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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV) is now a pandemic. It afflicts multiple organs, including the cardiovascular system. This occurs by direct invasion as well as opportunistic infections complicating acquired immunodeficiency syndrome. The presence of newer highly active antiretroviral therapy has led to longer survival of patients infected with HIV, but the cardiac abnormalities related to HIV have remained less well characterized. It is now evident that cardiac involvement in patients with acquired immunodeficiency syndrome is relatively common. This includes coronary artery disease, dilated cardiomyopathy, pericardial effusion, pulmonary hypertension, and ill effects of highly active antiretroviral therapy in the form of lipodystrophy, lipoatrophy, and dyslipidemia. In fact, HIV can now be viewed as a potential risk factor for coronary artery disease, and the dilemma facing clinicians is how to quantify this risk. Awareness of accelerated coronary artery disease and dilated cardiomyopathy is critical to implement preventive measures early in the course of HIV. However, better guidelines are still needed on the basis of prospective randomized controlled studies involving large populations. In conclusion, this review describes cardiac abnormalities associated with HIV, including possible molecular mechanisms. The co-morbid sequelae, their presentation, and pharmacologic management are also discussed.
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PMID:Cardiovascular manifestations in human immunodeficiency virus-infected patients. 1912 56

The introduction of highly active antiretroviral therapy (HAART) for the treatment of acquired immunodeficiency syndrome (AIDS) has resulted in greater survival of patients infected with the human immunodeficiency virus (HIV). However, the use of these drugs has been associated with lipodystrophic syndrome (LS), which is characterized by metabolic alterations (dyslipidemia, insulin resistance, diabetes, and lactic acidosis) and abnormal corporal fat distribution. Clinically, LS may manifest as three different forms: lipohipertrophy (accumulation of fat in the central part of the body), lipoatrophy (loss of fat in the extremities, face and buttocks) and mixed (lipohipertrophy + lipoatrophy). Although its physiopathology has not been elucidated, some mechanisms have been described, including leptin and adiponectin deficiency, mitochondrial dysfunction and use of antiretroviral drugs. The type, dose and duration of the antiretroviral treatment, as well as age and puberty are the main risk factors. LS is also associated with increased incidence of cardiovascular illnesses, atherosclerosis and diabetes mellitus. Treatment includes physical activity, cautious restriction of caloric intake, changes in antiretroviral therapy, and use of insulin-sensitizing and lipid-lowering agents. Follow up must be periodic, consisting of measurement of body fat distribution, evaluation of the lipid profile and insulin resistance.
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PMID:Lipodystrophic syndrome in children and adolescents infected with the human immunodeficiency virus. 1903 Jul 39

The introduction of newer antiretroviral drugs has provided greater levels of HIV suppression with fewer of the metabolic effects, lipoatrophy, and body habitus changes associated with earlier therapies. Previously classified under the collective term, lipodystrophy, lipoatrophy and body-fat changes are now known to occur independently in some HIV-infected patients, depending on the type and duration of antiretroviral therapy and a myriad of factors including HIV infection alone that contribute significantly to these changes. This article reviews the current scientific literature and recent clinical trial results that distinguish lipoatrophy or dyslipidemia pathophysiologically from body-fat changes seen as central and peripheral lipohypertrophy and fat redistribution, as well as the nature and extent of changes associated with HIV infection alone and newer antiretroviral therapies. This information may assist physicians in identifying individual risk factors and choosing the type of antiretroviral therapy that may minimize these changes without loss of virologic suppression.
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PMID:Body-fat abnormalities in patients with HIV: progress and challenges. 1905 8

Metabolic complications associated with HIV infection and treatment frequently present as a relative lack of peripheral adipose tissue associated with dyslipidemia and insulin resistance. In this review we explain the connection between abnormalities of intermediary metabolism, observed either in vitro or in vivo, and this group of metabolic effects. We review molecular mechanisms by which the HIV protease inhibitor (PI) class of drugs may affect the normal stimulatory effect of insulin on glucose and fat storage. We then propose that both chronic inflammation from HIV infection and treatment with some drugs in this class trigger cellular homeostatic stress responses with adverse effects on intermediary metabolism. The physiologic outcome is such that total adipocyte storage capacity is decreased, and the remaining adipocytes resist further fat storage. The excess circulating and dietary lipid metabolites, normally "absorbed" by adipose tissue, are deposited ectopically in lean (muscle and liver) tissue, where they impair insulin action. This process leads to a pathologic cycle of lipotoxicity and lipoatrophy and a clinical phenotype of body fat distribution with elevated waist-to-hip ratio similar to the metabolic syndrome.
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PMID:The role of protease inhibitors in the pathogenesis of HIV-associated lipodystrophy: cellular mechanisms and clinical implications. 1917 28

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of HIV disease with increased survival rates. However, some HAART regimens, especially those including protease inhibitors, have been shown to cause in a high proportion of HIV-infected patients metabolic (dyslipidemia, insulin resistance) and somatic (lipodystrophy/lipoatrophy) changes that are associated with an increased risk of cardiovascular disease (coronary artery disease and stroke). The pathogenesis of HAART-associated metabolic syndrome and of its atherogenic profile is complex, and several factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, activation of proinflammatory cytokines, and mitochondrial dysfunction. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients facing long-term HAART.
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PMID:Metabolic syndrome associated with HIV and highly active antiretroviral therapy. 1919 23

Lipodystrophy syndrome (LS) has been reported as visible markers that can identify HIV status. Changes in body shape are detrimental in terms of psychological welfare and may affect well-being and increase the stigma associated with HIV disease. In the current study, the psychosocial impact of LS was evaluated. A total of 84 HIV-infected patients receiving antiretroviral therapy and exhibiting dyslipidemia were interviewed in an urban hospital setting in Brazil in 2006 using a standardized questionnaire. Of the 84 patients exhibiting dyslipidemia, 40 patients also exhibited body changes, and of these, 25 had facial lipoatrophy. From a psychosocial perspective, patients presenting with facial lipoatrophy reported alterations in self-image and self-esteem and believed that other people noticed their body changes. The results are relevant for nurses who need to be well-prepared to recognize lipodystrophy, to implement nursing interventions including lifestyle changes, and to provide psychosocial support to patients with LS.
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PMID:Facial lipoatrophy: appearances are not deceiving. 1942 94

Patients treated with highly active antiretroviral therapy may develop metabolic side effects such as hyperlipidemia, insulin resistance, lipoatrophy and lactic acidosis. The pathophysiology of these metabolic abnormalities is unknown, although some, e.g., lactic acidosis and lipoatrophy, are more associated with nucleoside use while protease inhibitors (PIs) have been shown to contribute to hyperlipidemia and insulin resistance. Identifying new PIs that are not associated with dyslipidemia has been hindered by the lack of mechanistic information and the unavailability of relevant animal models. In order to understand the molecular mechanism behind the hyperlipidemia associated with other protease inhibitors, and to develop a more effective, faster screen for compounds with this liability, we have analyzed expression profiles from PI-treated animals. Previously, we have shown that treatment of rats with ritonavir results in increases in the expression of proteasomal subunit genes in the liver. We show this increase is similar in rats treated with bortezomib, a proteasome inhibitor. In addition, we have treated rats with additional protease inhibitors, including atazanavir, which is associated with lower rates of lipid elevations in the clinic when administered in the absence of ritonavir. Our results indicate a strong correlation between proteasomal induction and lipid elevations, and have allowed us to develop a rapid screen for identifying novel PIs that do not induce the proteasome.
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PMID:Identification of proteasome gene regulation in a rat model for HIV protease inhibitor-induced hyperlipidemia. 2022 37

Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2(AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARgamma. Importantly, lamin A/Cmutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their etiology is generally unknown, they could be associated with signs of autoimmunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first-generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardiovascular and hepatic complications.
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PMID:Human lipodystrophies: genetic and acquired diseases of adipose tissue. 2055 64

Adipose tissue redistribution occurred at first in HIV-infected patients about 15 years ago after initiation of combination antiretroviral treatment (ART) and the responsibility of drugs was rapidly considered. This lipodystrophic syndrome can associate lipoatrophy, affecting subcutaneous adipose tissue in priority with fat hypertrophy, in particular in the upper part of the body, and metabolic alterations, dyslipidemia and altered glucose tolerance with insulin resistance. The primary role of thymidine analogue reverse transcriptase inhibitors (tNRTI) in peripheral lipoatrophy has been clearly shown in vitro and in vivo, these drugs inducing a severe mitochondrial dysfunction and an increased oxidative stress together with fat inflammation leading to fat loss. In vitro and in vivo studies suggest that some protease inhibitors (PI) or non-NRTIs also exert adverse effects on adipocytes and could act in synergy to amplify the effect of tNRTI. While severe lipoatrophy is now less prevalent in HIV-infected patients, fat hypertrophy is frequently observed: a role for drugs from the different classes acting in synergy to induce fat hyperplasia and hypertrophy is suggested, with milder mitochondrial dysfunction but increased inflammation and activation of the cortisol system. In addition, it is now considered that long-term viral infection, even if controlled, could induce low-grade inflammation and prepare fat to the deleterious effect of ART. Both lipoatrophy and lipohypertrophy are involved in metabolic disorders and increased cardio-metabolic risk that likely participate to early aging reported in these patients. ART can also be directly responsible for metabolic alterations. Strategies to revert or reduce lipodystrophy are important to consider in these patients in addition to the required control of the metabolic disorders.
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PMID:Adipose tissue as a target of HIV-1 antiretroviral drugs. Potential consequences on metabolic regulations. 2068 86

Genetic screening for HIV-related complications is emerging as a clinically relevant prediction tool. A number of single nucleotide polymorphisms associated with conditions such as dyslipidemia and type 2 diabetes have been identified in both the general population and in HIV-infected individuals. Additionally, genome-wide association studies have looked at hepatitis C susceptibility in HIV-infected people, and genetic studies are ongoing for coronary artery disease, osteoporosis, and neurocognitive dysfunction. To date, understanding the contribution of genetic variation to the pathogenesis of lipoatrophy and kidney disease in HIV-infection is limited.
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PMID:Genetic screening for metabolic and age-related complications in HIV-infected persons. 2117 Mar 75


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