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41.
  • Ahlander, Britt-Marie, 1954- (författare)
  • Magnetic Resonance Imaging of the Heart Image quality, measurement accuracy and patient experience
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.
42.
  • Ahle, Margareta, 1966- (författare)
  • Necrotising Enterocolitis epidemiology and imaging
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.
43.
  • Ahlgren, Ewa, 1959- (författare)
  • Cerebral complications after cardiac surgery
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
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44.
  • Ahmadi, Ahmad, 1964- (författare)
  • Genetic predisposition and risk factors for neurodegenerative diseases
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.
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45.
  • Ahnström Waltersson, Marie, 1976- (författare)
  • Cell cycle alterations and 11q13 amplification in breast cancer prediction of adjuvant treatment response
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.
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46.
  • Aho, Nikolas, 1970- (författare)
  • Victimization, Prevalence, Health and Peritraumatic Reactions in Swedish Adolescents
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The aim of this thesis was to expand the knowledge of victimization in children and youth in Sweden. Victimization, prevalence, health and peritraumatic reactions were explored in a cross sectional, representative sample of 5,960 second grade high school students in Sweden. A computerized survey was developed and administered in class room setting.Lifetime victimization was found in 84.1% of the sample (m=83.0%, f=85.2%), and, in relation to the five domains, 66.4% had experienced conventional crime, 24% child maltreatment, 54.4% peer and sibling victimization, 21.8% sexual victimization, and 54% had experienced witness victimization. Females experienced significantly more child maltreatment, peer and sibling victimization, sexual victimization, and witnessed victimization, males more conventional crime (p<0.001). Using logistic regression risk factors for victimization were confirmed by a significant increase OR regarding gender, environment and lack of both parents.Symptoms (TSCC), were clearly associated with both victimizations per se and the number of victimizations. The results indicated a relatively linear increase in symptoms with an increase in number of events experienced. Mental health of the polyvictimized group was significantly worse than that of the non-polyvictimized group, with significantly elevated TSCC scores (t<0.001). Hierarchical regression analysis resulted in beta value reduction when polyvictimization was introduced supporting the independent effect on symptoms. Social anxiety was found in 10.2 % (n = 605) of the total group (n = 5,960). A significant gender difference emerged, with more females than males reporting social anxiety. Elevated PTSS was found in 14.8 % (n=883). Binary logistic regression revealed the highest OR for having had contact with child and adolescent psychiatry was found for the combined group with social anxiety and elevated PTSS (OR = 4.88, 95 % CI = 3.53–6.73, p<001). Significant associations were also found between use of child and adolescent psychiatry and female gender (OR = 2.05, 95 % CI = 1.70–2.45), Swedish birth origin (OR = 1.68, 95 % CI = 1.16–2.42) and living in a small municipality (OR = 1.33, 95 % CI = 1.02–1.73).Mediation models used peritraumatic reactions (PT): total, physiological arousal (PA), peritraumatic dissociation (PD), and intervention thoughts (IT) and JVQ and TSCC. Of the n=5,332 cases, a total of n=4,483 (84.1%) reported at least one victimizing event (m = 83.0%, f = 85.2%). Of these, 74.9% (n=3,360) also experienced a PT reaction of some kind. The effect mediated by PT tot was b= 0.479, BCa CI [0.342 – 0.640], representing a relatively small effect of 7.6%, κ2=0.076, 95% BCa CI [0.054- 0.101]. The mediating effect of JVQ on TSCC was mediated by PD more for males (b=0.394 BCa CI [0.170-0.636]) than for females (b=0.247, BCa CI [0.021-0.469]). The indirect effect of the JVQ on the TSCC tot mediated by the different PT reactions was significant for PD (b=0.355, BCa CI [0.199- 0.523]. In males a mediating effect of PD could be seen in the different models, while females had a more mixed result. IT did not show any indirect effect in males, but had a mixed effect for females.The empirical findings in this thesis lead to the conclusion that victimization is highly prevalent in children and youth and is related to health issues. The association of victimization on symptoms was mediated by peritraumatic reactions. Using a comprehensive instrument such as the JVQ provides the researcher or clinician the opportunity to acquire more complete measurement and also makes it possible to identify polyvictimization, a high-level category of events with severe impact on health.  
47.
  • Aili Fagerholm, Siri, 1980- (författare)
  • Insulin signaling in primary adipocytes in insulin sensitive and insulin resistant states
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Increasing numbers of people world-wide develops the disease type 2 diabetes. Development of type 2 diabetes is characterized by a shift from an insulin sensitive state to an insulin resistant state in peripheral insulin responding organs, which originates from the development of insulin resistance in the adipose tissue. Insulin resistance in combination with reduced pancreatic insulin secretion lead to overt type 2 diabetes.In this thesis, the insulin signaling network in primary adipocytes was analyzed. Key proteins and mechanisms were studied to gain deeper knowledge of signaling both in the insulin sensitive state and in the insulin resistant state produced by rapid weight gain as well as in type 2 diabetes.The surface of the adipocyte is dotted with invaginations in the cell membrane called caveolae that act as important metabolic and signaling platforms in adipocytes, and also harbor the insulin receptor. In paper I we show that insulin stimulation of primary adipocytes results in a rapid phosphorylation of the insulin receptor and caveolin-1, and that internalization of the proteins is mediated by endocytosis of caveolae.Weight gain due to overfeeding and obesity has been associated with the development of insulin resistance in insulin sensitive tissues such as the adipose tissue. In paper II we show that short-term overfeeding for one month of lean subjects results in an insulin resistant state. At the end of the study, the subjects had developed a mild systemic insulin resistance. Moreover, in isolated subcutaneous adipocytes we found several alterations of the insulin signaling pathway that mimicked alterations found in isolated subcutaneous adipocytes from subjects with type 2 diabetes.In paper III we present a first dynamic mathematical model of the insulin signaling network in human adipocytes that are based on experimental data acquired in a consistent fashion. The model takes account of insulin signaling in both the healthy, insulin sensitive state and in the insulin resistant state of type 2 diabetes. We show that attenuated mTORC1-mediated positive feedback to control of phosphorylation of IRS1 at Ser307 is an essential component of the insulin resistant state of type 2 diabetes. A future application of the model is the identification and evaluation of drug targets for the treatment of insulin resistance and type 2 diabetes.In paper IV we examine the protein kinase that catalyzes the insulin stimulated mTORC1- mediated feedback to IRS1. We find that the phosphorylation of IRS1 at Ser307 is not likely to be catalyzed by the kinases S6K1, mTOR or PKB. However, a catalyzing protein kinase for the in vitro phosphorylation of IRS1 at Ser307 was found to be associated with the complex mTORC1.In conclusion, this thesis provide new insights and characterize mechanisms of the intrinsically complex insulin signaling network of primary adipocytes, both in insulin sensitive and insulin resistant states.
48.
  • Akanda, Nesar, 1972- (författare)
  • Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl– through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl− to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl– channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.
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49.
  • Alehagen, Siw, 1953- (författare)
  • Fear pain stress hormones during labor
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The aims of the thesis were to develop a measure of fear during labor and to investigate women's experiences of fear and pain during labor and delivery as well as their levels of stress hormones. We also wanted to explore the associations between fear, pain, stress hormones and the duration of labor. Finally, we aimed to examine the relationships between pre-and postpartum fear, and fear and pain during labor.The measurement of fear was developed in two substudies. First we composed a list of 60 fear-related items and their contrasts and tested it in a group of 92 women in labor. After psychometrical analyses, 10 items were selected for the final scale. The scale was then tested in another group of 57 women in labor. Via semi-structured interviews the content of the items was documented and analyzed.Fifty-five nulliparous women participated in the investigation of women's experiences of fear, pain, levels of stress hormones and duration of labor. During gestation weeks 37-39, we measured levels of fear of childbirth, urinary catecholamines and salivary cortisol. During labor, hourly measurements were performed of fear, pain and levels of stress hormones. Finally, at two hours, two days and five weeks postpartum, fear of childbirth and stress hormones were measured.The questionnaire that measures fear during labor was called the Delivery Fear Scale (DFS). The DFS has an alpha coefficient of .8 and has good psychometric qualities in both nulliparous and parous women. It takes women in labor between 30 and 90 seconds to listen to and answer all the statements. We found that nulliparous women had higher fear during phase 1 of labor (cervix dilatation 3-Scm) than parous women. Fear during phase 1 of labor predicted the total amount of pain relief received during labor, but not the duration of remaining part of labor, nor the occurrence of instrumental vaginal delivery or emergency cesarean section.The results from the subsequently studies showed that there was an increase of the levels in stress hormones from pregnancy to labor. Epinephrine and cortisol increased more than 500% and norepinephrine approximately 50%. In women without EDA fear and cortisol increased throughout labor. In women with EDA cortisol did not increase, fear, pain and catecholamine levels first decreased after the administration of EDA but at the end of labor fear and pain increased. In phase 1, fear, but not pain, was more intensive in women who later subsequently received EDA than in those who did not. Fear and pain correlated positively during labor. A high level of epinephrine was associated with a shorter duration of phase 1 of labor. Postpartum fear of childbirth was higher in women who had received EDA during labor than in those who had not. Pre- and postpartum fear of childbirth correlated positively with fear but not with pain during phase 1 of labor.In conclusion, DFS is a new measure of fear during labor with good psychometric qualities. Childbirth is a stressful event associated with exceptionally high levels of stress hormones. In this study women's experiences of fear and pain were associated throughout labor. The administration of EDA heavily influenced the course of fear, pain and stress hormones. Women who later received EDA had higher scores of fear but not of pain early during labor than those who did not receive EDA. Late pregnant women who fear childbirth are prone to have a fearful delivery, as reported during the actual labor and postpartwn.
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50.
  • Alehagen, Urban, 1951- (författare)
  • Heart failure in primary health care : special emphasis on natriuretic peptides in the elderly
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Background: This thesis focuses on heart failure among elderly patients in the community who usually are not included in studies on heart failure. The heart failure syndrome is an increasing problem in Western society. Severe heart failure is often easy to diagnose compared with light to moderate heart failure, which is more frequent in patients in the community,Doppler echocardiography is the most commonly used method to objectively verify an abnormal cardiac function, mostly the systolic function. One goal of this thesis was to evaluate both the systolic and diastolic functions. Another goal was a study of the possible utility of the B-type natriuretic peptide, BNP (brain natriuretic peptide), and the amino terminal fragment of its precursor, proBNP (N-terminal proBNP) as tools in the diagnosis of heart failure in elderly patients.Methods: In a primary health care setting, 510 elderly patients (age range 65-82 years) with symptoms and signs possibly associated with heart failure were examined concerning patient history, ongoing pharmacological treatment, clinical examination, chest x-ray, electrocardiogram, Doppler echo cardiography, and selected biochemical measurements of blood samples. Additionally, the natriuretic peptide BNP and the aminoterminal fragment of proBNP were analyzed for a possible influence of gender, age, impaired cardiac function assessed using Doppler echocardiography, other diseases, and phannacological treatment. We followed our study population for six years, carefully registering mortality with death certificates. This information was used in analyzing the risk of cardiovascular death based on Cox proportional hazard regression. We present a model for estimating the risk of cardiovascular death in the individual patient.Results: Almost half of our study population [mean age 73 (SD 6) years] with symptoms of possible heart failure had signs of impaired cardiac function on Doppler echocardiography. Half of these individuals had isolated impairment of the diastolic function. Almost two thirds of the elderly patients who had an ejection fraction of less than 40% did not receive treatment with ACE inhibitors, one of the cornerstones in the treatment of heart failure.BNP and N-terminal proBNP were equally effective in detecting impaired cardiac function. As a response to increased filling pressure they probably provide earlier information on the haemodynamic situation than Doppler echocardiography does.In these elderly patients, functional class (NYHA class III: 7 times increased risk), in vivo examination by Doppler echo cardiography (EF<30%: 8 times increased risk) and the in vitro measurement of plasma BNP (>27.8 pmol/L: 11 times increased risk) and N-terminal proBNP (>109 pmol/L: 7 times increased risk) could be used as prognostic determinants in assessing the risk of cardiovascular death.Conclusion: The results indicate that a focused patient history and clinical examination provides important information that is often sufficient for the prognostic evaluation of a patient with heart failure symptoms. Additional information may be obtained with Doppler echo cardiographic examination and measurement of plasma BNP or N-terminal proBNP. The relationship between BNPIN-terminal proBNP concentration and risk of cardiovascular death may be analysed to define decision limits for the concentrations of these peptides as regards further diagnostic procedures and/or phannaceutical treatment.
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