Hyperlipidemias: United Kingdom

Wierzbicki AS, Humphries SE, Minhas R, Anonymous00232. · St Thomas' Hospital, London SE1 7EH. · BMJ. · Pubmed #18753174 No free full text.

This publication has no abstract.

Deans KA, Dominiczak MH. · Department of Biochemistry, Gartnavel General Hospital, Glasgow, UK. · Curr Opin Lipidol. · Pubmed #18957887 No free full text.

This publication has no abstract.

DeSilvey DL. · Waldo Cardiovascular Medicine, Belfast, ME 04915, USA. · Am J Geriatr Cardiol. · Pubmed #17086036 links to  free full text

This publication has no abstract.

Langford NJ, Kendall MJ. · Clinical Pharmacology Section, Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK. · J Clin Pharm Ther. · Pubmed #11722675 No free full text.

This publication has no abstract.

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.

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.

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.

Ceriello A. · Warwick Medical School, Clinical Science Research Institute, University Hospital -Coventry, CV2 2DX, UK. · Diab Vasc Dis Res. · Pubmed #18958835 links to  free full text

Abstract: High admission blood glucose levels after acute myocardial infarction are common and are associated with an increased risk of death in subjects with and without diabetes. In this review, the possible toxic effects of acute hyperglycaemia are discussed as a possible explanation for the worse prognosis in subjects with myocardial infarction and concomitant hyperglycaemia. In particular, evidence supporting the hypothesis that acute hyperglycaemia may favour the appearance of cardiovascular disease through the generation of oxidative stress is presented.

Bhatnagar D, Soran H, Durrington PN. · University of Manchester Cardiovascular Research Group, Core Technology Facility, Manchester M13 9NT. · BMJ. · Pubmed #18719012 No free full text.

This publication has no abstract.

Owen CG, Whincup PH, Kaye SJ, Martin RM, Davey Smith G, Cook DG, Bergstrom E, Black S, Wadsworth ME, Fall CH, Freudenheim JL, Nie J, Huxley RR, Kolacek S, Leeson CP, Pearce MS, Raitakari OT, Lisinen I, Viikari JS, Ravelli AC, Rudnicka AR, Strachan DP, Williams SM. · Division of Community Health Sciences, St George's, University of London, London, United Kingdom. · Am J Clin Nutr. · Pubmed #18689365 links to  free full text

Abstract: BACKGROUND: Earlier studies have suggested that infant feeding may program long-term changes in cholesterol metabolism. OBJECTIVE: We aimed to examine whether breastfeeding is associated with lower blood cholesterol concentrations in adulthood. DESIGN: The study consisted of a systematic review of published observational studies relating initial infant feeding status to blood cholesterol concentrations in adulthood (ie, aged >16 y). Data were available from 17 studies (17 498 subjects; 12 890 breastfed, 4608 formula-fed). Mean differences in total cholesterol concentrations (breastfed minus formula-fed) were pooled by using fixed-effect models. Effects of adjustment (for age at outcome, socioeconomic position, body mass index, and smoking status) and exclusion (of nonexclusive breast feeders) were examined. RESULTS: Mean total blood cholesterol was lower (P = 0.037) among those ever breastfed than among those fed formula milk (mean difference: -0.04 mmol/L; 95% CI: -0.08, 0.00 mmol/L). The difference in cholesterol between infant feeding groups was larger (P = 0.005) and more consistent in 7 studies that analyzed "exclusive" feeding patterns (-0.15 mmol/L; -0.23, -0.06 mmol/L) than in 10 studies that analyzed nonexclusive feeding patterns (-0.01 mmol/L; -0.06, 0.03 mmol/L). Adjustment for potential confounders including socioeconomic position, body mass index, and smoking status in adult life had minimal effect on these estimates. CONCLUSIONS: Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.

Bhindi R, Ormerod O, Newton J, Banning AP, Testa L. · Institute of Cardiology, John Radcliffe Hospital, Oxford, UK. · QJM. · Pubmed #18676683 No free full text.

Abstract: Since their introduction several years ago, the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase inhibitors-the statins-have been widely used for hyperlipidemia and for the primary/secondary prevention of cardiovascular diseases. They have been shown to be safe as well as efficacious in a number of different clinical trials; however, studies have suggested that they can interact with other co-administered therapies. More recently, the thienopyridines have been successfully integrated with the conventional medical treatment of coronary disease as they showed effectiveness in reducing platelet activity both in stable and unstable settings. They also improve the outcome of patients treated with percutaneous coronary intervention. The potential interaction of statins and thienopyridines is a matter of concern. Despite some preclinical data suggesting an interaction between statins metabolized by the liver cytochrome P3A4-such as atorvastatin, lovastatin and simvastatin-and clopidogrel, there is no compelling clinical evidence to stop their co-administration.

Soran H, Durrington P. · Central Manchester and Manchester Children University Hospital, Department of Endocrinology, Oxford Road, Manchester M13 9WL, UK. · Expert Opin Pharmacother. · Pubmed #18671469 No free full text.

Abstract: BACKGROUND: Rosuvastatin is a fully synthetic statin developed by AstraZeneca. It is a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase. OBJECTIVE: We reviewed the efficacy, characteristics, safety and clinical effectiveness of rosuvastatin. METHODS: We conducted a Pubmed and Medline literature search (January 2000 to March 2008) to identify all papers on rosuvastatin published in English. Other relevant papers and textbooks from the author's personal collection were also used as references. CONCLUSION: Rosuvastatin has a potent low-density lipoprotein cholesterol (LDL-C) lowering action. In addition it has potentially favourable effects on high-density lipoprotein (HDL), non-HDL-C, triglycerides and the apolipoprotein B : A1 ratio. Theoretically, if assumptions about these lipoprotein effects hold true and translate to better cardiovascular outcomes, rosuvastatin could prove to be the most clinically effective statin. However, while results from vascular imaging studies are encouraging overall, it is not clear whether these will translate into favourable cardiovascular outcomes because of lack of trial results. There are, as yet, no published mortality and cardiovascular outcome data from randomised, controlled trials to support LDL-C lowering with rosuvastatin rather than other statins. However, the early termination of one outcome trial has recently been announced because of clear benefits announced from rosuvastatin therapy compared with placebo.

Humphries SE, Norbury G, Leigh S, Hadfield SG, Nair D. · Division of Cardiovascular Genetics, British Heart Foundation Laboratories, Department of Medicine, Royal Free and UCL Medical School, London, UK. · Curr Opin Lipidol. · Pubmed #18607183 No free full text.

Abstract: PURPOSE OF REVIEW: Familial hypercholesterolaemia is a common genetic disorder of lipid metabolism in which patients have a significantly elevated risk of early coronary heart disease, which can be substantially lowered by treatment with the statin class of drugs. In many countries in Europe, tracing of relatives using DNA information, once the family mutation has been identified, is being actively carried out. The present review examines the specificity and clinical utility of DNA testing in patients with familial hypercholesterolaemia. RECENT FINDINGS: Technological progress has improved the detection rate in patients with the strongest clinical suspicion of familial hypercholesterolaemia to more than 70-80%. Patients carrying a mutation have, on average, higher low-density lipoprotein cholesterol levels and greater risk of early coronary heart disease, and studies have reported the utility of DNA information in the identification of affected relatives. More than 1000 different molecular causes of familial hypercholesterolaemia are documented in the University College London database, and although more than 90% of these clearly cause familial hypercholesterolaemia, the remainder require careful interpretation. SUMMARY: DNA testing, as an adjunct to the measurement of plasma low-density lipoprotein cholesterol levels, has clinical utility in providing an unequivocal diagnosis in patients and in identifying affected relatives at an early age so that they can be offered lifestyle advice and appropriate lipid-lowering therapies. Researchers and DNA diagnostic laboratories need to interpret novel sequence changes with caution in order to avoid a false positive diagnosis.

McTaggart F, Jones P. · Clinical Development, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. · Cardiovasc Drugs Ther. · Pubmed #18553127 links to  free full text

Abstract: PURPOSE: The objective was to systematically review clinical trial data on the effects of statins on high-density lipoproteins (HDL) and to examine the possibility that this provides cardiovascular benefits in addition to those derived from reductions in low-density lipoproteins (LDL). METHODS: The PubMed database was searched for publications describing clinical trials of atorvastatin, pravastatin, rosuvastatin, and simvastatin. On the basis of predefined criteria, 103 were selected for review. RESULTS: Compared with placebo, statins raise HDL, measured as HDL-cholesterol (HDL-C) and apolipoprotein A-I (apo A-I); these elevations are maintained in the long-term. In hypercholesterolemia, HDL-C is raised by approximately 4% to 10%. The percentage changes are greater in patients with low baseline levels, including those with the common combination of high triglycerides (TG) and low HDL-C. These effects do not appear to be dose-related although there is evidence that, with the exception of atorvastatin, the changes in HDL-C are proportional to reductions in apo B-containing lipoproteins. The most likely explanation is a reduced rate of cholesteryl ester transfer protein (CETP)-mediated flow of cholesterol from HDL. There is some evidence that the statin effects on HDL reduce progression of atherosclerosis and risk of cardiovascular disease independently of reductions in LDL. CONCLUSION: Statins cause modest increases in HDL-C and apo A-I probably mediated by reductions in CETP activity. It is plausible that such changes independently contribute to the cardiovascular benefits of the statin class but more studies are needed to further explore this possibility.

Harland JI, Haffner TA. · HarlandHall Associates, The Stables, Ranbury Ring, London Road, Poulton, Cirencester, Glos GL7 5HN, UK. · Atherosclerosis. · Pubmed #18534601 No free full text.

Abstract: AIMS: To determine the effect of a daily intake of circa 25 g soya protein on blood lipids in adults with normal or mildly elevated cholesterolaemia. METHODS: Medline and other scientific databases were searched to identify randomised controlled trials (RCTs); these were systematically reviewed against pre-determined criteria. Eligible RCTs evaluated the effect of 25 g (range 15-40 g) soya protein on measures of blood lipids. Results from RCTs were pooled using standard meta-analysis methods. RESULTS: Thirty studies containing 42 treatment arms (n=2913), with an average soya protein intake of 26.9 g met the inclusion criteria. Soya protein inclusion led to reductions in standard difference in mean low density lipoprotein (LDL), total cholesterol and blood triglycerides of 0.23 mmol/L (95% confidence interval (CI) -0.160 to -0.306, p<0.0001), 0.22 mmol/L (95% CI -0.142 to -0.291, p<0.0001) and 0.08 mmol/L (95% CI -0.004 to -0.158, p=0.04), respectively. There was no effect on mean difference in apolipoprotein A (ApoA), but ApoB was reduced by 0.021 g/L (p=0.01) in the soya group. Meta-regression analysis indicated no dose response relationship between soya protein intake in the range of 15-40 g and standard difference in LDL or HDL. All data were tested for heterogeneity and none identified. CONCLUSIONS: The inclusion of modest amounts soya protein (ca. 25 g) into the diet of adults with normal or mild hypercholesterolaemia resulted in small, highly significant reductions in total and LDL cholesterol, equivalent to ca. 6% LDL reduction. This practically achievable intake, particularly when combined with other dietary measures, can make a useful contribution to blood cholesterol management.

Ara R, Tumur I, Pandor A, Duenas A, Williams R, Wilkinson A, Paisley S, Chilcott J. · School of Health and Related Research (ScHARR), University of Sheffield, UK. · Health Technol Assess. · Pubmed #18485273 links to  free full text

Abstract: OBJECTIVES: To review the clinical and cost-effectiveness of ezetimibe as a combination therapy or monotherapy for the treatment of primary hypercholesterolaemia in the UK. DATA SOURCES: Twelve electronic databases were searched from inception to June 2006. Searches were supplemented by hand-searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings. REVIEW METHODS: A systematic review and meta-analysis (where appropriate) of the clinical efficacy evidence was undertaken following recommended guidelines. A Markov model was developed to explore the costs and health outcomes associated with ezetimibe treatment. RESULTS: No published clinical outcome trials (> 12 weeks) were identified. In the absence of clinical end-point data from trials, 13 (of which five were multi-arm) phase III multi-centre randomised controlled trials (RCTs) (of varying methodological quality) of short-term duration (12-48 weeks) with surrogate end-point data were included. For patients not adequately controlled with a statin alone, a meta-analysis of six studies showed that a fixed-dose combination of ezetimibe and statin treatment was associated with a statistically significant reduction in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (Total-c) compared with statin alone (p < 0.00001). Four studies (not eligible for meta-analysis) that titrated (either forced or stepwise) the statin doses to LDL-c targets generally showed that the co-administration of ezetimibe and statin was significantly more effective in reducing plasma LDL-c concentrations than statin monotherapy (p < 0.05 for all studies). For patients where a statin is not considered appropriate, a meta-analysis of seven studies demonstrated that ezetimibe monotherapy significantly reduced LDL-c levels compared with placebo (p < 0.00001). There were no statistically significant differences in LDL-c-lowering effects across different subgroups. Ezetimibe therapy (either in combination with a statin or monotherapy) appeared to be well tolerated compared to statin monotherapy or placebo, respectively. No ezetimibe studies reported data on health-related quality of life (HRQoL). There was a wide range in the economic results depending on the treatment strategies evaluated. When comparing ezetimibe monotherapy with no treatment in individuals with baseline LDL-c values of 3.0-4.0 mmol/l, the results range from 21,000 pounds to 50,000 pounds per quality-adjusted life-year (QALY). Results for individuals with baseline LDL-c values over 5.0 mmol/l are below 30,000 pounds per QALY. When comparing the costs and benefits of adding ezetimibe to ongoing statin treatment compared with maintaining statin treatment at the current dose, the majority of results are above values generally considered to be cost-effective (range 19,000 pounds to 48,000 pounds per QALY). Based on the evidence available, when comparing the costs and benefits associated with adding ezetimibe to ongoing statin treatment compared with a switch to a more potent statin, the results are governed by the difference in the cost of the treatment regimens compared and results range from 1500 pounds to 116,000 pounds per QALY. CONCLUSIONS: The short-term RCT clinical evidence demonstrated that ezetimibe was effective in reducing LDL-c when administered as monotherapy or in combination with a statin. However, when used as a monotherapy, ezetimibe is less effective than statins in lowering LDL-c. Given the limitations in the effectiveness data, there is great uncertainty in the economic results. These suggest that ezetimibe could be a cost-effective treatment for individuals with high baseline LDL-c values, for patients with diabetes and for individuals with heterozygous familial hypercholesterolaemia. Long-term clinical outcome studies are needed to allow more precise cost-effectiveness estimates to be calculated.

Thompson GR, Anonymous00219. · Imperial College, Hammersmith Hospital, London. · Atherosclerosis. · Pubmed #18371971 No free full text.

Abstract: Plasma exchange has been shown to increase life-expectancy in homozygous familial hypercholesterolaemia (FH) but increasingly is being replaced by LDL apheresis. Several methods are now available for undertaking this procedure, which lowers LDL cholesterol and Lp(a) efficiently and safely when performed weekly or bi-weekly and causes only slight decreases in HDL cholesterol. Hitherto the main clinical indication has been homozygous FH, including children and pregnant women, but there are limited data showing that LDL apheresis has effects on the progression of cardiovascular disease in FH heterozygotes which are similar to those of maximal lipid-lowering drug therapy. Hence it has the potential to be beneficial in hypercholesterolaemic patients with overt coronary disease who are refractory to or intolerant of drugs. It is therefore recommended that LDL apheresis should be the treatment of choice for: (1) all FH homozygotes from the age of seven onwards unless their serum cholesterol can be reduced by >50% and/or decreased to <or=9mmol/l by drug therapy; (2) individual patients with either heterozygous FH or a bad family history of premature cardiac death whose coronary disease progresses and where LDL cholesterol remains >5.0mmol/l or is decreased by <40% with maximal drug therapy. Apheresis may also occasionally be indicated on a case-by-case basis for patients with lower levels of LDL. (3) LDL apheresis should also be considered for patients with aggressive progressing coronary disease and Lp(a)>60mg/l whose LDL cholesterol remains >3.2mmol/l despite maximal drug therapy.

Hartweg J, Perera R, Montori V, Dinneen S, Neil HA, Farmer A. · University of Oxford, Division of Public Health & Primary Care, Old Road Campus, Oxford, UK OX3 7LF. · Cochrane Database Syst Rev. · Pubmed #18254017 No free full text.

Abstract: BACKGROUND: People with type 2 diabetes mellitus are at increased risk from cardiovascular disease. Dietary omega-3 polyunsaturated fatty acids (PUFAs) are known to reduce triglyceride levels, but their impact on cholesterol levels, glycemic control and vascular outcomes are not well known. OBJECTIVES: To determine the effects of omega-3 PUFA supplementation on cardiovascular outcomes, cholesterol levels and glycemic control in people with type 2 diabetes mellitus. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, bibliographies of relevant papers and contacted experts for identifying additional trials. SELECTION CRITERIA: All randomised controlled trials were included where omega-3 PUFA supplementation or dietary intake was randomly allocated and unconfounded in people with type 2 diabetes. Authors of large trials were contacted for missing information. DATA COLLECTION AND ANALYSIS: Trials were assessed for inclusion. Authors were contacted for missing information. Data was extracted and quality assessed independently in duplicate. Fixed-effect meta-analysis was carried out. MAIN RESULTS: Twenty three randomised controlled trials (1075 participants) were included with a mean treatment duration of 8.9 weeks. The mean dose of omega-3 PUFA used in the trials was 3.5 g/d. No trials with vascular events or mortality endpoints were identified. Among those taking omega-3 PUFA triglyceride levels were significantly lowered by 0.45 mmol/L (95% confidence interval (CI) -0.58 to -0.32, P < 0.00001) and VLDL cholesterol lowered by -0.07 mmol/L (95% CI -0.13 to 0.00, P = 0.04). LDL cholesterol levels were raised by 0.11 mmol/L (95% CI 0.00 to 0.22, P = 0.05). No significant change in or total or HDL cholesterol, HbA1c, fasting glucose, fasting insulin or body weight was observed. The increase in VLDL remained significant only in trials of longer duration and in hypertriglyceridemic patients. The elevation in LDL cholesterol was non-significant in subgroup analyses. No adverse effects of the intervention were reported. AUTHORS' CONCLUSIONS: Omega-3 PUFA supplementation in type 2 diabetes lowers triglycerides and VLDL cholesterol, but may raise LDL cholesterol (although results were non-significant in subgroups) and has no statistically significant effect on glycemic control or fasting insulin. Trials with vascular events or mortality defined endpoints are needed.

Wierzbicki AS, Graham CA, Young IS, Nicholls DP. · St. Thomas' Hospital, London SE 1 7EH, UK. · Curr Vasc Pharmacol. · Pubmed #18220935 No free full text.

Abstract: Familial combined hyperlipidaemia (FCH) was identified in early genetic studies of populations as a dominant condition associated with mixed hyperlipidaemia and early onset coronary heart disease. Later studies extended the phenotype and noted that this genetic hyperlipidaemia was sensitive to environmental effects. This article reviews the definitions, animal models and genetics of FCH. In contrast to familial hypercholesterolaemia, which is caused by mutations in a limited number of affected genes, the genetics of FCH have remained obscure and very few definite candidate genes have been identified. A strong role for the apoA-I, A-IV, A-V, C-III cluster on chromosome 11 was identified early on and multiple associations have been found to hyperlipidaemia in this region and more strongly to adjacent sections of the chromosome. More recently quantitative trait mapping has identified a number of candidate genes including upstream transcription factor -1 (USF-1) on 1 q21 and CD-36 on chromosome 4. Of these the strongest evidence, based on 4 analyses, links the lipid components of FCH to intronic variants in the USF-1 gene on chromosome 1q21-23. Unfortunately USF-1 yet fails to show clear associations with diabetes and the metabolic syndrome which co-map to this region and are also associated with mixed hyperlipidaemia. Large scale validation of USF-1 variants in other populations is still awaited. It is likely that FCH is a heterogeneous condition, that is subject to wide-scale environmental confounding from common traits such as obesity and the metabolic syndrome, and that the resolution of its genetics is going to prove a severe challenge.

Charlton-Menys V, Durrington PN. · Cardiovascular Research Group, School of Clinical & Laboratory Sciences, Core Technology Facility (3rd Floor), University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK. · Exp Physiol. · Pubmed #18165431 links to  free full text

Abstract: There has been a fascinating interplay between the discovery of some of the key enzymes, receptors and transporters in cholesterol biosynthesis and transfer and the development of drugs for the regulation of cholesterol metabolism. The discovery of the low-density lipoprotein (LDL) receptor led to the realization that circulating LDL cholesterol could be decreased when hepatic LDL receptor expression was stimulated by decreasing intrahepatic cholesterol levels. The first class of drugs which operate in this way were the bile-acid sequestrating agents, which, by interrupting the enterohepatic circulation of bile acids, deplete the liver of cholesterol used to replenish the pool of bile salts. Ezetimibe, which was developed to block cholesterol absorption from the intestine, led to the discovery of the Nieman-Pick C1-Like 1 sterol transporter channel. The statins, which have proved enormously successful in preventing cardiovascular disease, were discovered amongst fungal metabolites which inhibit hydroxyl methyl CoA reductase, the rate-limiting enzyme for hepatic cholesterol biosynthesis. Drugs which block enzymes at other stages of the cholesterol biosynthetic pathway, particularly the squalene synthase inhibitors, are entering the clinical phase of their development. Drugs which interfere with hepatic very low-density lipoprotein assembly in the liver, such as microsomal triglyceride transfer protein inhibitors and apolipoprotein B mRNA antisense oligonucleotides, are currently undergoing evaluation. Cholesteryl ester transfer protein (CETP) inhibitors, which decrease cholesteryl ester heteroexchange within the circulation, have undergone development to the point of clinical evaluation, and this will eventually settle the controversy about whether CETP is pro- or antiatherogenic.

Paraskevas KI. · Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK. · Int Urol Nephrol. · Pubmed #18066677 No free full text.

Abstract: Lipid abnormalities, and especially hypertriglyceridaemia, are a prominent feature of peritoneal dialysis (PD) patients. The results from several studies have shown that statins are effective and safe lipid-lowering agents in these individuals. Besides lipid lowering, current evidence suggests that these agents exert multiple beneficial effects on PD patients. Statins may maintain residual kidney function by altering the response of the kidneys to dyslipidaemia and, thus, slow the progression of renal failure in PD patients. Also, statins may reduce the incidence of cardiovascular events, as well as morbidity and mortality rates in this high-risk group. However, despite the multiple beneficial effects, PD patients receive suboptimal statin treatment. Apart from the German Dialysis and Diabetes (4D) study, no other prospective, randomised controlled trial has investigated the effects of statin treatment on dialysis patients. The results of large-scale, multi-centre randomised controlled studies (such as AURORA and SHARP) are expected to define the role of statin therapy in this high-risk population.

Velavan P, Huan Loh P, Clark A, Cleland JG. · Cardiothoracic Centre, Liverpool, UK. · Congest Heart Fail. · Pubmed #18046092 No free full text.

Abstract: Heart failure (HF) is a common and serious condition that is usually due to coronary artery disease (CAD). Hypercholesterolemia is a major risk factor for CAD but, paradoxically, patients with advanced HF often have low cholesterol, which is associated with a poor prognosis. Cholesterol lowering with statins reduces morbidity and mortality in patients with CAD who do not have HF and might also have improved outcome in patients with HF had they not been excluded from the reported trials. The results of large trials such as the Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Insufficienza Cardiaca (GISSI-HF) study addressing the effects of rosuvastatin in HF are keenly awaited. In addition to cholesterol lowering, statins have other biologic effects that might be responsible for some of their favorable effects. This article examines this cholesterol paradox and possible mechanisms.

Wan RK, Mark PB, Jardine AG. · BHF Cardiovascular Research Centre, University of Glasgow, and Renal Transplant Unit, Western Infirmary, Glasgow, United Kingdom. · Semin Dial. · Pubmed #17991195 No free full text.

Abstract: In the general population, elevated cholesterol is associated with cardiovascular disease and mortality and lowering cholesterol is associated with improved outcomes. This reflects the predominance of isolated atherosclerotic coronary disease in the general population. In patients with renal disease, however, the relationship between serum lipids and cardiovascular outcomes is much less clear and even reversed. In our opinion, the relationship between cholesterol and coronary disease is obscured by high levels of co-morbid disease, malnutrition, inflammation, atypical dyslipidemia and the fact that myocardial infarction is not the typical presentation of cardiovascular disease in patients with renal disease. Thus, cholesterol lowering will still be effective in patients with chronic kidney diseases.