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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fatty liver is extremely common in insulin-resistant patients with either obesity or lipodystrophy and it has been proposed that hepatic steatosis be considered an additional feature of the metabolic syndrome. Although insulin resistance can promote fatty liver, excessive hepatic accumulation of fat can also promote insulin resistance and could contribute to the pathogenesis of the metabolic syndrome. We sought to create a new nonobese rat model with hypertension, hepatic steatosis, and the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein (SREBP-1a) in the spontaneously hypertensive rat (SHR). SREBPs are transcription factors that activate the expression of multiple genes involved in the hepatic synthesis of cholesterol, triglycerides, and fatty acids. The new transgenic strain of SHR overexpressing a dominant-positive form of human SREBP-1a under control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibited marked hepatic steatosis with major biochemical features of the metabolic syndrome, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Both oxidative and nonoxidative skeletal muscle glucose metabolism were significantly impaired in the SHR transgenic strain and glucose tolerance deteriorated as the animals aged. The SHR transgenic strain also exhibited reduced body weight and reduced adipose tissue stores; however, the level of hypertension in the transgenic SHR was similar to that in the nontransgenic SHR control. The transgenic SHR overexpressing SREBP-1a represents a nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension that may provide new opportunities for studying the pathogenesis and treatment of the metabolic syndrome associated with hepatic steatosis.
Hypertension 2005 May
PMID:A new transgenic rat model of hepatic steatosis and the metabolic syndrome. 1580 59

Our objective is to analyse patients diagnosed with late-stage HIV infection in the highly active antiretroviral therapy (HAART) area. A prospective, observational study of all patients with an initial CD4 < 50 x 10(6)/L was carried out. Epidemiological, clinical and HAART-associated data were analysed. Survival rates were estimated and pairs of survival curves were compared. The statistical program used was SPSS (version 10). In all, 349 HIV-infected patients were diagnosed, 117 (33.5%) had late-stage disease, mean CD4 23.9 x 10(6)/L and mean viral load (VL) 5.38 log10. In 98 men, mean age 39.5 years, percentage of AIDS cases at their first attendance was 83.8%. The median follow-up period was 28 months and 27 died. Pneumocystis carinii was the most frequent cause of AIDS (24.4%) and death (18.5%). Survival rates at 12, 24 and 36 months were 95.6%, 85.8% and 72.4%. HAART was started in 82.1%. VLs < 50 copies/mL at one, two and three years of treatment were 55.2%, 55.7% and 58.0%. Resource utilization included 0.58 hospitalization/patient/year and 0.07 events/patient/year. HAART-related complications were as follows: 50% lipodystrophy, 9.7% hypertension, 22.2% hyperglycaemia, 26.4% hypercholesterolaemia, 31.9% hypertrygliceridaemia and 18.1% mixed hyperlipaemia. Over one-third of our patients have advanced HIV infection at diagnosis. However, the outcome is favourable, with a good immunovirological response and few new opportunistic events. HAART-related complications were frequent.
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PMID:Study of patients diagnosed with advanced HIV in the HAART era--OMEGA Cohort. 1582 28

Use of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection is associated with the development of cardiovascular risk factors, including dyslipidemia, insulin resistance, fat redistribution, and hypertension. The results of the Data Collection on Adverse Events of Anti-HIV Drugs study showed that HAART therapy is associated with a 26% relative risk increase in the rate of myocardial infarction per year of HAART exposure. A number of studies have shown that insulin resistance often precedes lipodystrophy, suggesting that insulin resistance may be a primary feature of the metabolic syndrome in this population. The rate-limiting step in the uptake of glucose is glucose transport, and the predominant glucose transporter (GLUT) in muscle and fat is GLUT-4. Specific protease inhibitors (PIs) have been associated with decreased GLUT-4-mediated glucose transport and insulin resistance both in vitro and in vivo, whereas newer protease inhibitors may have fewer effects on insulin sensitivity. Data also suggest that endothelial dysfunction, impaired fibrinolysis, and excess inflammation may contribute to increased cardiovascular risk in the population infected with HIV. Moreover, recent data suggest that evidence for coronary atherosclerotic disease can be revealed by means of carotid intimal medial thickness (IMT) assessments in specific groups of HIV patients. Pharmacologic strategies for the prevention and/or treatment of HAART-induced dyslipidemia and abnormal glucose homeostasis include 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), resins, nicotinic acid, fibrates, and insulin-sensitizing agents. However, newer PIs such as atazanavir may result in less insulin resistance and dyslipidemia and, as part of a HAART regimen, use of atazanavir may reduce the metabolic complications associated with HAART.
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PMID:Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. 1590 92

The HIV lipodystrophy syndrome, a condition characterized by subcutaneous fat loss sometimes associated with relative or absolute accumulation of central fat, has a high prevalence in the treatment of HIV infection. Associated metabolic alterations include peripheral and hepatic insulin resistance, impaired glucose tolerance, type 2 diabetes, hypertriglyceridemia, hypercholesterolemia, increased free fatty acids, and decreased HDL. Often, these metabolic abnormalities appear or deteriorate before the manifestation of fat redistribution. Hypertriglyceridemia is the leading lipid abnormality after initiation of HIV therapy frequently observed together with low HDL cholesterol. Raised levels of tissue plasminogen activator and plasminogen activator inhibitor-1 have been found in these patients, and there are reports about hypertension associated with antiretroviral therapy. Thus, the lipodystrophy syndrome in HIV therapy resembles a clinical situation that is known as the "metabolic syndrome" in HIV-negative patients. There is now good evidence that the metabolic abnormalities of HIV-infected patients harbor a significant risk for cardiovascular disease with as yet unknown consequences. In addition, several studies report a reduced quality of life in patients with body habitus changes leading to reduced therapy adherence. Current data indicate a rather multifactorial pathogenesis where HIV infection, its therapy, and patient-related factors are major contributors. Therapeutic and preventive strategies have, so far, been of only limited or no success. For reduction of the cardiovascular risk, recommendations proposed for non-HIV-infected patients like the National Cholesterol Education Program (NECP) have been adapted for HIV-infected patients. These should be regarded as rather preliminary and need to be evaluated in further clinical trials. General recommendations include dietary changes and physical activity, switch of antiretroviral drugs (replacement of protease inhibitors), and, finally, use of metabolically active drugs. Lipid-lowering agents can be considered for the treatment of severe hypertriglyceridemia, elevated LDL, or a combination of both. Some HMG-CoA reductase inhibitors, however, share common hepatic metabolization pathways with protease inhibitors (cytochrome P450 3A4 system), thereby potentially leading to additional liver and muscle toxicity. Although clinicians should assess cardiovascular risk factors and target risk reduction in HIV-infected patients, the primary goal in HIV therapy remains to be the effective suppression of viral replication leading to reduced morbidity and mortality.
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PMID:[Metabolic syndrome and hyperlipidemia in HIV-positive patients]. 1617 Jun 75

Insulin resistance is accepted as the underlying fundamental defect that predates and ultimately leads to the development of type 2 (adult onset) diabetes mellitus in the general non-human immunodeficiency virus (HIV)-infected population. Insulin resistance is also a major component of the metabolic syndrome that, in association with other factors such as hypertension, hypercholesterolemia, and central obesity, defines a pre-diabetic atherogenic state that leads to adverse cardiovascular events. Growing evidence now suggests that mitochondrial dysfunction in skeletal muscle may be the mechanism whereby insulin resistance is induced. The prevalence of insulin resistance, glucose intolerance, and diabetes in the HIV-infected population has dramatically increased following the common use of highly active antiretroviral therapy (HAART). The development of insulin resistance in the HIV-infected population is likely to be multifactorial reflecting genetic predisposition, direct and indirect effects of both the protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NRTI) class of antiretroviral therapy, and a possible contribution from chronic inflammatory changes induced by HIV. Indirect effects of antiretroviral therapy on insulin resistance may be mediated through both the visceral adiposity and peripheral fat depletion components of lipodystrophy as well as through fatty infiltration in liver and muscle. Based on current knowledge, mitochondrial dysfunction can be hypothesized to play a key role in each of these components.
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PMID:Insulin resistance in the HIV-infected population: the potential role of mitochondrial dysfunction. 1618 Nov 44

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV disease, with longer survival and improved quality of life of HIV-infected subjects. However, HAART regimens, especially those including protease inhibitors (PIs) have been shown to cause in a high proportion of HIV-infected patients a metabolic syndrome that may be associated with an increased risk of cardiovascular disease (about 1.4 cardiac events per 1,000 years of therapy according to the Framingham score). Metabolic features associated with somatic changes (lipodystrophy/lipoatrophy) include dyslipidemia (about 70% of patients), insulin resistance (elevated C-peptide and insulin), type 2 diabetes mellitus (8%-10% of the patients), hypertension (up to 75% of patients), coagulation abnormalities (25% of patients), lactic acidemia, and elevated hepatic transaminases (nonalcoholic steatohepatitis). HAART-associated metabolic syndrome is an increasingly recognized clinical entity. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the cardiovascular risk in patients under HAART. A careful stratification of the cardiovascular risk and cardiovascular monitoring of patients under HAART is needed according to the most recent clinical guidelines.
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PMID:Highly active antiretroviral therapy-associated metabolic syndrome: pathogenesis and cardiovascular risk. 1677 67

The survival of patients with HIV infection who have access to highly active antiretroviral therapy has dramatically increased. In HIV-infected persons, cardiovascular disease can be associated with HIV infection, opportunistic infections or neoplasias, use of antiretroviral drugs or treatment of opportunistic complications, mode of HIV acquisition (such as intravenous drug use), or with the classic non-HIV-related cardiovascular risk factors (such as smoking or age). Diseases of the heart associated with HIV infection or its opportunistic complications include pericarditis and myocarditis. Pericarditis may lead to pericardial effusion rarely causing tamponade. Cardiomyopathy is often clinically silent with asymptomatic left ventricular systolic dysfunction. Endocarditis is mainly the consequence of intravenous drug abuse, possibly leading to life-threatening valvular insufficiency with the need for cardiac surgery. A further serious condition associated with HIV infection is pulmonary hypertension potentially leading to right heart failure. The cardiovascular complications of HIV infection such as cardiomyopathy and pericarditis have been reduced by highly active antiretroviral therapy, but premature coronary atherosclerosis is now a growing problem because antiretroviral drugs can lead to serious metabolic disturbances resembling those in the metabolic syndrome. Lipodystrophy, a clinical syndrome of peripheral fat wasting, central adiposity, dyslipidemia, and insulin resistance, is most prevalent among patients treated with protease inhibitors. These patients should thus be screened for hyperlipidemia, hyperglycemia, and hypertension, and they may be candidates for lipid-lowering therapies. When initiating lipid-lowering therapy, interactions between statins and HIV protease inhibitors affecting cytochrome P450 function must be considered. Restenosis rate after percutaneous coronary intervention may be unexpectedly high.
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PMID:Cardiovascular disease in HIV infection. 1678 Dec 13

Membranous lipodystrophy represents a peculiar type of fat necrosis that is present in patients with various types of skin disease. It is characterized by the presence of microcysts and macrocysts and is lined by amorphous eosinophilic material with a crenelated arabesque appearance. These findings have been associated with lupus erythematosus, diabetes mellitus, erythema nodosum, trauma, etc. We report a case of a 43-year-old woman who had a red to purple asymptomatic indurated plaque, approximately seven cm in diameter and on the left arm. She was a chronic hepatitis B antigen carrier and had hypertension for four years. Histopathology of the biopsied lesion showed transepidermal elimination of altered collagen and elastic fibers, as well as membranous lipodystrophy changes. There were hypertensive vascular changes including lymphohistiocytic infiltration around the vascular wall, swelling of endothelial cells, increased thickness of the vascular walls, and narrowing of the lumen. We report a case showing transepidermal elimination with membranous lipodystrophy. We carefully suggest that the secondary phenomenon of transepidermal elimination was associated with membranous lipodystrophy and degenerate connective tissues.
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PMID:An unusual case with membranous lipodystrophy in a hypertensive patient with transepidermal elimination. 1680 95

Objective To describe new data about the wide phenotypic variability of diseases due to mutations in the lamin A/C gene (LMNA). Design We report a complex phenotype in a patient with familial partial lipodystrophy of the Dunnigan type (FPLD) and study the frequency of her unusual clinical signs in 19 other LMNA-mutated lipodystrophic patients from 8 different families and 14 non-mutated family members. Case Report The patient was diagnosed with FPLD due to the R482W LMNA mutation after familial screening. Surprisingly, she had no biological signs of insulin resistance. The presence of hypertension with hypokalaemia led to the diagnosis of primary hyperaldosteronism. Thyroid investigations showed a euthyroid multinodular goiter. In addition, the patient exhibited a juvenile akineto-hypertonic syndrome. Results Goiter was identified with a similar frequency (55%) in LMNA-mutated lipodystrophic patients (11 out of 20, originating from 5 families among 8) compared to non-mutated family controls (35%; 5 patients out of 14, all originating from the same family). No case of primary hyperaldosteronism or extrapyramidal syndrome was identified in other studied subjects, either LMNA-mutated or not. Conclusions This R482W-LMNA mutated patient showed an association of features (primary hyperaldosteronism, euthyroid goiter and extra-pyramidal syndrome, raising the question of a link with her laminopathy. Prevalence of goiter tended to be higher in LMNA-mutated than in non-mutated subjects. Hyperaldosteronism seems coincidental. Although extrapyramidal syndrome has never been reported in lipodystrophic patients, it may nevertheless be linked to the LMNA mutation since multiple neurological features have been associated with alterations in lamins A/C.
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PMID:Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular goitre, extrapyramidal syndrome and primary hyperaldosteronism. 1752 34


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