Search Results
Search for other papers by Lasse Oinonen in
Google Scholar
PubMed
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for other papers by Antti Tikkakoski in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Jenni Koskela in
Google Scholar
PubMed
Search for other papers by Arttu Eräranta in
Google Scholar
PubMed
Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland
Search for other papers by Mika Kähönen in
Google Scholar
PubMed
Search for other papers by Onni Niemelä in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Jukka Mustonen in
Google Scholar
PubMed
Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
Search for other papers by Ilkka Pörsti in
Google Scholar
PubMed
Parathyroid hormone has been related with the risk of hypertension, but the matter remains controversial. We examined the association of parathyroid hormone with central blood pressure and its determinants in 622 normotensive or never-treated hypertensive subjects aged 19–72 years without diabetes, cardiovascular or renal disease, or cardiovascular medications. The methods were whole-body impedance cardiography and analyses of pulse wave and heart rate variability. Cardiovascular function was examined in sex-specific tertiles of plasma parathyroid hormone (mean concentrations 3.0, 4.3 and 6.5 pmol/L, respectively) during head-up tilt. Explanatory factors for haemodynamics were further investigated using linear regression analyses. Mean age was 45.0 (s.d. 11.7) years, BMI 26.8 (4.4) kg/m2, seated office blood pressure 141/90 (21/12) mmHg, and 309 subjects (49.7%) were male. Only five participants had elevated plasma parathyroid hormone and calcium concentrations. Highest tertile of parathyroid hormone presented with higher supine and upright aortic diastolic blood pressure (P < 0.01) and augmentation index (P < 0.01), and higher upright systemic vascular resistance (P < 0.05) than the lowest tertile. The tertiles did not present with differences in pulse wave velocity, cardiac output, or measures of heart rate variability. In linear regression analyses, parathyroid hormone was an independent explanatory factor for aortic systolic (P = 0.005) and diastolic (P = 0.002) blood pressure, augmentation index (P = 0.002), and systemic vascular resistance (P = 0.031). To conclude, parathyroid hormone was directly related to central blood pressure, wave reflection, and systemic vascular resistance in subjects without cardiovascular comorbidities and medications. Thus, parathyroid hormone may play a role in the pathophysiology of primary hypertension.
Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Ulrik Ø Andersen in
Google Scholar
PubMed
Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Dijana Terzic in
Google Scholar
PubMed
Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Nicolai Jacob Wewer Albrechtsen in
Google Scholar
PubMed
Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Peter Dall Mark in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Peter Plomgaard in
Google Scholar
PubMed
Search for other papers by Jens F Rehfeld in
Google Scholar
PubMed
Search for other papers by Finn Gustafsson in
Google Scholar
PubMed
Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens P Goetze in
Google Scholar
PubMed
Aims
Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.
Methods and results
Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC0-270 min, P = 0.004) and 60% (AUC0-270 min, P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC0-270 min, P = 0.86, heart rate, AUC0-270 min, P = 0.96).
Conclusion
Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.
Search for other papers by Myrtille Fouché in
Google Scholar
PubMed
Search for other papers by Yves Bouffard in
Google Scholar
PubMed
Search for other papers by Mary-Charlotte Le Goff in
Google Scholar
PubMed
Search for other papers by Johanne Prothet in
Google Scholar
PubMed
Search for other papers by François Malavieille in
Google Scholar
PubMed
Search for other papers by Pierre Sagnard in
Google Scholar
PubMed
Search for other papers by Françoise Christin in
Google Scholar
PubMed
Search for other papers by Davy Hayi-Slayman in
Google Scholar
PubMed
Search for other papers by Arnaud Pasquer in
Google Scholar
PubMed
Search for other papers by Gilles Poncet in
Google Scholar
PubMed
Search for other papers by Thomas Walter in
Google Scholar
PubMed
EA 7426 Hospices Civils de Lyon-University Claude Bernard Lyon 1-Biomérieux ‘Pathophysiology of Injury-Induced Immunosuppression’ Pi3, Lyon, France
Search for other papers by Thomas Rimmelé in
Google Scholar
PubMed
Only few descriptions of intraoperative carcinoid syndrome (ioCS) have been reported. The primary objective of this study was to describe ioCS. A second aim was to identify risk factors of ioCS. We retrospectively analysed patients operated for small-bowel neuroendocrine tumour in our institution between 2007 and 2015, and receiving our preventive local regimen of octreotide continuous administration. ioCS was defined as highly probable in case of rapid (<5 min) arterial blood pressure changes ≥40%, not explained by surgical/anaesthetic management and regressive ≥20% after octreotide bolus injection. Probable cases were ioCS which did not meet all criteria of highly-probable ioCS. Suspected ioCS were detected on the anaesthesia record by an injection of octreotide due to a manifestation which did not meet the criteria for highly-probable or probable ioCS. A total of 81 patients (liver metastases: 59, prior carcinoid syndrome: 49, carcinoid heart disease: 7) were included; 139 ioCS occurred in 45 patients: 45 highly probable, 67 probable and 27 suspected. ioCs was hypertensive (91%) and/or hypotensive (29%). There was no factor, including the use of vasopressors, significantly associated with the occurrence of an ioCS. All surgeries were completed and one patient died from cardiac failure 4 days after surgery. After preoperative octreotide continuous infusion, ioCS were mainly hypertensive. No ioCS risk factors, including vasopressor use, were identified. No intraoperative carcinoid crisis occurred, suggesting the clinical relevance of a standardized octreotide prophylaxis protocol.
Search for other papers by Frans H H Leenen in
Google Scholar
PubMed
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
Search for other papers by Mordecai P Blaustein in
Google Scholar
PubMed
Search for other papers by John M Hamlyn in
Google Scholar
PubMed
In the brain, angiotensinergic pathways play a major role in chronic regulation of cardiovascular and electrolyte homeostasis. Increases in plasma angiotensin II (Ang II), aldosterone, [Na+] and cytokines can directly activate these pathways. Chronically, these stimuli also activate a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels and endogenous ouabain (EO). This pathway increases AT1R and NADPH oxidase subunits and maintains/further increases the activity of angiotensinergic pathways. These brain pathways not only increase the setpoint of sympathetic activity per se, but also enhance its effectiveness by increasing plasma EO and EO-dependent reprogramming of arterial and cardiac function. Blockade of any step in this slow pathway or of AT1R prevents Ang II-, aldosterone- or salt and renal injury-induced forms of hypertension. MR/AT1R activation in the CNS also contributes to the activation of sympathetic activity, the circulatory and cardiac RAAS and increase in circulating cytokines in HF post MI. Chronic central infusion of an aldosterone synthase inhibitor, MR blocker or AT1R blocker prevents a major part of the structural remodeling of the heart and the decrease in LV function post MI, indicating that MR activation in the CNS post MI depends on aldosterone, locally produced in the CNS. Thus, Ang II, aldosterone and EO are not simply circulating hormones that act on the CNS but rather they are also paracrine neurohormones, locally produced in the CNS, that exert powerful effects in key CNS pathways involved in the long-term control of sympathetic and neuro-endocrine function and cardiovascular homeostasis.
Search for other papers by Susanna Cirera in
Google Scholar
PubMed
Search for other papers by Sophia G Moesgaard in
Google Scholar
PubMed
Search for other papers by Nora E Zois in
Google Scholar
PubMed
Search for other papers by Nathja Ravn in
Google Scholar
PubMed
Department of Veterinary Clinical and Animal Sciences, Novo Nordisk A/S, Department of Clinical Biochemistry, Department of Cardiothoracic and Vascular Surgery, Department of Clinical Biochemistry, Department of Veterinary Disease Biology, Department of Clinical Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
Search for other papers by Jens P Goetze in
Google Scholar
PubMed
Search for other papers by Signe E Cremer in
Google Scholar
PubMed
Search for other papers by Tom Teerlink in
Google Scholar
PubMed
Search for other papers by Páll S Leifsson in
Google Scholar
PubMed
Search for other papers by Jesper L Honge in
Google Scholar
PubMed
Search for other papers by J Michael Hasenkam in
Google Scholar
PubMed
Search for other papers by Lisbeth H Olsen in
Google Scholar
PubMed
Objective
Non-ischemic mitral regurgitation (MR) is primarily caused by myxomatous mitral valve (MV) disease leading to adaptive remodeling, enlargement, and dysfunction of the left ventricle. The aim of this study was to examine the regulation of plasma markers and several cardiac key genes in a novel porcine model of non-ischemic MR.
Methods and results
Twenty-eight production pigs (Sus scrofa) were randomized to experimental MR or sham surgery controls. MR was induced by external suture(s) through the posterior MV leaflet and quantified using echocardiography. The experimental group was subdivided into mild MR (mMR, MR=20–50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with controls (CON, MR ≤10%, n=12). Eight weeks postoperatively, follow-up examinations were performed followed by killing. Circulating concentrations of pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine, and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary muscle, and left ventricular free wall tissues were collected to quantify mRNA expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR displayed markedly increased plasma proANP and SDMA concentrations compared with both controls and mMR (P<0.05). The expression of all genes examined differed significantly between the three localizations in the heart. miR-21 and miR-133a were differently expressed among the experimental groups (P<0.05).
Conclusions
Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are associated with severity of chronic MR in an experimental porcine model.
Search for other papers by Jing Hong in
Google Scholar
PubMed
Search for other papers by Wen-Yue Liu in
Google Scholar
PubMed
Search for other papers by Xiang Hu in
Google Scholar
PubMed
Search for other papers by Fei-Fei Jiang in
Google Scholar
PubMed
Search for other papers by Ze-Ru Xu in
Google Scholar
PubMed
Search for other papers by Fang Li in
Google Scholar
PubMed
Search for other papers by Fei-Xia Shen in
Google Scholar
PubMed
Search for other papers by Hong Zhu in
Google Scholar
PubMed
Background
A prolonged heart rate-corrected QT interval (QTc) has been associated with peripheral artery disease (PAD) in the general population. However, no study to date has identified a link between prolonged QTc and the severity of PAD in patients with diabetes mellitus and foot ulcers (DFUs). This study aimed to investigate this relationship.
Methods
This multicenter study enrolled 281 patients with DFUs. The severity of PAD was classified into no severe PAD group (without stenosis or occlusion) and severe PAD group (with stenosis or occlusion) based on duplex ultrasonography. The association of prolonged QTc with severe PAD was evaluated in a multivariable mixed-effect logistic regression model, with the hospital as a random effect. Directed acyclic graphs were used to drive the selection of variables to fit the regression model.
Results
Patients with severe PAD had longer QTc than those without. Based on the multivariable mixed-effect logistic regression model, a prolonged QTc was positively associated with severe PAD (odds ratio (OR) = 2.61; 95% CI: 1.07–6.35) and severe DFUs (Wagner grade score ≥ 3) (OR = 2.87; 95% CI: 1.42–5.81).
Conclusions
A prolonged QTc was associated with severe PAD in patients with DFUs. Further research is required to ascertain whether the association is causal.
Search for other papers by H A Booij in
Google Scholar
PubMed
Search for other papers by W D C Gaykema in
Google Scholar
PubMed
Search for other papers by K A J Kuijpers in
Google Scholar
PubMed
Search for other papers by M J M Pouwels in
Google Scholar
PubMed
Search for other papers by H M den Hertog in
Google Scholar
PubMed
Background
Poststroke fatigue (PSF) is a highly prevalent and debilitating condition. However, the etiology remains incompletely understood. Literature suggests the co-prevalence of pituitary dysfunction (PD) with stroke, and the question raises whether this could be a contributing factor to the development of PSF. This study reviews the prevalence of PD after stroke and other acquired brain injuries and its association with fatigue.
Summary
We performed a bibliographic literature search of MEDLINE and EMBASE databases for English language studies on PD in adult patients with stroke, traumatic brain injury (TBI) or aneurysmatic subarachnoid hemorrhage (aSAH). Forty-two articles were selected for review. Up to 82% of patients were found to have any degree of PD after stroke. Growth hormone deficiency was most commonly found. In aSAH and TBI, prevalences up to 49.3% were reported. However, data differed widely between studies, mostly due to methodological differences including the diagnostic methods used to define PD and the focus on the acute or chronic phase. Data on PD and outcome after stroke, aSAH and TBI are conflicting. No studies were found investigating the association between PD and PSF. Data on the association between PD and fatigue after aSAH and TBI were scarce and conflicting, and fatigue is rarely been investigated as a primary end point.
Key messages
Data according to the prevalence of PD after stroke and other acquired brain injury suggest a high prevalence of PD after these conditions. However, the clinical relevance and especially the association with fatigue need to be established.
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
Search for other papers by Signe Frøssing in
Google Scholar
PubMed
Department of Obstetrics & Gynecology, Herlev Gentofte Hospital, Copenhagen, Denmark
Search for other papers by Malin Nylander in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
Search for other papers by Caroline Kistorp in
Google Scholar
PubMed
Department of Obstetrics & Gynecology, Herlev Gentofte Hospital, Copenhagen, Denmark
Search for other papers by Sven O Skouby in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, Copenhagen University, Copenhagen, Denmark
Search for other papers by Jens Faber in
Google Scholar
PubMed
Context
Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP.
Objective
To investigate if treatment with liraglutide in women with PCOS reduces levels of the cardiovascular biomarkers MR-proADM, MR-proANP and copeptin.
Methods
Seventy-two overweight women with PCOS were treated with 1.8 mg/day liraglutide or placebo for 26 weeks in a placebo-controlled RCT. Biomarkers, anthropometrics, insulin resistance, body composition (DXA) and visceral fat (MRI) were examined.
Results
Baseline median (IQR) levels were as follows: MR-proADM 0.52 (0.45–0.56) nmol/L, MR-proANP 44.8 (34.6–56.7) pmol/L and copeptin 4.95 (3.50–6.50) pmol/L. Mean percentage differences (95% CI) between liraglutide and placebo group after treatment were as follows: MR-proADM −6% (−11 to 2, P = 0.058), MR-proANP −25% (−37 to −11, P = 0.001) and copeptin +4% (−13 to 25, P = 0.64). Reduction in MR-proANP concentration correlated with both increased heart rate and diastolic blood pressure in the liraglutide group. Multiple regression analyses with adjustment for BMI, free testosterone, insulin resistance, visceral fat, heart rate and eGFR showed reductions in MR-proANP to be independently correlated with an increase in the heart rate.
Conclusion
In an RCT, liraglutide treatment in women with PCOS reduced levels of the cardiovascular risk biomarkers MR-proANP with 25% and MR-proADM with 6% (borderline significance) compared with placebo. The decrease in MR-proANP was independently associated with an increase in the heart rate.
Search for other papers by Eng-Loon Tng in
Google Scholar
PubMed
Search for other papers by Yee Sian Tiong in
Google Scholar
PubMed
Search for other papers by Aye Thida Aung in
Google Scholar
PubMed
Search for other papers by Nicole Ya Yuan Chong in
Google Scholar
PubMed
Search for other papers by Zhemin Wang in
Google Scholar
PubMed
Background
Evidence on the efficacy and safety of anticoagulation in preventing stroke and thromboembolic events in people with thyrotoxic atrial fibrillation is scarce.
Objective
We evaluated the efficacy and safety of anticoagulation in people with thyrotoxic atrial fibrillation.
Methods
Our study protocol was published in the International Prospective Register of Systematic Reviews (registration no. CRD42020222782). Four databases and two systematic review registers were searched through 25 November 2020 for interventional and observational studies comparing anticoagulation therapy with active comparators, placebo, or no treatment in people with thyrotoxic atrial fibrillation. Random-effects meta-analysis and sensitivity analysis were performed. Quality of evidence was described using the GRADE framework.
Results
In the study, 23,145 records were retrieved. One randomized controlled trial and eight cohort studies were ultimately included. Effect estimates on the efficacy and safety of anticoagulation were extracted. Meta-analysis using the inverse variance and random-effects methods was conducted on four cohort studies with 3443 participants and 277 events. Anticoagulation in people with thyrotoxic atrial fibrillation reduced the risk of ischemic stroke and systemic thromboembolism by 3% (95% CI: 1–6%). Warfarin may prevent ischemic stroke in people with thyrotoxic atrial fibrillation if the CHA2DS2-VASc score exceeds 1 and when atrial fibrillation persists beyond 7 days. Direct oral anticoagulants may be associated with fewer bleeding events than warfarin.
Conclusions
Anticoagulation prevents ischemic stroke and systemic thromboembolism in people with thyrotoxic atrial fibrillation. Direct oral anticoagulants may be associated with fewer bleeding events.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Jan Calissendorff in
Google Scholar
PubMed
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Search for other papers by Henrik Falhammar in
Google Scholar
PubMed
Background
Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported.
Methods
All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency.
Results
Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications.
Conclusion
Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.
