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1.	Nunez, Julio, et al. (författare) Congestion in heart failure: a circulating biomarker-based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology 2022 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:10, s. 1751-1766 Forskningsöversikt (refereegranskat)abstract Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.
2.	de Boer, Rudolf A, et al. (författare) Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction 2011 Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 43:1, s. 60-68 Tidskriftsartikel (refereegranskat)abstract AIMS: galectin-3 is an emerging biomarker which has been studied in relatively small heart failure (HF) cohorts with predominantly systolic HF. We studied the prognostic value of base-line galectin-3 in a large HF cohort, with preserved and reduced left ventricular ejection fraction (LVEF), and compared this to other biomarkers. METHODS: we studied 592 HF patients who had been hospitalized for HF and were followed for 18 months. The primary end-point was a composite of all-cause mortality and HF hospitalization. RESULTS: a doubling of galectin-3 levels was associated with a hazard ratio (HR) of 1.97 (1.62-2.42) for the primary outcome (P < 0.001). After correction for age, gender, BNP, eGFR, and diabetes the HR was 1.38 (1.07-1.78; P = 0.015). Galectin-3 levels were correlated with higher IL-6 and CRP levels (P < 0.002). Changes of galectin-3 levels after 6 months did not add prognostic information to the base-line value (n = 291); however, combining plasma galectin-3 and BNP levels increased prognostic value over either biomarker alone (ROC analysis, P < 0.05). The predictive value of galectin-3 was stronger in patients with preserved LVEF (n = 114) compared to patients with reduced LVEF (P < 0.001). CONCLUSIONS: galectin-3 is an independent marker for outcome in HF and appears to be particularly useful in HF patients with preserved LVEF.
3.	McMurray, John J. V., et al. (författare) ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 : The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC 2012 Ingår i: European Journal of Heart Failure. - : Oxford University Press. - 1388-9842 .- 1879-0844. ; 14:8, s. 803-869 Tidskriftsartikel (refereegranskat)
4.	Metra, Marco, et al. (författare) y Effects of Serelaxin in Patients with Acute Heart Failure 2019 Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:8, s. 716-726 Tidskriftsartikel (refereegranskat)abstract BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.) In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.
5.	Seferovic, Petar M., et al. (författare) Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology 2019 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:10, s. 1169-1186 Tidskriftsartikel (refereegranskat)abstract The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.
6.	Teerlink, John R., et al. (författare) Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure 2021 Ingår i: New England Journal of Medicine. - Waltham, MA, United States : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:2, s. 105-116 Tidskriftsartikel (refereegranskat)abstract Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo. Background The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. Methods We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. Results During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. Conclusions Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, ; EudraCT number, 2016-002299-28.)
7.	Teerlink, John R., et al. (författare) Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction: GALACTIC-HF baseline characteristics and comparison with contemporary clinical trials 2020 Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:11, s. 2160-2171 Tidskriftsartikel (refereegranskat)abstract Aims The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial. Here we describe the baseline characteristics of participants in GALACTIC-HF and how these compare with other contemporary trials. Methods and results Adults with established HFrEF, New York Heart Association (NYHA) functional class >= II, ejection fraction <= 35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic-guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non-white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N-terminal pro-B-type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC-HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m(2) (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions GALACTIC-HF enrolled a well-treated, high-risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation.
8.	Tromp, Jasper, et al. (författare) Biomarker Profiles in Heart Failure Patients With Preserved and Reduced Ejection Fraction 2017 Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 6:4 Tidskriftsartikel (refereegranskat)abstract Background-Biomarkers may help us to unravel differences in the underlying pathophysiology between heart failure (HF) patients with a reduced ejection fraction (HFrEF) and a preserved ejection fraction (HFpEF). Therefore, we compared biomarker profiles to characterize pathophysiological differences between patients with HFrEF and HFpEF. Methods and Results-We retrospectively analyzed 33 biomarkers from different pathophysiological domains (inflammation, oxidative stress, remodeling, cardiac stretch, angiogenesis, arteriosclerosis, and renal function) in 460 HF patients (21% HFpEF, left ventricular ejection fraction amp;gt;= 45%) measured at discharge after hospitalization for acute HF. The association between these markers and the occurrence of all-cause mortality and/or HF-related rehospitalizations at 18 months was compared between patients with HFrEF and HFpEF. Patients were 70.6 +/- 11.4 years old and 37.4% were female. Patients with HFpEF were older, more often female, and had a higher systolic blood pressure. Levels of high-sensitive C-reactive protein were significantly higher in HFpEF, while levels of pro-atrial-type natriuretic peptide and N-terminal pro-brain natriuretic peptide were higher in HFrEF. Linear regression followed by network analyses revealed prominent inflammation and angiogenesis-associated interactions in HFpEF and mainly cardiac stretch-associated interactions in HrEF. The angiogenesis-specific marker, neuropilin and the remodeling-specific marker, osteopontin were predictive for all-cause mortality and/or HF-related rehospitalizations at 18 months in HFpEF, but not in HFrEF (P for interaction amp;lt;0.05). Conclusions-In HFpEF, inflammation and angiogenesis- mediated interactions are predominantly observed, while stretch-mediated interactions are found in HFrEF. The remodeling marker osteopontin and the angiogenesis marker neuropilin predicted outcome in HFpEF, but not in HFrEF.
9.	Adler, Eric D., et al. (författare) Improving risk prediction in heart failure using machine learning 2020 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:1, s. 139-147 Tidskriftsartikel (refereegranskat)abstract Background: Predicting mortality is important in patients with heart failure (HF). However, current strategies for predicting risk are only modestly successful, likely because they are derived from statistical analysis methods that fail to capture prognostic information in large data sets containing multi-dimensional interactions. Methods and results: We used a machine learning algorithm to capture correlations between patient characteristics and mortality. A model was built by training a boosted decision tree algorithm to relate a subset of the patient data with a very high or very low mortality risk in a cohort of 5822 hospitalized and ambulatory patients with HF. From this model we derived a risk score that accurately discriminated between low and high-risk of death by identifying eight variables (diastolic blood pressure, creatinine, blood urea nitrogen, haemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). This risk score had an area under the curve (AUC) of 0.88 and was predictive across the full spectrum of risk. External validation in two separate HF populations gave AUCs of 0.84 and 0.81, which were superior to those obtained with two available risk scores in these same populations. Conclusions: Using machine learning and readily available variables, we generated and validated a mortality risk score in patients with HF that was more accurate than other risk scores to which it was compared. These results support the use of this machine learning approach for the evaluation of patients with HF and in other settings where predicting risk has been challenging.
10.	de Boer, Rudolf A, et al. (författare) The WAP four-disulfide core domain protein HE4 : a novel biomarker for heart failure. 2013 Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1787 .- 2213-1779. ; 1:2, s. 164-169 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF).BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment.METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization.RESULTS: HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model.CONCLUSIONS: HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
11.	Hogenhuis, Jochem, et al. (författare) Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure. 2007 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 9:8, s. 787-94 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.
12.	Huzen, Jardi, et al. (författare) Telomere length and psychological well-being in patients with chronic heart failure. 2010 Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 39:2, s. 223-7 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: psychological stress and depressive symptoms have been implicated with accelerated ageing and increased progression of diseases. Shorter telomere length indicates a more advanced biological age. It is unknown whether psychological well-being is associated with telomere length in patients with the somatic condition of chronic heart failure (CHF). DESIGN: a cross-sectional analysis was used. SETTING: patients were admitted to the hospital with signs and symptoms of CHF. OBJECTIVE: the study aimed to assess the association between telomere length and psychological well-being in patients with CHF. METHODS: telomere length was determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association functional class II to IV CHF. We evaluated the perceived mental health by the validated RAND-36 questionnaire. Depressive symptoms were assessed by the Centre for Epidemiologic Studies Depression scale (CES-D), and the presence of type D personality was evaluated by the DS14. RESULTS: a lower perceived mental health on the RAND-36 score was associated with shorter telomere length. Adjustment for age and gender did not change our findings (standardised beta, 0.11; P-value, 0.002). Telomere length was not associated with the CES-D or DS14 score. CONCLUSION: decreased perceived mental health is associated with shorter leukocyte telomere length in patients with CHF. Future work should determine whether psychological stress accelerates biological ageing.
13.	Kleijn, Lennaert, et al. (författare) Inflammation and anaemia in a broad spectrum of patients with heart failure 2012 Ingår i: Heart. - : BMJ Publishing Group. - 1355-6037 .- 1468-201X. ; 98:16, s. 1237-1241 Tidskriftsartikel (refereegranskat)abstract AIMS: Anaemia in heart failure (HF) is associated with a poor prognosis. Although inflammation is assumed to be an important cause of anaemia, the association between anaemia and inflammatory markers in patients with HF has not been well established.METHODS: Data from a multicentre randomised clinical trial, in which patients were eligible if they were >18 years of age and admitted for HF (New York Heart Association II-IV), were used. In a subset of 326 patients, haemoglobin (Hb), haematocrit, high sensitivity C-reactive protein (hsCRP), interleukin-(IL) 6, soluble tumour necrosis factor receptor (sTNFR)-1 and erythropoietin (Epo) were measured at discharge and the primary endpoint was all-cause mortality. Follow-up was 18 months.RESULTS: Anaemia (Hb <13 g/dl (men) and <12 g/dl (women)) was present in 40% (130/326) of the study population. Median levels of IL-6, hsCRP and sTNFR-1 were significantly higher in anaemic patients than in non-anaemic patients. Logistic regression demonstrated that each increase in hsCRP values (OR 1.58 per SD log hsCRP; 95% CI 1.09 to 2.29; p=0.016) and each increase in sTNFR-1 values (OR 1.62 per SD log sTNFR-1; 95% CI 1.24 to 2.11; p<0.001) were independently associated with anaemia. Epo (HR 1.31 per log Epo; 95% CI 1.01 to 1.69; p=0.041) and sTNFR-1 (HR 1.47 per log sTNFR-1; 95% CI 1.16 to 1.86; p=0.001) levels were independently associated with outcome.CONCLUSION: Anaemia is present in 40% of patients hospitalised for HF and is independently associated with inflammation.
14.	Liu, Licette C Y, et al. (författare) Vitamin D status and outcomes in heart failure patients 2011 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 13:6, s. 619-625 Tidskriftsartikel (refereegranskat)abstract AIMS: Vitamin D status has been implicated in the pathophysiology of heart failure (HF). The aims of this study were to determine whether a low vitamin D status is associated with prognosis in HF and whether activation of the renin-angiotensin system (RAS) and inflammatory markers could explain this potential association. METHODS AND RESULTS: We measured 25-hydroxy-vitamin D (25(OH)D), plasma renin activity (PRA), interleukin-6 (IL-6), C-reactive protein (CRP), and the incidence of death or HF rehospitalization in 548 patients with HF. Median age was 74 (64-80) years, left ventricular ejection fraction was 30% (23-42), and mean follow-up was 18 months. Low 25(OH)D levels were associated with female gender (P< 0.001), higher age (P= 0.002), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (P< 0.001). Multivariable linear regression analysis showed that PRA (P= 0.048), and CRP levels (P= 0.006) were independent predictors of 25(OH)D levels. During follow-up, 155 patients died and 142 patients were rehospitalized. Kaplan-Meier analysis showed that lower 25(OH)D concentration was associated with an increased risk for the combined endpoint (all-cause mortality and HF rehospitalization; log rank test P= 0.045) and increased risk for all-cause mortality (log rank test P= 0.014). After adjustment in a multivariable Cox regression analysis, low 25(OH)D concentration remained independently associated with an increased risk for the combined endpoint [hazard ratio (HR) 1.09 per 10 nmol/L decrease; 95% confidence interval (CI) 1.00-1.16; P= 0.040] and all-cause mortality (HR 1.10 per 10 nmol/L decrease; 95% CI 1.00-1.22; P= 0.049). CONCLUSION: A low 25(OH)D concentration is associated with a poor prognosis in HF patients. Activation of the RAS and inflammation may confer the adverse effects of low vitamin D levels.
15.	Maisel, Alan, et al. (författare) Effect of Spironolactone on 30-Day Death and Heart Failure Rehospitalization (from the COACH Study) 2014 Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 114:5, s. 737-742 Tidskriftsartikel (refereegranskat)abstract The aim of our study is to investigate the effect of spironolactone on 30-day outcomes in patients with acute heart failure (AHF) and the association between treatment and outcomes stratified by biomarkers. We conducted a secondary analysis of the biomarker substudy of the multicenter COACH (Co-ordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure) trial involving 534 AHF patients for 30-day mortality and HF rehospitalizations. Spironolactone therapy was initiated and terminated at the discretion of the treating physician; 30-day outcomes were compared between patients who were treated with spironolactone and those who were not. Outcomes with spironolactone therapy. were explored based on N-terminal pro-B-type natriuretic peptide, ST2, galectin-3, and creatinine levels. Spironolactone was prescribed to 297 (55.6%) patients at discharge (158 new and 139 continued). There were 19 deaths and 30 HF rehospitalizations among 46 patients by 30 days. Patients discharged on spironolactone had significantly less 30-day event (hazard ratio 0.538, p = 0.039) after adjustment for multiple risk factors. Initiation of spironolactone in patients who were not on spironolactone before admission was associated with a significant reduction in event rate (hazard ratio 0.362, p = 0.027). The survival benefit of spironolactone was more prominent in patient groups with elevations of creatinine, N-terminal pro B-type natriuretic peptide, ST2, or galectin-3. In conclusion, AHF patients who received spironolactone during hospitalization had significantly fewer 30-day mortality and HF rehospitalizations, especially in high-risk patients.
16.	McMurray, John J. V., et al. (författare) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012 : The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC 2012 Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 33:14, s. 1787-1847 Tidskriftsartikel (refereegranskat)
17.	Meijers, Wouter C., et al. (författare) Biomarkers and low risk in heart failure. Data from COACH and TRIUMPH 2015 Ingår i: European Journal of Heart Failure. - : WILEY-BLACKWELL. - 1388-9842 .- 1879-0844. ; 17:12, s. 1271-1282 Tidskriftsartikel (refereegranskat)abstract AimTraditionally, risk stratification in heart failure (HF) emphasizes assessment of high risk. We aimed to determine if biomarkers could identify patients with HF at low risk for death or HF rehospitalization. Methods and resultsThis analysis was a substudy of The Coordinating Study Evaluating Outcomes of Advising and Counselling in Heart Failure (COACH) trial. Enrolment of HF patients occurred before discharge. We defined low risk as the absence of death and/or HF rehospitalizations at 180days. We tested a diverse group of 29 biomarkers on top of a clinical risk model, with and without N-terminal pro-B-type natriuretic peptide (NT-proBNP), and defined the low risk biomarker cut-off at the 10th percentile associated with high positive predictive value. The best performing biomarkers together with NT-proBNP and cardiac troponin I (cTnI) were re-evaluated in a validation cohort of 285 HF patients. Of 592 eligible COACH patients, the mean (SD) age was 71 (+/- 11) years and median (IQR) NT-proBNP was 2521 (1301-5634) pg/mL. Logistic regression analysis showed that only galectin-3, fully adjusted, was significantly associated with the absence of events at 180days (OR 8.1, 95% confidence interval 1.06-50.0, P=0.039). Galectin-3, showed incremental value when added to the clinical risk model without NT-proBNP (increase in area under the curve from 0.712 to 0.745, P=0.04). However, no biomarker showed significant improvement by net reclassification improvement on top of the clinical risk model, with or without NT-proBNP. We confirmed our results regarding galectin-3, NT-proBNP, and cTnI in the independent validation cohort. Conclusion We describe the value of various biomarkers to define low risk, and demonstrate that galectin-3 identifies HF patients at (very) low risk for 30-day and 180-day mortality and HF rehospitalizations after an episode of acute HF. Such patients might be safely discharged.
18.	Michaëlsson, Erik, et al. (författare) Myeloperoxidase Inhibition Reverses Biomarker Profiles Associated With Clinical Outcomes in HFpEF. 2023 Ingår i: JACC. Heart failure. - 2213-1787. ; 11:7, s. 775-87 Tidskriftsartikel (refereegranskat)abstract Systemic microvascular dysfunction and inflammation are postulated to play a pathophysiologic role in heart failure with preserved ejection fraction (HFpEF).This study aimed to identify biomarker profiles associated with clinical outcomes in HFpEF and investigate how inhibition of the neutrophil-derived reactive oxygen species-producing enzyme, myeloperoxidase, affects these biomarkers.Using supervised principal component analyses, the investigators assessed the associations between baseline plasma proteomic Olink biomarkers and clinical outcomes in 3 independent observational HFpEF cohorts (n=86, n=216, and n=242). These profiles were then compared with the biomarker profiles discriminating patients treated with active drug vs placebo in SATELLITE (Safety and Tolerability Study of AZD4831 in Patients With HeartFailure), a double-blind randomized 3-month trial evaluating safety and tolerability of the myeloperoxidase inhibitor AZD4831 in HFpEF (n=41). Pathophysiological pathways were inferred from the biomarker profiles by interrogation of the Ingenuity Knowledge database.TNF-R1, TRAIL-R2, GDF15, U-PAR, and ADM were the top individual biomarkers associated with heart failure hospitalization or death, and FABP4, HGF, RARRES2, CSTB, and FGF23 were associated with lower functional capacity and poorer quality of life. AZD4831 downregulated many markers (most significantly CDCP1, PRELP, CX3CL1, LIFR, VSIG2). There was remarkable consistency among pathways associated with clinical outcomes in the observational HFpEF cohorts, the top canonical pathways being associated with tumor microenvironments, wound healing signaling, and cardiac hypertrophy signaling. These pathways were predicted to be downregulated in AZD4831 relative to placebo-treated patients.Biomarker pathways that were most strongly associated with clinical outcomes were also the ones reduced by AZD4831. These results support the further investigation of myeloperoxidase inhibition in HFpEF.
19.	Tromp, Jasper, et al. (författare) Fibrosis Marker Syndecan-1 and Outcome in Patients With Heart Failure With Reduced and Preserved Ejection Fraction 2014 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 7:3, s. 457-U119 Tidskriftsartikel (refereegranskat)abstract Background-Syndecan-1 is a member of the proteoglycan family involved in cell-matrix interactions. Experimental studies showed that syndecan-1 is associated with inflammation in acute myocardial infarction and remodeling. The goal of this study was to explore the role of syndecan-1 in human heart failure (HF). Methods and Results-We analyzed plasma syndecan-1 levels in 567 patients with chronic HF. Primary end point was a composite of all-cause mortality and rehospitalization for HF at 18 months. Mean age was 71.0 +/- 11.0 years, 38% was women, and mean left ventricular ejection fraction was 32.5 +/- 14.0%. Median syndecan-1 levels were 20.1 ng/mL (interquartile range, 13.9-27.7 ng/mL). Patients with higher syndecan-1 levels were more often men, had higher N-terminal probrain-type natriuretic peptide levels, and worse renal function. Multivariable regression analyses showed a positive correlation between syndecan-1 levels and markers of fibrosis and remodeling but no correlation with inflammation markers. Interaction analysis revealed an interaction between left ventricular ejection fraction and syndecan-1 (P=0.047). A doubling of syndecan-1 was associated with an increased risk of the primary outcome in patients with HF with preserved ejection fraction (hazard ratio, 2.10; 95% confidence interval, 1.14-3.86; P=0.017) but not in patients with HF with reduced ejection fraction (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P=0.729). Finally, syndecan-1 enhanced risk classification in patients with HF with preserved ejection fraction when added to a prediction model with established risk factors. Conclusions-In patients with HF, syndecan-1 levels correlate with fibrosis biomarkers pointing toward a role in cardiac remodeling. Syndecan-1 was associated with clinical outcome in patients with HF with preserved ejection fraction but not in patients with HF with reduced ejection fraction.
20.	Tromp, Jasper, et al. (författare) N-terminal pro-B-type natriuretic peptide and prognosis in Caucasian vs. Asian patients with heart failure 2018 Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 5:2, s. 279-287 Tidskriftsartikel (refereegranskat)abstract N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the most frequently used biomarker in heart failure (HF), but its prognostic utility across ethnicities is unclear.
21.	van der Harst, Pim, et al. (författare) Possible association between telomere length and renal dysfunction in patients with chronic heart failure 2008 Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 102:2, s. 207-210 Tidskriftsartikel (refereegranskat)
22.	van der Harst, Pim, et al. (författare) Telomere length and outcome in heart failure. 2010 Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 42:1, s. 36-44 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Telomeres are causally involved in senescence. Senescence is a potential factor in the pathogenesis and progression of heart failure. In heart failure telomeres are shorter, but the prognostic value associated with telomere length has not been defined. METHODS: Telomere length was prospectively determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association (NYHA) functional class II to IV heart failure. After 18 months, we examined the association between telomere length and the predefined primary end-point: time to death or hospitalization for heart failure. RESULTS: Mean age of the patients was 71 years, 39% were women, 51% were in NYHA class II, and 49% were in class III/IV. A total of 344 patients reached the primary end-point (130 deaths and 214 hospitalizations). Patients with shorter telomeres were at an increased risk of reaching the primary end-point (hazard ratio 1.79; 95% confidence interval (CI) 1.21-2.63). In multivariate analysis shorter telomere length remained associated with a higher risk for death or hospitalization (hazard ratio, 1.74; 95% CI 1.07-2.95) after adjustment for age of heart failure onset, gender, hemoglobin, renal function, and N-terminal pro-B-type natriuretic peptide level, a history of stroke, atrial fibrillation, and diabetes. CONCLUSIONS: Shorter length of telomeres predicts the occurrence of death or hospitalization in patients with chronic heart failure.
23.	Wong, Liza S M, et al. (författare) Anaemia is associated with shorter leucocyte telomere length in patients with chronic heart failure. 2010 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:4, s. 348-53 Tidskriftsartikel (refereegranskat)abstract AIMS: Anaemia is highly prevalent and associated with poor prognosis in patients with chronic heart failure (CHF). Reduced erythroid proliferation capacity of haematopoietic progenitor cells is associated with reduced telomere length, a marker of cellular ageing. We hypothesize that short telomere length contributes to the susceptibility to develop anaemia in patients with CHF. METHODS AND RESULTS: We studied 875 CHF patients, of whom 254 (29%) fulfilled the WHO criteria of anaemia. Telomere length in DNA from peripheral leucocytes was measured with real-time quantitative polymerase chain reaction. Age, gender, and baseline differences adjusted telomere length was correlated with haemoglobin levels (partial r = 0.130; P = 0.011). One standard deviation shorter telomere length was associated with an increased risk of having anaemia [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.12-1.53; P = 0.001]. This observation was not affected by adjustment for potential confounders (OR, 1.38; 95% CI, 1.05-1.81; P = 0.021 after adjustment for age, gender, erythropoietin levels, renal function, left ventricular ejection fraction, age of CHF onset, blood pressure, history of stroke, diabetes, and B-type natriuretic peptide levels). CONCLUSION: Shorter telomere length increases the odds of having anaemia in CHF patients. This finding supports the hypothesis that cellular ageing in CHF contributes to the susceptibility to develop anaemia.
24.	Wong, Liza S M, et al. (författare) Renal dysfunction is associated with shorter telomere length in heart failure. 2009 Ingår i: Clinical research in cardiology : official journal of the German Cardiac Society. - : Springer Science and Business Media LLC. - 1861-0692. ; 98:10, s. 629-34 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Renal dysfunction is a frequent comorbidity associated with high mortality in patients with chronic heart failure (CHF). The intrinsic biological age might affect the ability of the kidney to cope with the challenging environment caused by CHF. We explored the association between leukocyte telomere length, a marker for biological age, and renal function in patients with CHF. METHODS AND RESULTS: Telomere length was determined by a real-time quantitative polymerase chain reaction in 866 CHF patients. Renal function was estimated with the simplified Modification of Diet in Renal Disease equation. The median age was 74 (interquartile range 64-79) years, 61% male, left ventricular ejection fraction of 30 (23-44)%, and the estimated glomerular filtration rate was 53 (40-68) ml/min/1.73 m(2). Telomere length was associated with renal function (correlation coefficient 0.123, P < 0.001). This relationship remained significant after adjustment for age, gender, age of CHF onset (standardized-beta 0.091, P = 0.007). Also additionally adjusting for the severity of CHF and baseline differences did not change our findings. CONCLUSION: The association between shorter leukocyte telomere length and reduced renal function in heart failure suggests that intrinsic biological aging affects the ability of the kidney to cope with the systemic changes evoked by heart failure.
25.	Armstrong, Paul W, et al. (författare) Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. 2020 Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:20, s. 1883-1893 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear.METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure.RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30).CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).
26.	Belonje, Anne M S, et al. (författare) Endogenous erythropoietin and outcome in heart failure. 2010 Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 121:2, s. 245-51 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Endogenous erythropoietin is increased in patients with heart failure (HF). Previous small-scale data suggest that these erythropoietin levels are related to prognosis. This study aims to analyze the clinical and prognostic value of erythropoietin levels in relation to hemoglobin in a large cohort of HF patients. METHODS AND RESULTS: In patients hospitalized for HF, endogenous erythropoietin levels were measured at discharge and after 6 months. In anemic patients, the relation between erythropoietin and hemoglobin levels was determined by calculating the observed/predicted ratio of erythropoietin levels. We studied data from 605 patients with HF. Mean age was 71+/-11 years; 62% were male; and mean left ventricular ejection fraction was 0.33+/-0.14. Median erythropoietin levels were 9.6 U/L at baseline and 10.5 U/L at 6 months. Higher erythropoietin levels at baseline were independently related to an increased mortality at 18 months (hazard ratio, 2.06; 95% confidence interval, 1.40 to 3.04; P<0.01). In addition, persistently elevated erythropoietin levels (higher than median at baseline and at 6 months) were related to an increased mortality risk (hazard ratio, 2.24; 95% confidence interval, 1.02 to 4.90; P=0.044). The observed/predicted ratio was determined in a subset of anemic patients, 79% of whom had erythropoietin levels lower than expected and 9% had levels higher than expected on the basis of their hemoglobin. Multivariate Cox regression analysis revealed that a higher observed/predicted ratio was related to an increased mortality risk (hazard ratio, 3.52; 95% confidence interval, 1.53 to 8.12; P=0.003). CONCLUSIONS: Erythropoietin levels predict mortality in HF patients, and persistently elevated levels have an independent prognostic value. In anemic HF patients, the majority had a low observed/predicted ratio. However, a higher observed/predicted ratio may be related to an independent increased mortality risk.
27.	Chen, Yuntao, et al. (författare) A heart failure phenotype stratified model for predicting 1-year mortality in patients admitted with acute heart failure: results from an individual participant data meta-analysis of four prospective European cohorts 2021 Ingår i: BMC Medicine. - : BMC. - 1741-7015. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background Prognostic models developed in general cohorts with a mixture of heart failure (HF) phenotypes, though more widely applicable, are also likely to yield larger prediction errors in settings where the HF phenotypes have substantially different baseline mortality rates or different predictor-outcome associations. This study sought to use individual participant data meta-analysis to develop an HF phenotype stratified model for predicting 1-year mortality in patients admitted with acute HF. Methods Four prospective European cohorts were used to develop an HF phenotype stratified model. Cox model with two rounds of backward elimination was used to derive the prognostic index. Weibull model was used to obtain the baseline hazard functions. The internal-external cross-validation (IECV) approach was used to evaluate the generalizability of the developed model in terms of discrimination and calibration. Results 3577 acute HF patients were included, of which 2368 were classified as having HF with reduced ejection fraction (EF) (HFrEF; EF < 40%), 588 as having HF with midrange EF (HFmrEF; EF 40-49%), and 621 as having HF with preserved EF (HFpEF; EF >= 50%). A total of 11 readily available variables built up the prognostic index. For four of these predictor variables, namely systolic blood pressure, serum creatinine, myocardial infarction, and diabetes, the effect differed across the three HF phenotypes. With a weighted IECV-adjusted AUC of 0.79 (0.74-0.83) for HFrEF, 0.74 (0.70-0.79) for HFmrEF, and 0.74 (0.71-0.77) for HFpEF, the model showed excellent discrimination. Moreover, there was a good agreement between the average observed and predicted 1-year mortality risks, especially after recalibration of the baseline mortality risks. Conclusions Our HF phenotype stratified model showed excellent generalizability across four European cohorts and may provide a useful tool in HF phenotype-specific clinical decision-making.
28.	Damman, Kevin, et al. (författare) Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure : results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH). 2009 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 11:9, s. 847-54 Tidskriftsartikel (refereegranskat)abstract AIMS: The effect of worsening renal function (WRF) after discharge on outcome in patients with heart failure is unknown. METHODS AND RESULTS: We assessed estimated glomerular filtration rate (eGFR) and serum creatinine at admission, discharge, and 6 and 12 months after discharge, in 1023 heart failure patients. Worsening renal function was defined as an increase in serum creatinine of >26.5 micromol/L and >25%. The primary endpoint was a composite of all-cause mortality and heart failure admissions. The mean age of patients was 71 +/- 11 years, and 62% was male. Mean eGFR at admission was 55 +/- 21 mL/min/1.73 m(2). In-hospital WRF occurred in 11% of patients, while 16 and 9% experienced WRF from 0 to 6, and 6 to 12 months after discharge, respectively. In multivariate landmark analysis, WRF at any point in time was associated with a higher incidence of the primary endpoint: hazard ratio (HR) 1.63 (1.10-2.40), P = 0.014 for in-hospital WRF, HR 2.06 (1.13-3.74), P = 0.018 for WRF between 0-6 months, and HR 5.03 (2.13-11.88), P < 0.001 for WRF between 6-12 months. CONCLUSION: Both in- and out-hospital worsening of renal function are independently related to poor prognosis in patients with heart failure, suggesting that renal function in heart failure patients should be monitored long after discharge.
29.	Hogenhuis, Jochem, et al. (författare) BNP and functional status in heart failure. 2004 Ingår i: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 18:6, s. 507; author reply 509- Tidskriftsartikel (refereegranskat)
30.	Hogenhuis, Jochem, et al. (författare) Correlates of B-type natriuretic peptide and 6-min walk in heart failure patients. 2006 Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 108:1, s. 63-7 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: B-type natriuretic peptide (BNP) and 6-min walk test (6MWT) are both related to the severity and prognosis in chronic heart failure (CHF), but may reflect different aspects of CHF. We related BNP and 6MWT to left ventricular ejection fraction (LVEF), New York Heart Association functional class (NYHA), and two indices of quality of life (physical subscales): the Minnesota Living with Heart Failure Questionnaire (MLwHFQph) and the RAND-36ph. METHODS: Plasma BNP and 6MWT were measured at discharge in 229 patients who had been admitted for CHF. LVEF and NYHA were determined, and patients completed the MLwHFQ and RAND-36 questionnaires. RESULTS: BNP was weakly correlated to LVEF (r=-0.29, P<0.01) and NYHA (r=0.20, P<0.01), but not to MLwHFQph and RAND-36ph. On the other hand, 6MWT is related to MLwHFQph (r=-0.23, P<0.01), RAND-36ph (r=0.52, P<0.01), and NYHA (r=-0.46, P<0.01), but not to LVEF (r=-0.15, P=0.05). There is also no correlation between BNP and 6MWT (r=-0.01, P=0.87). CONCLUSIONS: The present data show that BNP and 6MWT represent different aspects of the clinical syndrome of CHF. The outcomes of this study suggest that BNP plasma levels are more related to cardiac function, while 6MWT reflects functional capacity and quality of life.
31.	Hogenhuis, Jochem, et al. (författare) Influence of age on natriuretic peptides in patients with chronic heart failure : a comparison between ANP/NT-ANP and BNP/NT-proBNP. 2005 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 7:1, s. 81-86 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Natriuretic peptides are currently used in the diagnosis and follow-up of patients with Chronic Heart Failure (CHF). However, it is unknown whether there are different influences of age on atrial natriuretic peptide (ANP)/N-terminal-ANP (NT-ANP) or B-type natriuretic peptide (BNP)/N-terminal-proBNP (NT-proBNP). AIMS: To compare the influence of age and gender on plasma levels of ANP/NT-ANP and BNP/NT-proBNP in CHF patients. METHODS AND RESULTS: Natriuretic peptides were measured in 311 CHF patients (68+/-8 years, 76% males, left ventricular ejection fraction (LVEF) 0.23+/-0.08). All natriuretic peptides were significantly related to age (p<0.05) on multivariate regression analysis, with partial correlation coefficients of 0.18, 0.29, 0.28 and 0.25 for ANP, NT-ANP, BNP and NT-proBNP, respectively. The relative increase of both BNP/NT-proBNP were more pronounced than of ANP/NT-ANP (p<0.01). Furthermore, the relative increase of BNP with age was markedly larger than of NT-proBNP (p<0.01). Levels of all natriuretic peptides were also significantly related to cardiothoracic ratio, renal function and LVEF. CONCLUSION: In patients with CHF, BNP/NT-proBNP were more related to age than ANP/NT-ANP, and BNP was more related to age than NT-proBNP. However, in these CHF patients the influence of age on the levels of all natriuretic peptides was modest, and comparable to several other factors.
32.	Hogenhuis, Jochem, et al. (författare) Low prevalence of B-type natriuretic peptide levels < 100 pg/mL in patients with heart failure at hospital discharge. 2006 Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 151:5, s. 1012.e1-5 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: In patients with acute heart failure (HF) presenting at the emergency department, a B-type natriuretic peptide (BNP) level < 100 pg/mL was found in only 10% of the patients. However, in a more stable outpatient HF population from another study, a BNP level < 100 pg/mL was found in as many as 21% of the patients. Therefore, we aimed to investigate the prevalence and characteristics of stabilized patients with BNP levels < 100 pg/mL before discharge after admission for decompensated heart failure HF. METHODS: We investigated 601 patients with HF who were part of a large-scale multicenter study in The Netherlands. All patients had been admitted for decompensated HF, and their BNP levels were measured before discharge when they had been clinically stabilized. Clinical characteristics of patients with BNP levels < 100 and > or = 100 pg/mL were compared. RESULTS: Patients were 70 +/- 12 years old, 61% were men, and mean left ventricular ejection fraction was 0.34 +/- 0.14. Of these patients, 10% had BNP levels < 100 pg/mL. Patients with a BNP level < 100 pg/mL were similar in age and sex but had higher left ventricular ejection fraction (0.41 +/- 0.14 vs 0.33 +/- 0.13, P < .001), body mass index, and hemoglobin and hematocrit concentrations compared with those with BNP levels > or = 100 pg/mL. CONCLUSIONS: In clinically stable patients with a recent admission for decompensated HF, only 10% had BNP levels > or = 100 pg/mL. These patients with low BNP levels seemed to have less severe HF and more frequently had preserved systolic function compared with patients with BNP levels > or = 100 pg/mL.
33.	Linssen, Gerard C M, et al. (författare) Clinical and prognostic effects of atrial fibrillation in heart failure patients with reduced and preserved left ventricular ejection fraction 2011 Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 13:10, s. 1111-1120 Tidskriftsartikel (refereegranskat)abstract AIMS: Atrial fibrillation (AF) is common in heart failure (HF), but few data regarding the prognostic relevance of AF are available in HF patients with preserved left ventricular ejection fraction (HF-PEF). We aimed to study the clinical impact of AF vs. sinus rhythm (SR) in stabilized HF patients with reduced left ventricular ejection fraction (HF-REF) and in those with preserved left ventricular ejection fraction (HF-PEF). METHODS AND RESULTS: We studied 927 patients with stable HF, of whom 336 (36%) had AF. N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were measured at baseline and patients were followed for 18 months. We compared time to first HF (re-)hospitalization or death between patients with AF and SR. Atrial fibrillation was present at baseline in 215 (35%) patients with HF-REF (mean LVEF 0.25 + 0.08) and in 121 (40%) patients with HF-PEF (mean LVEF 0.50 + 0.09). Plasma NT-proBNP levels were similar in AF and SR patients (median 2398 vs. 2532 pg/mL, P = 0.74). Atrial fibrillation was independently associated with elevated NT-proBNP levels in HF-PEF, but not in HF-REF patients (multivariable B = 0.33, P= 0.047 and B = 0.03; P = 0.89, respectively). After 18 months of follow-up, the presence of AF was an independent predictor of death or HF hospitalization in HF-PEF (multivariable hazard ratio 1.49 (95% CI 1.04-2.14), P = 0.03), but not in HF-REF patients (1.05 (CI 95% 0.80-1.38), P = 0.72). CONCLUSION: Atrial fibrillation is equally common in patients with HF-PEF and HF-REF. In HF-PEF, but not in HF-REF patients, AF was associated with higher NT-proBNP levels and was independently related to death or HF hospitalization.
34.	Lok, Dirk J., et al. (författare) Prognostic value of N-terminal pro C-type natriuretic peptide in heart failure patients with preserved and reduced ejection fraction 2014 Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B / Wiley. - 1388-9842 .- 1879-0844. ; 16:9, s. 958-966 Tidskriftsartikel (refereegranskat)abstract AimsA-type and B-type natriuretic peptides are established markers in chronic heart failure (HF). C-type natriuretic peptide (CNP) belongs to the same peptide family, but is predominantly localized in the endothelium. The prognostic role of CNP in heart failure has not been established. The aim of the study was to determine the prognostic power and clinical correlates of the N-terminal part of pro CNP (NT-proCNP) in patients with chronic HF. Methods and resultsIn 567 hospitalized heart failure patients, NT-proCNP levels were measured at hospital discharge. The primary endpoint was a combined endpoint of all-cause mortality and HF hospitalization after 18 months. Heart failure with a preserved ejection fraction (HFpEF) was pre-defined as an LVEF greater than40%. Mean (SD) age was 71 +/- 11years, 62% were male, mean LVEF was 32 +/- 14%, and 23% had HFpEF. In multivariate linear regression, NT-proCNP levels showed a positive correlation with NT-proBNP levels and parameters of renal function, whereas a negative correlation with female sex and vascular endothelial growth factor was observed. After 18 months follow-up, 240 patients reached the combined endpoint. We observed interaction between NT-proCNP and LVEF for outcome (P=0.046). Multivariate analyses revealed NT-proCNP to be strongly predictive for the primary endpoint [hazard ratio (HR) 1.78, 95% confidence interval (CI) 1.18-2.67, P=0.006) in patients with HFpEF, but not in patients with a reduced ejection fraction (HFrEF) (HR 1.07, 95% CI 0.81-1.43, P=0.616). Finally, reclassification showed significant additive value in patients with HFpEF (Pless than0.001), but not in those with HFrEF (P=0.453). Conclusionless thanp id="ejhf140-para-0003"greater thanNT-proCNP is a strong independent marker for outcome in patients with HFpEF, but not in those with HFrEF.
35.	Maggioni, Aldo P., et al. (författare) EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot) 2013 Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B. - 1388-9842 .- 1879-0844. ; 15:7, s. 808-817 Tidskriftsartikel (refereegranskat)abstract The ESC-HF Pilot survey was aimed to describe clinical epidemiology and 1-year outcomes of outpatients and inpatients with heart failure (HF). The pilot phase was also specifically aimed at validating structure, performance, and quality of the data set for continuing the survey into a permanent Registry. The ESC-HF Pilot study is a prospective, multicentre, observational survey conducted in 136 Cardiology Centres in 12 European countries selected to represent the different health systems across Europe. All outpatients with HF and patients admitted for acute HF on 1 day per week for eight consecutive months were included. From October 2009 to May 2010, 5118 patients were included: 1892 (37) admitted for acute HF and 3226 (63) patients with chronic HF. The all-cause mortality rate at 1 year was 17.4 in acute HF and 7.2 in chronic stable HF. One-year hospitalization rates were 43.9 and 31.9, respectively, in hospitalized acute and chronic HF patients. Major regional differences in 1-year mortality were observed that could be explained by differences in characteristics and treatment of the patients. The ESC-HF Pilot survey confirmed that acute HF is still associated with a very poor medium-term prognosis, while the widespread adoption of evidence-based treatments in patients with chronic HF seems to have improved their outcome profile. Differences across countries may be due to different local medical practice as well to differences in healthcare systems. This pilot study also offered the opportunity to refine the organizational structure for a long-term extended European network.
36.	Massie, Barry M, et al. (författare) Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. 2010 Ingår i: The New England journal of medicine. - 1533-4406. ; 363:15, s. 1419-28 Tidskriftsartikel (refereegranskat)abstract Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.
37.	Meyer, Sven, et al. (författare) Neurohormonal and clinical sex differences in heart failure 2013 Ingår i: European Heart Journal. - : Oxford University Press (OUP): Policy B. - 0195-668X .- 1522-9645. ; 34:32, s. 2538- Tidskriftsartikel (refereegranskat)abstract Despite disparities in pathophysiology and disease manifestation between male and female patients with heart failure, studies focusing on sex differences in biomarkers are scarce. The purpose of this study was to assess sex-specific variation in clinical characteristics and biomarker levels to gain more understanding of the potential pathophysiological mechanisms underlying sex differences in heart failure. less thanbrgreater than less thanbrgreater thanBaseline demographic and clinical characteristics, multiple biomarkers, and outcomes were compared between men and women in 567 patients. The mean age of the study group was 71 11 years and 38 were female. Women were older, had a higher body mass index and left ventricular ejection fraction, more hypertension, and received more diuretic and antidepressant therapy, but less ACE-inhibitor therapy compared with men. After 3 years, all-cause mortality was lower in women than men (37.0 vs. 43.9, multivariable hazard ratio 0.64; 95 confidence interval 0.450.92, P 0.016). Levels of biomarkers related to inflammation [C-reactive protein, pentraxin 3, growth differentiation factor 15 (GDF-15), and interleukin 6] and extracellular matrix remodelling (syndecan-1 and periostin) were significantly lower in women compared with men. N-terminal pro-brain natriuretic peptide, TNF-R1a, and GDF-15 showed the strongest interaction between sex and mortality. less thanbrgreater than less thanbrgreater thanFemale heart failure patients have a distinct clinical presentation and better outcomes compared with male patients. The lower mortality was independent of differences in clinical characteristics, but differential sex associations between several biomarkers and mortality might partly explain the survival difference.
38.	Qin, Hailun, et al. (författare) Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM 2024 Ingår i: ESC HEART FAILURE. - 2055-5822. Tidskriftsartikel (refereegranskat)abstract Aims Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. Methods and results We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) <= 40%] in New York Heart Association class II-IV were randomized to candesartan or placebo. Every 2 weeks, patients were up-titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 +/- 12.6 mg in men and 20.7 +/- 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person-years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person-years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P-value for all > 0.05). There was no significant interaction between sex and treatment-related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). Conclusions In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment-related discontinuation due to adverse events were also similar between men and women.
39.	Svedlund, Sara, et al. (författare) Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results. 2023 Ingår i: Journal of cardiac failure. - 1532-8414. ; 30:1, s. 104-10 Tidskriftsartikel (refereegranskat)abstract Inflammation is a key driver of heart failure (HF) with preserved left ventricular ejection fraction (LVEF). AZD4831 inhibits extracellular myeloperoxidase, reduces inflammation and improves microvascular function in preclinical disease models.In this double-blind phase 2a study (SATELLITE; NCT03756285), patients with symptomatic HF, LVEF ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary endpoint: myeloperoxidase specific activity) and safety of AZD4831.Due to COVID-19, the study was terminated early after randomizing 41 patients (median age, 74.0 years; 53.7% male). Myeloperoxidase activity was reduced by >50% from baseline to day 30 and 90 in the AZD4831 group, with a placebo-adjusted reduction of 75% (95% confidence interval: 48, 88; nominal P <0.001). No improvements were noted in secondary/exploratory endpoints, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus and diarrhoea (all n=1).AZD4831 inhibited myeloperoxidase and was well tolerated in patients with HF and LVEF ≥40%. Efficacy findings were exploratory due to early termination but warrant further clinical investigation of AZD4831.Few treatments are available for patients with the forms of heart failure known as 'heart failure with preserved or mildly reduced ejection fraction'. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which reduces inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 reduces the symptoms of heart failure and improves patients' ability to take physical exercise.
40.	Tromp, Jasper, et al. (författare) Serum Potassium Levels and Outcome in Acute Heart Failure (Data from the PROTECT and COACH Trials) 2017 Ingår i: American Journal of Cardiology. - : EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC. - 0002-9149 .- 1879-1913. ; 119:2, s. 290-296 Tidskriftsartikel (refereegranskat)abstract Serum potassium is routinely measured at admission for acute heart failure (AHF), but information on association with clinical variables and prognosis is limited. Potassium measurements at admission were available in 1,867 patients with AHF in the original cohort of 2,033 patients included in the Patients Hospitalized with acute heart failure and Volume Overload to Assess Treatment Effect on Congestion and Renal FuncTion trial. Patients were grouped according to low potassium (amp;lt;3.5 mEq/l), normal potassium (3.5 to 5.0 mEq/l), and high potassium (amp;gt;5.0 mEq/l) levels. Results were verified in a validation cohort of 1,023 patients. Mean age of patients was 71 +/- 11 years, and 66% were men. Low potassium was present in 115 patients (6%), normal potassium in 1,576 (84%), and high potassium in 176 (9%). Potassium levels increased during hospitalization (0.18 +/- 0.69 mEq/l). Patients with high potassium more often used angiotensin-converting enzyme inhibitors and mineralocorticoid receptor antagonists before admission, had impaired baseline renal function and a better diuretic response (p = 0.005), independent of mineralocorticoid receptor antagonist usage. During 180-day follow-up, a total of 330 patients (18%) died. Potassium levels at admission showed a univariate linear association with mortality (hazard ratio [log] 2.36, 95% confidence interval 1.07 to 5.23; p = 0.034) but not after multivariate adjustment. Changes of potassium levels during hospitalization or potassium levels at discharge were not associated with outcome after multivariate analysis. Results in the validation cohort were similar to the index cohort. In conclusion, high potassium levels at admission are associated with an impaired renal function but a better diuretic response. Changes in potassium levels are common, and overall levels increase during hospitalization. In conclusion, potassium levels at admission or its change during hospitalization are not associated with mortality after multivariate adjustment. (C) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativeconunons.org/licenses/by/4.0/).
41.	van Deursen, Vincent M., et al. (författare) Co-morbidities in patients with heart failure: an analysis of the European Heart Failure Pilot Survey 2014 Ingår i: European Journal of Heart Failure. - : Oxford University Press (OUP): Policy B. - 1388-9842 .- 1879-0844. ; 16:1, s. 103-111 Tidskriftsartikel (refereegranskat)abstract Aims Co-morbidities frequently accompany heart failure (HF), contributing to increased morbidity and mortality, and an impairment of quality of life. We assessed the prevalence, determinants, regional variation, and prognostic implications of co-morbidities in patients with chronic HF in Europe. Methods and results A total of 3226 European outpatients with chronic HF were included in this analysis of the European Society of Cardiology (ESC) Heart Failure Pilot Survey. The following co-morbidities were considered: diabetes, hyper- and hypothyroidism, stroke, COPD, sleep apnoea, chronic kidney disease (CKD), and anaemia. Prognostic implications of co-morbidities were evaluated using population attributable risks (PARs), and patients were divided into geographic regions. Clinical endpoints were all-cause mortality and HF hospitalization. The majority of patients (74%) had a least one co-morbidity, the most prevalent being CKD (41%), anaemia (29%), and diabetes (29%). Co-morbidities were independently associated with higher age (P less than 0.001), higher NYHA functional class (P less than 0.001), ischaemic aetiology of HF (P less than 0.001), higher heart rate (P = 0.011), history of hypertension (P less than 0.001), and AF (P less than 0.001). Only diabetes, CKD, and anaemia were independently associated with a higher risk of mortality and/or HF hospitalization. There were marked regional differences in prevalence and prognostic implications of co-morbidities. Prognostic implications of co-morbidities (PARs) were: CKD = 41%, anaemia = 37%, diabetes = 14%, COPD = 10%, and less than10% for all other co-morbidities. Conclusion In this pilot survey, co-morbidities are prevalent in patients with chronic HF and are related to the severity of the disease. The presence of diabetes, CKD, and anaemia was independently related to increased mortality and HF hospitalization, with the highest PAR for CKD and anaemia.
42.	van Deursen, Vincent M., et al. (författare) Prognostic Value of Plasma Neutrophil Gelatinase-Associated Lipocalin for Mortality in Patients With Heart Failure 2014 Ingår i: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 7:1, s. 35-42 Tidskriftsartikel (refereegranskat)abstract Background In patients with heart failure, renal dysfunction is associated with a poor outcome. We aimed to assess the prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL), a novel marker of renal tubular damage, in patients with heart failure with or without renal dysfunction, and compare it with 2 frequently used biomarkers of chronic kidney disease. Methods and Results Plasma NGAL, estimated glomerular filtration rate (eGFR), and cystatin C were assessed in 562 patients with heart failure. Chronic kidney disease was defined as eGFRless than60 mL/min per 1.73 m(2). Outcome was all-cause mortality at 36 months. Mean age was 7111 years, 61% were men, and 97% were in New York Heart Association functional class II/III. Mean baseline eGFR was 54 +/- 20 mL/min per 1.73 m(2), mean cystatin C was 11.2 (7.7-16.2) mg/L, and median plasma NGAL was 85 (60-123) ng/mL. Higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality, in patients with and without chronic kidney disease (hazard ratio [per SD increase in log NGAL]=1.45 [1.22-1.72]; Pless than0.001 and hazard ratio=1.51 [1.06-2.16]; P=0.023, respectively). Similarly, both in patients with high and low cystatin C (median cut-off), higher plasma NGAL levels were independently associated with an increased risk of all-cause mortality. Moreover, when NGAL was entered in the multivariable risk prediction model, eGFR (P=0.616) and cystatin C (P=0.937) were no longer associated with mortality. Conclusions Plasma NGAL predicts mortality in patients with heart failure, both in patients with and without chronic kidney disease and is a stronger predictor for mortality than the established renal function indices eGFR and cystatin C.
43.	van Veldhuisen, Dirk J., et al. (författare) B-Type Natriuretic Peptide and Prognosis in Heart Failure Patients With Preserved and Reduced Ejection Fraction 2013 Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 61:14, s. 1498-1506 Tidskriftsartikel (refereegranskat)abstract Objectives This study sought to determine the prognostic value of B-type natriuretic peptide (BNP) in patients with heart failure with preserved ejection fraction (HFPEF), in comparison to data in HF patients with reduced left ventricular (LV) EF (andlt;= 40%). less thanbrgreater than less thanbrgreater thanBackground Management of patients with HFPEF is difficult. BNP is a useful biomarker in patients with reduced LVEF, but data in HFPEF are scarce. less thanbrgreater than less thanbrgreater thanMethods In this study, 615 patients with mild to moderate HF (mean age 70 years, LVEF 33%) were followed for 18 months. BNP concentrations were measured at baseline and were related to the primary outcome, that is, a composite of all-cause mortality and HF hospitalization, and to mortality alone. The population was divided in quintiles, according to LVEF, and patients with reduced LVEF were compared with those with HFPEF. less thanbrgreater than less thanbrgreater thanResults There were 257 patients (42%) who had a primary endpoint and 171 (28%) who died. BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p andlt; 0.001). BNP was a strong predictor of outcome, but LVEF was not. Importantly, if similar levels of BNP were compared across the whole spectrum of LVEF, and for different cutoff levels of LVEF, the associated risk of adverse outcome was similar in HFPEF patients as in those with reduced LVEF. less thanbrgreater than less thanbrgreater thanConclusions BNP levels are lower in patients with HFPEF than in patients with HF with reduced LVEF, but for a given BNP level, the prognosis in patients with HFPEF is as poor as in those with reduced LVEF. (J Am Coll Cardiol 2013;61:1498-506)
44.	Vegter, Eline L., et al. (författare) Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations 2017 Ingår i: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 106:8, s. 598-609 Tidskriftsartikel (refereegranskat)abstract Objective Circulating microRNAs (miRNAs) have been implicated in both heart failure and atherosclerotic disease. The aim of this study was to examine associations between heart failure specific circulating miRNAs, atherosclerotic disease and cardiovascular-related outcome in patients with heart failure. Methods The levels of 11 heart failure-specific circulating miRNAs were compared in plasma of 114 heart failure patients with and without different manifestations of atherosclerotic disease. We then studied these miRNAs in relation to biomarkers associated to atherosclerosis and to cardiovascular-related rehospitalizations during 18 months of follow-up. Results At least one manifestation of atherosclerotic disease was found in 70 (61%) of the heart failure patients. A consistent trend was found between an increasing number of manifestations of atherosclerosis (peripheral arterial disease in specific), and lower levels of miR-18a-5p, miR27a-3p, miR-199a-3p, miR-223-3p and miR-652-3p (all P amp;lt; 0.05). Target prediction and network analyses identified several interactions between miRNA targets and biomarkers related to inflammation, angiogenesis and endothelial dysfunction. Lower miRNA levels were associated with higher levels of these atherosclerosis-related biomarkers. In addition, lower miRNA levels were significantly associated with rehospitalizations due to cardiovascular causes within 18 months, with let-7i-5p as strongest predictor [HR 2.06 (95% CI 1.29-3.28), C-index 0.70, P = 0.002]. Conclusions A consistent pattern of lower levels of circulating miRNAs was found in heart failure patients with atherosclerotic disease, in particular peripheral arterial disease. In addition, lower levels of miRNAs were associated with higher levels of biomarkers involved in atherosclerosis and an increased risk of a cardiovascular-related rehospitalization.
45.	Willemsen, Suzan, et al. (författare) The role of advanced glycation end-products and their receptor on outcome in heart failure patients with preserved and reduced ejection fraction 2012 Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 164:5, s. 742-U146 Tidskriftsartikel (refereegranskat)abstract Introduction Advanced glycation end products (AGEs) are increased in patients with heart failure (HF). We studied the predictive value of plasma AGEs N-E-(carboxymethyl) lysine (CML), pentosidine, and the soluble form of its receptor (sRAGE) in a large HF population. less thanbrgreater than less thanbrgreater thanMethods In 580 patients hospitalized with HF, plasma AGEs were measured before discharge when patients were clinically stable. Patients were followed for a period of 18 months. Primary end point was a composite of death and HF admissions. CML was determined by liquid chromatography mass spectrometry, pentosidine by high-performance liquid chromatography and sRAGE by sequential sandwich immunoassay. less thanbrgreater than less thanbrgreater thanResults Mean age was 71 +/- 11 years, 62% were men, and mean left ventricular ejection fraction was 0.32 +/- 0.14. At baseline, mean CML level was 2.16 +/- 0.73 mu mol/L, median pentosidine was 0.043 (0.030-0.074) mu mol/L, and median sRAGE level was 2.92 (1.90-4.59) ng/mL. CML and pentosidine levels were independently related to the composite end-point (HR, 1.20 per SD; 95% CI, 1.05-1.37; P = .01 and HR, 1.15 per SD; 95% CI, 1.00-1.31; P = .045, respectively) and HF hospitalization (HR, 1.27 per SD; 95% CI, 1.10-1.48; P = .001 and HR, 1.27 per SD; 95% CI, 1.10-1.47; P = .001, respectively). Furthermore, CML levels were independently related to increased mortality (P = .006). Whereas sRAGE levels were univariately predictive for outcome, in multivariate models sRAGE did not reach statistical significance. less thanbrgreater than less thanbrgreater thanDiscussion In HF patients, both CML and pentosidine predict HF hospitalization and the combined primary end-point (mortality or HF-hospitalization), whereas sRAGE did not predict events. In addition, CML was significantly and independently associated with a higher risk for mortality. (Am Heart J 2012;164:742-749.e3.)

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