Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology
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The kidneys excrete excess dietary phosphate, and patients with chronic kidney disease may suffer from phosphate overload and hyperphosphatemia. In chronic kidney disease, hyperphosphatemia has emerged as a risk factor for vascular calcification, cardiovascular mortality, left ventricular hypertrophy, and progression of chronic kidney disease. Serum phosphate at the upper limits of normal has also been associated with adverse outcomes in patients with relatively preserved kidney function. ⋯ In this regard, increased circulating fibroblast growth factor-23, a phosphatonin that is released in response to phosphate overload, is independently associated with adverse outcomes in patients with and without chronic kidney disease. Direct effects of extracellular phosphate on vascular calcification or cardiovascular cell biology; adverse consequences of adaptive mechanisms activated to limit phosphate overload, such as left ventricular hypertrophy induced by fibroblast growth factor-23; or epidemiological associations of additional cardiovascular risk factors with chronic kidney disease may underlie these observations. We now review the pathophysiology of phosphate, its relationship with cardiovascular outcomes, the potential consequences for patient care related to dietary phosphate and phosphate binders, and the clinical relevance for patients without overt chronic kidney disease.
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Several culprits may be identified at postmortem in sudden death (SD) victims, including coronary artery, myocardial, valve, conduction system, and congenital heart diseases. However, particularly in young people, the heart can be found grossly and histologically normal in a not-so-minor amount of cases (the so-called unexplained SD or "mors sine materia") and inherited ion channel diseases are implicated (long and short QT syndromes, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia). ⋯ Postmortem investigation may still represent the first opportunity to make the proper diagnosis also in the setting of a structurally normal heart and the employment of molecular biology techniques is of help to solve the puzzle of such "silent" autopsies. For these reasons, autopsy investigation of cardiac SD should always include sampling for genetic testing to search for the invisible inherited arrhythmogenic disorders, as recommended in the recent guidelines by the Association for European Cardiovascular Pathology.
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Cardiovasc. Pathol. · Jan 2008
ReviewA comparison of genetic chromosomal loci for intracranial, thoracic aortic, and abdominal aortic aneurysms in search of common genetic risk factors.
Genetic factors are likely to be involved in the pathogenesis of intracranial, ascending thoracic aorta, and infrarenal aortic abdominal aneurysms. Common genetic risk factors for these three types of aneurysms have been suggested. This review describes the results of whole-genome linkage studies on intracranial, thoracic aorta, and aortic abdominal aneurysms, and compares the genomic loci identified in these studies in search of possible common genetic risk factors for the three aneurysmal types. ⋯ Five chromosomal regions that may include common genetic factors for intracranial, thoracic aorta, and aortic abdominal aneurysms were identified. Further studies are needed to explore these chromosomal regions in different aneurysm patient groups and may further help to unravel the disease pathogenesis of aneurysms in general.
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The incidence of heart failure has been steadily increasing over the past several decades. High readmission rates in patients with acute decompensated heart failure led to the search for biomarkers that could predict future clinical course and would, in an ideal case, enable monitoring of patients with heart failure and guidance of their therapy. ⋯ Other known markers, such as atrial natriuretic peptide and endothelin-1, are currently used for research purposes. The development of additional biomarkers will be an important step from improving diagnosis and treatment of patients with chronic and acute decompensated heart failure.
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Cardiovasc. Pathol. · Jul 2005
ReviewTwenty years of progress and beckoning frontiers in cardiovascular pathology: cardiomyopathies.
In the last 20 years, with the advent of cardiac transplantation and the availability of molecular biology techniques, major advancements were achieved in the understanding of cardiomyopathies. Novel cardiomyopathies have been discovered (arrhythmogenic right ventricular, primary restrictive, and noncompacted myocardium) and added in the update of WHO classification. ⋯ The extraordinary progress accomplished in molecular genetics of inherited cardiomyopathies allowed to establish hypertrophic and restrictive cardiomyopathies as sarcomeric ("force generation") diseases, dilated cardiomyopathies as cytoskeleton ("force transmission") disease, and arrhythmogenic right ventricular cardiomyopathy (ARVC) as cell junction disease. If we consider also cardiomyopathy as ion channel disease (long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia), because they are diseases of the myocardium associated with electrical dysfunction, then a genomic/postgenomic classification of inherited cardiomyopathies may be put forward: cytoskeletal cardiomyopathy, sarcomeric cardiomyopathy, cell junction cardiomyopathy and ion channel cardiomyopathy.