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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A wide range of morphologic alterations and lipid metabolism abnormalities have been recently described in HIV-infected patients receiving a protease inhibitor-based highly active antiretroviral therapy. The hyperlipidaemia may involve up to 70-80% of HIV-positive subjects treated with a protease inhibitor-containing regimen, and it is frequently (but not always) associated with the fat redistribution syndrome or lipodystrophy. The potential clinico-pathological consequences of HIV-associated hyperlipidaemia are not completely known, but several anecdotal observations reported an increased risk of prematury coronary artery diseases in young HIV-positive individuals receiving protease inhibitors, besides peripheral atherosclerosis and acute pancreatitis. A hypolipidaemic diet and regular physical exercise may act favourably on dyslipidaemia, but pharmacological therapy becomes necessary when hyperlipidaemia is severe or pesists for a long time. The choice of hypolipidaemic drugs is problematic because of potential pharmacological interactions with antiretroviral compounds and other antimicrobial agents, associated with an increased risk of toxicity and intolerance.
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PMID:[Lipodystrophy and lipid metabolism alterations in HIV-infected patients receiving highly active antiretroviral therapy (HAART)]. 1520 80

Body fat changes and metabolic abnormalities such as hyperlipidaemia and diabetes have been increasingly reported following the successful introduction of highly active antiretroviral therapy (HAART). These side effects were attributed initially to the use of protease inhibitors (PIs). As a consequence, a series of trials were conducted where patients with well-controlled HIV viraemia either continued on PIs or were switched to a simplified maintenance therapy (SMT) without PIs. Evidence from these trials is still insufficient to show that switching from PIs to either abacavir, nevirapine or efavirenz is safe. However, patients with suboptimal pre-HAART treatment are at increased risk of virological failure if switched to an SMT. Patients switched from PI regimens tend to stay longer on an SMT and those switched to abacavir show a reduction in total cholesterol, but there is no evidence of any additional benefit from non-PI-based SMT. There is a clear need for a better understanding of HAART-related lipodystrophy and metabolic toxicity, and pharmacogenetic tests to identify those patients most at risk. The advent of simpler formulations for all drug classes, and new PIs with less metabolic toxicity, is likely to reshape completely the role of SMT.
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PMID:Protease inhibitor-sparing simplified maintenance therapy: a need for perspective. 1526

HIV infection is a global public health issue that is frequently associated with cardiovascular involvement. These HIV-associated cardiovascular manifestations are often clinically occult or attributed incorrectly to other non-cardiac disease processes. A heightened awareness and routine screening for cardiovascular involvement in HIV-infected patients leads to earlier detection and the hope for a reduction in associated morbidity and mortality. Left ventricular dysfunction, an independent predictor of mortality in HIV-infected patients, is the result of many causes in this population and may result in dilated cardiomyopathy and congestive heart failure in about 10% of patients. Other HIV-associated cardiovascular problems include infective endocarditis, cardiovascular malignancy, pulmonary arterial hypertension, vasculitis, pericardial effusion, premature atherosclerosis, and arrhythmias. HIV-associated cardiovascular emergencies include congestive heart failure, pulmonary edema, supraventricular and ventricular arrhythmias, endocarditis, and tamponade. Anti-infective and immunomodulatory therapies may be particularly helpful in this population to reduce associated cardiovascular disease. Highly active antiretroviral therapy may result in lipodystrophy, hyperlipidemia, truncal adiposity, and insulin resistance that can be improved by physical activity and training programs. Cardiovascular complications of therapeutic drugs in HIV-infected patients include torsade de pointes, congestive heart failure, dyslipidemia, accelerated atherosclerosis, and myocardial infarction. In summary, cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients that can be detected early in many cases and treated effectively.
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PMID:HIV-related cardiovascular disease and drug interactions. 1544 73

Widespread use of highly active antiretroviral therapy (HAART) to manage HIV infection is now associated with the development of lipodystrophy syndrome. This syndrome is a combination of such morphologic and metabolic changes as hyperlipidemia, fat redistribution, and insulin resistance. Although many of the long-term effects of HAART have not been fully recognized, it is thought that lipodystrophy syndrome may now contribute to early-onset hypercholesterolemia, heart disease, and diabetes, and may have a negative psychological impact on the individual living with HIV infection.
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PMID:Lipodystrophy syndrome: the morphologic and metabolic effects of antiretroviral therapy in HIV infection. 1553 16

The use of highly active anti-retroviral therapy (HAART) is associated with long-term adverse metabolic events including lipodystrophy, dyslipidemia, and insulin resistance. The purpose of the present study was to prospectively examine the mechanism of HAART-induced hyperlipidemia in HIV-seropositive, HAART-naive men prior to the development of frank lipodystrophy. Patient's (n = 13) weight, BMI, lean mass, and percent fat mass, waist circumference did not change after 8 weeks of treatment with HAART. Plasma FFA concentration was already elevated in HAART-naive patients compared to healthy, untreated, HIV negative control individuals and was further increased after 8 weeks of HAART in the former. Insulin-mediated suppression of plasma FFA concentrations was impaired both prior to and following introduction of HAART, compared to healthy, matched controls. VLDL-apoB and VLDL-TG concentrations rose significantly from normal levels after HAART. Compared to healthy control subjects, VLDL fractional catabolic rate and clearance in HIV-seropositive individuals was reduced by approximately 40%, a defect that was not corrected after HAART. The increase in VLDL after HAART was explained by an increase of VLDL-apoB and VLDL-TG secretion towards normal while the impaired VLDL clearance remained unchanged. We conclude that elevation of circulating VLDL early in the course of HAART is caused by the combination of impaired VLDL clearance already present in HAART-naive HIV-seropositive patients and HAART-mediated increase in VLDL secretion. These changes occur concomitantly with an elevation of plasma free fatty acids but before significant change in body composition.
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PMID:Mechanism of highly active anti-retroviral therapy-induced hyperlipidemia in HIV-infected individuals. 1558 14

Accumulation of dorsocervical fat, or a "buffalo hump" (BH), is commonly reported in adults with HIV-associated lipodystrophy (HIVLD). The pathogenesis underlying this aspect of a syndrome characterized by loss of subcutaneous fat from other body sites is poorly understood. We aimed to identify risk factors for a BH in HIV-infected adults in cross-sectional analyses of 2 HIV-infected ambulatory populations. The first group (Australian Lipodystrophy Prevalence Survey [APS]) consisted of 1348 Australian HIV-infected adults (95% male) irrespective of changes in body composition. The second group (Lipodystrophy Case Definition [LDCD] study) comprised 417 subjects (83% male) with at least 1 reported moderate or severe feature of HIVLD. A BH was reported in 24 (2%) APS subjects and 79 (19%) LDCD study subjects. A BH was not an isolated finding. Patients with a BH had a high prevalence of other features of HIVLD, similar to lipodystrophic patients without a BH, such as facial lipoatrophy reported in 100% and 61% BH-positive subjects from the APS and LDCD study, respectively. In both groups, those with a BH had higher fasting insulin (P<or=0.007), a higher body mass index (P<or=0.003), a higher waist/hip ratio (P<or=0.001), higher limb fat (P<or=0.003), and higher systolic blood pressure (P<0.05). On multivariate analysis, higher serum insulin, systolic blood pressure, age, and duration of exposure to ritonavir were independently associated with a BH in the APS group. In the LDCD group, higher insulin, diastolic blood pressure, and duration of exposure to zidovudine were independently associated with a BH. There was no association between a BH and hyperlipidemia. These data show that a BH is associated with other physical features of the lipodystrophy phenotype and suggest that hyperinsulinemia, a feature common to HIVLD, obesity, and hypercortisolism, is an important component of this phenotype, thus warranting closer monitoring of BH-positive patients for glucose intolerance and diabetes.
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PMID:Buffalo hump seen in HIV-associated lipodystrophy is associated with hyperinsulinemia but not dyslipidemia. 1567

Highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection, but the presence of adverse events may limit its efficacy. Nucleoside reverse transcriptase inhibitors can cause mitochondrial toxicity and anemia, non-nucleoside reverse transcriptase inhibitors are associated with rash and central nervous system disturbance; protease inhibitors elicit gastrointestinal adverse effects and metabolic abnormalities including lipodystrophy syndrome, hyperlipidemia and insulin resistance. These complications have the potential to increase morbidity and mortality significantly in those requiring long-term treatment of HIV-infection. The presence of such abnormalities also has an impact on adherence to treatment. Besides providing health benefits, HAART may have a negative impact on patients' quality of life. Identifying and treating these complications has important implications for patient survival.
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PMID:[Side effects of antiretroviral therapy]. 1568 51

The metabolic consequences of HIV and AIDS are accentuated in the setting of highly active antiretroviral therapy. Peripheral lipodystrophy, central adiposity, hyperlipidaemia, insulin resistance and diabetes mellitus are frequent associations of protease inhibitor containing highly active antiretroviral therapy regimens. Ninety patients aged 25-50 years (males 52, females 38), seropositive for HIV 1 and 2 or both were selected to see the glycaemic profiles in asymptomatic early HIV disease with CD4 counts > 100/microl and to compare this with the glycaemic profile of (a) advanced HIV disease (CD4 counts < 200/microl), not on highly active antiretroviral therapy and (b) advanced HIV disease (CD4 counts < 200/microl), on uninterrupted non-protease inhibitor highly active antiretroviral therapy > 6 months. All the patients were grouped into 3: (1) Group A: CD4 counts > 500/microl (n=37), highly active antiretroviral therapy naive, (2) group B: CD4 counts < 200/microl (n=21), not on highly active antiretroviral therapy, and (3) group C: CD4 counts < 200/microl, receiving uninterrupted non-protease inhibitor based highly active antiretroviral therapy for > 6 months (n=32). The fasting blood glucose, glycosylated Hb (HbA1c) levels, were measured in all the patients in 3 groups and significance of difference between means was calculated among various groups. Body weight and waist-hip ratio were also measured. The results were analysed and compared with other studies.
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PMID:Glycaemic consequences of HIV and highly active antiretroviral therapy: a pilot study and review of literature. 1571 8

Xanthomas most often occur in conjunction with a primary or secondary disorder of lipid metabolism. A range of metabolic disturbances has been described in association with protease inhibitors, including lipodystrophy, hyperglycemia, and hyperlipidemia. Ritonavir has been repeatedly shown to be the most common protease inhibitor to induce these metabolic abnormalities. This report highlights a case of both tuberous and tendinous xanthomata secondary to ritonavir-associated hyperlipidemia.
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PMID:Tuberous and tendinous xanthomata secondary to ritonavir-associated hyperlipidemia. 1585 17

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


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