Hyperlipidemias: Australia

Simons LA, Sullivan DR. · University of South Wales, Lipid Research Department, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia. · Med J Aust. · Pubmed #15777144 links to  free full text

Abstract: An elevated concentration of low-density-lipoprotein cholesterol (LDL-C) plays a causal role in the development of coronary heart disease and ischaemic stroke. Placebo-controlled intervention studies of statin drugs for lowering LDL-C provide clear evidence of cardiovascular disease prevention. LDL-C concentration below 2.5 mmol/L is an arbitrary goal, and recent trials support the benefit of achieving this goal, or even lower levels. Pharmacological treatment is warranted in patients with high absolute risk of future cardiovascular events. Effective monotherapy is available for predominant hypercholesterolaemia and predominant hypertriglyceridaemia, but combination therapy may be required for severe cases or in those with mixed hyperlipidaemia. Side-effects are infrequent and usually mild, but widespread use of lipid-modifying medication demands caution because of the possibility of muscle or liver dysfunction or drug interactions.

Tomkin GH. · Department of Diabetes and Endocrinology, Trinity College Dublin, The Adelaide and Meath Hospital, Dublin, Ireland. · Ir J Med Sci. · Pubmed #15736358 No free full text.

This publication has no abstract.

Dickinson S, Brand-Miller J. · Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, NSW 2006, Australia. · Curr Opin Lipidol. · Pubmed #15650566 No free full text.

Abstract: PURPOSE OF REVIEW: Several lines of evidence indicate that exaggerated postprandial glycemia puts individuals without diabetes at greater risk of developing cardiovascular disease. In large, prospective observational studies, including meta-analyses, higher 120 min post-load blood glucose and glycated hemoglobin (a measure of average blood glucose level over time) independently predict cardiovascular mortality and morbidity in individuals without diabetes. These findings imply that the glycemic nature of dietary carbohydrates may also be relevant. We aim to provide a clearer perspective on how the glycemic impact of carbohydrates may modulate development of cardiovascular disease. RECENT FINDINGS: In ecological studies, average dietary glycemic index (a measure of the postprandial glycemic potential of carbohydrates) and glycemic load (average glycemic index x amount of carbohydrate) predicts coronary infarct and cardiovascular disease risk factors, including HDL cholesterol, triglycerides and C-reactive protein. In short-term intervention studies of overweight and hyperlipidemic patients, low glycemic index diets lead to improvements in cardiovascular disease risk factors, including reduced LDL cholesterol and improved insulin sensitivity, as well as greater body fat loss on energy-restricted diets. Molecular studies indicate that physiological hyperglycemia induces overproduction of superoxide by the mitochondrial electron-transport chain, resulting in inflammatory responses and endothelial dysfunction. SUMMARY: Taken together, the findings suggest that conventional high-carbohydrate diets with their high glycemic index may be suboptimal, particularly in insulin-resistant individuals. Because around one in four adults has impairments in postprandial glucose regulation, the glycemic potential of carbohydrates warrants further investigation in cardiovascular disease prevention.

Woodman RJ, Chew GT, Watts GF. · School of Medicine and Pharmacology, University of Western Australia, and West Australian Heart Research Institute, Perth, Western Australia, Australia. · Drugs. · Pubmed #15610050 No free full text.

Abstract: Endothelial dysfunction and increased arterial stiffness occur early in the pathogenesis of diabetic vasculopathy. They are both powerful independent predictors of cardiovascular risk. Advances in non-invasive methodologies have led to widespread clinical investigation of these abnormalities in diabetes mellitus, generating a wealth of new knowledge concerning the mechanisms of vascular dysfunction, risk factor associations and potential treatment targets. Endothelial dysfunction primarily reflects decreased availability of nitric oxide (NO), a critical endothelium-derived vasoactive factor with vasodilatory and anti-atherosclerotic properties. Techniques for assessing endothelial dysfunction include ultrasonographic measurement of flow-mediated vasodilatation of the brachial artery and plethysmography measurement of forearm blood flow responses to vasoactive agents. Arterial stiffness may be assessed using pulse wave analysis to generate measures of pulse wave velocity, arterial compliance and wave reflection. The pathogenesis of endothelial dysfunction in type 2 diabetes is multifactorial, with principal contributors being oxidative stress, dyslipidaemia and hyperglycaemia. Elevated blood glucose levels drive production of reactive oxidant species (ROS) via multiple pathways, resulting in uncoupling of mitochondrial oxidative phosphorylation and endothelial NO synthase (eNOS) activity, reducing NO availability and generating further ROS. Hyperglycaemia also contributes to accelerated arterial stiffening by increasing formation of advanced glycation end-products (AGEs), which alter vessel wall structure and function. Diabetic dyslipidaemia is characterised by accumulation of triglyceride-rich lipoproteins, small dense low-density lipoprotein (LDL) particles, reduced high-density lipoprotein (HDL)-cholesterol and increased postprandial free fatty acid flux. These lipid abnormalities contribute to increasing oxidative stress and may directly inhibit eNOS activity. Although lipid-regulating agents such as HMG-CoA reductase inhibitors (statins), fibric acid derivatives (fibrates) and fish oils are used to treat diabetic dyslipidaemia, their impact on vascular function is less clear. Studies in type 2 diabetes have yielded inconsistent results, but this may reflect sampling variation and the potential over-riding influence of oxidative stress, dysglycaemia and insulin resistance on endothelial dysfunction. Results of positive intervention trials suggest that improvement in vascular function is mediated by both lipid and non-lipid mechanisms, including anti-inflammatory, anti-oxidative and direct effects on the arterial wall. Other treatments, such as renin-angiotensin-aldosterone system antagonists, insulin sensitisers and lifestyle-based interventions, have shown beneficial effects on vascular function in type 2 diabetes. Novel approaches, targeting eNOS and AGEs, are under development, as are new lipid-regulating therapies that more effectively lower LDL-cholesterol and raise HDL-cholesterol. Combination therapy may potentially increase therapeutic efficacy and permit use of lower doses, thereby reducing the risk of adverse drug effects and interactions. Concomitant treatments that specifically target oxidative stress may also improve endothelial dysfunction in diabetes. Vascular function studies can be used to explore the therapeutic potential and mechanisms of action of new and established interventions, and provide useful surrogate measures for cardiovascular endpoints in clinical trials.

Nicholls S, Lundman P. · Heart Research Institute, Sydney, Australia. · Semin Vasc Med. · Pubmed #15478040 No free full text.

Abstract: Low-density lipoprotein cholesterol has a well-established role in atherogenesis and the development of coronary heart disease. However, despite effective lowering of low-density lipoprotein cholesterol, many patients continue to have cardiovascular events. It has subsequently emerged that several additional dyslipidemic states promote atherogenesis. In particular, the atherogenic lipoprotein phenotype comprising an elevation of triglycerides and triglyceride-rich lipoproteins; decreased concentrations of high-density lipoprotein cholesterol; and increased small, dense low-density lipoprotein cholesterol, in addition to impaired postprandial lipemia, have been demonstrated to have profound effects on the arterial wall. As such, these factors have become important targets in the development of effective strategies to prevent atherosclerotic cardiovascular disease.

Lau GT, Lowe HC, Kritharides L. · Department of Cardiology, Concord Repatriation General Hospital, Hospital Rd, Concord, NSW 2139, Australia. · Semin Vasc Med. · Pubmed #15478036 No free full text.

Abstract: Coronary artery bypass grafting is an effective treatment for myocardial ischaemia and is particularly important in patients with multivessel disease and diabetes. However, up to 40% of saphenous vein grafts will occlude within 10 years of surgery. The predominant mechanisms for saphenous vein graft disease are thrombosis, intimal hyperplasia, and accelerated atherosclerosis. The pathology of these changes and the role of key factors such as nitric oxide, cellular proliferation, and the role of hypercholesterolemia and hypertriglyceridaemia, are reviewed. Saphenous vein graft disease is among the first cardiovascular conditions to show significant benefit from gene therapy and promises to show remarkable developments in the near future.

Fulcher GR, Amarena JV, Conner GW, Gilbert RE, Hankey GJ, Anonymous00302. · Royal North Shore Hospital, Sydney, NSW. · Med J Aust. · Pubmed #15377260 links to  free full text

This publication has no abstract.

Boak L, Chin-Dusting JP. · Alfred and Baker Medical Unit, Wynn Domain, Baker Heart Research Institute, Melbourne, Australia. · Curr Vasc Pharmacol. · Pubmed #15320832 No free full text.

Abstract: There is increasing evidence that dietary supplementation, such as L-arginine, anti-oxidant vitamins, soy phytoestrogens, flavonoids and omega-3 fatty acids exert vascular protective benefits particularly in terms of restoring endothelial function in cardiovascular disease states. The endothelium has been a major focus over the past 20 years as being a primary site at which dysfunction occurs in association with, and contributing to, vascular pathologies. Such states include mild compromise of the cardiovascular system as observed in smokers, hypercholesterolemics and hypertensives, through to end-point heart failure. This review will focus on the experimental and clinical evidence examining the effect of nutriceuticals on vascular function, in particular endothelium-derived factors, and argues that there is a role for nutriceuticals in the clinical management of the cardiovascular compromised individual.

Whitfield AJ, Barrett PH, van Bockxmeer FM, Burnett JR. · School of Surgery and Pathology, University of Western Australia, Crawley. · Clin Chem. · Pubmed #15308601 links to  free full text

Abstract: BACKGROUND: Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles. CONTENT: The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo- and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described. SUMMARY: Missense mutations in the LDL-receptor-binding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.

Norman PE, Eikelboom JW, Hankey GJ. · School of Surgery and Pathology, Fremantle Hospital, PO Box 480, Fremantle, WA 6959, Australia. · Med J Aust. · Pubmed #15287833 links to  free full text

Abstract: The prevalence of peripheral arterial disease (PAD) in people aged over 55 years is 10%-25% and increases with age; 70%-80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Patients with PAD alone have the same relative risk of death from cardiovascular causes as those with coronary or cerebrovascular disease, and are four times more likely to die within 10 years than patients without the disease. The ankle-brachial pressure index (ABPI) is a simple, non-invasive bedside tool for diagnosing PAD - an ABPI less than 0.9 is considered diagnostic of PAD. About half of patients with PAD (defined by an abnormal ABPI) have symptomatic coronary or cerebral vascular disease. The ABPI is an independent predictor of coronary and cerebrovascular morbidity and mortality. Patients with PAD require medical management to prevent future coronary and cerebral vascular events. There are currently insufficient data to recommend routine population screening for asymptomatic PAD using the ABPI.

Chan DC, Barrett HP, Watts GF. · Lipoprotein Research Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia. · Am J Cardiovasc Drugs. · Pubmed #15285698 No free full text.

Abstract: Visceral obesity is frequently associated with high plasma triglycerides and low plasma high density lipoprotein-cholesterol (HDL-C), and with high plasma concentrations of apolipoprotein B (apoB)-containing lipoproteins. Atherogenic dyslipidemia in these patients may be caused by a combination of overproduction of very low density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance. Weight reduction, increased physical activity, and moderate alcohol intake are first-line therapies to improve lipid abnormalities in visceral obesity. These lifestyle changes can effectively reduce plasma triglycerides and low density lipoprotein-cholesterol (LDL-C), and raise HDL-C. Kinetic studies show that in visceral obesity, weight loss reduces VLDL-apoB secretion and reciprocally upregulates LDL-apoB catabolism, probably owing to reduced visceral fat mass, enhanced insulin sensitivity and decreased hepatic lipogenesis. Adjunctive pharmacologic treatments, such as HMG-CoA reductase inhibitors, fibric acid derivatives, niacin (nicotinic acid), or fish oils, may often be required to further correct the dyslipidemia. Therapeutic improvements in lipid and lipoprotein profiles in visceral obesity can be achieved by several mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. Clinical trials have provided evidence supporting the use of HMG-CoA reductase inhibitors and fibric acid derivatives to treat dyslipidemia in patients with visceral obesity, insulin resistance and type 2 diabetes mellitus. Since drug monotherapy may not adequately optimize dyslipoproteinemia, dual pharmacotherapy may be required, such as HMG-CoA reductase inhibitor/fibric acid derivative, HMG-CoA reductase inhibitor/niacin and HMG-CoA reductase inhibitor/fish oils combinations. Newer therapies, such as cholesterol absorption inhibitors, cholesteryl ester transfer protein antagonists and insulin sensitizers, could also be employed alone or in combination with other agents to optimize treatment. The basis for a multiple approach to correcting dyslipoproteinemia in visceral obesity and the metabolic syndrome relies on understanding the mechanisms of action of the individual therapeutic components.

Barter P. · The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney NSW 2050, Australia. · Endocrinol Metab Clin North Am. · Pubmed #15158525 No free full text.

Abstract: The dyslipidemia typically found in subjects with the metabolic syndrome includes an elevated concentration of plasma triglyceride,a low-density lipoprotein fraction in which the particles are smaller and denser than normal, and a low concentration of highdensity lipoprotein (HDL) cholesterol. This article is concerned with the low HDL component. It provides an overview of HDL structure and metabolism and describes the functions of HDLs that may be cardioprotective. The article then outlines what is known about the concentration and subpopulation distribution of HDLs in the metabolic syndrome. Possible mechanisms responsible for the low HDL are discussed. The consequences of a low HDL concentration in this syndrome are addressed before the article concludes with a discussion of whether low HDL in the metabolic syndrome should be a therapeutic target.

Nelson MR. · Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Victoria. · Aust Fam Physician. · Pubmed #15129461 links to  free full text

Abstract: BACKGROUND: Risk factors tend to cluster and are shared across common diseases seen in general practice. The 'metabolic syndrome' is a cluster of fasting hyperglycaemia, abdominal adiposity, dyslipidaemia and hypertension. This syndrome is associated with both insulin resistance and behaviourally modifiable risk factors such as smoking, physical activity and unhealthy diet. OBJECTIVE: This article aims to provide pragmatic guidance on conditions that are lifestyle based and present as a number of disease states that require multiple interventions. Management of comorbidity and multiple risk factors is discussed using a case vignette. DISCUSSION: Metabolic disease states have common bases and their management is directed toward identifying all the risk factors, establishing absolute risk and intervening sequentially.

Keogh A. · Victor Chang Cardiac Research Institute and Heart Lung Transplant Unit, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia. · J Heart Lung Transplant. · Pubmed #15093806 No free full text.

Abstract: The use of calcineurin inhibitors (CNIs; cyclosporine and tacrolimus) has dramatically increased medium-term life expectancy after heart transplantation but has had only limited impact on long-term outcomes for heart transplant recipients. The original oil-based formulation of cyclosporine has been superceded by a microemulsion formulation (Neoral), which has more predictable pharmacokinetics and allows more precise dose-tailoring. Cyclosporine microemulsion and tacrolimus (Prograf) have a similar efficacy in the prevention of acute rejection of heart transplants, but their use is accompanied by nephrotoxicity and by cardiovascular side effects. The efficacy of immunosuppression can be improved by adjunctive therapy, such as azathioprine, mycophenolate mofetil (MMF; Cellcept), corticosteroids, and induction therapy. One of the most important predictors of patient mortality at >5 years after heart transplantation is cardiac allograft vasculopathy (CAV)/late graft failure, which accounts for 31% of deaths. Neither cyclosporine nor tacrolimus have been shown to prevent the development of CAV. In terms of efficacy, MMF provides a modest advantage over azathioprine in preventing CAV, and the combination of cyclosporine plus MMF results in significantly lower mortality than cyclosporine plus azathioprine. Overall, CNIs have multiple cardiovascular side effects, such as hypertension, hyperlipidemia and new-onset diabetes after transplantation, although cyclosporine and tacrolimus have somewhat different cardiovascular side-effect profiles. The challenge in choosing the best immunosuppressive regimen is to balance efficacy and safety to optimize graft and patient survival over the course of many decades. Because cyclosporine and tacrolimus have similar efficacy against acute rejection the choice of CNI for heart transplant recipients should be based on the relative risk of cardiovascular and renal side effects.

Hughes KJ, Hodgson DR, Dart AJ. · University Veterinary Centre, Faculty of Veterinary Science, The University of Sydney, Werombi Road, Camden, New South Wales 2570. · Aust Vet J. · Pubmed #15088977 No free full text.

This publication has no abstract.

Biden TJ, Robinson D, Cordery D, Hughes WE, Busch AK. · Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia. · Diabetes. · Pubmed #14749282 links to  free full text

Abstract: Type 2 diabetes can be viewed as a failure of the pancreatic beta-cell to compensate for peripheral insulin resistance with enhanced insulin secretion. This failure is explained by both a relative loss of beta-cell mass as well as secretory defects that include enhanced basal secretion and a selective loss of sensitivity to glucose. These features are reproduced by chronic exposure of beta-cells to fatty acids (FAs), suggesting that hyperlipidemia might contribute to decompensation. Using MIN6 cells pretreated for 48 h with oleate or palmitate, we have previously defined alterations in global gene expression by transcript profiling and described additional secretory changes to those already established (Busch A-K, Cordery D, Denyer G, Biden TJ: Diabetes 51:977-987, 2002). In contrast to a modest decoupling of glucose-stimulated insulin secretion, FA pretreatment markedly enhanced the secretory response to an acute subsequent challenge with FAs. We propose that this apparent switch in sensitivity from glucose to FAs would be an appropriate response to hyperlipidemia in vivo and thus plays a positive role in beta-cell compensation for insulin resistance. Altered expression of dozens of genes could contribute to this switch, and allelic variations in any of these genes could (to varying degrees) impair beta-cell compensation and thus contribute to conditions ranging from impaired glucose tolerance to frank diabetes.

Monagle P. · Division of Laboratory Services, Royal Children's Hospital, Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. · Semin Thromb Hemost. · Pubmed #14719171 No free full text.

Abstract: Cardiac disease and thrombosis are intimately related in adults, but primary myocardial infarction in children is rare. Homozygous familial hyperlipidemia occurs in approximately 1 million children, and causes severe coronary artery disease during childhood. Kawasaki's disease is an acquired inflammatory disorder, which, if untreated, leads to coronary artery aneurysms and subsequent myocardial infarction. The current understanding of the pathophysiology and management of these conditions is discussed. More commonly, the relationship between cardiac disease in children and thrombosis is that children being treated for congenital structural cardiac disease develop iatrogenic thrombosis, most commonly precipitated by central venous access. The epidemiology of common treatment-induced thrombosis is described, and management guidelines presented. Finally, many cardiac surgical procedures increase the risk of thrombosis, and prophylactic antithrombotic therapy is commonly used. The current evidence for prophylaxis in different clinical situations is presented. Additional study is required in all areas to improve the outcome for children affected by cardiac disease and thrombosis.

Nolan D. · Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia, Australia. · Drugs. · Pubmed #14636077 No free full text.

Abstract: HIV protease inhibitors were introduced into clinical practice over 7 years ago as an important component of combination antiretroviral drug regimens which in many ways revolutionised the treatment of HIV infection. The significant improvements in prognosis that have resulted from the use of these regimens, combined with the need for lifelong treatment, have increasingly focused attention on the adverse effects of antiretroviral drugs and on the metabolic complications of HIV protease inhibitors in particular. In this review, the cluster of metabolic abnormalities characterised by triglyceride-rich dyslipidaemia and insulin resistance associated with HIV protease inhibitor therapy are considered, along with implications for cardiovascular risk in patients affected by these complications. Toxicity profiles of individual drugs within the HIV protease inhibitor class are examined, as there is an increased recognition of significant intra-class differences both in terms of absolute risk of metabolic complications as well as the particular metabolic phenotype associated with these drugs. Guidelines for clinical assessment and treatment are emphasised, along with pathophysiological mechanisms that may provide a rational basis for the treatment of metabolic complications. Finally, these drug-specific effects are considered within the context of HIV-specific effects on lipid metabolism as well as lifestyle factors that have contributed to a rapidly increasing incidence of similar metabolic syndromes in the general population. These data highlight the importance of individualising patient management in terms of choice of antiretroviral regimen, assessment of metabolic outcomes and use of therapeutic interventions, based on the assessment of baseline (pre-treatment) metabolic status as well as the presence of potentially modifiable cardiovascular risk factors.

Willoughby S, Holmes A, Loscalzo J. · Cardiology Unit, The Queen Elizabeth Hospital, Adelaide University, South Australia, Adelaide, Australia. · Eur J Cardiovasc Nurs. · Pubmed #14622657 No free full text.

Abstract: Platelets play an important, but often under-recognized role in cardiovascular disease. For example, the normal response of the platelet can be altered, either by increased pro-aggregatory stimuli or by diminished anti-aggregatory substances to produce conditions of increased platelet activation/aggregation and occur in active cardiovascular disease states both on a chronic (e.g. stable angina pectoris) and acute basis (e.g. acute myocardial infarction). In addition, platelet hyperaggregability is also associated with the risk factors for coronary artery disease (e.g. smoking, hypertension, and hypercholesterolaemia). Finally, the utility of an increasing range of anti-platelet therapies in the management of the above disease states further emphasizes the pivotal role platelets play in the pathogenesis of cardiovascular disease. This paper provides a comprehensive overview of the normal physiologic role of platelets in maintain homeostasis, the pathophysiologic processes that contribute to platelet dysfunction in cardiovascular disease and the associated role and benefits of anti-platelet therapies.

Bate KL, Jerums G. · Endocrinology Unit, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia. · Med J Aust. · Pubmed #14583083 links to  free full text

Abstract: Diabetes complications are common and almost triple the annual cost of managing diabetes. Microvascular complications are the major risk in type 1 diabetes, while macrovascular complications are the major cause of morbidity and mortality in type 2 diabetes. Control of hyperglycaemia (target HbA(1c) level < or = 7%) and hypertension (target blood pressure < or = 130/80 mmHg) prevents microvascular complications in both types of diabetes; a multifactorial approach, comprising behaviour modification and pharmacological therapy for all risk factors, reduces the development of micro- and macrovascular complications in type 2 diabetes. The benefit of treating dyslipidaemia is at least as great in the diabetic population as in the non-diabetic population. Angiotensin-converting enzyme inhibitors and low-dose aspirin are indicated in people with diabetes and other cardiovascular risk factors. Regular annual screening for diabetes complications allows treatable disease to be identified. Aggressive management of hyperglycaemia and other risk factors can prevent many complications

Burnett JR. · Department of Core Clinical Pathology & Biochemistry, Royal Perth Hospital, School of Surgery and Pathology, University of Western Australia, Wellington Street, GPO Box X2213, Perth, WA 6847, Australia. · Curr Opin Investig Drugs. · Pubmed #14582458 No free full text.

Abstract: FM-VP4 is a phytosterol analog under development by Forbes Medi-Tech for the potential treatment of hyperlipidemia and hypercholesterolemia. By March 2002, FM-VP4 had entered phase I clinical trials and phase II trials were underway by late 2002.

Carr A. · HIV Immunology and Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, 2010, Australia. · J Acquir Immune Defic Syndr. · Pubmed #14562861 No free full text.

Abstract: Highly active antiretroviral therapy (HAART) commonly leads to persistent dyslipidemia and insulin resistance that appear likely to confer an increased incidence of cardiovascular disease (CVD). Both protease inhibitors (PIs) and, to a lesser extent, nucleoside analog reverse transcriptase inhibitors (NRTIs) appear to be involved, through direct metabolic effects of PIs and an indirect effect of PI and NRTI-related lipodystrophy. Several studies have found a variable relationship between CVD incidence and HAART, but these studies were not prospective and may not have been adequately powered. A variety of treatment strategies have been evaluated for dyslipidemia and insulin resistance, including lifestyle changes, drugs, and antiretroviral switching, but their relative safety, efficacy and roles are unclear. Although treatment of dyslipidemia and insulin resistance is commonly recommended, it should be remembered that such therapy is likely to be of greater benefit in those with a greater perceived CVD risk (i.e., multiple risk factors) and the lowest risk of HIV disease progression.

Behrens GM, Stoll M, Schmidt RE. · Division of Clinical Immunology, Hannover Medical School, Hannover, Germany. · Adv Cardiol. · Pubmed #14533548 No free full text.

This publication has no abstract.

Wilcken DE. · Department of Cardiovascular Medicine, The Prince of Wales Hospital and The University of New South Wales, Barker Street, Randwick, Sydney, NSW 2031 Australia. · J Inherit Metab Dis. · Pubmed #12889664 No free full text.

Abstract: Inherited metabolic disorders contribute importantly to adverse cardiovascular outcomes and affect all tissue types. This review summarizes some of the more important aspects. In the venous system, heterozygosities for the factor V Leiden and prothrombin 20210G > A mutations are common and occur in 4% and 1%, respectively, of caucasians. They confer a 2- to 3- fold increase in risk of venous, but not arterial, thrombosis. Marfan syndrome affects the systemic circulation and has a population prevalence of about 1 in 4000. The more than 200 mutations responsible are in the fibrillin-1 gene (15q21.1) and mediate the characteristic skeletal, lens and aortic changes. There are two potentially lethal inherited disorders of cardiac conduction, the long QT and Brugada syndromes. The prevalence for each is about 1 in 10,000. On the other hand, autosomal dominant hypertrophic cardiomyopathies are relatively common, at 1 in 500, but with variable penetrance. Mutations are in the sarcomere proteins and more than 140 are known. Hypertrophic cardiomyopathy may be confused with Fabry disease, for which effective treatment is now available. Mutations in several genes have been shown to produce dilated cardiomyopathy in the young, but there is as yet no specific treatment. In fatty acid oxidation disorders, arrhythmias and cardiomyopathy occur during acute decompensation. An important recently established cause of cardiomyopathy is carnitine transporter defect; it is treated effectively with oral carnitine. The autosomal dominant arrhythmogenic right ventricular dysplasia occurs with a prevalence of about 1 in 15,000 and presents with arrythmias and a dilated right ventricle. The mutations responsible have been mapped to chromosomes 1, 2, 10 and 14. Lysosomal storage disorders, the Ehlers-Danlos syndrome and other connective-tissue disorders affect cardiac valves and vessels. In addition to the relatively common inherited lipoprotein disorders familial hypercholesterolaemia and familial combined hyperlipidaemia, an important dominantly inherited lipid variable contributing to coronary risk is lipoprotein(a). The gene is localized to chromosome 6 and there is full expression in childhood. Elevated lipoprotein(a) levels contribute to the occurrence and severity of early-onset coronary disease and add to the already enhanced risk in patients with familial hypercholesterolaemia.

Behrens GM, Meyer-Olson D, Stoll M, Schmidt RE. · Department of Clinical Immunology, Hannover Medical School, Hannover, Germany. · AIDS. · Pubmed #12870541 No free full text.

Abstract: Metabolic complications and altered fat distribution associated with HIV infection and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). The high prevalence of multiple cardiovascular risk factors in a significant number of HIV patients is a cause for concern in both patients and physicians. Non-invasive strategies to measure subclinical CAD have been inconclusive. Long-term studies are underway to determine cardiac event rates, intervention strategies and consequences for the clinical management of HIV disease. In the present paper, we summarize the most prevalent risk factors in individuals with HIV infection receiving highly active antiretroviral therapy by focusing on the clinical implications of metabolic abnormalities and HIV-related lipodystrophy on CAD.