Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At present, there is growing evidence implicating GH and/or IGF-I in the intricate cascade of events connected with the regulation of heart development and hypertrophy. Moreover, GH excess and/or deficiency have been shown to include in their advanced clinical manifestations almost always an impaired cardiac function, which may reduce life expectancy. This finding is related both to a primitive impairment of heart structure and function and to metabolic changes such as hyperlipidemia, increase of body fat and premature atherosclerosis. Patients with childhood or adulthood-onset GH deficiency have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remain markedly depressed during exercise. Conversely, in acromegaly the cardiac enlargement, which is disproportionate to the increase in size of other internal body organs, has been a rather uniform finding. The severity of the acromegalic cardiomyopathy was reported to be correlated better with the disease duration than with circulating GH and/or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often results in concentric hypertrophy of both ventricles. The treatment of GH deficiency and excess improved cardiac function. Interestingly, based on the evidence that GH increases cardiac mass, recombinant GH was administered to patients with idiopathic dilated cardiomyopathy. It increased the myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement of hemodynamics, myocardial energy metabolism and clinical status. These promising results open new perspectives for the use of GH in heart failure.
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PMID:Is growth hormone bad for your heart? Cardiovascular impact of GH deficiency and of acromegaly. 938 93

High vascular morbidity and mortality is associated with acromegaly. The aim of the present study was to assess the effects of octreotide therapy on several known cardiovascular risk factors and to correlate them with octreotide-induced hormonal changes. Lipid levels, LDL particle size distribution as evaluated by single vertical spin density gradient ultracentrifugation, apolipoproteins AI and B, lipoprotein (a) [Lp(a)] concentrations and apo(a) phenotypes were evaluated in 20 non-diabetic acromegalic patients (6 M, 14 F), with normal thyroid, adrenal and gonadal function, aged 29-66 years. Normal subjects (20), matched for age, sex and BMI served as control for lipid variables. Acromegalic patients were characterized by lower HDL cholesterol (and apoA-I) and by higher Lp(a) concentrations in comparison to controls. Treatment with octreotide (100 microg t.i.d. for 3 months) led to: an increase in HDL cholesterol (median: + 22%), a decrease in LDL cholesterol (-14%) and a decrease of the Lp(a) levels (all phenotypes) (-28%). The expected decreases of IGF-I levels (median: -48%) and 7-h AUC of GH (-50%), insulin (-40%) and glucagon (-20%) were observed. Only Lp(a) modifications showed a correlation with GH modifications. The study of LDL physical properties showed that acromegalic patients had smaller and/or more dense LDL particles, in comparison with normal controls (relative flotation rate, Rf: 0.40 +/- 0.03 versus 0.42 +/- 0.02 P < 0q05), an alteration that might contribute to the high vascular risk of acromegalic patients. However, the LDL subfraction distribution remained unmodified during octreotide therapy (Rf 0.39 +/- 0.03). In conclusion, this study shows that in acromegalic patients octreotide treatment is indeed associated with an amelioration of some lipoprotein parameters, i.e. LDL, HDL, and Lp(a) concentrations. However, this treatment has no effect on the small and/or dense LDL particles present in these patients.
Atherosclerosis 2000 Aug
PMID:LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients. Effects of octreotide therapy. Italian Multicenter Octreotide Study Group. 1092 34

Growth hormone (GH) deficiency and acromegaly may be associated with increased cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transferase (LCAT) has the ability to esterify free cholesterol (FC) in HDL. Cholesteryl ester transfer protein (CETP) is able to transfer cholesteryl esters (CE) from HDL to very low and low density lipoproteins (VLDL and LDL). During phospholipid transfer protein (PLTP)-mediated HDL remodelling, small pre beta-HDL particles are generated which serve as acceptors for cellular cholesterol and provide the initial LCAT-substrate. We documented plasma lipids, LCAT, CETP and PLTP activity levels as well as plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) in 12 adult men with acquired GH deficiency, 12 acromegalic men and 24 healthy male subjects. All GH deficient and acromegalic patients received conventional hormonal replacement therapy if necessary. VLDL + LDL cholesterol and plasma triglycerides were higher in GH deficient (P < 0.01 and P < 0.05) and acromegalic patients (P < 0.05 and P < 0.01) than in healthy subjects. HDL cholesterol and HDL CE were lower (P < 0.05 for both) and the HDL FC/CE ratio was higher (P < 0.01) in these patient groups compared to healthy subjects. Plasma LCAT, CETP and PLTP activity levels were lower in acromegalic patients (P < 0.01 for all) and CETP activity was lower in GH deficient patients (P < 0.01) compared to healthy subjects. Plasma EST and CET were decreased in both acromegalic (P < 0.01 for both) and GH deficient patients (P < 0.05 for both). Multiple regression analysis demonstrated independent negative relationships of plasma insulin-like growth factor I with plasma LCAT (P = 0.0001), CETP (P = 0.009) and PLTP activity levels (P = 0.021). Plasma LCAT (P = 0.0001) and CETP activity (P = 0.0001) were also negatively associated with (substitution therapy for) adrenal insufficiency. In conclusion, GH deficient and acromegalic patients show abnormalities in HDL, consistent with impaired LCAT action. Decreases in plasma EST and CET in such patients, as well as a low PLTP activity in acromegaly suggest that reverse cholesterol transport may be impaired, contributing to increased cardiovascular risk.
Atherosclerosis 2000 Dec
PMID:Low plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins. 1116 39

Cardiovascular disease is a common finding in patients with acromegaly. In such patients, heart failure frequently leads to death. Cardiovascular manifestations of acromegaly include cardiomegaly and very often hypertension, coronary atherosclerosis, and diabetes. Primary valvular disease is less commonly observed. Because it is not clear whether acromegaly-related cardiomyopathy is a specific entity and since there are not many necropsy reports regarding mitral valve prolapse in acromegalic patients, we report the case of severe mitral regurgitation due to rupture of the chordae tendinae in a patient with mitral valve prolapse and acromegaly.
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PMID:[Severe mitral insufficiency caused by the rupture of the chordae tendinae in acromegaly. Report of a case]. 1167 23

Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.
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PMID:Cardiovascular complications in acromegaly: methods of assessment. 1250 75

Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment. There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival. In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly. Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease. There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles. Left ventricular hypertrophy is common even in young patients with short duration of disease. Some of these structural changes can be reversed by effective treatment. Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced. Diastolic function improves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits. What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture. The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment. Similarly, early arterial structural changes, such as thickened intima media layer, appear more common in acromegalics, and there are hints that this may diminish with effective treatment, although more studies are required for a definite conclusion on this topic. In conclusion, impaired cardiac and endothelial structure and function in acromegaly are risk factors for vascular mortality and should be regarded as legitimate therapeutic targets in the overall management of this condition.
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PMID:Cardiovascular function in acromegaly. 1278 99

A substantial and increasing proportion of death and disability in the EU (and elsewhere) is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity). Beside type II diabetes, other diseases like obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian syndrome, and acromegaly are indeed associated with insulin resistance.
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PMID:The insulin-sensitive side of SHIP2. 1280 74

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.
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PMID:Systemic complications of acromegaly: epidemiology, pathogenesis, and management. 1476 29

Atherosclerosis and insulin resistance are common complications of adult growth hormone deficiency (GHD) and acromegaly. Circulating adiponectin, an adipocyte-derived protein, has both anti-atherogenic and insulin-sensitising effects. In this study, we measured serum adiponectin levels in patients with either adult GHD or acromegaly to clarify the impact of GH secretory states on the regulation of serum adiponectin levels. Serum adiponectin level was measured by radioimmunoassay in 32 patients with adult GHD, 49 patients with acromegaly and 25 normal subjects. The relationships between adiponectin and insulin sensitivity index assessed as quantitative insulin sensitivity check index (QUICKI), BMI, and serum GH and IGF-I levels were then investigated. The values of QUICKI were significantly lower in patients with acromegaly or adult GHD compared to normal subjects (0.33 +/- 0.03, P < 0.01, 0.35 +/- 0.04, P < 0.05 and 0.36 +/- 0.01, respectively). While patients with adult GHD had significantly lower serum adiponectin levels than patients with acromegaly (6.5 +/- 3.9, 9.2 +/- 5.0, P < 0.01) these levels were not significantly different from those found in normal subjects (7.8 +/- 4.3 mug/ml). There was an inverse correlation between serum adiponectin levels and BMI in both patient groups (GHD r = -0.39, P < 0.05; Acromegaly r = -0.35, P < 0.05). However, serum adiponectin levels correlated positively with QUICKI (R(s) = 0.37, P < 0.05) only in patients with adult GHD. In patients with acromegaly, the levels of circulating adiponectin showed an inverse correlation with serum IGF-I levels (R(s) = -0.34, P < 0.05), but not with basal GH levels. These results demonstrate that adiponectin levels are significantly lower in patients with adult GHD than in patients with acromegaly. Adiponectin levels are similar in patients with GHD and healthy controls, whereas in patients with acromegaly, insulin resistance appears to be not closely related to adiponectin levels compared with BMI. The different relationship between adiponectin and QUICKI observed in the adult GHD and acromegaly groups presumably reflects differences in the mechanisms of insulin resistance under states of GH deficiency or excess.
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PMID:Serum adiponectin levels in adult growth hormone deficiency and acromegaly. 1551 53

It is well accepted that mortality in acromegaly is increased because of cardiovascular and respiratory diseases while neoplastic complications account less to mortality. Amongst different cardiovascular complications the most frequent is biventricular hypertrophy, which occurs independently of hypertension and metabolic complications that, in turn, aggravate the cardiomyopathy. Diastolic and systolic dysfunction develops in a variable number of patients, depending on age and disease duration. Other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis and endothelial dysfunction have been less characterized but all appear to be present in acromegaly, depicting the so called "acromegalic cardiomyopathy". The best characterized respiratory disease is the sleep apnea. Ventilatory dysfunction recognizes bony changes of thoracic cage and lung overgrowth as relevant pathogenetic factors. Earlier evidences that patients with acromegaly have an increased risk of developing malignancies have become more realistic in recent years. Most studies have reported an increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment. Malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level and are not a main cause of mortality. Bone changes are also feature of the disease. They involve theoretically all bones and, particularly, the appendicular and the axial skeleton. Patients with long-standing disease are more prone to develop degenerative changes. Control of acromegaly by surgery or pharmacotherapy, especially by somatostatin analogs, improves cardiovascular morbidity and sleep apnea. There is still no demonstration that improvement of different complications corresponds a reduction in mortality.
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PMID:Severe systemic complications of acromegaly. 1611 80


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