Abstract:
AIMS:Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. We aim to better understand the underlying pathophysiological processes associated with aging in HFrEF potentially leading to targeted therapies in this vulnerable population. METHODS AND RESULTS:From a panel of 363 cardiovascular biomarkers available in 1,611 patients with HFrEF in the BIOSTAT-CHF index cohort and cross-validated in 823 patients in the BIOSTAT-CHF validation cohort, we tested which biomarkers were dysregulated in patients aged > 75yr versus <65yr. Secondly, pathway overrepresentation analyses were performed to identify biological pathways linked to higher plasma concentrations of biomarkers in elderly versus younger patients. After adjustment, multiple test correction (FDR 1%), and cross-validation, 27/363 biomarkers were associated with older age, 22 positively, and 5 negatively. The biomarkers that were positively associated with older age were associated with tumor cell regulation, extra-cellular matrix organization, and inflammatory processes, whereas biomarkers negatively associated with older age were associated with pathways that may point to cell proliferation and tumorigenesis. Among the 27 biomarkers, WFDC2 (WAP Four-Disulfide-Core-Domain-2) - that broadly functions as a protease inhibitor - was associated with older age and had the strongest association with all outcomes. No protein-by-sex interaction was observed. CONCLUSIONS:In elderly HFrEF patients, pathways associated with extra-cellular matrix organization, inflammatory processes, and tumor cell regulation were activated, while pathways associated with tumor proliferation functions were down-regulated. These findings may help in a better understanding of the aging processes in HFrEF and identify potential therapeutic targets. TRANSLATIONAL PERSPECTIVE:Elderly patients with heart failure with reduced ejection fraction (HFrEF) have worse prognosis and less often receive guideline-recommended therapies. Using a large set of circulating proteins, elderly patients had higher concentrations of proteins associated with tumor cell regulation, extra-cellular matrix organization, and inflammatory processes, whereas pathways that may point to cell proliferation and tumorigenesis were down-regulated. WAP Four-Disulfide-Core-Domain-2 was associated with older age and had the strongest association with an increased risk of all outcomes. Understanding the underlying pathophysiological processes associated with aging in HFrEF may potentially lead to targeted therapies in this vulnerable population.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Ferreira JP,Ouwerkerk W,Santema BT,van Veldhuisen DJ,Lang CC,Ng LL,Anker SD,Dickstein K,Metra M,Cleland JGF,Nilesh SJ,Filippatos G,Aboumsallem JP,de Boer RA,Figarska S,Sama IE,Voors AA,Zannad Fdoi
10.1093/cvr/cvaa279subject
Has Abstractpub_date
2020-10-01 00:00:00eissn
0008-6363issn
1755-3245pii
5917017pub_type
杂志文章abstract::The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pre...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.10.649
更新日期:1985-10-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. DESIGN:In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.2.101
更新日期:1991-02-01 00:00:00
abstract:AIMS:TGF-β regulates tissue fibrosis: TGF-β promotes fibrosis, whereas bone morphogenetic protein (BMP)-7 is antifibrotic. To demonstrate that (i) left ventricular (LV) remodelling after pressure overload is associated with disequilibrium in the signalling mediated by these cytokines, and (ii) BMP-7 exerts beneficial e...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw076
更新日期:2016-06-01 00:00:00
abstract:AIMS:The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration, proliferation, and capillary-like tube formation in vitro. It is unknown whether S1P stimulates in vivo angiogenesis induced under tissue ischaemia. We investigated the effects of both exogenously...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn002
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:Previous studies showed that treatment of hearts with nisoldipine improves recovery of cardiac function following ischaemia, improves reperfusion, and reduces the constrictor sensitivity to endothelin. The aim of the present study was to assess the reduction in vasodilator responses that occurs following isch...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.990
更新日期:1993-06-01 00:00:00
abstract:OBJECTIVES:The state of the vasodilator systems in congestive heart failure is poorly defined. Plasma atrial natriuretic peptide is increased, whereas endothelium derived relaxing factor activity can be decreased. Atrial natriuretic peptide and endothelium derived relaxing factor both cause vascular relaxation by gener...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.6.1094
更新日期:1993-06-01 00:00:00
abstract:AIMS:Mast cells participate importantly in abdominal aortic aneurysms (AAAs) by releasing inflammatory cytokines to promote vascular cell protease expression and arterial wall remodelling. Mast cells accumulate in AAA lesions during disease progression, but the exact chemokines by which mast cells migrate to the site o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs262
更新日期:2012-12-01 00:00:00
abstract::The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.5.288
更新日期:1980-05-01 00:00:00
abstract::There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.10.740
更新日期:1986-10-01 00:00:00
abstract::The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(00)00086-9
更新日期:2000-08-18 00:00:00
abstract:AIMS:Baicalin is the major component found in Scutellaria baicalensis root, a widely used herb in traditional Chinese medicine. Although it has been used for thousands of years to treat stroke, the mechanisms of action of S. baicalensis have not been clearly elucidated. In this report, we studied the modulation of angi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq296
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:In many species arrhythmias induced by myocardial ischaemia appear to be in part dependent upon cardiac sympathetic nerves. However, previous experiments in rats did not suggest that myocardial or other catecholamines are involved in ischaemic arrhythmogenesis in this species. The aim of this study was to inv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00103-0
更新日期:1999-09-01 00:00:00
abstract::The hypothesis that cardiac surgery to interrupt accessory pathways also interrupts autonomic nerves to the canine ventricle and to the atrioventricular node was tested in four groups of dogs. Group 1 (n = 6) underwent dissection of the atrioventricular fat tissue and cryolesion created by application of a cryoprobe a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.3.163
更新日期:1988-03-01 00:00:00
abstract:AIMS:Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. METHODS AND RESULTS:Here, we have identified naïve T cells in the aorta of wild-type and T-cell receptor transgenic mice and we demonstrate that naï...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz102
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:The alpha adrenoceptor antagonist phentolamine prevents ischaemia related arrhythmias in rat, guinea pig, and cat heart. This effect has been related to the attenuation of ischaemia induced shortening of the action potential and has been ascribed to its alpha adrenoceptor antagonist properties. The aim of thi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.6.847
更新日期:1994-06-01 00:00:00
abstract:AIMS:Vascular inflammation is a major atherogenic factor and Toll-like receptor (TLR) 2 ligands, including bacterial and serum lipoproteins, seem to be involved in atherogenesis. On this basis, we analysed the effect of lipoproteins and different lipid components on TLR2-dependent signalling. METHODS AND RESULTS:In TL...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn087
更新日期:2008-08-01 00:00:00
abstract:AIMS:Diabetes impinges upon mechanisms of cardiovascular repair. However, the biochemical adaptation of cardiac stem cells to sustained hyperglycaemia remains largely unknown. Here, we investigate the molecular targets of high glucose-induced damage in cardiac progenitor cells (CPCs) from murine and human hearts and at...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs291
更新日期:2013-01-01 00:00:00
abstract::The progress made in our understanding of the pathophysiology and treatment of congestive heart failure (CHF) would not have been possible without a number of animal models of heart failure and hypertrophy, each one having unique advantages as well as disadvantages. The species and interventions used to create CHF dep...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(98)00110-2
更新日期:1998-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to examine the effect of ischaemia on vascular responses to endothelium-dependent and endothelium-independent vasodilators and on vasoconstrictor responses. Furthermore, the ability of preconditioning to prevent ischaemia-induced changes in vascular reactivity was examined in the rat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00167-8
更新日期:1996-12-01 00:00:00
abstract:OBJECTIVE:Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood-air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial functio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00063-1
更新日期:1997-06-01 00:00:00
abstract:AIMS:Vascular calcification often occurs with advancing age, atherosclerosis, and metabolic disorders such as diabetes mellitus and end-stage renal disease. Vascular calcification is associated with cardiovascular events and increased mortality. Nitric oxide (NO) is crucial for maintaining vascular function, but little...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm049
更新日期:2008-01-01 00:00:00
abstract::This study is the first report describing the sequence of biochemical alterations of myocardium during the progression of naturally occurring hypertrophy in spontaneously hypertensive rats (SHRs) and then with its reversal by alpha-methyldopa therapy. Changes in DNA, RNA, hydroxyproline, as well as incorporation of 14...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.2.254
更新日期:1976-03-01 00:00:00
abstract::Infarct size can be limited by reducing the determinants of infarct size or increasing collateral blood flow by treatment initiated before the ischaemic event. Reperfusion is the definitive treatment for permanently reducing infarct size and restoring some degree of contractile function to the affected myocardium. Inn...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp129
更新日期:2009-07-15 00:00:00
abstract:AIMS:Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr145
更新日期:2011-10-01 00:00:00
abstract:OBJECTIVE:Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation, the latter involving Hsp90 as a chaperone protein. Here, we investigated the potential of regional Hsp90 overexpression to induce therapeutic neovascularization in vivo in a chronic rabbit hindlimb ischemia model. ME...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.10.019
更新日期:2005-02-15 00:00:00
abstract::This study concerns the longterm effects of both epicardial and endocardial cryosurgery with particular reference to the coronary arteries. Sheep were subjected to epicardial cryosurgery without cardiopulmonary bypass, and to endocardial application with bypass. In both groups the heart was kept beating throughout the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.2.61
更新日期:1983-02-01 00:00:00
abstract::Mouse models have been frequently used in the study of Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) infections. This gram-negative obligate intracellular bacterium causes respiratory infections, followed by dissemination of the bacterium to various organs throughout the body, including cardiovascular ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.09.031
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVES:M cells have been described in many mammalian species. They are thought to be relevant for the genesis of long QT intervals, afterdepolarizations and for dispersion in action potential duration and in repolarization time. Their role in the human heart is subject to debate. METHODS:We simulated action potent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.02.016
更新日期:2004-05-01 00:00:00
abstract:OBJECTIVE:We studied the effects of temporary myocardial ischemia and reperfusion on myocyte injury and ventricular remodelling in wildtype and intercellular adhesion molecule-1- (ICAM-1) deficient mice. METHODS:ICAM-1-/- and ICAM-1+/+ mice were subjected to 30 min of myocardial ischemia and subsequent reperfusion for...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00261-3
更新日期:2001-02-01 00:00:00
abstract::Estimation of infarct size from enzyme activities in plasma or serum presupposes known values of circulatory parameters such as the extravascular distribution volume Ve and the permeability constant P for the transport of enzyme between intravascular volume Vi and Ve. In man, parameter values are used that are extrapo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/13.10.578
更新日期:1979-10-01 00:00:00