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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Asklepios Study is a longitudinal population study focusing on the interplay between ageing, cardiovascular haemodynamics and inflammation in (preclinical) cardiovascular disease. The 2524 participants (1301 women) are a representative cohort of 35-55-year-old individuals, free from overt cardiovascular disease at study initiation, randomly sampled from the twinned Belgian communities of Erpe-Mere and Nieuwerkerken. Baseline examinations (all single-observer, single-device, single-site, single 2-year consecutive timeframe) include: questionnaires, conventional risk factors and biochemistry. Additional phenotypes under study include: (a) vascular structure and function: carotid and femoral atherosclerosis (intima-media thickness, plaque), arterial distension and pressure curves (brachial, carotid, femoral; wall-tracking and applanation tonometry); (b) cardiac structure and function. A novel aspect of the study is 'integrated' non-invasive biomechanical assessment of cardiac, arterial and ventriculovascular function through a combination of modeling, fundamental hydraulical measurements and system identification techniques. Integrated phenotypes result from combining at least two sets of curves (flow/pressure/distension). The value of this 'integrated' haemodynamic phenotype in the detection, prediction and prevention of clinical cardiovascular pathology (atherosclerosis progression, atherothrombosis, development of heart failure) will be tested. A second novel aspect is the systematic determination of peripheral blood leukocyte telomere length as a marker for biological ageing. During follow-up, baseline examinations will be repeated and the incidence of cardiovascular events will be monitored. Sex-specific baseline risk factor and biochemical data are provided in the current analyses. The primary aim is to build a combined dataset that will act as a tool to answer a cluster of questions about ageing, haemodynamics and the emergence of cardiovascular disease, especially the incidence of atherothrombotic events and the development of adverse haemodynamic profiles (arterial stiffening, heart failure). The study will reassess current risk factors and provide a long-term base for the detection of novel (epi)genetic and non-genetic risk factors and for more performant risk stratification modalities. Within these broader goals, a constant will be to strive towards more fundamental mechanistic-haemodynamic insights into cardiovascular disease processes.
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PMID:Rationale, design, methods and baseline characteristics of the Asklepios Study. 1744 95

Osteoprotegerin, a member of the tumor necrosis factor receptor superfamily, has pleiotropic effects on bone metabolism, endocrine function, and the immune system. Myocardial expression and circulating levels of osteoprotegerin are increased in heart failure. The relationship between osteoprotegerin levels in the general population and indices of left ventricular structure and function is unknown. Plasma osteoprotegerin levels and cardiac MRI indices of left ventricular structure and function were available in 2715 subjects (median age: 44 years; 45% male) enrolled in the Dallas Heart Study. The associations between osteoprotegerin concentration and indices of left ventricular structure and function were assessed by linear regression analysis, adjusting for possible confounders. By gender-specific linear regression analysis, higher osteoprotegerin levels were significantly associated with higher left ventricular mass, left ventricular wall thickness, left ventricular concentricity index, and lower left ventricular ejection fraction (P<0.001 for all). After adjustment for age, race, fat-free mass, fat mass, hypertension, diabetes, coronary artery disease, estimated glomerular filtration rate, hypercholesterolemia, smoking status, hormone replacement therapy, coronary artery calcium score >10, and presence of aortic plaque, osteoprotegerin remained significantly associated with each of these left ventricular indices among male subjects (P<0.05 for each). Among female subjects, higher osteoprotegerin was independently associated with higher left ventricular end-systolic volume and lower ejection fraction (P<0.0001 for each) but not with indices of left ventricular hypertrophy. These findings are compatible with the theory that osteoprotegerin may play a pathophysiological role in the development of left ventricular hypertrophy and systolic dysfunction.
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PMID:Plasma osteoprotegerin levels in the general population: relation to indices of left ventricular structure and function. 1747 Jul 18

Telomeres are specialized DNA-protein structures located at the ends of eukaryotic chromosomes whose length is progressively reduced in most somatic cells during ageing. Over the past decade, emerging evidence has shown that the telomeres are essential regulators of cellular life span and chromosome integrity in a dynamic fashion. By inducing genomic instability, replicative senescence and apoptosis, shortening of telomeres is thought to contribute to organismal ageing. While the aetiology of cardiovascular diseases and diabetes represent a complex interaction between various risk factors overlaid on different genetic backgrounds, the conventional risk factors often did not explain the inter-individual variability related to predisposition of disease states. This underscores the need for biological indicators of ageing in evaluating the aetiology of several age-related disorders, and recent studies indicate that telomere length could qualify as an ideal marker of biological ageing. Short telomeres have been detected in senescent endothelial cells and vascular smooth muscle cells from human atherosclerotic plaque as well as in myocardial tissue from patients with end-stage heart failure and cardiac hypertrophy. In addition, telomere shortening has been demonstrated in WBCs from patients with coronary heart disease, premature myocardial infarction, hypertension and diabetes mellitus. In this review, we discuss the telomere hypothesis of ageing as well as human studies that address the role of telomeres in cardiovascular, diabetes and other cardio-metabolic pathologies.
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PMID:Telomere shortening & metabolic/vascular diseases. 1749 67

Cardiac mast cells proliferate in cardiovascular diseases. In myocardial ischemia, mast cell mediators contribute to coronary vasoconstriction, arrhythmias, leukocyte recruitment, and tissue injury and repair. Arrhythmic dysfunction, coronary vasoconstriction, and contractile failure are also characteristic of cardiac anaphylaxis. In coronary atherosclerosis, mast cell mediators facilitate cholesterol accumulation and plaque destabilization. In cardiac failure, mast cell chymase causes myocyte apoptosis and fibroblast proliferation, leading to ventricular dysfunction. Chymase and tryptase also contribute to fibrosis in cardiomyopathies and myocarditis. In addition, mast cell tumor necrosis factor-alpha promotes myocardial remodeling. Cardiac remodeling and hypertrophy in end-stage hypertension are also induced by mast cell mediators and proteases. We recently discovered that cardiac mast cells contain and release renin, which initiates local angiotensin formation. Angiotensin causes coronary vasoconstriction, arrhythmias, fibrosis, apoptosis, and endothelin release, all demonstrated mechanisms of mast-cell-associated cardiac disease. The effects of angiotensin are further amplified by the release of norepinephrine from cardiac sympathetic nerves. Our discovery of renin in cardiac mast cells and its release in pathophysiological conditions uncovers an important new pathway in the development of mast-cell-associated heart diseases. Several steps in this novel pathway may constitute future therapeutic targets.
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PMID:Renin: at the heart of the mast cell. 1749 56

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis. This may then result in cardiac remodelling. Serum biomarkers are available which can be used for diagnosis of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The problems with potential ischaemia markers are specificity and the reference diagnostic standard against which they can be judged. To date, only one, ischaemia-modified albumin(R), has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, have become recognised as the diagnostic reference standard for myocardial necrosis. The sensitive nature of these tests has also revealed that myocardial necrosis is also found in a range of other clinical situations, highlighting the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B-type natriuretic peptides can be shown to be diagnostic and prognostic in both ACS and detecting the sequelae of post-infarction myocardial insufficiency. The role of the B-type natriuretic peptides in detection of cardiac failure, both acute and chronic, is well defined but remains the subject of further studies, in ACS.
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PMID:Biomarkers of cardiovascular damage. 1754 Dec 89

Acute coronary syndromes (ACS) are due to the rupture or erosion of atheromatous plaques. This produces, depending on plaque size, vascular anatomy and degree of collateral circulation, progressive tissue ischaemia which may progress to cardiomyocyte necrosis and subsequent cardiac remodelling. Cardiac biomarkers can be used for diagnosis and assessment of all of these stages. Markers to detect myocardial ischaemia at the pre-infarction stage are potentially the most interesting but also the most challenging. An ischaemia marker offers the opportunity to intervene to prevent progression to infarction. The challenges with potential ischaemia markers are specificity and the diagnostic reference standard for assessment. To date, only one, ischaemia modified albumin, has reached the point where clinical studies can be performed. The measurement of the cardiac troponins, cardiac troponin T and cardiac troponin I, has become the diagnostic standard as the biomarker of myocardial necrosis. The sensitive nature of troponin measurement has also revealed that myocardial necrosis is also found in a range of other clinical situations. This illustrates the need to use all clinical information for diagnosis of acute myocardial infarction. The measurement of B type natriuretic peptides can be shown to be diagnostic and prognostic for both acute ACS and detecting the sequelae of post infarction myocardial insufficiency. The role of the B type natriuretic peptides in detection of cardiac failure, acute and chronic, is well defined. Their role in ACS remains the subject of further studies.
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PMID:Biomarkers of cardiovascular damage and dysfunction--an overview. 1761 29

There is increasing evidence that statins reduce cardiovascular events such as coronary artery disease or stroke in hypercholesterolemic patients in both primary and secondary prevention. The striking benefit achieved with statin treatments in patients with a wide range of cholesterol levels cannot be attributed to their cholesterol lowering effect alone. Substantial data has recently accumulated showing that statins exert various effects on multiple targets, namely pleiotropic effects, especially targeting the concept of 'vascular failure', including the improvement of vascular endothelial function, inhibition of vascular smooth muscle cell proliferation and migration, anti-inflammatory actions, anti-oxidative effects or stabilization of vulnerable plaques. These effects have potential in the treatments of coronary artery disease in various settings, such as prevention of its onset as well as its progression, or plaque rupture. Statin therapy should be more extensively applied even in normolipidemic patients if there are additional risk factors such as hypertension, diabetes mellitus, or others. Furthermore, statins may be used to intervene in earlier stage risk conditions such as postprandial hyperlipidemia or hyperglycemia, insulin resistant state, masked hypertension, or metabolic syndrome to further reduce mortality or morbidity of coronary artery disease and heart failure.
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PMID:Statin therapy for vascular failure. 1768 28

An 81 year old female patient with chronic heart failure and atrial fibrillation receiving anticoagulant therapy, was admitted with progressive pain on her right leg for the past 24 hours, associated to local erythema, edema and warmth. The lesion evolved at the same site where she presented a chronic ulcer for the previous 5 months managed only with local care. At admission a necrotic plaque on the affected site was perceived; there was no hypotension or mental confusion but signs of a deep venous thrombosis on the involved leg were found. She was febrile (37.8 degrees C) and with tachychardia (126 per minute). Laboratory evaluation revealed normal white blood cell count and a subtherapheutic anticoagulant INR value. A chest x-ray showed infiltrates on the left lower lung lobe. On the following hours the lesion evolved with increasing pain, haemorrhagic bullae and a purulent discharge through the ulcer, with the patient developing mental deterioration, hypotension, respiratory failure and shock. The patient received intravenous ciprofloxacin and clindamycin and was operated 15 hours after admission performing an over-the knee amputation. A cardiac catheterization demonstrated a low cardiac output (2.3 L/min), and both a high systemic vascular resistance (2888 din.s.cm(-5)) and pulmonary capillary wedge pressure (17 cm H(2)0), results compatible with cardiogenic shock. Evolution was progressively worse and she died of multiple organic failure 36 hours after admission. Two blood culture samples grew Serratia marcescens. No necropsy was performed and cultures taken from the leg remained negative.
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PMID:[Fatal necrotizing fasciitis due to Serratia marcescens]. 1772 22

Focal disorganization of gap junctional distribution and down-regulation of the major gap junctional protein connexin 43 are typical features of myocardial remodelling in the failing human heart. Increasing evidence indicates that connexin 43 interacts with zonula-occludens-1 (ZO-1), and it has recently been shown that ZO-1 promotes the formation and growth of gap junctional plaques. In the present study, distribution patterns of ZO-1 and connexin 43 were studied in normal and in heart failure patients using double-label immunohistochemistry and confocal microscopy. ZO-1 was found to be co-localized with connexin 43 at intercalated disks. Importantly, in patients with heart failure due to dilated or ischaemic cardiomyopathy, areas of diminished connexin 43 expression were characterized by a markedly reduced ZO-1 staining. Based on these data it is concluded that in patients with heart failure, down-regulation of ZO-1 matches the diminished expression levels of connexin 43, suggesting that ZO-1 plays an important role in gap junction formation and gap junction plaque stability.
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PMID:Zonula occludens-1 and connexin 43 expression in the failing human heart. 1776 Aug 48

Matrix metalloproteinases (MMPs) are an expanding group of proteolytic enzymes that participate in numerous physiological and pathological processes including embryogenesis, connective tissue turn-over, healing, angiogenesis, etc. Disturbances in matrixin activity are observed in carcinogenesis, some degenerative processes, and in inflammation, including atherogenesis. The role of matrixins in the pathology of the cardiovascular system seems to be particularly important in two processes: (1) atherosclerotic plaque development and rupture (leading to an acute coronary event) and (2) post-infarction remodeling of myocardium, leading to heart failure. The purpose of this paper is to gather and summarize information about the role of MMPs in acute coronary syndromes (ACS), in both the processes leading to coronary artery occlusion and the "myocardial consequence" of this event. In addition, some benefits and disadvantages of pharmacological intervention into this enzymatic network will be addressed.
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PMID:The role of matrix metalloproteinases in acute coronary syndromes. 1782 57


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