Hyperlipidemias: Europe

Marchetti F, Cannioto Z. · Clinica Pediatrica, IRCCS Burlo Garofalo, Università, Trieste. · Recenti Prog Med. · Pubmed #19388217 No free full text.

Abstract: The recommendation of statin treatment to younger patients too, as recently issued by the American Academy of Pediatrics, appeared to be controversial, especially looking at the lack of evidence in term of efficacy on primary end-point and long term safety data.

Farnier M. · Endocrinologie maladies métaboliques, Point Médical, F-21000, Dijon, France. · Presse Med. · Pubmed #19376680 No free full text.

Abstract: Plasma lipids should - and can reliably - be measured within 24 hours of the onset of symptoms of acute coronary syndrome. They should again be measured from 1 to 3 months after the event. The level of low-density lipoproteins(LDL) cholesterol remains the marker for treatment initiation and for evaluation of therapeutic goals. The total number of atherogenic particles is a better determinant of cardiovascular risk than the LDL-cholesterol level, as are the levels of non-high-density lipoprotein (HDL)-cholesterol and apolipoprotein B. The use of apolipoprotein B by primary care physicians is limited by the lack of standardization and must be restricted to specific clinical cases. Non-HDL-cholesterol can be recommended as a secondary target in patients with high triglyceride levels. In coronary patients treated with a statin, management of abnormal levels of triglycerides and HDL-cholesterol is important to minimize the risk of recurrence.

Resl M, Hülsmann M, Pacher R, Clodi M. · Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Austria. · Wien Med Wochenschr. · Pubmed #19343290 No free full text.

Abstract: Interactions of glucose metabolism and chronic heart failure have been confirmed by many epidemiologic studies. The association of HbA1c with an increasing risk of heart failure clearly underlines the connection between both diseases. Coronary artery disease (CAD), hypertension and diabetic cardiomyopathy are long-term complications of diabetes mellitus, resulting in diabetic heart failure. Dysfunction of many regulation systems leads to specific diabetic cardiomyopathy, which has been firstly described by Rubler. A reduction in the cardiac expression of the Na-Ca exchanger pump and SERCA2a protein results in an imbalance in cardiac calcium handling. The overactive renin angiotensin aldosteron system (RAAS) also contributes to the impairment of myocardial function. Hyperlipidaemia, hpyerinsulinaemia and hyperglycaemia directly trigger diabetic cardiomyopathy. Generally chronic heart failure is a clinical diagnosis verified by blood tests like NT-proBNP and cardiac ultrasound. Recommendations on treatment of diabetic heart failure are based on subgroup analysis of the large heart failure trials.

Kauppila LI. · Terveystalo Healthcare, Helsinki, Finland. · Eur J Vasc Endovasc Surg. · Pubmed #19328027 No free full text.

Abstract: OBJECTIVES: Atherosclerosis can obstruct branching arteries of the abdominal aorta, including four paired lumbar arteries and the middle sacral artery that feed the lumbar spine. The diminished blood flow could result in various back problems. The aim of this systematic literature review was to assess associations between atherosclerosis and disc degeneration (DD) or low-back pain (LBP). DATA SOURCES: A systematic search of the Medline/PubMed database for all original articles on atherosclerosis and DD/LBP published until October 2008. The search was performed with the medical subject headings atherosclerosis, cardiovascular risk factor, or vascular disease and keywords "disc degeneration", "disc herniation", and "back pain" on the basis of MeSH tree and as a text search. In addition reference lists were studied and searched manually. Observational studies investigating the association of atherosclerosis or its risk factors and lumbar DD/LBP were selected. REVIEW METHODS: The following data were extracted: study characteristics, duration of follow-up, year of publication, findings of atherosclerosis/cardiovascular risk factors and DD/LBP. Disc herniation was regarded as a form of disc degeneration and cardiovascular risk factors were regarded as surrogate for atherosclerosis in epidemiological studies. RESULTS: One hundred and seventy-nine papers were identified. After exclusion of case reports, letters, editorials, papers not related to the lumbar spine, and animal studies, 25 papers were included. Post-mortem studies showed an association between atheromatous lesions in the aorta and DD, as well as between occluded lumbar arteries and life-time LBP. In clinical studies, aortic calcification was associated with LBP, and stenosis of lumbar arteries was associated with both DD and LBP. In epidemiological studies, smoking and high serum cholesterol levels were found to have the most consistent associations with DD and LBP. CONCLUSION: Aortic atherosclerosis and stenosis of the feeding arteries of the lumbar spine were associated with DD and LBP. Cardiovascular risk factors had weaker associations, being clearly apparent only in cohorts on elderly people or in large study samples. More prospective clinical studies are needed to further clarify the association of atherosclerosis and low-back disorders.

Corti R, Flammer AJ, Hollenberg NK, Lüscher TF. · Cardiovascular Center, Cardiology, University Hospital, Raemistrasse 100, CH-8091 Zurich, Switzerland. · Circulation. · Pubmed #19289648 No free full text.

Abstract: Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.

Ott C, Schmieder RE. · Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen, Germany. · Curr Hypertens Rep. · Pubmed #19278604 No free full text.

Abstract: The metabolic syndrome is a cluster of cardiometabolic risk factors associated with higher risk for atherosclerotic cardiovascular (CV) disease and diabetes. Its prevalence is about 20% to 30% among adults worldwide and is increasing. The primary goal is reduction of CV risk through lifestyle changes and drug therapy if required. Post hoc analyses of prospective trials showed the benefit of lowering low-density lipoprotein (LDL) cholesterol in patients with the metabolic syndrome. Statin therapy exerts beneficial effects not only by lowering LDL cholesterol but also via its so-called pleiotropic effects. These effects seem particularly important for reducing risk of CV disease in patients with the metabolic syndrome. Thus, evidence is accumulating that statins are very effective therapeutic agents in the treatment of individuals with the metabolic syndrome.

Corsini A, Windler E, Farnier M. · Department of Pharmacological Sciences, University of Milan, Milan, Italy. · Eur J Cardiovasc Prev Rehabil. · Pubmed #19237992 No free full text.

Abstract: Several recent meta-analyses of numerous lipid-lowering outcome trials confirm the direct relationship between low-density lipoprotein-cholesterol (LDL-C) lowering and cardiovascular risk reduction. As a consequence, LDL-C goals are continuously being set lower. To achieve lipid lowering, several efficient drugs are available, however, the current pharmacopoeia remains limited for some critical patient situations. Colesevelam hydrochloride is a specifically engineered bile acid sequestrant that features a more favourable tolerability and drug interaction profile than traditional bile acid sequestrants, because of a better affinity and binding capacity to bile acids. In addition, colesevelam retains the nonsystemic mode of action of bile acid sequestrants. Moreover, colesevelam lowers LDL-C by 15-19% and 10-16%, respectively, in monotherapy and in combination to various lipid-lowering drugs, such as statins, ezetimibe and fenofibrates. Along with an efficient and sustainable effect on lipid profiles, colesevelam - as other bile acid sequestrants - has been shown to lower the glycosylated haemoglobin HbA1c by 0.5% on average in patients with type 2 diabetes. Overall, colesevelam represents an interesting add-on treatment to be used in high-risk patients with hypercholesterolaemia for whom standard lipid-lowering therapies are not enough or not well tolerated.

Rizzo M, Berneis K, Spinas GA, Rini GB, Kapur NK. · Department of Internal Medicine and Emerging Diseases, University of Palermo, Palermo, Italy. · Int J Clin Pract. · Pubmed #19222633 No free full text.

Abstract: BACKGROUND: Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. AIM: The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). METHODS: We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: 'LDL-cholesterol', 'LDL size', 'LDL subclasses', 'small dense LDL', 'apolipoprotein B, apo B' and 'rosuvastatin' up to 11 November 2008. The authors also manually reviewed the references of selected articles for any pertinent material. RESULTS: Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B. DISCUSSION AND CONCLUSIONS: The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.

Athyros VG, Kakafika AI, Tziomalos K, Karagiannis A, Mikhailidis DP. · Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, HippocrationHospital, Thessaloniki, Greece. · Curr Pharm Des. · Pubmed #19199976 No free full text.

Abstract: The present review considers the potential pleiotropic effects of statins and the evidence indicative of the "real world" benefit from these effects in patients with cardiovascular disease (CVD). Some of these cholesterol-independent effects of statins involve improved endothelial function, stability of atherosclerotic plaques, attenuation of oxidative stress and inflammation, as well as inhibition of the thrombogenic response. Clinical evidence from early statin administration in acute coronary syndromes and in revascularisation procedures is reported. Moreover, the "metabolic" effects of statin treatment, such as renal function improvement and reduction in serum uric acid levels, in patients with stable coronary heart disease are discussed. Evidence suggests that in high CVD risk patient groups pleiotropic effects of statins may play a role in the reduction of morbidity and mortality. However, this concept requires proof in appropriately designed trials that will include clinically relevant end points in order to set specific targets in new CVD-related biomarkers, in addition to lipid levels, that should be used to fully assess the statin contribution to CVD treatment.

Stefani M, Liguri G. · Department of Biochemical Sciences and Research Centre on Neurodegeneration (CIMN), University of Florence, Florence, Italy. · Curr Alzheimer Res. · Pubmed #19199871 No free full text.

Abstract: The role of cholesterol as a susceptibility factor or a protective agent in neurodegeneration and, more generally, in amyloid-induced cytotoxicity is still controversial. Epidemiological studies on the hypercholesterolemia-AD risk relation and some reports indicating a beneficial effect of statin therapy suggest cholesterol as a susceptibility factor in AD. The ApoE4 genotype as a prevalent genetic risk factor for AD and the function of ApoE as main cholesterol carrier in the brain also underlie a close cholesterol load-AD risk relation. Finally, cell biology evidences support a critical involvement of lipid raft cholesterol in the modulation of beta- and gamma-secretase cleavage of APP with altered Abeta production. However, little exchange does exist between circulating and brain cholesterol, the latter arising from endogenous synthesis. In addition, increasing evidence supports the idea that amyloid cytotoxicity in most cases is initiated by oligomer recruitment at the cell membrane with loss of membrane integrity, Ca(2+) ingress into the cell, oxidative stress and apoptosis. In such a scenario, increased membrane cholesterol seems to be protective by disfavouring aggregate binding to the membrane. Recent findings also indicate that a reduction of cellular cholesterol favours co-localization of BACE1 and APP in non-raft membrane domains and hinders generation of plasmin, an Abeta-degrading enzyme. Finally, recent researches on Seladin-1, involved in cholesterol biosynthesis, show that modulation of membrane cholesterol affects Abeta generation and cell resistance against Abeta oligomer toxicity. These data confirm previous findings indicating a reduction of the cholesterol/phospholipid ratio in aged and AD brains. The aim of this review is to critically discuss some of the main results reported in the recent years in this field supporting a role of cholesterol either as a susceptibility factor or as a protective agent in AD.

Abifadel M, Rabès JP, Devillers M, Munnich A, Erlich D, Junien C, Varret M, Boileau C. · Institut Nationale de la Santé et de la Recherche Médicale (INSERM), U781, Paris, France. · Hum Mutat. · Pubmed #19191301 No free full text.

Abstract: Hypercholesterolemia is one of the major causes of coronary heart disease (CHD). The genes encoding the low-density lipoprotein receptor and its ligand apolipoprotein B, have been the two genes classically implicated in autosomal dominant hypercholesterolemia (ADH). Our discovery in 2003 of the first mutations of the proprotein convertase subtilisin kexin 9 gene (PCSK9) causing ADH shed light on an unknown actor in cholesterol metabolism that since then has been extensively investigated. Several PCSK9 variants have been identified, some of them are gain-of-function mutations causing hypercholesterolemia by a reduction of low-density lipoprotein (LDL) receptor levels; while others are loss-of-function variants associated with a reduction of LDL-cholesterol (LDL-C) levels and a decreased risk of CHD. In this review, we focus on reported variants, and their biological, clinical, and functional relevance. We also highlight the spectrum of hypercholesterolemia or hypobetalipoproteinemia phenotypes that are already associated with mutations in PCSK9. Finally, we present future prospects concerning this therapeutic target that might constitute a new approach to reduce cholesterol levels and CHD, and enhance the effectiveness of other lipid-lowering drugs.

Rodríguez C, Slevin M, Rodríguez-Calvo R, Kumar S, Krupinski J, Tejerina T, Martínez-González J. · Centro de Investigación Cardiovascular (CSIC-ICCC), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. · Pathobiology. · Pubmed #19188746 No free full text.

Abstract: The endothelium regulates vascular homeostasis and is responsible for angiogenesis, a process mediated by the sprouting of endothelial cells from pre-existing vessels. Several lines of evidence indicate that endothelial progenitor cells (EPCs) also play a role in adult neovascularization as well as in the maintenance of endothelial integrity and function. Hypercholesterolemia is associated with increased cardiovascular risk by inducing a cascade of events leading to endothelial dysfunction and injury. Growing evidence indicates that low-density lipoproteins (LDLs) impair endothelial reparative processes by inducing endothelial cell apoptosis but also by reducing the number and function of EPCs. The involvement of LDLs in mechanisms associated with vascular repair and neovascularization is also suggested by data from studies using lipid-lowering drugs (statins). This review is focused on the central role of the cholesterol pathway in the biology of the endothelium and EPCs.

Riegersperger M, Sunder-Plassmann G. · Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Austria. · J Ren Care. · Pubmed #19160880 No free full text.

Abstract: Chronic kidney disease (CKD) and end stage renal disease (ESRD) are severe medical conditions, increasing threats to human health and socio-economic burdens in industrialized countries. CKD is assessed by an estimation of the glomerular filtration rate (eGFR). ESRD is an indication for renal replacement therapy by either dialysis or kidney-transplantation. Major risk factors for CKD are arterial hypertension, hyperglycemia and hyperlipidemia. The multifactorial pathogenesis of CKD and ESRD offers various therapeutic interventions: treatment of the underlying disease, anti-hypertensive therapy, glycemic control and anti-diabetic therapy, anti-proteinuric therapy, renoprotection, and life style management. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) lower the systemic blood-pressure, reduce proteinuria and may slow or even halt the deterioration of renal function. Alert glycemic control is important to avoid or protract diabetic nephropathy. Restricted protein intake, cessation of cigarette smoking and chronic analgesic-abuse may also prevent the progression of chronic nephropathy.

Cravedi P, Ruggenenti P, Remuzzi G. · Department of Medicine and Transplantation, Ospedali Riuniti di Bergamo, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. · J Ren Care. · Pubmed #19160879 No free full text.

Abstract: The level of proteinuria is one of the most important predictors for progressive renal function loss in kidney disease. Reduction of urinary protein levels by renin-angiotensin-system (RAS) inhibitors limits renal function decline in patients with non-diabetic and diabetic nephropathies to the point that remission of the disease and regression of renal lesions have been reported. The increasing use of these drugs is possibly at the basis of the stabilization of rates of new cases of kidney failure reported to the US Renal Data System after a 2-decade period of progressive increases. RAS inhibition, however, may not be effective to the same degree in all patients. For those patients who do not reach a complete remission of proteinuria, treatment procedures to implement renoprotection should include strict blood pressure control (and metabolic control in diabetics), lowering of blood lipids, and lifestyle modifications. Early intervention may be important to maximize renoprotection, especially in diabetics.

Török J. · Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic. · Physiol Res. · Pubmed #19154086 links to  free full text

Abstract: This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency.

Khan FY, Ibrahim W. · Department of Medicine, Hamad General Hospital, Doha, Qatar. · Curr Clin Pharmacol. · Pubmed #19149497 No free full text.

Abstract: We report a case of rosuvastatin induced rhabdomyolysis in a low risk patient, who presented with five-day history of generalized muscle pain, weakness and easy fatigability associated with passing dark urine. Initial investigations showed creatinine 140micromol/L, creatine kinase (CK) 4566 U/L and serum myoglobin 2694 ng/ml with a significant increase in urine myoglobin. Although there were no obvious risk factors, the patient was diagnosed with rosuvastatin induced rhabdomyolysis. The drug was stopped on the first day of admission and the patient was initiated on intravenous fluid with cautious monitoring of serum electrolytes. On the following days the level of creatine kinase and serum myoglobin returned toward normal and consequently he was discharged without statins but on dietary therapy. On follow-up evaluation, the patient was symptom free his serum creatinine was 106micromol/L, whereas his LDL cholesterol was 2.1mmol/L. The rosuvastatin induced rhabdomyolysis is discussed and the danger of its use in low risk patients is emphasized.

Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, Durrington PN, Chilcott J. · Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK. · J Intern Med. · Pubmed #19141093 No free full text.

Abstract: OBJECTIVES: To study the evidence on the efficacy and safety of ezetimibe monotherapy for the treatment of primary (heterozygous familial and non-familial) hypercholesterolaemia. DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Eleven electronic bibliographic databases covering the biomedical, scientific and grey literature were searched from inception and supplemented by contact with experts in the field. Two reviewers independently determined the eligibility of RCTs, with a minimum treatment duration of 12 weeks, which compared ezetimibe monotherapy (10 mg per day) with placebo. RESULTS: In the absence of data from clinical outcome trials, surrogate endpoints such as changes in lipid concentrations were used as indicators of clinical outcomes. A meta-analysis of eight randomized, double-blind, placebo-controlled trials (all 12 weeks) showed that ezetimibe monotherapy was associated with a statistically significant mean reduction in LDL cholesterol (from baseline to endpoint) of -18.58%, (95% CI: -19.67 to -17.48, P < 0.00001) compared with placebo. Significant (P < 0.00001) changes were also found in total cholesterol (-13.46%, 95% CI: -14.22 to -12.70), HDL cholesterol (3.00%, 95% CI: 2.06-3.94) and triglyceride levels (-8.06%, 95% CI: -10.92 to -5.20). Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo. CONCLUSIONS: In a meta-analysis restricted to short-term trials in hypercholesterolaemia, significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy. Further long-term studies with cardiovascular and other clinical outcome data are needed to assess the efficacy and safety of ezetimibe more fully.

Arribas López JR. · Consulta de Medicina Interna II, Unidad VIH, Hospital La Paz, Madrid, España. · Enferm Infecc Microbiol Clin. · Pubmed #19133218 links to  free full text

Abstract: Maraviroc is the first inhibitor of CCR5 co-receptors to be marketed as an antiretroviral. The pre-clinical studies and phase III trials have shown that it has a very favourable safety profile. No characteristic adverse effect of maraviroc has been identified. Unlike with aplaviroc, where its clinical development was stopped due to serious hepatoxicity, no increase in liver toxicity has been demonstrated in patients treated with maraviroc even if they are co-infected by hepatotropic virus. Nor was there any evidence of an increase in the incidence of neoplasms or serious infections in patients treated with maraviroc. In a study on naive patients, maraviroc produced nonsignificant changes in total cholesterol, LDL, HDL and triglycerides. Although CCR5 co-receptors play a role in the immune response of the body, it has not been shown whether individuals homozygote for its deletion (delta-32 mutation) have an increased risk of serious infections, with the possible exception of encephalitis due to the West Nile virus. However, long-term follow up is required on patients treated with to be able to rule out any increased susceptibility to infections or neoplasms.

Pirro M, Bagaglia F, Paoletti L, Razzi R, Mannarino MR. · Medicina Interna, Angiologia e Malattie da Arteriosclerosi, Università degli Studi di Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy. · Ther Adv Cardiovasc Dis. · Pubmed #19124431 No free full text.

Abstract: Hypercholesterolemia has been associated with increased cardiovascular risk by contributing to mechanical endothelial injury and dysfunction. There is evidence that chronic exposure to increased plasma cholesterol levels might also impair the repair of lipoprotein-mediated endothelial injury, possibly by reducing the availability and function of circulating endothelial progenitors. This review summarizes current knowledge about the mechanisms of lipoprotein-mediated endothelial injury and endothelial progenitor cell assisted vascular repair; the influence of hypercholesterolemia on endothelial progenitor cell dysfunction will be also addressed.

Greve AM, Wachtell K. · Department of Medicine B, Rigshospitalet, The Heart Center, Copenhagen, Denmark. · Ther Adv Cardiovasc Dis. · Pubmed #19124427 No free full text.

Abstract: Several studies suggest that atherosclerotic disease is not a focal disease restricted to culprit lesions in the intima of the arterial wall, but seems to act as a general disease affecting the entire cardiovascular system. Evolving research has lately focused on the atherosclerotic component in calcific aortic stenosis (AS) as it seems that the valve is affected in a pattern similar to that of the vasculature. The hope is therefore, that we someday in the management of patients with calcific AS can apply some of the same treatment strategies as in atherosclerotic vascular disease. This article reviews the pathophysiological mechanisms of calcific AS, reviews current clinical trials of statin use in aortic stenosis and reports on on-going trials, evaluating whether cholesterol lowering therapy can slow disease progression in different populations. Finally, we review if computerized tomography, biomarkers, and clinical characteristics such as left ventricular ejection fraction, can be useful in stratifying patients to potential benefit of statin therapy.

Murphy MH, Blair SN, Murtagh EM. · Sport and Exercise Sciences Research Institute, University of Ulster, Newtownabbey, County Antrim, Northern Ireland. · Sports Med. · Pubmed #19093694 No free full text.

Abstract: Current physical activity guidelines endorse the notion that the recommended amount of daily physical activity can be accumulated in short bouts performed over the course of a day. Although intuitively appealing, the evidence for the efficacy of accumulated exercise is not plentiful. The purpose of this review was to compare the effects of similar amounts of exercise performed in either one continuous or two or more accumulated bouts on a range of health outcomes. Sixteen studies met the selection criteria for inclusion in the review, in which at least one outcome known to affect health was measured before and after continuous and accumulated exercise training interventions. Where improvements in cardiovascular fitness were noted, most studies reported no difference in the alterations between accumulated and continuous patterns of exercise. In the few studies where a normalization of blood pressure was observed from baseline to post-intervention, there appear to be no differences between accumulated and continuous exercise in the magnitude of this effect. For other health outcomes such as adiposity, blood lipids and psychological well-being, there is insufficient evidence to determine whether accumulated exercise is as effective as the more traditional continuous approach. Seven short-term studies in which at least one health-related outcome was measured during the 0- to 48-hour period after a single continuous bout of exercise and a number of short bouts of equivalent total duration were included in the review. Many of the studies of such short-term effects considered the plasma triglyceride response to a meal following either accumulated short or continuous bouts of exercise. Collectively, these studies suggest that accumulated exercise may be as effective at reducing postprandial lipaemia. Further research is required to determine if even shorter bouts of accumulated exercise (<10 minutes) confer a health benefit and whether an accumulated approach to physical activity increases adherence among the sedentary population at whom this pattern of exercise is targeted.

De Lorenzo F, Collot-Teixeira S, Boffito M, Feher M, Gazzard B, McGregor JL. · Beta cell Diabetes Centre, Chelsea and Westminster Hospital NHS Foundation Trust, 369 Fulham Road, London, SW10 9NH, UK. · Curr Med Chem. · Pubmed #19075647 No free full text.

Abstract: Human immunodeficiency virus (HIV)-infected patients are at a significantly higher risk from coronary heart diseases (CHD) and myocardial infarction (MI) compared to gender- and age-matched non-infected individuals. Combination antiretroviral therapy (cART) has transformed a fatal illness into a chronic stable condition. However, cART induces metabolic abnormalities in HIV-infected patients, while its role in vascular atherosclerosis is still under investigation. The use of cART is linked to inflammation - a key mechanism in atherosclerotic progression and destabilisation that precedes clinical events like MI. There is evidence of visceral fat abnormal distribution in HIV infected patients, and inflammatory changes in HIV infected patients drive the initiation, progression and, ultimately, thrombotic clinical complications induced by atherosclerosis. Visceral adipose tissue, a virtual factory for manufacturing pro-inflammatory mediators, affects the liver function. The inflamed liver promotes the development of pro-atherogenic dyslipidaemia. Pro-inflammatory cytokines released by adipocytes travel to the skeletal muscles and other peripheral tissues, worsening insulin sensitivity and leading to hyperglycaemia. Increased high sensitivity C-reactive protein (hs-CRP) inflammatory marker is associated with endothelial dysfunction in HIV-infected patients. Increased levels of monocytic nuclear factor kappa-B (NFkappa-B), a master switch in the inflammatory cascade, are documented in patients with elevated hs-CRP levels. It can be assumed that, as a result of NFkappa-B activation, hs-CRP up-regulates cytokines that contribute to MI by recruiting leukocytes and promoting thrombosis. This review focuses on the association of HIV-infection, metabolic abnormalities and known mechanisms involved in inducing accelerated atherosclerosis and inflammation in HIV-infected patients, as well as the role of lipid lowering agents in potentially preventing CHD.

Wanner C, Ritz E. · Department of Internal Medicine, University of Würzburg, Würzburg, Germany. · Kidney Int Suppl. · Pubmed #19034322 No free full text.

Abstract: Lipid parameters are altered in the earliest stages of primary kidney disease, some even when measured glomerular filtration rate (GFR) is still normal. The main problem is that routinely measured lipid parameters are deceivingly normal except low high-density lipoprotein (HDL) and moderately elevated triglycerides (TGs) (>150 mg per 100 ml). Behind this unimpressive spectrum, serious anomalies are hidden: increased very low-density lipoprotein (VLDL) and chylomicron remnants, accumulation of delipidated small dense low-density lipoprotein (LDL), post translational modification of lipoproteins, abnormal concentrations of Lp(a) and nonprotective HDL. A routine parameter with some predictive value is the concentration of non-HDL cholesterol. Several of these abnormal lipoprotein particles stimulate cellular free oxygen radical formation which in turn induce inflammation and impact on endothelial function.A bone of contention is the indication for treatment with statins in endstage renal disease. Poor survival is paradoxically predicted by low cholesterol. This appears to be the result of confounding by microinflammation. One controlled interventional study in hemodialysed type 2 diabetics, the 4-D study, failed to show a significant benefit on the primary cardiovascular endpoint. We discuss potential explanations for this 'negative' outcome and the implications for statin treatment.

Cravedi P, Remuzzi G. · Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Villa Camozzi, Ranica, Bergamo, Italy. · Kidney Int Suppl. · Pubmed #19034321 No free full text.

Abstract: The incidence of chronic renal and cardiovascular diseases is increasing worldwide. Since renal disease is the strongest risk factor for cardiovascular morbidity and mortality, strategies able to reduce renal disease progression are expected to translate into a decreased incidence of cardiovascular events. To this purpose, inhibition of the renin-angiotensin system, both by angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, represents the best available option. Several large, randomized studies have convincingly shown that these treatments are associated with a significant reduction in the risk for renal disease progression in diabetic and non diabetic patients with chronic kidney disease. Importantly, improvement of renal outcomes is paralleled by a reduction of the cardiovascular risk. However, a significant proportion of patients with chronic nephropathies still progresses to end-stage renal failure or dies for cardiovascular events. A more complex strategy, including strict control of BP and proteinuria, lowering of blood lipids, tight metabolic control of diabetes, and lifestyle changes may improve morbidity and mortality of patients with chronic renal disease as compared with single or dual intervention on the renin-angiotensin system. Moreover, prevention strategies are urgently needed to face the burden of chronic renal disease and cardiovascular morbidity and mortality. This is particularly true for developing countries, where the incidence of these chronic diseases is growing with the highest rate.

Horswell SD, Ringham HE, Shoulders CC. · Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, Du Cane Rd., London, W12 0NN United Kingdom. · J Lipid Res. · Pubmed #19023136 No free full text.

Abstract: This review summarizes the progress made in cutting through the biological and genetic complexity of the Gordian knot that is familial combined hyperlipidemia. We particularly focus on how the application of new genomic technologies, especially massively parallel sequencing and high-throughput genotyping platforms, promise to accelerate the gene discovery process in this common, highly atherogenic disorder, with important diagnostic and therapeutic implications.