| 1. |
- Fedorowski, Artur, et al.
(författare)
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Antiadrenergic autoimmunity in postural tachycardia syndrome
- 2017
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Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 19:7, s. 1211-1219
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Tidskriftsartikel (refereegranskat)abstract
- Aims Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). Methods and results Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity. Conclusion These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.
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| 2. |
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| 3. |
- Hamrefors, Viktor, et al.
(författare)
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Orthostatic Hypotension and Elevated Resting Heart Rate Predict Low-Energy Fractures in the Population : The Malmö Preventive Project
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:4, s. 0154249-0154249
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autonomic disorders of the cardiovascular system, such as orthostatic hypotension and elevated resting heart rate, predict mortality and cardiovascular events in the population. Low-energy-fractures constitute a substantial clinical problem that may represent an additional risk related to such autonomic dysfunction.AIMS: To test the association between orthostatic hypotension, resting heart rate and incidence of low-energy-fractures in the general population.METHODS AND RESULTS: Using multivariable-adjusted Cox regression models we investigated the association between orthostatic blood pressure response, resting heart rate and first incident low-energy-fracture in a population-based, middle-aged cohort of 33 000 individuals over 25 years follow-up. The median follow-up time from baseline to first incident fracture among the subjects that experienced a low energy fracture was 15.0 years. A 10 mmHg orthostatic decrease in systolic blood pressure at baseline was associated with 5% increased risk of low-energy-fractures (95% confidence interval 1.01-1.10) during follow-up, whereas the resting heart rate predicted low-energy-fractures with an effect size of 8% increased risk per 10 beats-per-minute (1.05-1.12), independently of the orthostatic response. Subjects with a resting heart rate exceeding 68 beats-per-minute had 18% (1.10-1.26) increased risk of low-energy-fractures during follow-up compared with subjects with a resting heart rate below 68 beats-per-minute. When combining the orthostatic response and resting heart rate, there was a 30% risk increase (1.08-1.57) of low-energy-fractures between the extremes, i.e. between subjects in the fourth compared with the first quartiles of both resting heart rate and systolic blood pressure-decrease.CONCLUSION: Orthostatic blood pressure decline and elevated resting heart rate independently predict low-energy fractures in a middle-aged population. These two measures of subclinical cardiovascular dysautonomia may herald increased risks many years in advance, even if symptoms may not be detectable. Although the effect sizes are moderate, the easily accessible clinical parameters of orthostatic blood pressure response and resting heart rate deserve consideration as new risk predictors to yield more accurate decisions on primary prevention of low-energy fractures.
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| 4. |
- Hamrefors, Viktor, et al.
(författare)
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Syndromes of orthostatic intolerance and syncope in young adults
- 2017
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Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore the clinical and neuroendocrine characteristics of syndromes of orthostatic intolerance and syncope in young adults. Methods Two hundred and thirty-six patients aged 18-40 years with orthostatic intolerance and/or syncope were examined by head-up tilt test (HUT). Plasma levels of epinephrine, norepinephrine, renin, C-terminal-pro-arginine-vasopressin (CT-proAVP), C-terminal-endothelin-1 and mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP) were analysed. Patients' history, haemodynamic parameters and plasma biomarkers were related to main diagnoses such as vasovagal syncope (VVS), postural tachycardia syndrome (POTS), orthostatic hypotension (OH) and negative HUT. Results No self-reported symptom of orthostatic intolerance was highly specific for any diagnosis. Patients with VVS (n=103) were more likely to be men (p=0.011) and had lower resting heart rate (HR; 66±11) compared with POTS (73±11; n=72; p=0.001) and negative HUT (74±11; n=39; p=0.001). Patients with POTS demonstrated greater rise in norepinephrine (p=0.008) and CT-proAVP (p=0.033) on standing compared with negative HUT, and lower resting MR-proANP compared with VVS (p=0.04) and OH (p=0.03). Patients with OH had lower resting renin (p=0.03). Subjects with a resting HR <70 and MR-proANP >45 pm/L had an OR of 3.99 (95 % CI 1.68 to 9.52; p=0.002) for VVS compared with subjects without any of these criteria; if male sex was added the OR was 21.8 (95% CI 3.99 to 119; p<0.001). Conclusions Syndromes of orthostatic intolerance and syncope share many characteristics in younger persons. However, patients with VVS are more likely to be men, have lower HR and higher MR-proANP at rest compared with POTS, which might be taken into account at an early stage of evaluation.
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| 5. |
- Härstedt, Maria, et al.
(författare)
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Cardiovascular biomarkers and risk of low-energy fractures among middle-aged men and women—A population-based study
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low-energy fractures are a growing health challenge as their incidence increases with advancing age. As cardiovascular instability may be associated with higher likelihood of traumatic falls, we aimed to investigate the associations between four cardiovascular biomarkers and the risk of low-energy fractures in a middle-aged population. Methods: A total of 5291 individuals from the prospective Malmö Diet and Cancer (MDC) study (mean age, 57 years; 59% women) with data on baseline levels of four cardiovascular biomarkers: mid-regional-fragment of pro-adrenomedullin-peptide (MR-pro-ADM), mid-regional-fragment of pro-atrial-natriuretic-peptide (MR-proANP), N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and C-terminal-pro-arginine-vasopressin (CT-pro-AVP/Copeptin) were included. The associations between biomarker levels and first incident low-energy fracture were tested in Cox proportional-hazard models, taking potential interactions and traditional risk factors into account. Results: Participants were followed for a median time of 21.0 years, during which 1002 subjects (19%) experienced at least one low-energy fracture. Subjects with incident fracture were older, more likely to be women, had lower BMI and higher prevalence of previous fractures. Among biomarkers, there was a significant interaction between gender and MR-pro-ADM on the risk of fracture (p = 0.002). MR-pro-ADM predicted fractures in men only (hazard ratio, 1.23; 95% CI 1.09-1.40; p = 0.001), whereas there was no association among women. Levels of MR-pro-ANP, NT-pro-BNP and CT-pro-AVP did not predict fractures. Conclusions Higher circulating levels of MR-pro-ADM predict low-energy fractures among middle-agedmen, whereas levels of MR-pro-ANP, NT-pro-BNP and CT-pro-AVP are not associated with increased fracture risk. Further controlled studies should test the hypothesis whether MRpro- ADM may improve prediction of bone fractures.
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| 6. |
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| 7. |
- Härstedt, Maria, et al.
(författare)
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Polypharmacy and adverse outcomes after hip fracture surgery
- 2016
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to explore the effects of polypharmacy and specific drug classes on readmissions and mortality after hip surgery. Methods: We analyzed data on 272 consecutive hip fracture patients (72.1% females; age 82±9 years) who underwent acute hip replacement. We collected detailed data on the pharmacological treatment upon admission and discharge. Patients were followed up over a period of 6 months after discharge using the Swedish National Hospital Discharge Register and the Swedish National Cause of Death Register. Results: After 6 months, 86 patients (31.6%) were readmitted, while 36 patients (13.2%) died. The total number of medications upon discharge was predictive of rehospitalization (odds ratio (OR) 1.08, 95%CI 1.01-1.17, p = 0.030) but not predictive of mortality. The use of antiosteoporotic agents (OR 1.86, 95%CI 1.06-3.26, p = 0.03), SSRIs (OR 1.90, 95%CI 1.06-3.42, p = 0.03), and eye drops (OR 4.12, 95%CI 1.89-8.97, p = 0.0004) were predictive of rehospitalization. Treatment with vitamin K antagonists (OR 4.29, 95%CI 1.19-15.39, p = 0.026), thiazides (OR 4.10, 95%CI 1.30-12.91, p = 0.016), and tramadol (OR 2.84, 95%CI 1.17-6.90, p = 0.021) predicted readmissions due to a new fall/trauma. Conclusions: The total number of medications, use of antiosteoporotic agents, SSRIs, and eye drops predicted rehospitalization after hip fracture surgery, while use of vitamin K antagonists, thiazides, and tramadol was associated with readmissions due to a traumatic fall. Trial registration: Hip fractures and polypharmacy in the elderly. Stimulus Project for the Elderly 2009-2011 (Reg no 2009-11-26). Swedish National Board of Health and Welfare.
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| 8. |
- Isma, Nazim, et al.
(författare)
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Higher levels of von Willebrand factor in patients with syncope due to orthostatic hypotension.
- 2015
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Ingår i: Journal of Hypertension. - 1473-5598. ; 33:8, s. 1594-1601
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Tidskriftsartikel (refereegranskat)abstract
- Orthostatic hypotension has been linked with increased mortality and cardiovascular morbidity; however, the underlying mechanisms are still unknown. The aim of the study was to assess markers of coagulability in patients with and without orthostatic hypotension who suffered transient loss of consciousness.
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| 9. |
- Johansson, Madeleine, et al.
(författare)
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Cardiovascular biomarkers predict fragility fractures in older adults
- 2019
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:6, s. 449-454
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Tidskriftsartikel (refereegranskat)abstract
- Objective To assess the role of four biomarkers of neuroendocrine activation and endothelial dysfunction in the longitudinal prediction of fragility fractures. Methods We analysed a population-based prospective cohort of 5415 community-dwelling individuals (mean age, 68.9±6.2 years) enrolled in the Malmö Preventive Project followed during 8.1±2.9 years, and investigated the longitudinal association between C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), the mid-regional fragments of pro-adrenomedullin (MR-proADM) and pro-atrial natriuretic peptide (MR-proANP), and incident vertebral, pelvic and extremity fractures. Results Overall, 1030 (19.0%) individuals suffered vertebral, pelvic or extremity fracture. They were older (70.7±5.8 vs 68.4±6.3 years), more likely women (46.9% vs 26.3%), had lower body mass index and diastolic blood pressure, were more often on antihypertensive treatment (44.1% vs 38.4%) and had more frequently history of fracture (16.3% vs 8.1%). Higher levels of MR-proADM (adjusted HR (aHR) per 1 SD: 1.51, 95% CI 1.01 to 2.28, p<0.001) and MR-proANP (aHR: 1.23, 95% CI 1.05 to 1.45, p<0.001) were independently associated with increased risk of any fracture. The fracture risk increased linearly across MR-proANP quartiles. Individuals who were in the top quartile of all four biomarkers had a significant higher risk of fracture at any site (aHR: 2.32, 95% CI 1.86 to 2.91), vertebral fracture (aHR: 3.16, 95% CI 1.97 to 5.07) and femoral fracture (aHR: 2.35, 95% CI 1.64 to 3.36). Conclusions Elevated levels of MR-proADM and MR-proANP independently predict fragility fractures in older adults. In subjects with top quartile levels of all four biomarkers there is a twofold to threefold increase in risk of vertebral and femoral fractures.
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| 10. |
- Johansson, Madeleine, et al.
(författare)
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Circulating levels of growth hormone in postural orthostatic tachycardia syndrome
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case-control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.
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