration, and heart rate and the risk of HF over a 2-year follow-up period using Cox regression analysis.Of 2471 included patients with LBBB, 464 (18.8%) developed HF during follow-up. A significant interaction was found between QRS duration and heart rate (p<0.01), and the analyses were stratified on these parameters. Using a QRS duration <150 ms and a heart rate <70 beats per minute (bpm) as the reference, all groups were statistically significantly associated with the development of HF. Patients with a QRS duration ≥150 ms and heart rate ≥70 bpm had the highest risk of developing HF (HR 3.17 (95% CI 2.41 to 4.18, p<0.001). There was no association between the PR interval and HF after adjustment.ConclusionProlonged QRS duration and higher heart rate were associated with increased risk of HF among primary care patients with LBBB, while no association was observed with PR interval. Patients with LBBB with both a prolonged QRS duration (≥150 ms) and higher heart rate (≥70 bpm) have the highest risk of developing HF.


2005 ◽  
Vol 110 (1) ◽  
pp. 117-123 ◽  
Author(s):  
Jan Börgel ◽  
Tino Schulz ◽  
Nina K. Bartels ◽  
Jörg T. Epplen ◽  
Nikolaus Büchner ◽  
...  

OSA (obstructive sleep apnoea) stimulates sympathetic nervous activity and elevates resting HR (heart rate) and BP (blood pressure). In the present study in a cohort of 309 untreated OSA patients, the resting HR and BP during the daytime were correlated with AHI (apnoea/hypopnea index) and compared with patients with R389R (n=162), R389G (n=125) and G389G (n=22) genotypes of the β1-adrenoreceptor R389G polymorphism. We analysed the impact of the genotype on the decline of HR and BP in a subgroup of 148 patients (R389R, n=86; R389G, n=54; G389G, n=8) during a 6-month follow-up period under CPAP (continuous positive airway pressure) therapy during which cardiovascular medication remained unchanged. In untreated OSA patients, we found an independent relationship between AHI and resting HR (β=0.096, P<0.001), systolic BP (β=0.09, P=0.021) and diastolic BP (β=0.059, P=0.016). The resting HR/BP, however, did not differ among carriers with the R389R, R389G and G389G genotypes. CPAP therapy significantly reduced HR [−2.5 (−1.1 to −4.0) beats/min; values are mean difference (95% confidence intervals)] and diastolic BP [−3.2 (−1.5 to −5.0) mmHg]. The decline in HR was more significantly pronounced in the R389R group compared with the Gly389 carriers [−4.1 (−2.3 to −5.9) beats/min (P<0.001) compared with −0.2 (2.1 to −2.6) beats/min (P=0.854) respectively; Student's t test between groups, P=0.008]. Diastolic BP was decreased significantly (P<0.001) only in Gly389 carriers (R389G or G389G) compared with R389R carriers [−5.0 (−2.3 to −7.6) mmHg compared with −2.0 (0.4 to −4.3) mmHg respectively]. ANOVA revealed a significant difference (P=0.023) in HR reduction between the three genotypes [−4.1 (±8.4) beats/min for R389R, −0.5 (±9.3) beats/min for R389G and +1.9 (±7.2) beats/min for G389G]. In conclusion, although the R389G polymorphism of the β1-adrenoceptor gene did not influence resting HR or BP in untreated OSA patients, it may modify the beneficial effects of CPAP therapy on these parameters.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.


1999 ◽  
Vol 87 (6) ◽  
pp. 2025-2031 ◽  
Author(s):  
Holger Kraiczi ◽  
Jarkko Magga ◽  
Xiang Ying Sun ◽  
Heikki Ruskoaho ◽  
Xiaohe Zhao ◽  
...  

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.


1993 ◽  
Vol 265 (5) ◽  
pp. R1132-R1140 ◽  
Author(s):  
N. B. Olivier ◽  
R. B. Stephenson

Open-loop baroreflex responses were evaluated in eight conscious dogs before and during congestive heart failure to determine the effects of failure on baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance. Heart failure was induced by rapid ventricular pacing. Baroreflex function was determined by calculation of the range and gain of the open-loop stimulus-response relationships for the effect of carotid sinus pressure on blood pressure, heart rate, cardiac output, and total peripheral resistance. The range and gain of blood pressure responses were substantially reduced as early as 3 days after induction of heart failure (161 +/- 6 to 99 +/- 8 mmHg and -2.7 +/- 0.3 to -1.5 +/- 0.1, respectively) and remained depressed for the 21 days of heart failure. This depression in baroreflex control of blood pressure was associated with similar depressions in reflex range and gain for heart rate (125 +/- 9 to 78 +/- 11 beats/min and -2.05 +/- 0.2 to -1.16 +/- 0.2 beats/min, respectively) and cardiac output (1.74 +/- 0.2 to 0.46 +/- 0.2 l/min and -0.81 +/- 0.02 to -0.027 +/- 0.008 l/min, respectively). The group-averaged range and gain for reflex control of vascular resistance were not altered by heart failure. In three dogs, discontinuation of rapid ventricular pacing led to resolution of heart failure within 7 days and partial restoration of the range and gain of reflex control of blood pressure. We conclude that heart failure reversibly depresses baroreflex control of blood pressure principally through a concurrent reduction in reflex control of cardiac output, whereas reflex control of vascular resistance is not consistently affected.


BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S183-S184
Author(s):  
Emma Davies ◽  
Maham Khan ◽  
Claire Jones

AimsTo establish whether physical health monitoring for CYP on ADHD medication is according to NICE guidance (2018).To determine the impact of COVID-19 pandemic restrictions on physical health monitoring for CYP on ADHD medication.Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, characterised by a persistent pattern of inattention and/or hyperactivity-impulsivity, directly impacting on academic, occupational, or social functioning. It affects between 1-5% of children and young people (CYP) most often presenting in early-mid childhood.Pharmacological treatment can be considered in CYP if certain criteria are met, where licensed medications include methylphenidate, dexamfetamine, lisdexamfetamine, atomoxetine and guanfacine. Stimulant and non-stimulant medications require frequent physical health monitoring due to their side effects including an increase in blood pressure and/or heart rate, loss of appetite, growth restriction and tics.MethodStandards and criteria were derived from the NICE guidance (2018), whilst local trust policies were reviewed, demonstrating discrepancies. Standards were expected to be met for 100% of patients.Electronic patient records were reviewed retrospectively from a representative cohort of CYP reviewed by clinicians in a community CAMHS service during March-November 2020. Data were entered manually into a spreadsheet for evaluation.ResultA total of 27 CYP records were reviewed, average age 13yo, on a range of stimulant/non-stimulant preparations.5 (19%) had height checked every 6 months, with 4 delayed to 7-8 months.For those >10yo, only 5 (19%) had weight checked every 6 months.Only 2 (7%) had their height and weight plotted on a growth chart and reviewed by the healthcare professional responsible for treatment.Just 4 (15%) had heart rate and blood pressure recorded before and after each dose change, whilst similarly only 4 (not the same) had these parameters recorded every 6 months.17 patients were reviewed by telephone/video call, where 5 patients provided physical health parameters (measured at home).ConclusionAcross all parameters, standards are not being met for the required physical health monitoring for CYP on ADHD medication.The COVID-19 pandemic has significantly changed the working conditions for community teams, impacting face to face reviews, creating challenges for physical health monitoring.Our ongoing implementations for change include the use of a proforma for physical health measurements, improving psychoeducation for families, exploring potential barriers with senior colleagues and collaborating with pharmacy colleagues to update local guidelines in accordance with the latest NICE recommendations. We aim to re-audit in June 2021.


2021 ◽  
Author(s):  
Rada R Veeneman ◽  
Jentien M Vermeulen ◽  
Abdel Abdellaoui ◽  
Eleanor Sanderson ◽  
Robyn E Wootton ◽  
...  

Importance: Individuals with schizophrenia have a reduced life-expectancy compared to the general population, largely due to an increased risk of cardiovascular disease (CVD). Clinical and epidemiological studies have been unable to fully unravel the nature of this relationship. Objective: Investigate genetic correlations and potential bi-directional effects between liability to schizophrenia and CVD. Design, setting, and participants: We obtained summary-data of genome-wide-association studies of schizophrenia (N=130,644), heart failure (N=977,323), coronary artery disease (N=332,477), systolic and diastolic blood pressure (N=757,601), heart rate variability (N=46,952), QT interval (N=103,331), early repolarization and dilated cardiomyopathy ECG patterns (N=63,700). We computed genetic correlations with linkage disequilibrium score regression and conducted bi-directional Mendelian randomization (MR). With multivariable MR, we investigated whether associations were mediated by smoking, body mass index, physical activity, lipid levels, or type 2 diabetes. To ensure robustness, we applied a range of sensitivity methods. Main outcomes and measures: Schizophrenia, heart failure, coronary artery disease, systolic blood pressure, diastolic blood pressure, heart rate variability, QT interval, early repolarization, dilated cardiomyopathy. Results: Genetic correlations between liability to schizophrenia and CVD were close to zero (-0.02 to 0.04). With MR, we found robust evidence that liability to schizophrenia increases heart failure risk. This effect remained consistent with multivariable MR. There was also evidence that liability to schizophrenia increases early repolarization risk, largely mediated by BMI and lipid levels. Finally, there was evidence that liability to schizophrenia increases heart rate variability, a direction of effect contrasting previous studies. In the other direction, there was weak evidence that higher systolic, but not diastolic, blood pressure increases schizophrenia risk. Conclusions and relevance: Our findings indicate that liability to schizophrenia increases the risk of heart failure, and that this is not mediated by key health behaviours. This is consistent with the notion that schizophrenia is characterised by a systemic dysregulation of the body (including inflammation and oxidative stress) with detrimental effects on the heart. To decrease cardiovascular mortality among schizophrenia patients, priority should lie with optimal treatment and interventions in early stages of psychoses. We also identified early repolarization, currently understudied, as a potential CVD marker among patients with schizophrenia.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz Baudenbacher ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
Susan Eagle ◽  
...  

Patients with metabolic syndrome are at higher risk for cardiac arrest (CA), and also have worse neurologic outcome after CA related to their comorbidities (e.g., Type 2 Diabetes Mellitus [T2DM]). Using Zucker Diabetic Fatty (ZDF) rats as a new and relevant model with common comorbidities for CA and cardiopulmonary resuscitation (CPR), we hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Two groups of rats (8 ZDF, 7 lean) were monitored for 37±2 weeks. The rats were anesthetized and intubated; heart rate was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids and medications, respectively. Before ventilation was stopped to initiate asphyxial CA, rocuronium was given. After 8 minutes of CA, ventilation was re-initiated with FiO 2 1.0, epinephrine and sodium-bicarbonate were administered, and pneumatic chest compression were started with 200 compressions per minute. Chest compressions were stopped when a systolic blood pressure of 120 mmHg was achieved. During 4 hours of observation, vital parameters were closely monitored, blood gases were measured, and ejection fraction (EF %) was assessed with ultrasound. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α.05. At baseline, ZDF rats showed significantly higher blood glucose levels (504±52 vs 174±14 mg/dl) compared to their lean littermates. All ZDF and lean rats achieved ROSC, and measurements taken directly after ROSC and after the first hour showed no relevant differences. After four hours, there was no difference in heart rate between ZDF and lean rats. However, diabetic rats had a significantly higher mean arterial blood pressure (142±24vs. 107±19 mmHg) and ejection fraction (42±16%vs 20±8%) compared to their lean littermates. The hypothesis that ROSC-rate in diabetic rats would be lower could not be proven. Conversely, the ZDF rats showed a significantly higher blood pressure related to an increased EF%. Further analysis in this study will focus on the impact of T2DM on cardiac and neurological ischemia-reperfusion injury.


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