Hyperlipidemias: Australia

Sullivan D, Anonymous00139. · Department of Biochemistry, Royal Prince Alfred Hospital, NSW 2050, Australia. · Heart Lung Circ. · Pubmed #17188936 No free full text.

This publication has no abstract.

Tognarini DP, Sullivan DR, Thomas DW, Sikaris K. · Aesir Medical Research, Victoria, Australia. · Aust Fam Physician. · Pubmed #18523695 links to  free full text

Abstract: BACKGROUND: Recent updates to National Heart Foundation of Australia (NHFA) Lipid management guidelines and Pharmaceutical Benefits Scheme (PBS) criteria for subsidised lipid lowering therapy have resulted in greater alignment between the two documents. However, several recommendations, such as the need to focus on low density lipoprotein cholesterol level rather than total cholesterol, while well supported in the literature, may initially create confusion for both patients and clinicians. OBJECTIVE: This article summarises the likely pathology reporting changes that will occur as a result of a recent review of NHFA guidelines by the Australian Pathology Lipid Interest Group; compares current PBS criteria for subsidised lipid lowering therapy to the NHFA high risk categories and treatment targets; and provides an algorithm for treatment based on the PBS criteria integrating risk factors and lipid levels. DISCUSSION: Although pathology testing plays an important role in the assessment of risk in patients, it is ultimately the clinician who must determine the patient's absolute risk based on all relevant previous and current clinical information before the initiation or review of appropriate treatment.

Ooi EM, Barrett PH, Chan DC, Watts GF. · Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, GPO Box X2213, Perth, WA 6847, Australia. · Clin Sci (Lond). · Pubmed #18399797 No free full text.

Abstract: The concurrence of visceral obesity, insulin resistance and dyslipidaemia comprises the concept of the metabolic syndrome. The metabolic syndrome is an escalating problem in developed and developing societies that tracks with the obesity epidemic. Dyslipidaemia in the metabolic syndrome is potently atherogenic and, hence, is a major risk factor for CVD (cardiovascular disease) in these subjects. It is globally characterized by hypertriglyceridaemia, near normal LDL (low-density lipoprotein)-cholesterol and low plasma HDL (high-density lipoprotein)-cholesterol. ApoC-III (apolipoprotein C-III), an important regulator of lipoprotein metabolism, is strongly associated with hypertriglyceridaemia and the progression of CVD. ApoC-III impairs the lipolysis of TRLs [triacylglycerol (triglyceride)-rich lipoproteins] by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. In the circulation, apoC-III is associated with TRLs and HDL, and freely exchanges among these lipoprotein particle systems. However, to fully understand the complex physiology and pathophysiology requires the application of tracer methodology and mathematical modelling. In addition, experimental evidence shows that apoC-III may also have a direct role in atherosclerosis. In the metabolic syndrome, increased apoC-III concentration, resulting from hepatic overproduction of VLDL (very-LDL) apoC-III, is strongly associated with delayed catabolism of triacylglycerols and TRLs. Several therapies pertinent to the metabolic syndrome, such as PPAR (peroxisome-proliferator-activated receptor) agonists and statins, can regulate apoC-III transport in the metabolic syndrome. Regulating apoC-III metabolism may be an important new therapeutic approach to managing dyslipidaemia and CVD risk in the metabolic syndrome.

Skilton MR. · Human Nutrition Research Centre, Université Claude Bernard, Lyon, France. · Pediatrics. · Pubmed #18310207 links to  free full text

Abstract: Evidence from noninvasive ultrasound studies of the neonatal aorta and fetal and early childhood postmortem studies indicates that impaired fetal growth, in utero exposure to maternal hypercholesterolemia, and diabetic macrosomia may all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis. Although the exact mechanisms that underlie these associations remain unclear, animal models have suggested that the use of antioxidant, lipid-lowering, and other innovative therapies may counteract the impact of these intrauterine risk factors for cardiovascular disease. This review summarizes the current evidence for intrauterine factors that have a direct impact on atherosclerosis and provides potential treatment and prevention strategies.

Chan DC, Chen MM, Ooi EM, Watts GF. · Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. · Int J Clin Pract. · Pubmed #18201179 No free full text.

Abstract: BACKGROUND: Hypertriglyceridaemia, commonly found in subjects with obesity and type 2 diabetes mellitus, is associated with increased risk of coronary heart disease (CHD). Apolipoprotein C-III (apoC-III) plays an important role in regulating the metabolism of triglyceride-rich lipoproteins (TRLs) and may provide a new approach to assessing hypertriglyceridaemia. AIMS: We review the role of apoC-III in regulating TRL metabolism and address the potential importance of apoC-III in clinical practice. DISCUSSION: Hypertriglyceridaemia is chiefly a consequence of alterations in the kinetics of TRLs, including overproduction and delayed clearance of very-low density lipoprotein (VLDL). ApoC-III is an inhibitor of lipoprotein lipase and of TRLs remnant uptake by hepatic lipoprotein receptors. Elevated apoC-III, usually resulting from hepatic overproduction of VLDL apoC-III, may cause accumulation of plasma TRLs leading to hypertriglyceridaemia. The results from recent observational studies demonstrate that apoC-III is a strong predictor of risk for CHD, but this chiefly relates to apoC-III in apoB-containing lipoproteins. Lifestyle and pharmacological intervention can correct hypertriglyceridaemia by a mechanism of action that regulates apoC-III transport. CONCLUSIONS: Targeting apoC-III metabolism may therefore be an important, new therapeutic approach to managing dyslipidaemia and CHD risk in obesity, insulin resistance and type 2 diabetes mellitus. However, further work is required to establish the practical aspects of measuring apoC-III in routine laboratory service and the precise therapeutic targets for serum total apoC-III and/or apoC-III in apoB-containing lipoproteins. While showing much promise as a potentially useful cardiovascular risk factor, apoC-III is not yet ready for prime time use in clinical practice.

Charlesworth JA, Gracey DM, Pussell BA. · Department of Nephrology, Prince of Wales Hospital and The University of New South Wales, Sydney, New South Wales, Australia. · Nephrology (Carlton). · Pubmed #18199102 No free full text.

Abstract: Irrespective of aetiology, the nephrotic syndrome presents a range of potentially serious complications. These include thrombo-embolism, infection and hyperlipidaemia. Despite the prevalence of the nephrotic state among renal patients, there has been little prospective analysis of the therapeutic approach to these potentially life-threatening events even though their pathogenesis has been examined in some detail. Most of these complications are more prevalent once the albumin concentration falls below 20 g/L and it is recognized that restoration of serum albumin significantly diminishes their frequency. However, this may be difficult to achieve, especially in adults. The problems of thrombo-embolism and infection are of immediate concern but, in persistent cases, the additional issues of hyperlipidaemia and loss of bone density also require consideration for therapy. Thus, in addition to specific attempts to reduce proteinuria, it is recommended that high-risk nephrotic patients receive anticoagulation, pneumococcal vaccination and lipid lowering therapy. Strategies for the preservation of bone density should also be considered, particularly in patients who receive high-dose corticosteroids. Among a range of non-specific treatments for proteinuria, angiotensin-converting enzyme inhibitors appear best in terms of efficacy and safety. Prospective trials are required to clarify the longitudinal impact of these generic strategies on the protection of the persistently nephrotic patient.

Emery J, Barlow-Stewart K, Metcalfe SA, Sullivan D. · Discipline of General Practice, University of Western Australia. · Aust Fam Physician. · Pubmed #17925900 links to  free full text

Abstract: BACKGROUND: Advances in our understanding of the genetics of common chronic disease is beginning to impact on clinical practice and preventive health care. OBJECTIVE: This article discusses the potential for genetic medicine to inform disease prevention strategies. It describes two examples already affecting clinical general practice: familial hypercholesterolaemia and hereditary haemochromatosis. These represent important inherited conditions that, if diagnosed early, can be simply treated and their complications avoided. DISCUSSION: General practitioners can play an important role in the early diagnosis of these conditions and subsequent screening of at risk relatives. These conditions highlight the potential for genetic medicine to be applied to support tailored disease prevention in general practice.

Kaisar M, Isbel N, Johnson DW. · Centre for Kidney Disease Research, University of Queensland at Princess, Alexandra Hospital, Brisbane, QLD Australia. · Minerva Urol Nefrol. · Pubmed #17912225 No free full text.

Abstract: Cardiovascular disease (CVD) remains the most common cause of premature death in the chronic kidney disease (CKD) population. Individuals with CKD are at 10-20 times greater risk of cardiac death than controls without CKD, despite stratification for age, race, sex and diabetes. Heightened CVD mortality begins with mild kidney disease and rises further with more advanced kidney disease. Traditional risk factors account for up to 50% of cardiovascular disease in CKD, whilst renal specific markers, including anemia, disordered bone mineral metabolism and oxidative stress, also likely contribute to the total cardiovascular burden in CKD. Despite the increased mortality, there has been a dearth of interventional cardiovascular randomized controlled trials (RCTs) in the CKD population. Furthermore, many patients with kidney disease have been excluded from the majority of mainstream cardiovascular interventional trials. While recently published RCTs on traditional and non-traditional risk factors including dyslipidemia (PPP, 4D and ALERT, VA-HIT), cardiomyopathy (FOSIDIAL, telmisartan, carvedilol), anemia (US Normal Hematocrit, CHOIR and CREATE trials), hyperhomocystenemia (ASFAST, US folic acid trial, HOST), disordered bone mineral metabolism (Cunningham meta-analysis, DCOR), oxidative stress therapy (SPACE, HOPE and ATIC, N-acetylcysteine) and multidisciplinary multiple cardiovascular risk factor intervention clinics (LANDMARK) have added to the available pool of clinical data, level 1 clinical evidence remains significantly lacking. The negative findings in many of these trials highlight the potential dangers of extrapolating findings from non kidney disease patients to those with CKD. Further large, well-designed trials are urgently required to address this issue.

Barter PJ, Rye KA. · The Heart Research Institute, Sydney, Australia 2050. · Arterioscler Thromb Vasc Biol. · Pubmed #17717290 links to  free full text

Abstract: The outcomes of fibrate trials have varied: positive with gemfibrozil in the primary prevention Helsinki Heart Study and the secondary prevention VA-HIT trial; positive with reservations in the primary prevention WHO trial (clofibrate); and mixed with bezafibrate in the secondary prevention BIP study and with fenofibrate in the combined primary and secondary prevention FIELD study. Overall, the mixed results, combined with potential for adverse effects when given in combination with statins, have limited the use of these fibrates as cardioprotective agents. However, post hoc analyses of several of the fibrate studies have shown that people with features of the metabolic syndrome, particularly overweight people with high plasma triglyceride levels and low levels of HDL cholesterol, derive a disproportionately large reduction in cardiovascular events when treated with these agents. Thus, there is a strong case for the use of a fibrate to reduce the cardiovascular risk in overweight people with high triglyceride and low HDL-C. However, it should be noted that such people also have their cardiovascular risk reduced by statin therapy. It remains to be determined whether the combination of a fibrate plus statin reduces the risk beyond that achieved with a statin alone.

Chen J, Seviour R. · Cancer Biology Program, Diamantia Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Brisbane, Queensland 4102, Australia. · Mycol Res. · Pubmed #17590323 No free full text.

Abstract: Non-cellulosic beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. These beta-glucans consist of a backbone of glucose residues linked by beta-(1-->3)-glycosidic bonds, often with attached side-chain glucose residues joined by beta-(1-->6) linkages. The frequency of branching varies. The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes. Their mechanisms of action involve them being recognized as non-self molecules, so the immune system is stimulated by their presence. Several receptors have been identified, which include: dectin-1, located on macrophages, which mediates beta-glucan activation of phagocytosis and production of cytokines, a response co-ordinated by the toll-like receptor-2. Activated complement receptors on natural killer cells, neutrophils, and lymphocytes, may also be associated with tumour cytotoxicity. Two other receptors, scavenger and lactosylceramide, bind beta-glucans and mediate a series of signal pathways leading to immunological activation. Structurally different beta-glucans appear to have different affinities toward these receptors and thus generate markedly different host responses. However, the published data are not always easy to interpret as many of the earlier studies used crude beta-glucan preparations with, for the most part, unknown chemical structures. Careful choice of beta-glucan products is essential if their benefits are to be optimized, and a better understanding of how beta-glucans bind to receptors should enable more efficient use of their biological activities.

Lambert G. · Université de Nantes, Inserm U539, CHU Hôtel-Dieu, Nantes, France. · Curr Opin Lipidol. · Pubmed #17495605 No free full text.

Abstract: PURPOSE OF REVIEW: Proprotein convertase subtilisin kexin type 9 (PCSK9) has emerged as a potential target for lowering plasma LDL cholesterol levels. This review summarizes recent studies published in print or online before January 2007 which have investigated the functional significance of this intriguing protease. RECENT FINDINGS: Increasing interest in PCSK9 has given rise to landmark epidemiological studies, the generation of animal models, the discovery of new human mutations, as well as numerous in-vitro studies. These studies have helped to unravel the molecular functions of PCSK9. SUMMARY: Mutations of PCSK9 are associated either with hypercholesterolemia or with hypocholesterolemia. In the latter case, the incidence of coronary heart disease is reduced, thereby demonstrating that low LDL cholesterol levels from birth are highly beneficial. PCSK9 promotes the degradation of the LDL receptor in hepatocytes apparently both intracellularly and by being a secreted protein that can bind the LDL receptor and be internalized. By virtue of its role as a major inhibitor of the LDL receptor, PCSK9 is a promising therapeutic target. Specific PCSK9 pharmacological inhibitors may prove to be useful in amplifying the well documented benefits of statins.

Patch CS, Tapsell LC, Williams PG, Gordon M. · National Centre of Excellence in Functional Foods, Northfields Avenue, University of Wollongong, New South Wales, Australia. · Vasc Health Risk Manag. · Pubmed #17319460 links to  free full text

Abstract: Plant sterol-enriched foods are an effective dietary adjuvant in reducing cardiovascular risk by lowering total cholesterol and low density lipoprotein-cholesterol (LDL-C) in serum by up to approximately 15%. The mechanism of action of plant sterols is different from those of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) and thus their effect is additive. Combining plant sterols with other dietary components known to reduce cholesterol in a portfolio approach has proven to be most effective for reduction of hypercholesterolemia and provide an alternative treatment option for clinicians. Plant sterol-enriched foods provides clinicians with a relatively cheap, safe, and effective way to help patients manage their cardiovascular risk.

Whitworth JA, Williamson PM, Mangos G, Kelly JJ. · John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia. · Vasc Health Risk Manag. · Pubmed #17315601 links to  free full text

Abstract: Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia. This review analyses the relationship of cortisol excess, both locally and at tissue level, to these cardiovascular risk factors, and to putative mechanisms for hypertension. Previous studies have examined correlations between cortisol, blood pressure, and other parameters in the general population and in Cushing's syndrome. This review also details changes induced by short-term cortisol administration in normotensive healthy men.

Berk M, Fitzsimons J, Lambert T, Pantelis C, Kulkarni J, Castle D, Ryan EW, Jespersen S, McGorry P, Berger G, Kuluris B, Callaly T, Dodd S. · Department of Clinical and Biomedical Sciences, Barwon Health, The University of Melbourne, Geelong, Melbourne, Victoria, Australia. · CNS Drugs. · Pubmed #17284094 No free full text.

Abstract: Clozapine is an important antipsychotic agent that has a unique profile of clinical benefits, but that has also been associated with several serious and potentially life-threatening safety concerns. In order to minimise the impact of haematological adverse events, health professionals treating patients with clozapine are currently required to register their patients on a centrally administered data network and to conform to strict protocols. The consensus statement documented in this article extends existing protocols by recommending monitoring of patients treated with clozapine for additional adverse effects during treatment. This consensus statement reflects the current practice at five major public psychiatric hospitals in Victoria, Australia, for the monitoring and management of clozapine-related adverse events, and has been implemented at these sites because of emerging safety concerns associating clozapine with cardiovascular and metabolic adverse effects.

Singh D, Kaur R, Chander V, Chopra K. · Department of Medical Pharmacology & Toxicology, University of California Davis, Davis, CA, USA. · J Med Food. · Pubmed #17201628 No free full text.

Abstract: Reactive oxygen species (ROS) play a key role in the pathophysiological processes of renal diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of ROS in the stationary state (oxidative stress). Oxidative stress mediates a wide range of renal impairments, from acute renal failure, rhabdomyolysis, obstructive nephropathy, hyperlipidemia, and glomerular damage to chronic renal failure and hemodialysis. Therefore, interventions favoring the scavenging and/or depuration of ROS (dietary and pharmacological antioxidants) should attenuate or prevent the oxidative stress, thereby mitigating against the subsequent renal damage.

Cohn JS. · Nutrition and Metabolism Group, Heart Research Institute, 114 Pyrmont Bridge Road, Camperdown, NSW 2050, Australia. · Clin Lab Med. · Pubmed #17110239 No free full text.

Abstract: Increased postprandial lipemia or elevated levels of triglyceride-rich remnant lipoproteins in fasting plasma are associated with increased risk of coronary artery disease. Despite many studies showing that postprandial triglyceride-rich lipoproteins play a central role in the pathogenesis of atherosclerosis, suitably standardized methods to measure postprandial lipemia or remnant lipoproteins in the clinical setting are lacking. This approach for cardiovascular risk assessment is confined to research laboratories and for the time being is not a standard procedure in clinical practice.

Burnett JR. · Royal Perth Hospital, Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine WA, Wellington Street, GPO Box X2213, Perth, WA 6847, Australia. · Curr Opin Mol Ther. · Pubmed #17078389 No free full text.

Abstract: ISIS-301012 is an antisense oligonucleotide inhibitor of apolipoprotein B-100, which is being developed by Isis Pharmaceuticals Inc for the potential treatment of hypercholesterolemia. A subcutaneous injectable formulation is currently undergoing phase 11 clinical trials, while phase I trials are underway with an oral formulation of the drug.

Tofler GH, Muller JE. · Cardiology Department, Royal North Shore Hospital, Sydney, Australia. · Circulation. · Pubmed #17060396 links to  free full text

This publication has no abstract.

Burnett JR, Huff MW. · Royal Perth Hospital, Department of Core Clinical Pathology & Biochemistry, PathWest Laboratory Medicine WA, Wellington Street Campus, GPO Box X2213, Perth, WA 6847, Australia. · Expert Opin Investig Drugs. · Pubmed #17040195 No free full text.

Abstract: The development of cholesterol-lowering drugs (including a variety of statins, bile acid-binding resins and recently discovered inhibitors of cholesterol absorption) has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined targets for LDL cholesterol concentrations. Combination therapy with drugs that have different or complementary mechanisms of action is often needed to achieve lipid goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to conventional drug treatment and remain at high risk for the development and progression of atherosclerotic cardiovascular disease and alternative approaches are needed. The discovery and development of ezetimibe (a novel, selective and potent cholesterol absorption inhibitor) has advanced the treatment of hypercholesterolaemia. New agents including the phytostanol preparation FM-VP4 and inhibitors of acyl coenzyme A:cholesterol acyltransferase, the apical Na(+)-dependent bile acid transporter and microsomal triglyceride transfer protein may also play a future role in combination therapy. This review focuses on the recent progress in the molecular mechanisms of intestinal cholesterol absorption and transport, and novel therapeutic approaches to inhibit the cholesterol absorption process.

Johnson DW, Usherwood T. · University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland. · Aust Fam Physician. · Pubmed #16299624 links to  free full text

Abstract: BACKGROUND: Chronic kidney disease (CKD), defined as a glomerular filtration rate less than 60 mL/min/1.73 m2 and/or evidence of kidney damage for a period of at least 3 months, is an increasingly common, serious and under-recognised condition. A recent population study demonstrated that one in every 6 Australian adults has CKD (of which the vast majority are unaware). OBJECTIVE: This article aims to provide timely information to health professionals about how to classify and manage CKD. DISCUSSION: Management of CKD involves regular monitoring of cardiovascular and renal risk factors, identifying and treating common CKD complications, and avoiding medications that may worsen CKD. Early detection and timely appropriate management of CKD (especially with respect to blood pressure control) will substantially reduce kidney failure progression and cardiovascular risk by up to 50%.

Hoenig MR, Rolfe BE, Campbell JH. · Royal Brisbane and Women's Hospital, Level 5 Pigeon Holes, Herton Road, Herston, Brisbane, Qld 4029, Australia. · Atherosclerosis. · Pubmed #16216250 No free full text.

Abstract: Statins have been the mainstay of lipid-lowering therapy since their introduction. However, as lower LDL cholesterol targets are sought, adjunct therapies are becoming increasingly important. Few patients reach new targets with statin monotherapy. We propose that the cholestanol:cholesterol ratio can be used to guide lipid-lowering therapy and result in greater numbers of patients reaching target LDL cholesterol. By determining whether a patient is mainly a synthesizer or absorber of cholesterol, customized regimens can be used and are expected to improve patient outcomes and minimize costs of treatment.

Hankey GJ. · Department of Neurology, Royal Perth Hospital, Perth, Australia. · J Thromb Haemost. · Pubmed #16102029 No free full text.

Abstract: Stroke is a major cause of death and disability in the world. The main causes of stroke are atherothromboembolism and cardiogenic embolism. The main causal and treatable risk factors for atherothromboembolic ischemic stroke are increasing blood pressure (BP), increasing cholesterol, cigarette smoking and diabetes; and the main risk factors for cardiogenic ischemic stroke are atrial fibrillation (AF) and ischemic heart disease. Strategies to reduce the incidence of stroke include prevention of first-ever and recurrent stroke, and treatment of patients with acute stroke to reduce death and disability. The two main strategies of stroke prevention are the 'population' (or 'mass') approach and the 'high risk' approach. The 'population' approach aims to reduce stroke by lowering the prevalence and mean level of causal risk factors in the community, by means of public education and government legislation. The 'high risk' approach aims to reduce stroke by identifying individuals at high risk of stroke, and lowering their risk by means of optimal medical therapies. Level 1 evidence from randomized controlled trials indicates that effective treatments for high risk patients include control of causal risk factors (lowering BP, lowering blood cholesterol), antithrombotic therapy (antiplatelet therapy with aspirin, clopidogrel, or the combination of aspirin and dipyridamole for patients in sinus rhythm, and anticoagulation with warfarin or ximelagatran for patients in AF) and, where appropriate, carotid revascularization for patients with severe carotid stenosis.

Stocks N, Allan J, Mansfield PR. · Department of General Practice, University of Adelaide, South Australia. · Aust Fam Physician. · Pubmed #15931403 links to  free full text

Abstract: BACKGROUND: Hyperlipidaemia is a general term for elevated concentrations of any or all lipids in the plasma. An elevated cholesterol is one of several risk factors for coronary heart disease (CHD). In Australia, the use of cholesterol lowering drugs, mainly statins, consumes over 880 million dollars or 16% of the Pharmaceutical Benefits Scheme drug budget and is growing. OBJECTIVE: This article focuses on primary hypercholesterolaemia, its relationship with CHD, and its management in the community setting. DISCUSSION: There is strong evidence that treating middle aged men with statins who have established CHD will reduce overall mortality, CHD morbidity, or mortality and stroke. There is weaker but reasonable evidence for treating men aged over 65 years and women of any age who have CHD, or people without CHD but at high risk. There may be some benefits for patients with stroke and peripheral vascular disease who are at risk of CHD. While discontinuation rates are high, the occurrence of serious adverse reactions are infrequent.

Harris M, Wan Q. · Research Centre for Primary Health Care and Equity, School of Public Health and Community Medicine, University of New South Wales. · Aust Fam Physician. · Pubmed #15931402 links to  free full text

Abstract: BACKGROUND: Cardiovascular disease (CVD) is an important and preventable complication and major cause of death in diabetes. OBJECTIVE: This article outlines the prevention and early detection of CVD in people with type 2 diabetes. DISCUSSION: Diabetes is a major risk factor for CVD, both independently and because it tends to occur in association with other behavioural and physiological risk factors. There is good evidence that careful control of these risk factors can significantly delay the development of heart disease, and that this is possible to achieve in general practice. Key interventions are smoking cessation; diet and physical activity; targeted use of medications to achieve glycaemic, blood pressure and lipid control; and aspirin. Interventions require a whole practice approach involving practice staff, practice systems and links with other care providers.

Jerums G, MacIsaac RJ. · Endocrinology Unit, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia. · Treat Endocrinol. · Pubmed #15799209 No free full text.

Abstract: The incidence of type 2 diabetes mellitus is increasing world-wide, and is now one of the leading causes of end-stage renal disease in Western countries. Type 2 diabetes mellitus is also a major risk factor for cardiovascular events. Therefore, the early identification of patients at greatest risk, and the subsequent initiation of renal and cardiovascular protective treatments, are of the utmost importance. Microalbuminuria refers to a subclinical increase in urinary albumin excretion. By definition it corresponds to an albumin excretion rate of 20 to 200 microg/min (30 to 300 mg/day) or an albumin to creatinine ratio (mg/mmol) of 2.5 to 25 in males and 3.5 to 35 in females. Microalbuminuria is an important clinical finding because it is not only associated with an increased risk of progression to overt proteinuria (macroalbuminuria) and renal failure, but also cardiovascular events. In patients who progress to overt nephropathy, microalbuminuria usually precedes macroalbuminuria by an interval of 5 to 10 years. In patients with type 1 diabetes mellitus, blood pressure increases and renal function declines after the onset of macroalbuminuria. However, in patients with type 2 diabetes mellitus, hypertension and a decline in renal function may occur when albumin excretion is still in the microalbuminuric range. Large clinical trials have demonstrated that achieving tight glycemic (i.e. glycosylated hemoglobin < 7.0%) and blood pressure (i.e. < 130/85mm Hg) control retards the progression of renal disease. There is accumulating evidence to suggest that the use of antihypertensive agents which target the renin-angiotensin system (RAS) can slow the progression of renal disease and provide cardioprotection in patients with type 2 diabetes mellitus and microalbuminuria. Antihypertensive agents which target the RAS also appear to have advantages over and above reductions in systemic blood pressure. In summary, the annual screening of patients with type 2 diabetes mellitus for microalbuminuria, and the initiation of measures to retard the progression of renal and cardiovascular disease, are now considered part of routine clinical practice. In particular, the finding of microalbuminuria should provoke an intensified modification of the common risk factors for renal and cardiovascular disease, that is hyperglycemia, hypertension, dyslipidemia and smoking. Antihypertensive therapy in patients with microalbuminuria and type 2 diabetes mellitus should be initiated with angiotensin converting enzyme (ACE) inhibitors or angiotensin-II type 1 receptor antagonists.