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  • 1.
    Agvall, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care Centres.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    The benefits of using a heart failure management programme in Swedish primary healthcare2013In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 15, no 2, p. 228-236Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is a common condition with which high mortality, morbidity, and poor quality of life are associated. It has previously been shown that use of HF management programmes (HFMPs) in HF clinics can be beneficial. The purpose of this study was to evaluate if the use of HFMPs also has beneficial effects on HF patients in primary healthcare (PHC). less thanbrgreater than less thanbrgreater thanThis is a randomized, prospective, open-label study including 160 patients from five PHC centres with systolic HF and a mean age of 75 years (standard deviation 7.8). In the intervention group, an intensive follow-up was performed by HF nurses and physicians providing information and education about HF and the optimization of HF treatment according to recognized guidelines. There was a significant improvement of composite endpoints in the intervention group. Significantly more patients with reduced N-terminal pro brain natriuretic peptide (P 0.012), improved cardiac function (P 0.03), fewer healthcare contacts (P 0.04), and fewer emergency room visits and admittances (P 0.0002 and P 0.03, respectively) could be seen in the intervention group when compared with the control group. less thanbrgreater than less thanbrgreater thanThe use of a HFMP in a PHC setting was found to have beneficial effects in terms of reducing the number of healthcare contacts and hospital admissions, and improving cardiac function in patients with systolic HF, even if the result should be interpreted with caution. It can therefore be recommended that HFMPs should be used in PHC.

  • 2.
    Agvall, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Paulsson, Thomas
    Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Belgium.
    Foldevi, Mats
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alehagen, Urban
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Resource use and cost implications of implementing a heart failure program for patients with systolic heart failure in Swedish primary health care2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 176, p. 731-738Article in journal (Refereed)
    Abstract [en]

    Aim: Heart failure (HF) is a common but serious condition which involves a significant economic burden on the health care economy. The purpose of this study was to evaluate cost and quality of life (QoL) implications of implementing a HF management program (HFMP) in primary health care (PHC).

    Methods and results: This was a prospective randomized open-label study including 160 patientswith a diagnosis of HF from five PHC centers in south-eastern Sweden. Patients randomized to the intervention group received information about HF from HF nurses and from a validated computer-based awareness program. HF nurses and physicians followed the patients intensely in order to optimize HF treatment according to current guidelines. The patients in the control group were followed by their regular general practitioner (GP) and received standard treatment according to local management routines. No significant changes were observed in NYHA class and quality-adjusted life years (QALY), implying that functional class and QoL were preserved. However, costs for hospital care (HC) and PHC were reduced by EUR 2167, or 33%. The total cost was EUR 4471 in the intervention group and EUR 6638 in the control group.

    Conclusions: Introducing HFMP in Swedish PHC in patients with HF entails a significant reduction in resource utilization and costs, and maintains QoL. Based on these results, a broader implementation of HFMP in PHC may be recommended. However, results should be confirmed with extended follow-up to verify  long-term effects.

  • 3.
    Alehagen, Urban
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Heart failure in primary health care: special emphasis on natriuretic peptides in the elderly2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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.

    List of papers
    1. Heart failure in the elderly: characteristics of a Swedish primary health care population
    Open this publication in new window or tab >>Heart failure in the elderly: characteristics of a Swedish primary health care population
    2002 (English)In: Heart Drug, ISSN 1422-9528, E-ISSN 1424-0556, Vol. 2, no 5, p. 211-220Article in journal (Refereed) Published
    Abstract [en]

    Background: Heart failure (HF) is a challenge to diagnose and treat according to guidelines. Few studies have been performed in elderly subjects with symptoms that might be associated with HF in primary health care.

    Objective: To study elderly patients presenting with symptoms possibly associated with HF, with respect to systolic and diastolic function, B-type natriuretic peptide (BNP) levels and treatment.

    Methods: A cardiologist examined 415 elderly (65–82 years) patients with symptoms of dyspnoea, fatigue and/or peripheral oedema. All patients underwent echocardiography and plasma BNP determination. Systolic function was determined semiquantitatively, and ejection fraction (EF) <40% was considered to be reduced. Abnormal diastolic function was defined as a reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio; age adjusted) or an abnormal pattern of pulmonary venous flow.

    Results: Forty-eight percent of the patients showed abnormal systolic (26%) or diastolic function (22%). A majority of the patients with diastolic HF had relaxation abnormalities and neither pseudonormal nor restrictive filling patterns. Increased levels of BNP were found in the group with impaired systolic function. More than half of those with EF <40% were not receiving angiotensin-converting enzyme inhibitions at all, or were on a suboptimal dose, whereas others were on treatment for an HF diagnosis despite normal cardiac function.

    Conclusion: Diagnostic tools that are more objective than clinical examination are needed for the diagnosis of HF.

    Keywords
    Elderly patients, Heart failure, Primary health care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-46849 (URN)10.1159/000067723 (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    2. Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care
    Open this publication in new window or tab >>Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care
    2003 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 8, p. 1337-1346Article in journal (Refereed) Published
    Abstract [en]

    Background: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.

    Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.

    Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.

    Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26758 (URN)10.1373/49.8.1337 (DOI)11356 (Local ID)11356 (Archive number)11356 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
    3. The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population
    Open this publication in new window or tab >>The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population
    2005 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 17-27Article in journal (Refereed) Published
    Abstract [en]

    Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure.

    Aim: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients.

    Methods: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction <40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality.

    Conclusion: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction <40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-33737 (URN)10.1016/j.ijcard.2004.03.031 (DOI)19779 (Local ID)19779 (Archive number)19779 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
    4. Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.
    Open this publication in new window or tab >>Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Heart failure is common in the elderly population and carries a serious prognosis. Identification of risk factors for cardiovascular mortality among primary care patients is important.

    Aim

    To evaluate EDTA-plasma brain natriuretic peptide (BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly with symptoms of mild to moderate heart failure.

    Methods

    From 474 patients attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema blood was sampled in plastic tubes containing EDTA in order to measure BNP by non-extraction immunoradiometric assay and of N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and clinical- and laboratory examinations with particular reference to cardiac structure and function. Follow-up time was 6 years. A Cox regression analysis was performed to identify the weight of risk variables.

    Conclusion

    During the follow-up period of 6 years the total mortality was 16 % (75 patients out of 474), and cardiovascular mortality was 11% (52 patients). Cardiovascular mortality increased with increased plasma concentration of BNP or N-terminal proBNP. Both pep tides were useful prognostic markers for cardiovascular mortality in patients with heart failure. In those with the highest quartile of plasma concentration of BNP and N=terminal proBNP, 9.9 times and 5.0 times increased risk for CV death were identified respectively.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84703 (URN)
    Available from: 2012-10-17 Created: 2012-10-17 Last updated: 2013-09-26Bibliographically approved
  • 4.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, N-2226 Kongsvinger, Norway.
    Selenium and coenzyme Q10 interrelationship in cardiovascular diseases - A clinician's point of view2015In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 31, p. 157-162Article in journal (Refereed)
    Abstract [en]

    A short review is given of the potential role of selenium deficiency and selenium intervention trials in atherosclerotic heart disease. Selenium is an essential constituent of several proteins, including the glutathione peroxidases and selenoprotein P. The selenium intake in Europe is generally in the lower margin of recommendations from authorities. Segments of populations in Europe may thus have a deficient intake that may be presented by a deficient anti-oxidative capacity in various illnesses, in particular atherosclerotic disease, and this may influence the prognosis of the disease. Ischemic heart disease and heart failure are two conditions where increased oxidative stress has been convincingly demonstrated. Some of the intervention studies of anti-oxidative substances that have focused on selenium are discussed in this review. The interrelationship between selenium and coenzyme Q10, another anti-oxidant, is presented, pointing to a theoretical advantage in using both substances in an intervention if there are deficiencies within the population. Clinical results from an intervention study using both selenium and coenzyme Q10 in an elderly population are discussed, where reduction in cardiovascular mortality, a better cardiac function according to echocardiography, and finally a lower concentration of the biomarker NT-proBNP as a sign of lower myocardial wall tension could be seen in those on active treatment, compared to placebo.

  • 5.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.2015In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 41, no 6, p. 443-452Article in journal (Refereed)
    Abstract [en]

    Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. © 2015 BioFactors, 41(6):443-452, 2015.

  • 6.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, p. e0141641-Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class. Methods Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered. Findings Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95% CI 0.36-0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95% CI 0.27-0.97; P = 0.04), but also in the different functional classes. Conclusions In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

  • 7.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, article id e0157541Article in journal (Refereed)
    Abstract [en]

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 mu g Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 mu g/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; amp;lt;65 mu g/L, 65-85 mu g/L, and amp;gt;85 mu g/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of amp;gt;85 mu g/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 mu g/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations amp;lt; 65 mu g/L in comparison with those having a selenium concentration amp;gt; 85 mu g/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, amp;lt;= 85 at inclusion. In those with serum seleniumamp;gt; 85 mu g/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.

  • 8.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 5, p. 862-870Article in journal (Refereed)
    Abstract [en]

    Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

  • 9.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 2, p. 252-260Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 10.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Can NT-proBNP predict risk of cardiovascular mortality within 10 years? Results from an epidemiological study of elderly patients with symptoms of heart failure2009In: International journal of cardiology, ISSN 0167-5273, Vol. 133, no 2, p. 233-240Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure has a serious prognosis. However, among elderly patients the panorama of concomitant diseases makes it difficult to implement the results from epidemiological studies. The aim of this study was to evaluate the influence of different clinical variables on cardiovascular mortality during a long-term follow-up.

    Methods and results: In all, 474 elderly patients (age 65-82 years) in primary health care were evaluated and followed during a 10 year period. All patients had symptoms associated with heart failure and were examined by a cardiologist. Blood samples including NT-proBNP were analyzed, and ECG and Doppler echocardiography were assessed. Both the systolic and diastolic function was evaluated. Functional capacity was evaluated according to the NYHA classification.

    During the 10 years of follow-up those with the highest quartile of plasma concentration of NT-proBNP had almost four times increased risk of cardiovascular mortality. Impaired systolic function, diabetes and reduced functional capacity were all markers of increased risk of cardiovascular mortality. All variables were also evaluated after 5 years, with higher risk ratios for a majority of variables.

    Conclusion: In this study 474 patients with symptoms of heart failure were followed during 10 years. High plasma concentration of NT-proBNP could predict almost four times increased risk of cardiovascular mortality up to 10 years. Also, impaired cardiac function according to echocardiography, and reduced functional capacity as well as diabetes all had influence on risk of cardiovascular mortality up to 10 years.

     

  • 11.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Rehfeld, J. F.
    University of Copenhagen, Denmark .
    Gotze, J. P.
    University of Copenhagen, Denmark .
    Combined measurement of copeptin, high sensitivity Troponin T, and NT-proBNP improves the identification of elderly patients at risk of cardiovascular death in REGULATORY PEPTIDES, vol 177, issue , pp S14-S142012In: REGULATORY PEPTIDES, Elsevier , 2012, Vol. 177, p. S14-S14Conference paper (Refereed)
    Abstract [en]

    n/a

  • 12.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Cartensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Refeld, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Goetze, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Combined measurement of copeptin, high-sensitivity troponin T, and N-terminal proBNP improves the identification of patients at risk of cardiovascular death2012In: Cardiovascular Endocrinology, ISSN 2162-688X, Vol. 1, no 4, p. 68-73Article in journal (Refereed)
    Abstract [en]

    Objectives: A multimarker strategy for the handling of patients with heart failure has been suggested in the literature. Therefore, the potential prognostic relevance of combined copeptin, high-sensitivity troponin T (HS-TnT), and N-terminal proBNP (NT-proBNP) measurement in plasma from elderly patients with symptoms of heart failure was evaluated

    Methods: This study included 470 elderly patients (mean age 73 years) from a rural municipality with symptoms of heart failure. Clinical examination, echocardiography, and biomarker measurements were performed. All patients were followed for 13 years and all mortality was registered. Cardiovascular mortality was evaluated using Kaplan-Meier plots and multivariate Cox proportional hazard regression analyses.

    Results: Copeptin, HS-TnT, and NT-proBNP measurements provided independent prognostic information in a multivariate setting over 5 years (hazard ratio, HR: 3.66; 95% confidence interval, CI 1.27-10.53, HR: 2.52; 95% CI 1.20-5.28, HR: 2.73; 95% CI 1.19-6.26, respectively). Also, the group with all three biomarkers below cut-off values had a low risk for cardiovascular death (1.8% of the patients in this group died in the 5-year follow-up period). In the 13-year follow-up, combined copeptin and HS-TnT measurement did not provide independent prognostic information.

    Conclusion: Combined copeptin, HS-TnT, and NT-proBNP plasma measurements provide prognostic information on cardiovascular mortality that is superior to single biomarker use.

  • 13.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care2009In: EUROPEAN JOURNAL OF HEART FAILURE, ISSN 1388-9842, Vol. 11, no 4, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker. Four hundred and sixty-four primary health-care patients (mean age 73 years, range 65-87) with symptoms of HF were examined. All patients were evaluated using Doppler echocardiography and blood samples, including measurement of cystatin C and NT-proBNP. The patients were followed over a 10-year period. Patients with serum cystatin C levels within the highest quartile had almost three times the risk (HR: 2.92; 95% CI: 1.23-4.90) of CV mortality compared with those patients who had levels within the first, second, or third quartiles. If, at the same time, the patient had a plasma concentration of NT-proBNP within the highest quartile, the risk increased to andgt; 13 times (HR: 13.61; 95% CI: 2.56-72.24) during 10 years of follow-up or andgt; 17 times (HR: 17.04; 95% CI: 1.80-163.39) after 5 years of follow-up. Combined analysis of cystatin C and NT-proBNP could provide important prognostic information among elderly patients in the community with symptoms of HF.

  • 14.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure2004In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 92, no 6, p. 1250-1258Article in journal (Refereed)
    Abstract [en]

    D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.

  • 15.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.2010In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, ISSN 1473-5733, Vol. 21, no 1, p. 62-9Article in journal (Refereed)
    Abstract [en]

    Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

  • 16.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F
    University of Copenhagen, Denmark.
    Goetze, Jens P
    University of Copenhagen, Denmark.
    Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure2011In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, ISSN 0098-7484, Vol. 305, no 20, p. 2088-2095Article in journal (Refereed)
    Abstract [en]

    Context Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. Objective To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Design, Setting, and Participants Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. Main Outcome Measures All-cause mortality and cardiovascular mortality. Results After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P=.01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; Pandlt;.001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P=.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; Pandlt;.001). Conclusion Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

  • 17.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark .
    Goetze, Jens P.
    University of Copenhagen, Denmark .
    Pro-A-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal Pro-B-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure2013In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 19, no 1, p. 31-39Article in journal (Refereed)
    Abstract [en]

    Objective: Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP), midregional pro A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care. less thanbrgreater than less thanbrgreater thanMethods and Results: The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echocardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with andgt;4-fold increased risk for cardiovascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT-proBNP 3-fold increased risk within 5 years. In the 5-13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) andlt;40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF andgt;50% NT-proBNP exhibited andgt;3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients. less thanbrgreater than less thanbrgreater thanConclusions: The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care. (J Cardiac Fail 2013;19:31-39)

  • 18.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Rehfeld, Jens F
    University of Copenhagen.
    Goetze, Jens P
    University of Copenhagen.
    Prognostic Assessment of Elderly Patients with Symptoms of Heart Failure by Combining High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide Measurements2010In: CLINICAL CHEMISTRY, ISSN 0009-9147, Vol. 56, no 11, p. 1718-1724Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker in heart failure assessment, whereas measurement of cardiac troponin is central in the diagnosis of patients with acute coronary syndromes. This report examined the prognostic use of combining high-sensitivity cardiac troponin T (hs-cTnT) and NT-proBNP measurements in elderly patients presenting to a primary care center with symptoms associated with heart failure. METHODS: A total of 470 elderly patients (age range 65-86 years) presenting with symptoms of heart failure were recruited from primary healthcare. In addition to clinical examination and echocardiography, hs-cTnT and NT-proBNP plasma concentrations were measured. All patients were followed for 10 years, and cardiovascular mortality was registered. RESULTS: By use of the hs-cTnT assay, 80.4% of the population had plasma concentrations above the lower detection limit of the assay. Of those displaying a plasma concentration of hs-cTnT andgt;99th percentile of a healthy population, 43% also had an NT-proBNP concentration in the fourth quartile (andgt;507 ng/L). In the multivariate analysis, we observed a 2.5-fold increased risk for cardiovascular mortality in individuals with a plasma NT-proBNP concentration andgt;507 ng/L (P andlt; 0.0001). Conversely, patients with hs-cTnT andgt;99th percentile displayed an approximately 2-fold increased risk for cardiovascular mortality (P = 0.0002). Combining the 2 biomarkers, NT-proBNP concentrations andgt;507 ng/L with hs-cTnT andgt;99th percentile increased the risk 3-fold, even after adjustment for clinical variables such as age, sex, impaired estimated glomerular filtration rate, and anemia (P andlt; 0.0001). CONCLUSIONS: hs-cTnT and NT-proBNP measurements combined provide better prognostic information than using either biomarker separately in elderly patients with symptoms associated with heart failure.

  • 19.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ericsson, Anne
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Are There Any Significant Differences Between Females and Males in the Management of Heart Failure? Gender Aspects of an Elderly Population With Symptoms Associated With Heart Failure2009In: JOURNAL OF CARDIAC FAILURE, ISSN 1071-9164, Vol. 15, no 6, p. 501-507Article in journal (Refereed)
    Abstract [en]

    Background: An increasing interest has been shown in potential l., 11 With heart failure (HF), a serious condition for the individual. To evaluate whether there are any differences ill the prevalence of HF, cardiac function, biomarkers. and the treatment of HF with respect to gender. Methods and Results: All persons ages 70 to 80 in a rural municipality were invited to participate ill the project 876 persons accepted. Three cardiologists evaluated the patients including a new history, clinical examination. electrocardiogram, chest x-ray. blood samples. and Doppler echocardiography to assess both Systolic and diastolic function. The patients were followed during a mean period of 8 years. Conclusion: Females hypertension more frequently and included fewer smokers than their male Counterparts. A Female preponderance was seen in those with preserved systolic function. whereas males predominated among those with systolic dysfunction. During the follow-up period, 20% of the males and 14% of the females died of cardiovascular diseases. The results did not show any inferior treatment of females with HF. but it clearly was more difficult to correctly classify female patients presenting with symptoms of HE

  • 20.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, H
    Hall, C
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    B-type natriuretic peptides as markers of left ventricular function in the elderly2001In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 22, p. 304-304Conference paper (Other academic)
  • 21.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, H
    Nylander, E
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Overtreatment as well as undertreatment of heart failure is common in elderly patients in primary health care. Objective diagnostics tools are needed2001In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 22, p. 143-143Conference paper (Other academic)
  • 22.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Eriksson, H.
    Department of Medicine, Sahlgrenska Univ. Hosp.-Östra, Gothenburg, Sweden.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Heart failure in the elderly: characteristics of a Swedish primary health care population2002In: Heart Drug, ISSN 1422-9528, E-ISSN 1424-0556, Vol. 2, no 5, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure (HF) is a challenge to diagnose and treat according to guidelines. Few studies have been performed in elderly subjects with symptoms that might be associated with HF in primary health care.

    Objective: To study elderly patients presenting with symptoms possibly associated with HF, with respect to systolic and diastolic function, B-type natriuretic peptide (BNP) levels and treatment.

    Methods: A cardiologist examined 415 elderly (65–82 years) patients with symptoms of dyspnoea, fatigue and/or peripheral oedema. All patients underwent echocardiography and plasma BNP determination. Systolic function was determined semiquantitatively, and ejection fraction (EF) <40% was considered to be reduced. Abnormal diastolic function was defined as a reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio; age adjusted) or an abnormal pattern of pulmonary venous flow.

    Results: Forty-eight percent of the patients showed abnormal systolic (26%) or diastolic function (22%). A majority of the patients with diastolic HF had relaxation abnormalities and neither pseudonormal nor restrictive filling patterns. Increased levels of BNP were found in the group with impaired systolic function. More than half of those with EF <40% were not receiving angiotensin-converting enzyme inhibitions at all, or were on a suboptimal dose, whereas others were on treatment for an HF diagnosis despite normal cardiac function.

    Conclusion: Diagnostic tools that are more objective than clinical examination are needed for the diagnosis of HF.

  • 23.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Goetze, JP
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Reference intervals and decision limits for B-type natriuretic peptide (BNP) and its precursor (Nt-proBNP) in the elderly2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 382, no 1-2Article in journal (Refereed)
    Abstract [en]

    Background: Elderly patients have the highest prevalence of heart failure (HF). The aims of the study were to establish a reference interval for B-type natriuretic peptide (BNP) and (Nt-proBNP) in elderly people, and to identify clinically relevant decision limits based on long-term outcome. Methods: Plasma concentrations of BNP and Nt-proBNP were measured from two elderly populations: 218 healthy subjects (mean age 73 years, population I), and 474 patients (mean age 73 years, population II) with symptoms associated with HF. Study population II was followed for 6 years with registration of all cardiovascular mortality. Results: An association between both BNP and Nt-proBNP concentrations and age was found. The upper limit for the reference intervals in the healthy elderly (population I) was: BNP ≤ 28 pmol/L (≤ 97 ng/L), and Nt-proBNP ≤ 64 pmol/L (≤ 540 ng/L). Based on cardiovascular mortality, decision limits for BNP (∼ 50 pmol/L, ∼ 170 ng/L) and Nt-proBNP (∼ 200 pmol/L, ∼ 1700 ng/L) (population II) were determined. Conclusions: Besides establishing reference intervals for BNP and Nt-proBNP in an elderly population, a higher clinically relevant decision limit for BNP and Nt-proBNP was identified, indicating additive prognostic information of the peptides on top of measurements by echocardiography. Therefore, both reference intervals and decision limits should be included in clinical practice. © 2007.

  • 24.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Janzon, Magnus
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    A clinician’s experience of using the Cardiac Reader NT-proBNP point-of-care assay in a clinical setting2008In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 10, no 3, p. 260-266Article in journal (Refereed)
    Abstract [en]

    The evaluation of natriuretic peptides has become increasingly valuable in a clinical setting, where information is often needed promptly.

    Objectives: To compare the usefulness of the recently released Roche Cardiac Reader ® NT-proBNP assay against the Roche Elecsys® NT-proBNP laboratory system in a clinical setting.

    Design and Results: Blood samples from 440 patients admitted for acute coronary syndromes, worsening of heart failure, or as policlinic heart failure patients were evaluated. The relation between the assays was analysed and the diagnostic concordance calculated. A good correlation was found between the assays (r=0.96, 95% CI: 0.94-0.97) with a diagnostic concordance of 0.93. A separate analysis was performed in the range where most clinical decisions are made (60-3000 ng/L), with a diagnostic concordance of 88%. The usefulness in a clinical setting where time is important was high.

    Conclusion: The Roche Cardiac Reader® NT-proBNP assay has been evaluated in a clinical setting. The point-of-care method shows good results, although with a restricted analytical range compared with the reference.

  • 25.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Björnstedt, Mikael
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 5, p. 1860-1866Article in journal (Refereed)
    Abstract [en]

    Background

    Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

    Methods

    A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.

    The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

    Results

    During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).

    Conclusion

    Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.

  • 26.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björnstedt, Mikael
    Division of Pathology F42, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Relatively high mortality risk in elderly Swedish subjects with low selenium status2016In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 70, no 1, p. 91-96Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.

    Subjects/Methods: 

    Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.

    Results: 

    The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.

    Conclusion: 

    The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

  • 27.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Svensson, Erland
    Swedish Def Research Agency, Sweden.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0137680-Article in journal (Refereed)
    Abstract [en]

    Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q(10) , important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q(10) combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area.

  • 28.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindstedt, G.
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Results from a 6-year follow-up of a Swedish population in primary care regarding b-type natriuretic peptide (bnp) and the aminoterminal fragment of proBNP (n-terminal proBNP) and risk for cardiovascular death in elderly patients with possible heart failure.Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Heart failure is common in the elderly population and carries a serious prognosis. Identification of risk factors for cardiovascular mortality among primary care patients is important.

    Aim

    To evaluate EDTA-plasma brain natriuretic peptide (BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly with symptoms of mild to moderate heart failure.

    Methods

    From 474 patients attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema blood was sampled in plastic tubes containing EDTA in order to measure BNP by non-extraction immunoradiometric assay and of N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and clinical- and laboratory examinations with particular reference to cardiac structure and function. Follow-up time was 6 years. A Cox regression analysis was performed to identify the weight of risk variables.

    Conclusion

    During the follow-up period of 6 years the total mortality was 16 % (75 patients out of 474), and cardiovascular mortality was 11% (52 patients). Cardiovascular mortality increased with increased plasma concentration of BNP or N-terminal proBNP. Both pep tides were useful prognostic markers for cardiovascular mortality in patients with heart failure. In those with the highest quartile of plasma concentration of BNP and N=terminal proBNP, 9.9 times and 5.0 times increased risk for CV death were identified respectively.

  • 29.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindstedt, G
    Göteborgs universitet.
    Levin, Lars-Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Risk of cardiovascular death in elderly patients with possible heart failure. B-type natriuretic peptide (BNP) and the aminoterminal fragment of ProBNP (N-terminal proBNP) as prognostic indicators in a 6-year follow-up of a primary care population2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 125-133Article in journal (Refereed)
    Abstract [en]

    Heart failure is common in the elderly population and carries a serious prognosis. We evaluated EDTA-plasma B-type natriuretic peptide (brain natriuretic peptide, BNP) and the aminoterminal fragment of proBNP (N-terminal proBNP) as prognostic markers in elderly primary care patients with symptoms of heart failure. Methods: From 474 patients attending primary care for symptoms of dyspnea, fatigue and/or peripheral edema, blood was sampled in plastic tubes containing EDTA to measure BNP by non-extraction immunoradiometric assay and N-terminal proBNP by non-extraction radioimmunoassay. Patients were evaluated with respect to history and function by NYHA classification and Doppler echocardiography. Follow-up time was 6 years. Cox regression analysis was performed to identify the weight of risk variables. Conclusion: Total 6-year mortality was 20% (102 patients out of 510), and cardiovascular (CV) mortality was 14% (71 patients, 70% of total mortality). BNP and N-terminal proBNP were essentially equally useful as prognostic markers. In patients with the highest quartiles of plasma concentration of BNP and N-terminal proBNP, respectively, the risk of cardiovascular mortality was 10 and 4.8 times, respectively, higher than that in those in the lowest quartile. Peptide concentrations varied widely within all functional groups including those with normal echocardiographic findings. Plasma concentrations of BNP and N-terminal proBNP give important prognostic information concerning risk of cardiovascular mortality. Cost-effective "clinical pathways" should be outlined for patients with elevated peptide concentrations. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 30.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre. Linköping University, Faculty of Health Sciences.
    Lindstedt, G.
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Levin, Lars-Åke
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    The risk of cardiovascular death in elderly patients with possible heart failure: results from a 6-year follow-up of a Swedish primary care population2005In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 100, no 1, p. 17-27Article in journal (Refereed)
    Abstract [en]

    Little is known about the prognosis and clinical variables influencing the prognosis among elderly patients in primary health care with mild to moderate heart failure.

    Aim: To evaluate the risk of cardiovascular mortality in elderly patients with symptoms of heart failure with respect to systolic and diastolic function, and functional impairment. To evaluate prognostic determinants and to risk-stratify the patients.

    Methods: A cardiologist examined 510 patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed New York Heart Association (NYHA) functional class. Examination by Doppler echocardiography was done in 454 patients, 56 patients being excluded because of, e.g., atrial fibrillation. Abnormal systolic function was defined as ejection fraction <40%. The diastolic function was evaluated using the mitral inflow and pulmonary venous flow variables. Different clinical and echocardiographic variables were analysed using a Cox regression analysis to identify those most influencing the risk of cardiovascular mortality.

    Conclusion: Abnormal systolic and/or diastolic function was found in 219 patients (48% of the 454 patients who could be echocardiographically completely investigated). The follow-up period was 6 years. Total mortality was 20%, and cardiovascular mortality was 14% (70% of total mortality). Cardiovascular mortality was high in patients with severely impaired functional capacity and ejection fraction <40% at the start of the study. Risk variables identified were male gender, diabetes mellitus, impaired functional capacity and abnormal cardiac function by echocardiography. A prognostic score model using simple clinical variables (gender, NYHA class, cardiac function) was developed to assess the risk of cardiovascular death in order to identify patients with high, moderate or low risk. In a ROC curve analysis, the AUC for clinical variables was only 0.75, whereas the AUC for clinical variables and echocardiography was 0.78, indicating that the additional prognostic information obtained by Doppler echocardiography was rather small.

  • 31.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Lindstedt, Göran
    Sahlgren Academy at Gothenburg University, Gothenburg, Sweden.
    Eriksson, Henry
    Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
    Utility of the amino-terminal fragment of pro-brain natriuretic peptide in plasma for the evaluation of cardiac dysfunction in elderly patients in primary health care2003In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 49, no 8, p. 1337-1346Article in journal (Refereed)
    Abstract [en]

    Background: The aims of this study were to measure the N-terminal fragment of pro-brain natriuretic peptide (proBNP) in plasma in medical conditions commonly found in primary care and to evaluate the utility of these measurements in identifying impaired cardiac function in elderly patients with symptoms associated with heart failure.

    Methods: We studied 415 patients (221 men and 194 women; mean age, 72 years) who had contacted a primary healthcare center for dyspnea, fatigue, and/or peripheral edema. One cardiologist evaluated the patients in terms of history, physical examination, functional capacity, electrocardiography, and suspicion of heart failure. Plasma N-terminal proBNP was measured by an in-house RIA. An ejection fraction ≤40% by Doppler echocardiography was regarded as reduced cardiac function. Abnormal diastolic function was defined as an abnormal mitral inflow defined as reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio), or as abnormal pulmonary venous flow pattern.

    Results: Patients with impaired functional capacity, impaired systolic function, and/or impaired renal function had significantly increased N-terminal proBNP concentrations. By multiple regression analysis, N-terminal proBNP concentrations were also influenced by ischemic heart disease, cardiac enlargement, and certain medications but not by increased creatinine. No gender differences were observed. Patients with isolated diastolic dysfunction attributable to relaxation abnormali-ties had lower concentrations than those with normal cardiac function, whereas those with pseudonormal E/A ratios or restrictive filling patterns had higher concentrations.

    Conclusions: Plasma N-terminal proBNP concentrations increase as a result of impaired systolic function, age, impaired renal function, cardiac ischemia and enlargement, and certain medications. Values are high in diastolic dysfunction with pseudonormal patterns, but not in patients with relaxation abnormalities. An increase in plasma N-terminal proBNP might be an earlier sign of abnormal cardiac function than abnormalities identified by currently used echocardiographic measurements.

  • 32.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Rahmqvist, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics.
    Paulsson, Thomas
    AstraZeneca Sverige AB.
    Levin, Lars-Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics.
    Quality-adjusted life year weights among elderly patients with heart failure2008In: European journal of heart failure, ISSN 1388-9842, Vol. 10, no 10, p. 1033-1039Article in journal (Refereed)
    Abstract [en]

    Background

    When assessing health-related quality of life (HRQoL) in elderly patients with heart failure (HF), the process of obtaining quality-adjusted life year (QALY) weights is generally complicated and time-consuming.

    Aim

    To evaluate whether information regarding HRQoL and QALY weights can be derived directly from the established and widely used New York Heart Association (NYHA) functional classification system.

    Methods

    NYHA functional status was assessed independently both by the individual patients and by the examining cardiologist in 323 elderly patients with symptoms of HF recruited from primary care. HRQoL was evaluated using the SF-36 questionnaire and a time trade-off (TTO) scenario. The TTO technique generates direct QALY weights.

    Results

    Both the TTO technique and SF-36 values demonstrated a statistically significant correlation with NYHA functional status. The TTO values also correlated with all SF-36 dimensions. Increasing impairment was associated with statistically significant drops in both SF-36 values and TTO-based QALY weights. For patients in NYHA classes I–IV the QALY weights were 0.77, 0.68, 0.61, and 0.50, respectively. Thus in elderly patients, symptoms of HF have a major impact on perceived quality of life.

    Conclusion

    The results of the present study show that QALY weights, an important instrument in the health economic evaluation of treatment strategies, can be derived directly from NYHA classification in elderly HF patients.

  • 33.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Svensson, E.
    Swedish Defence Research Agency, Division of Command and Control Systems, Department of Man-System Interaction, Linköping, Sweden.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Natriuretic Peptide Biomarkers as Information Indicators in Elderly Patients With Possible Heart Failure Followed Over Six Years: A Head-to-Head Comparison of Four Cardiac Natriuretic Peptides2007In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 13, no 6, p. 452-461Article in journal (Refereed)
    Abstract [en]

    Background: Little is known about the differences between natriuretic peptides used to evaluate elderly patients with heart failure. The aim of the study was to evaluate the information and the power to predict cardiovascular mortality derived from an analysis of cardiac natriuretic peptides from the same study population and at the same time. Methods and Results: In all, 415 elderly patients (age 65-82 years) in primary health care were evaluated and followed for 6 years. All patients had symptoms of heart failure and were examined by a cardiologist. An electrocardiogram and chest x-rays were taken, and the systolic and diastolic functions were assessed using Doppler echocardiography. Brain natriuretic peptide (BNP), N-terminal proBNP, atrial natriuretic peptide (ANP), and N-terminal proANP were analyzed. All 4 peptides were associated with age, and only 1 of them showed any gender difference. Three of the 4 peptides (not ANP) provided important information for identifying patients with impaired systolic function and diastolic dysfunction (pseudonormal or restrictive filling pattern), and for assessing the risk of cardiovascular death. Conclusions: Cardiac natriuretic peptides are useful tools for evaluating elderly patients with heart failure. Three of the 4 peptides were very similar. ANP exhibits inferior properties and cannot be recommended in clinical practice. © 2007 Elsevier Inc. All rights reserved.

  • 34.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gender difference in adiponectin associated with cardiovascular mortality2015In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 16, no 9Article in journal (Refereed)
    Abstract [en]

    Background: It is important to identify cardiovascular diseases in patients at high risk. To include genetics into routine cardiological patients has therefore been discussed recently. We wanted to evaluate the association between high-molecular weight adiponectin and cardiovascular risk, and secondly in the same population evaluate if specific genotype differences regarding risk could be observed, and thirdly if gender differences could be seen. Method: Four hundred seventy-six elderly participants recruited from a rural community were included. All participants underwent a clinical examination, echocardiography, and blood sampling and the single nucleotide polymorphism (SNP) (rs266729) of adiponectin was analysed. Follow-up time was 6.7 years. Results: Those with high serum concentration of adiponectin had a more 2 fold increased cardiovascular risk, and it might be that females exhibits even higher risk where a more than 5 fold increased risk could be seen. The result could be demonstrated even in a multivariate model adjusting for well-known clinical risk factors. However, as the sample size was small the gender differences should be interpreted with caution. In the genotype evaluation the C/C carriers of the female group had a more than 9-fold increased risk of cardiovascular mortality, however the confidence interval was wide. Such genotype difference could not be found in the male group. Conclusion: High level of adiponectin was associated with increased cardiovascular risk. Also a gender difference in the genotype evaluation could be seen where the C/C carriers obtained higher risk in the female group but not in the male group. Thus, in order to identify patients at risk early, genetic analyses may add to the armamentarium used in the clinical routine. However, information should be regarded as hypothesis generating as the sample size was small and should stimulate further research in individualized cardiovascular prevention and treatment.

  • 35.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Eriksson, Per
    Karolinska Institute, Stockholm.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Debasso, Rachel
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Gender-Specific Association of the Plasminogen Activator Inhibitor-1 4G/5G Polymorphism With Central Arterial Blood Pressure2011In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, no 7, p. 802-808Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. METHODS We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. RESULTS The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). CONCLUSIONS Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

  • 36.
    Björck, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Persson, Karin
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Rundkvist, Louise
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Hamsten, A
    Karolinska Institute.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, P
    Karolinska Institute, Stockholm.
    Association of genetic variation on chromosome 9p21.3 and arterial stiffness2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 265, no 3, p. 373-381Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies have consistently reported associations between a region on chromosome 9p21.3 and a broad range of vascular diseases, such as coronary artery disease (CAD), aortic and intracranial aneurysms and type-2 diabetes (T2D). However, clear associations with intermediate phenotypes have not been described so far. To shed light on a possible influence of this chromosomal region on arterial wall integrity, we analysed associations between single nucleotide polymorphisms (SNPs) and degree of stiffness of the abdominal aorta in elderly individuals.

    A total of 400 subjects, 212 men and 188 women, aged 70-88 years were included. Arterial stiffness was examined at the midpoint between the renal arteries and the aortic bifurcation. Two CAD- and aneurysm-associated SNPs (rs10757274 and rs2891168) and one T2D-associated SNP (rs1081161) within the 9p21.3 region were genotyped. Aortic compliance and distensibility coefficients were higher in carriers of the rs10757274G and rs2891168G alleles in men reflecting a decrease in aortic stiffness. Adjustment for age and mean arterial pressure had no effect on these associations. The two SNPs were not associated with intima-media thickness or lumen diameter of the abdominal aorta. There were no associations between the rs10811661 SNP and any measure of aortic stiffness.

    Impaired mechanical properties of the arterial wall may explain the association between chromosome 9p21.3 polymorphisms and vascular disease.

  • 37. Boquist, Lennart
    et al.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ca2+ transport in isolated mouse liver mitochondria; role of reductive carboxylation and citrate?1986In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 7, no 4, p. 275-282Article in journal (Refereed)
    Abstract [en]

    The uptake of Ca2+ in isolated mouse liver mitochondria respiring on succinate in the presence of rotenone and added Pi, was inhibited by dibucaine, fluorocitrate, p-hydroxymercuribenzoate (PMB), malonate, palmitoyl-CoA, succinyl-CoA and trifluoroperazine. The release of accumulated Ca2+ was stimulated by arsenite, malonate, PMB, palmitoyl-CoA and succinyl-CoA, whereas the release was inhibited by dibucaine, fluorocitrate, trifluoroperazine, and by oligomycin, especially in the presence of ADP. The pyridine nucleotides were oxidized in mitochondria incubated with PMB. The observations suggest a possible contributory role of reductive carboxylation for the uptake of Ca2+, and a possible role of citrate for the retention of Ca2+ in isolated mouse liver mitochondria.

  • 38. Boquist, Lennart
    et al.
    Boquist, S
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Mitochondrial changes and associated alterations induced in mice by streptozotocin administered in vivo and in vitro.1987In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 3, no 4, p. 179-190Article in journal (Refereed)
    Abstract [en]

    Isolated mouse liver mitochondria incubated with streptozotocin showed decreased rate and extent of Ca2+ uptake, and, dependent on the concentration of streptozotocin and the addition of alpha-ketoglutarate, glutamate, fluorocitrate or guanosine 5'-triphosphate, the retention of Ca2+ was either increased or decreased. Similar observations were made in liver mitochondria incubated with succinyl-CoA. In mitochondria isolated from the kidneys and islets of mice injected with streptozotocin, with and without additional injections of glucose and/or glucagon, the rate and extent of Ca2+ uptake were reduced and the release of accumulated Ca2+ was stimulated. Electron microscopy and X-ray microanalysis showed dislocation of Ca2+-containing precipitates from the mitochondria to the cytosol, and stereology disclosed increased mitochondrial volume in the B cells of streptozotocin-treated mice. State 3 and state 4 respiration with NAD-linked substrates was inhibited, but succinate oxidation was unaffected, in mitochondria isolated from the kidneys of mice treated with streptozotocin. In the kidneys of streptozotocin-injected mice, the concentration of succinyl-CoA was increased, that of citrate and guanosine 5'-triphosphate was decreased, that of glucose 6-phosphate, fructose 6-phosphate and fructose 1,6-diphosphate was unaffected, and the metabolite concentration ratios suggested increased mitochondrial [NAD+]/[NADH] ratio and decreased cytoplasmic [NAD+]/[NADH] ratio. It is suggested as a new hypothesis that the cytotoxicity and the diabetogenicity of streptozotocin are dependent on inhibited citric acid cycle enzyme activity (primarily that of succinyl-CoA synthetase and citrate synthetase) with altered metabolite concentrations, leading to impairment of the mitochondrial uptake of Ca2+ and the activation of the pyruvate, isocitrate and alpha-ketoglutarate dehydrogenases.

  • 39.
    Broström, Anders
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Department of Nursing, School of Health and Welfare, Jönköping University, Sweden.
    Wahlin, Ake
    Institute of Gerontology, School of Health and Welfare, Jönköping University, Sweden.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ulander, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology.
    Johansson, Peter
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Sex-Specific Associations Between Self-reported Sleep Duration, Cardiovascular Disease, Hypertension, and Mortality in an Elderly Population.2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 5, p. 422-428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both short and long sleep durations have been associated to increased mortality. Knowledge about sex-specific differences among elderly regarding associations between sleep duration, cardiovascular health, and mortality is sparse.

    OBJECTIVE: The aims of this study are to examine the association between self-reported sleep duration and mortality and to investigate whether this association is sex specific and/or moderated by cardiovascular morbidity, and also to explore potential mediators of sleep duration effects on mortality.

    METHODS: A population-based, observational, cross-sectional design with 6-year follow-up with mortality as primary outcome was conducted. Self-rated sleep duration, clinical examinations, echocardiography, and blood samples (N-terminal fragment of proBNP) were collected. A total of 675 persons (50% women; mean age, 78 years) were divided into short sleepers (≤6 hours; n = 231), normal sleepers (7-8 hours; n = 338), and long sleepers (≥9 hours; n = 61). Data were subjected to principal component analyses. Cardiovascular disease (CVD) and hypertension factors were extracted and used as moderators and as mediators in the regression analyses.

    RESULTS: During follow-up, 55 short sleepers (24%), 68 normal sleepers (20%), and 21 long sleepers (34%) died. Mediator analyses showed that long sleep was associated with mortality in men (hazard ratio [HR], 1.8; P = .049), independently of CVD and hypertension. In men with short sleep, CVD acted as a moderator of the association with mortality (HR, 4.1; P = .025). However, when using N-terminal fragment of proBNP, this effect became nonsignificant (HR, 3.1; P = .06). In woman, a trend to moderation involving the hypertension factor and short sleep was found (HR, 4.6; P = .09).

    CONCLUSION: Short and long sleep duration may be seen as risk markers, particularly among older men with cardiovascular morbidity.

  • 40.
    Bustamante, Mariana
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Sven
    Linköping University, Department of Medical and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Atlas-based analysis of 4D flow CMR: Automated vessel segmentation and flow quantification2015In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 87Article in journal (Refereed)
    Abstract [en]

    Background: Flow volume quantification in the great thoracic vessels is used in the assessment of several cardiovascular diseases. Clinically, it is often based on semi-automatic segmentation of a vessel throughout the cardiac cycle in 2D cine phase-contrast Cardiovascular Magnetic Resonance (CMR) images. Three-dimensional (3D), time-resolved phase-contrast CMR with three-directional velocity encoding (4D flow CMR) permits assessment of net flow volumes and flow patterns retrospectively at any location in a time-resolved 3D volume. However, analysis of these datasets can be demanding. The aim of this study is to develop and evaluate a fully automatic method for segmentation and analysis of 4D flow CMR data of the great thoracic vessels. Methods: The proposed method utilizes atlas-based segmentation to segment the great thoracic vessels in systole, and registration between different time frames of the cardiac cycle in order to segment these vessels over time. Additionally, net flow volumes are calculated automatically at locations of interest. The method was applied on 4D flow CMR datasets obtained from 11 healthy volunteers and 10 patients with heart failure. Evaluation of the method was performed visually, and by comparison of net flow volumes in the ascending aorta obtained automatically (using the proposed method), and semi-automatically. Further evaluation was done by comparison of net flow volumes obtained automatically at different locations in the aorta, pulmonary artery, and caval veins. Results: Visual evaluation of the generated segmentations resulted in good outcomes for all the major vessels in all but one dataset. The comparison between automatically and semi-automatically obtained net flow volumes in the ascending aorta resulted in very high correlation (r(2) = 0.926). Moreover, comparison of the net flow volumes obtained automatically in other vessel locations also produced high correlations where expected: pulmonary trunk vs. proximal ascending aorta (r(2) = 0.955), pulmonary trunk vs. pulmonary branches (r(2) = 0.808), and pulmonary trunk vs. caval veins (r(2) = 0.906). Conclusions: The proposed method allows for automatic analysis of 4D flow CMR data, including vessel segmentation, assessment of flow volumes at locations of interest, and 4D flow visualization. This constitutes an important step towards facilitating the clinical utility of 4D flow CMR.

  • 41.
    Charitakis, Emmanouil
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Walfridsson, Ulla
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Nylander, Eva
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Strömberg, Anna
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation (SMURF): a protocol for an observational study with a randomised interventional component2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 12, article id e008723Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence of 1.5-2%. It is an independent risk factor for ischaemic stroke and is estimated to cause about 20-25% of all stroke cases. AF has a great impact on health-related quality of life (HRQoL); however, one unresolved issue related to AF is the wide variation in its symptoms.

    METHODS AND ANALYSIS: The symptom burden, metabolic profile, ultrasound findings, rhythm, neurohormonal activation, haemodynamics and HRQoL in patients with AF (Symptom burden, Metabolic profile, Ultrasound findings, Rhythm, neurohormonal activation, haemodynamics and health-related quality of life in patients with atrial Fibrillation, SMURF) study is a prospective observational, cohort study, with a randomised interventional part. The aim of the study is to investigate, in patients with AF, the relationship between symptom burden and metabolic aspects, atrial function and different neurohormones, and the effect of radiofrequency ablation (RFA). The interventional part of the study will give an insight into the neurohormonal and intracardiac pressure changes directly after initiation of AF. Consecutive patients with symptomatic AF accepted for treatment with RFA for the first time at Linköping University Hospital are eligible for participation. The enrolment started in January 2012, and a total of 200 patients are to be included into the study, with 45 of them being enrolled into the interventional study with initiation of AF. The sample size of the interventional study is based on a small pilot study with 5 patients induced to AF while 2 served as controls. The results indicated that, in order to find a statistically significant difference, there was a need to include 28 patients; for safety reasons, 45 patients will be included.

    ETHICS AND DISSEMINATION: The SMURF study is approved by the Regional Ethical Review Board at the Faculty of Health Sciences, Linköping, Sweden. The results will be presented through peer-review journals and conference presentation.

    TRIAL REGISTRATION NUMBER: NCT01553045; Pre-results.

  • 42.
    Chisalita, Ioana Simona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population: impact of ACE inhibitors2011In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 165, no 6, p. 891-898Article in journal (Refereed)
    Abstract [en]

    Objective: There are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors. Design and methods: A total of 851 persons aged 66-81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years. Results and conclusion: Patients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) less than40% compared with EF greater than= 40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P less than 0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (P=0.03). This was significant after adjustment for well-known CV risk factors and ACE inhibitors (P=0.03). Conclusions: Our results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality.

  • 43.
    Chisalita, Ioana Simona
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Health Care in Linköping.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Proinsulin and IGFBP-1 predicts mortality in an elderly population2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 174, no 2, p. 260-267Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    High IGFBP-1 in elderly subjects is related to all-cause and cardiovascular (CV) mortality. We studied the relation of IGFBP-1 to cardiometabolic risk factors and cardiovascular and all-cause mortality, and also the impact of proinsulin and insulin on this association in an unselected elderly primary health care population.

    HYPOTHESIS:

    Our hypothesis was that proinsulin and insulin may have an impact on the association of high IGFBP-1 levels with all-cause and CV-mortality in elderly.

    DESIGN, SETTING AND PARTICIPANTS:

    A cross-sectional and prospective study was carried out in a rural Swedish population. 851 persons aged 66-81 years were evaluated by medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples, and were followed prospectively for up to 12 years.

    RESULTS:

    At baseline, in a multivariate analysis, IGFBP-1 was associated with gender, N-terminal proBNP (NT pro-BNP), blood glucose, body mass index (BMI), insulin and proinsulin, estimated glomerular filtration rate (eGFR) and haemoglobin (Hb). During the follow-up period there were 230 deaths (27%), of which 134 (16%) were due to CV mortality. When divided into tertiles there was a significant difference for CV mortality and all-cause mortality between tertiles of IGFBP-1 and proinsulin. For insulin there was a significant difference only for all-cause mortality. After adjustment for well-known risks factors, proinsulin and IGFBP-1 had significant impact on all-cause mortality but only proinsulin on CV mortality.

    CONCLUSION:

    Only proinsulin is an independent predictor for both all-cause mortality and CV mortality when comparing IGFBP-1, insulin, and proinsulin as prognostic biomarkers for CV and all-cause mortality in an elderly population.

  • 44.
    Dahlström, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Alehagen, Urban
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Natriuretic peptides as diagnostic tool. The analysis should be a routine in heart failure diagnosis.2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, p. 927-929Article in journal (Other academic)
    Abstract [en]

       

  • 45.
    Eckerdal, O
    et al.
    University of Umeå, Umeå.
    Ahlqvist, J
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Wing, K
    Length dimensions and morphologic variations of the external bony auditory canal. A radiographic and histologic investigation.1978In: Dento-Maxillo-Facial Radiology, ISSN 0250-832X, E-ISSN 1476-542X, Vol. 7, no 1, p. 43-50Article in journal (Refereed)
    Abstract [en]

    Autopsy material comprising a total of 58 specimes of the temporal bone and the proximal part of the mandible was investigated tomographically and by microtome in comparative layers. Microradiographs and histologic sections were used as the main sources of information to determine the length dimensions of the different parts of the external auditory canal. The morphology and its developmental variations are compared and described. The diagnostic implications are discussed. In the authors' opinion, tomography is the method of choice to illustrate the morphologic properties of the external auditory canal. It is suggested that when the tomographic image reveals morphologic developmental or pathologic defects which give rise to problematic diagnosis, a control examination of the contralateral side should be performed.

  • 46.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, p. 558-565Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

    MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

    RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

    CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

  • 47.
    Goetze, Jens P.
    et al.
    Department of Clinical Biochemistry, University of Copenhagen, Copenhagen, Denmark.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Flyvbjerg, Allan
    Aarhus University Hospital, Aarhus, Denmark.
    Rehfeld, Jens
    Aarhus University Hospital, Aarhus, Denmark.
    Comment: Making sense of chromogranin A in heart disease2013In: The Lancet Diabetes & Endocrinology, ISSN 2213-8587, Vol. 1, no 1, p. 7-8Article in journal (Other academic)
    Abstract [en]

    n/a

  • 48.
    Goetze, Jens P
    et al.
    Rigshospitalet, University of Copenhagen, Denmark .
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Flyvbjerg, Allan
    Aarhus University Hospital, Denmark.
    Rehfeld, Jens F
    Rigshospitalet, University of Copenhagen, Denmark .
    Chromogranin A as a biomarker in cardiovascular disease2014In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 8, no 1, p. 133-140Article, review/survey (Refereed)
    Abstract [en]

    Chromogranin A is known as an important marker of neuroendocrine tumors. In cardiovascular medicine, however, chromogranin A measurement has only recently gained interest, since increased concentrations in the circulation are associated with risk of clinical worsening and death in patients with acute coronary syndromes or chronic heart failure. In this article, we summarize the current clinical data on chromogranin A as a biomarker in cardiovascular disease from high-risk conditions; for example, obesity, hypertension and diabetes, to overt heart failure. Biological activity of the various chromogranin A fragments, including the intact precursor itself, will not be covered in the present review. Instead, we highlight the complexity of chromogranin A as a plasma marker, where the protein is extensively and variably processed to a plethora of peptide fragments. Current immunological methods for clinical measurement differ dramatically with respect to both epitope choice and clinical validation.

  • 49.
    Goetze, Jens P
    et al.
    Rigshospitalet, University of Copenhagen, Denmark .
    Hilsted, Linda M
    Rigshospitalet, University of Copenhagen, Denmark .
    Rehfeld, Jens F
    Rigshospitalet, University of Copenhagen, Denmark .
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Plasma chromogranin A is a marker of death in elderly patients presenting with symptoms of heart failure2014In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 3, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    Cardiovascular risk assessment remains difficult in elderly patients. We examined whether chromogranin A (CgA) measurement in plasma may be valuable in assessing risk of death in elderly patients with symptoms of heart failure in a primary care setting. A total of 470 patients (mean age 73 years) were followed for 10 years. For CgA plasma measurement, we used a two-step method including a screening test and a confirmative test with plasma pre-treatment with trypsin. Cox multivariable proportional regression and receiver-operating curve (ROC) analyses were used to assess mortality risk. Assessment of cardiovascular mortality during the first 3 years of observation showed that CgA measurement contained useful information with a hazard ratio (HR) of 5.4 (95% CI 1.7–16.4) (CgA confirm). In a multivariate setting, the corresponding HR was 5.9 (95% CI 1.8–19.1). When adding N-terminal proBNP (NT-proBNP) to the model, CgA confirm still possessed prognostic information (HR: 6.1; 95% CI 1.8–20.7). The result for predicting all-cause mortality displayed the same pattern. ROC analyses in comparison to NT-proBNP to identify patients on top of clinical variables at risk of cardiovascular death within 5 years of follow-up showed significant additive value of CgA confirm measurements compared with NT-proBNP and clinical variables. CgA measurement in the plasma of elderly patients with symptoms of heart failure can identify those at increased risk of short- and long-term mortality.

  • 50.
    Goetze, Jens P.
    et al.
    University of Copenhagen, Denmark; Aarhus University, Denmark.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark.
    Alehagen, Urban
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Cholecystokinin in plasma predicts cardiovascular mortality in elderly females2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 209, p. 37-41Article in journal (Refereed)
    Abstract [en]

    Background: Cholecystokinin (CCK) and gastrin are related gastrointestinal hormones with documented cardiovascular effects of exogenous administration. It is unknown whether measurement of endogenous CCK or gastrin in plasma contains information regarding cardiovascular mortality. Methods: Mortality risk was evaluated using Cox proportional hazard regression and Kaplan-Meier analyses. Elderly patients in a primary care setting with symptoms of cardiac disease, i.e. shortness of breath, peripheral edema, and/or fatigue, were evaluated (n = 470). Primary care patients were followed for 13 years (from 1999); the 5-year all-cause and cardiovascular mortality was used as end point. Results: In univariate analysis, patients in the 4th CCK quartile had an increased risk of 5-year cardiovascular mortality (hazard ratio 3.9, 95% confidence interval: 2.1-7.0, p &lt; 0.0001). In multivariate analysis including established factors associated with cardiovascular mortality, CCK concentrations in the 4th quartile were still associated with increased 5-year cardiovascular mortality risk (HR 3.1, 95% C.I.: 1.7-5.7, p = 0.0004), even when including 4th quartile NT-proBNP concentrations in the same model. We observed a marked difference between the genders, where CCK concentrations in the 4th quartile were associated with a higher 5-year cardiovascular mortality in female patients (HR 8.99, 95% C.I.: 3.49-102.82, p = 0.0007) compared to men (1.47, 95% C.I.: 0.7-3.3, p = 0.35). In contrast, no significant information was obtained from 4th quartile gastrin concentrations on 5-year cardiovascular mortality risk. Conclusions: CCK in plasma is an independent marker of cardiovascular mortality in elderly female patients. The study thus introduces measurement of plasma CCK in gender-specific cardiovascular risk assessment. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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