Absence of Adverse Effects of Tiotropium/Olodaterol Compared with the Monocomponents on Long-Term Heart Rate and Blood Pressure in Patients with Moderate-to-Very-Severe COPD

Background: The newly introduced device Mobil-O-Graph (IEM, Stolberg, Germany) combines brachial cuff oscillometry and pulse wave analysis, enabling the determination of pulse wave velocity (PWV) via complex mathematic algorithms during 24-h ambulatory blood pressure monitoring (ABPM). However, the determinants of oscillometric PWV in the end-stage kidney disease (ESKD) population remain poorly understood. Methods: In this study, 81 ESKD patients undergoing long-term peritoneal dialysis underwent 24-h ABPM with the Mobil-O-Graph device. The association of 24-h oscillometric PWV with several demographic, clinical and haemodynamic parameters was explored using linear regression analysis. Results: In univariate analysis, among 21 risk factors, 24-h PWV exhibited a positive relationship with age, body mass index, overhydration assessed via bioimpedance spectroscopy, diabetic status, history of dyslipidaemia and coronary heart disease, and it had a negative relationship with female sex and 24-h heart rate. In stepwise multivariate analysis, age ( β: 0.883), 24-h systolic blood pressure (BP) ( β: 0.217) and 24-h heart rate ( β: −0.083) were the only three factors that remained as independent determinants of 24-h PWV (adjusted R 2 = 0.929). These associations were not modified when all 21 risk factors were analysed conjointly or when the model included only variables shown to be significant in univariate comparisons. Conclusion: The present study shows that age together with simultaneously assessed oscillometric BP and heart rate are the major determinants of Mobil-O-Graph-derived PWV, explaining >90% of the total variation of this marker. This age dependence of oscillometric PWV limits the validity of this marker to detect the premature vascular ageing, a unique characteristic of vascular remodelling in ESKD.

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Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.6.2025 ◽

1999 ◽

Vol 87 (6) ◽

pp. 2025-2031 ◽

Cited By ~ 30

Author(s):

Holger Kraiczi ◽

Jarkko Magga ◽

Xiang Ying Sun ◽

Heikki Ruskoaho ◽

Xiaohe Zhao ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Body Weight ◽

Atrial Natriuretic Peptide ◽

Right Ventricular ◽

Natriuretic Peptide ◽

Intermittent Hypoxia ◽

Spontaneously Hypertensive ◽

Wistar Kyoto

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.

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Effects of short- and long-term exposure to ozone on heart rate and blood pressure of emphysematous rats

Environmental Research ◽

10.1016/s0013-9351(89)80087-8 ◽

1989 ◽

Vol 48 (1) ◽

pp. 76-86 ◽

Cited By ~ 7

Author(s):

Iwao Uchiyama ◽

Eiji Yokoyama

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Short And Long Term

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Does 20 mg long-acting methylphenidate alter blood pressure and heart rate in children with ADHD?

Paediatrica Indonesiana ◽

10.14238/pi51.5.2011.282-7 ◽

2011 ◽

Vol 51 (5) ◽

pp. 282

Author(s):

Tjhin Wiguna ◽

Sasanto Wibisono ◽

Sudigdo Sastroasmoro ◽

Fransiscus D. Suyatna

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiovascular Effects ◽

Children With Adhd ◽

Normal Ranges ◽

Blood Pressures ◽

Drug Naïve ◽

Repeated Analysis ◽

Long Acting

Objective To identify the cardiovascular effects of long-acting methylphenidate administered for twelve weeks in Indonesian children with ADHD.Methods This was an 18-week, time series study on children with ADHD who were given 20 mg of long-acting methylphenidate for twelve weeks. During the study period we made ten serial observations of the subjects, including before, during and 6 weeks following drug administration. We included drug naive children with ADHD between the ages of 7 – 10 years. Children with mental retardation and chronic physical or mental disorders were excluded. Blood pressure was measured by sphygmomanometer with a child’s cuff at the brachial artery. We also collected data on heart rate, side effects, complaints and other medications used during the study. Repeated analysis was performed on the data with a P level of 0.05.Results Twenty-one subjects were recruited for this study. Mean blood pressure fluctuated insignificantly during the research period, for both mean systolic and mean diastolic blood pressures (P=0.115 and P=0.059). Mean heart rate also fluctuated insignificantly (P=0.091). All fluctuations were within the normal ranges. During the study, there were complaints of dizziness, nausea, and gastrointestinal upset, but they were reportedly mild and disappeared before the second week of observation.Conclusion Administration of 20 mg long-acting methylphenidate for twelve weeks in children with ADHD altered mean blood pressures and heart rates, but within the normal range for children of their age. However, cardiovascular risk observation is still needed when administering methylphenidate to children with ADHD, especially for those using the medication long-term.[Paediatr Indones. 2011;51:282-7].

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Evaluation of the Cardiovascular Effects of Clonidine in Neonates Treated for Neonatal Abstinence Syndrome

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.6.473 ◽

2018 ◽

Vol 23 (6) ◽

pp. 473-478

Author(s):

Raymond P. Meddock ◽

Deirdre Bloemer

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Diastolic Blood Pressure ◽

Neonatal Intensive Care ◽

Dose Range ◽

Safety Data ◽

Cardiovascular Effects ◽

Neonatal Abstinence Syndrome ◽

Abstinence Syndrome

OBJECTIVES Neonatal abstinence syndrome (NAS) is characterized by withdrawal symptoms in neonates exposed to legal or illegal substances in utero, and it is often managed with medications such as opiates, phenobarbital, and clonidine. Clonidine use is increasing, but further safety data regarding its use in neonates are warranted. This study evaluated the effects of clonidine on heart rate and blood pressure in neonates treated for NAS at doses up to 24 mcg/kg/day. METHODS A retrospective review via the electronic medical record of infants at least 35 weeks' gestation treated adjunctively with clonidine for NAS in the neonatal intensive care unit at St Elizabeth was conducted. Heart rate, and systolic and diastolic blood pressure were recorded at baseline, while on different dose ranges of clonidine (small: ≤1.5 mcg/kg per dose every 3 hours; medium: >1.5 to 2 mcg/kg per dose every 3 hours; and large: >2 mcg/kg to 3 mcg/kg per dose every 3 hours), and upon discontinuation. RESULTS A total of 64 infants treated with clonidine for NAS between August 2015 and December 2016 were included. Heart rate decreased in all clonidine dose ranges compared with baseline (average reduction of 7 bpm [CI: −12 to −2], 9 bpm [CI: −16 to −2], and 10 bpm [CI: −18 to −1] for the small, medium, and large dose ranges, respectively; p < 0.0001). Systolic and diastolic blood pressure were not significantly different from baseline when infants were receiving any dose of clonidine, except diastolic blood pressure while on medium–dose range clonidine, where diastolic blood pressure was higher than baseline (p = 0.0128). Increases in systolic and diastolic blood pressure were evident upon discontinuation of clonidine (p < 0.0001 and p = 0.0156, respectively). CONCLUSIONS Clonidine doses up to 24 mcg/kg/day are well tolerated in neonates ≥35 weeks' gestation treated for NAS. Any decreases in heart rate are likely clinically insignificant, and increases in blood pressure upon discontinuing clonidine are mild and may be mitigated further with extended discontinuation protocols. Further trials should be conducted to evaluate the long-term safety of clonidine in this population.

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P1462IMPACT OF HEART RATE AND BETA-BLOCKER USE ON THE LONG-TERM SURVIVAL OF CHRONIC HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1462 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Takuhiro Moromizato ◽

Kunitoshi Iseki ◽

OCTOPUS Study Group

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cox Regression ◽

Chronic Hemodialysis ◽

Time Varying ◽

Term Survival ◽

Blood Pressures ◽

Β Blocker ◽

Time Varying Covariates

Abstract Background and Aims Increase in resting heart rate might influence mortalities of dialysis patients, and the use of β-blocker might improve their survival probability. However, the influence of heart rate and benefits of β-blocker on their survival are difficult to quantify because of following obstacles: prone to measurement errors; inherent association of heart rate with blood pressures, comorbidities, and medication use; and a necessity of repeated measurements of vital signs and medication use. Therefore, at the design process of our previous randomized control trial on the Olmesartan Clinical Trial in Okinawan patients under OKIDS (OCTOPUS), we included the repeated measures design to quantify the influence of vital sign values on the survival retrospectively. We combined the repeated measurement data and additional the long-term prognosis information of the participants obtained after the OCTOPUS with aim of investigating the influence of time varying covariates: heart rates, blood pressures, and β-blocker use, on the long-term survival of hemodialysis patients. Method We investigated 461 adult OCTOPUS participants who received chronic hemodialysis and antihypertensive medications in Okinawa. The OCTOPUS trial, which was conducted between June 2006 and June 2011, did not detect the survival benefit of angiotensin receptor blocker (ARB)NDT 2013, but the study and the additional follow-up of participants’ prognosis provided us with information to investigate influence of predictors on long-term survival in the population. Throughout the OCTOPUS trial, study participants were measured pre-dialysis blood pressures, pre-dialysis resting heart rates, and their medication use for one week at their dialysis centers every six months after their participations. Following the trial, we collected the prognosis information of all participants until July 31st, 2018. Finally, we merged the multiple-measured data during the OCTOPUS with the prognosis data. Mean values of three measurements of blood pressures and heart rates and β-blocker use were introduced to the Cox-regression model as time-varying covariates with essential non-time varying covariates, which include age, gender, and diabetes. Results In this retrospective cohort study, 221 (47.9%) out of 461 participants deceased, and the median follow-up length was 10.21 years. Initial mean resting heart rate and pre-dialysis mean blood pressure were 78(±10) per minute and 159.5(±14) mmHg, respectively. 10% of participants were prescribed β-blocker initially. The resting heart rate of all participants significantly decreased by 1.75 and 2.45 per minutes after two and four years respectively. β-blocker could significantly decrease the mean heart rate by 3.54 and 2.90 per minutes after two and four years. With our Cox-regression with the time varying covariates, increase of heart rate was significantly associated with higher mortality (P=0.002), but the use of β-blocker was not associated with the mortality. (P=0.691) Additionally, we could not detect the interaction of heart rate and β-blocker use on the mortality. (P= 0.796) Although lower blood pressure was significantly associated with higher mortality in our initial Cox-regression analysis, an introduction of interaction term of heart rate and blood pressure remove the significance of influence of blood pressure on the survival. Conclusion In hypertensive chronic hemodialysis patients, higher heart rate is associated with higher mortality. However, use of beta-blocker was not associated with improvement of their mortality.

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Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to long-term high-altitude hypoxemia

Journal of Applied Physiology ◽

10.1152/jappl.1995.78.5.1793 ◽

1995 ◽

Vol 78 (5) ◽

pp. 1793-1799 ◽

Cited By ~ 10

Author(s):

M. Kamitomo ◽

T. Ohtsuka ◽

R. D. Gilbert

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiac Output ◽

Right Ventricular ◽

High Altitude ◽

Arterial Blood Pressure ◽

Left Ventricular ◽

Arterial Blood ◽

Isoproterenol Infusion

We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.

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0744 Cardiac Safety Profile of Pitolisant in Patients with Narcolepsy

SLEEP ◽

10.1093/sleep/zsaa056.740 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A283-A283

Author(s):

W Winter ◽

S P Wanaski ◽

A Patroneva ◽

J M Dayno

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Pooled Analysis ◽

Mean Difference ◽

Qtc Interval ◽

Cardiac Safety ◽

Open Label ◽

Long Term Study ◽

End Of Treatment

Abstract Introduction Cardiovascular diseases are comorbid in patients with narcolepsy. Cardiovascular adverse effects are of concern with narcolepsy medications because of this comorbidity and most patients require lifelong pharmacotherapy. Pitolisant, a selective histamine 3 (H3)-receptor antagonist/inverse agonist, increases histamine transmission in the brain. In a QT study of healthy volunteers, pitolisant (35.6 mg/day) led to a mean increase of 4.2 msec in QTc interval. This analysis further characterized the cardiac safety of pitolisant (maximum dose, 35.6 mg/day) in adults with narcolepsy. Methods Data were obtained from a pooled analysis of 2 randomized, placebo-controlled, 7- or 8-week studies and from a 12-month, open-label study. Results Pooled analysis included 166 patients (pitolisant, n=85; placebo, n=81). Mean change in heart rate from baseline to end-of-treatment was -0.5 beats/min with pitolisant and -0.2 beats/min with placebo (LS mean difference, -0.4; P=0.744). Mean change was also similar for pitolisant versus placebo in systolic (LS mean difference, 0.0; P=0.983) and diastolic (LS mean difference, -0.6; P=0.552) blood pressure, as was mean change in QTc interval (LS mean difference, 0.4; P=0.911). Cardiac adverse events with pitolisant included heart rate increase (n=4), right bundle branch block (n=1), sinus tachycardia (n=1), and palpitations (n=1), and with placebo included blood pressure increase (n=1). In the long-term study, mean change from baseline in QTc interval was 3.1 msec at Month 6 (n=70) and 6.1 msec at Month 12 (n=67); 3 patients had a postbaseline increase >60 msec but none had QTc >500 msec. Conclusion In this analysis, no cardiac safety signals were observed during treatment with pitolisant administered up to the maximum recommended dose. Because concomitant use of pitolisant with other drugs known to increase the QT interval may add to the QT effects of pitolisant, avoid use of pitolisant in combination with these medications. Support Bioprojet Pharma and Harmony Biosciences, LLC.

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P3821Resting heart rate in late adolescence and long term risk of cardiomyopathy - A nationwide study of one million Swedish men

European Heart Journal ◽

10.1093/eurheartj/ehz745.0663 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Lindgren ◽

J R Robertson ◽

M A Adiels ◽

M S Schaufelberger ◽

M A Aberg ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Cardiorespiratory Fitness ◽

Myocardial Dysfunction ◽

Late Adolescence ◽

Resting Heart Rate ◽

Drug Induced ◽

Arterial Blood ◽

Causal Pathway

Abstract Background/Introduction Elevated resting heart rate (RHR) is a known risk factor for HF. Whether elevated RHR is also associated with cardiomyopathy (CM), a common cause of heart failure in the young, is unknown. Purpose To investigate the association of resting heart rate (RHR) measured in late adolescence with long term risk of various subtypes of CM with special attention to cardiorespiratory fitness (CRF), an important predictor of RHR and myocardial dysfunction. Methods We followed a cohort of Swedish men enrolled for conscription in 1968–2005 (n=1,008,485; mean age=18.3 years) until December 2014. Outcomes of CM were collected from the national inpatient- (IPR), outpatient- (OPR) and cause of death registries and were divided into categories: 1) dilated, 2) hypertrophic, 3) alcohol/drug-induced, and 4) other. Cox proportional hazard models were used to analyze the longitudinal association between RHR and outcomes while adjusting for potential confounders, including body mass index (BMI), arterial blood pressure and cardiorespiratory fitness (CRF). CRF was measured by maximum capacity ergometer testing as part of the enlistment protocol. Results During a mean follow up of 34 years, there were 3500 cases of a first hospitalization for CM (mean age at diagnosis, 50.1 years). Comparing the highest with the lowest quintile of the RHR distribution, we found a positive association between RHR and dilated CM (hazard ratio (HR) = 1.58 [confidence interval (CI) = 1.37–1.82]) after adjustment for BMI, age at conscription, conscription year, test center, and baseline comorbidities (diabetes, hypertension, congenital heart disease). There no significant association with alcohol/drug-induced (HR=1.32 [CI=0.94–1.85]) or other categories of CM. Conclusion Adolescent RHR is associated with future risk CM, independently of blood pressure, BMI and CRF. The association was driven by dilated CM. These findings are suggestive of a causal pathway between elevated heart rate and adverse cardiac remodeling that warrants further investigation. Acknowledgement/Funding The Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish Council for Health, Working Life and Welfare

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