Hyperlipidemias: Netherlands

Rabelink TJ. · University Medical Center Utrecht, Internal Medicine, Room G 02.228, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Nephrol Dial Transplant. · Pubmed #14671033 links to  free full text

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Vogt L, Laverman GD, Dullaart RP, Navis G. · Department of internal Medicine, Division of Nephrology, University Medical Center Groningen, Hanzeplein 1, 9713 GX Groningen, The Netherlands. · Nephrol Dial Transplant. · Pubmed #14671028 links to  free full text

This publication has no abstract.

Scheepers-Hoeks AM, Wessels-Basten SJ, Scherders MJ, Bravenboer B, Loonen AJ, Kleppe RT, Grouls RJ. · Catharinaziekenhuis Eindhoven, apotheek, Postbus 1350, 5602 ZA Eindhoven. · Tijdschr Psychiatr. · Pubmed #18951343 links to  free full text

Abstract: BACKGROUND: Cardiovascular morbidity and mortality are higher in patients with schizophrenia than in the general population because the metabolic side-effects of antipsychotics and schizophrenia increase the risk of cardiovascular disease (cvd) and diabetes mellitus type 2 (DM2). The metabolic syndrome is defined in order to discover which patients have a high risk of developing cvd and DM2. AIM: To survey the current knowledge about the relationship between schizophrenia and the metabolic syndrome, the influence of the use of antipsychotics on the development of the metabolic syndrome, and the possible differences in the effects that first and second generation antipsychotics have on the syndrome. METHOD: The PubMed and Medscape databases were searched for relevant articles published between 2000 and July 2008. results Schizophrenia and the use of antipsychotics increase the prevalence of abdominal obesity, dyslipidemia and DM2 (i.e. the metabole syndrome). Second generation antipsychotics tend to cause a marked increase in the prevalence of abdominal obesity and dyslipidemia, whereas first generation antipsychotics hardly have any of these effects. Both first and second generation antipsychotics increase the risk of DM2. CONCLUSION: The metabolic syndrome has a significant effect on the morbidity and mortality of patients with schizophrenia because it increases the risk they will develop cvd and DM2. The risk increases still further if patients are taking antipsychotics. The risk of cvd can be decreased if patients with schizophrenia are screened in time and are monitored regularly.

Visser ME, Jakulj L, Kastelein JJ, Stroes ES. · Department of Vascular Medicine, Room F4-159.2, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Curr Cardiol Rep. · Pubmed #18950563 No free full text.

Abstract: Recent trials have emphasized that more intensive low-density lipoprotein cholesterol (LDL-C) lowering results in a further reduction in cardiovascular disease risk. Uptitration of statins has limited incremental LDL-C-lowering effects and leads to an increased incidence of side effects. Therefore, attention has shifted toward alternative LDL-C-lowering modalities. Several promising compounds have entered the clinical trial arena, although with mixed results. Acyl-coenzyme A: cholesterol O-acyltransferase (ACAT) inhibitors failed to show benefit. Microsomal triglyceride transfer protein and squalene synthase inhibitors, in spite of beneficial lipid profile changes, have shown adverse event profiles. In contrast, inhibitors of intestinal cholesterol absorption have shown LDL-C-lowering efficacy associated with few side effects. The inhibition of apolipoprotein B100 synthesis by antisense oligonucleotides has now been tested in phase 2 clinical trials, with promising results. Finally, compounds modifying protein convertase subtilisin/kexin type 9 levels are currently in the preclinical phase. In the present article, we discuss these LDL-C-lowering strategies.

Peters B, Maitland-van der Zee AH. · Utrecht University, Faculty of Science, Division of Pharmacoepidemiology and Pharmacotherapy, The Netherlands. · Pharmacogenomics. · Pubmed #18781848 No free full text.

Abstract: In developed countries, cardiovascular disease is one of the leading causes of death. Among other statins, pravastatin is abundantly prescribed to reduce risk of coronary artery disease by lowering cholesterol. Genetic factors are thought to be partly responsible for the interindividual variation in the response to pravastatin. This article reviews the most important studies conducted on the pharmacogenetics of pravastatin. Currently there is no evidence to advocate pharmacogenetic testing before initiating therapy.

Winters SM, Visser H, Steerneman AH, Thomas G, Bots ML, van der Heijden GJ. · Julius Center for Health Sciences and Primary Care, Str. 6.131, Heidelberglaan 100, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. · Prim Care Diabetes. · Pubmed #18684421 No free full text.

Abstract: PURPOSE: To study the need for dietary measures to further reduce LDL cholesterol in patients with type 2 diabetes mellitus on statin therapy. METHODS: A Pubmed, Embase, CINAHL and Cochrane library search was performed to identify relevant articles. After critical appraisal six articles were ranked according to relevance, validation and level of evidence. RESULTS: There were no studies performed among type II diabetics. Among patients with hypercholesterolaemia, diet led to an additional LDL reduction from 0.20 to 0.88 mmol/l, translating into 23% reduction in vascular risk. CONCLUSION: We recommend a low-fat diet on top of statin therapy in patients with type 2 diabetes mellitus assuming that effects found in hypercholesterolaemic patients also apply to type 2 diabetics.

del Sol AI, Nanayakkara PW. · VU University Medical Center, Department of Internal Medicine, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. · Expert Opin Drug Metab Toxicol. · Pubmed #18611121 No free full text.

Abstract: BACKGROUND: It is well known that statins lead to a markable reduction in cardiovascular morbidity and mortality. One of the first and best studied statins is pravastatin, which has been studied in both primary and secondary prevention trials. With 40 mg pravastatin daily, total cholesterol can be reduced by 25-34% with a very consistent risk reduction of 24% of death from cardiovascular diseases. Side effects are rare and usually consist of myopathy. Following the Adult Treatment Panel III (ATPIII) guidelines on cholesterol management, apart from therapeutic lifestyle changes, in high-risk patients (including patients with diabetes mellitus), cholesterol-lowering therapy should be targeted at a treatment goal of LDL cholesterol<2.5 mmol/l. Statin-lowering therapy should be commenced to adequately lower cardiovascular risk. Therefore, when the expected 25-34% LDL cholesterol lowering would be enough to reach an LDL<2.5 mmol/l, treatment should be started with pravastatin. METHOD: Trials have shown that treatment with pravastatin is safe in older patients as well as in children with familial hypercholesterolemia. RESULTS/CONCLUSION: Since obesity seems to become a worldwide problem and given the low costs of generic pravastatin, it may even be cost-effectively used in developing countries.

DeRuiter MC, Alkemade FE, Gittenberger-de Groot AC, Poelmann RE, Havekes LM, van Dijk KW. · Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands. · Curr Opin Lipidol. · Pubmed #18607178 No free full text.

Abstract: PURPOSE OF REVIEW: In the last 20 years, an increasing amount of epidemiological and pathological evidence has become available illustrating the relationship between an adverse in-utero environment and increased risk of vascular disease in the offspring. It is now generally accepted that epigenetic phenomena, such as either DNA methylation or chromatin modifications or both mediate the long-term memory and thus developmental programming of cells and tissues. RECENT FINDINGS: In utero, the placenta and fetus are exposed to the metabolic, antioxidant and pro-inflammatory and anti-inflammatory signals from the mother and will likely respond specifically. In the fetus, these responses may lead to permanent changes either in DNA methylation or chromatin modification or both and these changes may lead to increased atherosclerosis susceptibility in adulthood. However, the molecular mechanisms responsible for the translation of an adverse maternal environment into permanent epigenetic changes are poorly understood. SUMMARY: In this review, we briefly summarize the possible signals crossing the placental barrier and discuss the molecular mechanisms of epigenetic programming in the developing fetus leading to increased athero-susceptibility of the vessel wall.

Alipour A, Elte JW, van Zaanen HC, Rietveld AP, Castro Cabezas M. · Department of Internal Medicine, Sint Franciscus Gasthuis, Rotterdam, The Netherlands. · Atheroscler Suppl. · Pubmed #18595782 No free full text.

Abstract: Postprandial hyperlipidemia is considered to be a substantial risk factor for atherosclerosis. Interestingly, this concept has never been supported by randomized clinical trials. The difficulty lies in the fact that most interventions aimed to reduce postprandial lipemia, will also affect LDL-C levels. The atherogenic mechanisms of postprandial lipids and lipoproteins can be divided into direct lipoprotein-mediated and indirect effects; the latter, in part, by inducing an inflammatory state. Elevations in postprandial triglycerides (TG) have been related to the increased expression of postprandial leukocyte activation markers, up-regulation of pro-inflammatory genes in endothelial cells and involvement of the complement system. This set of events is part of the postprandial inflammatory response, which is one of the recently identified potential pro-atherogenic mechanisms of postprandial lipemia. Especially, complement component 3 levels show a close correlation with postprandial lipemia and are also important determinants of the metabolic syndrome. In clinical practice, fasting TG are frequently used as reflections of postprandial lipemia due to the close correlation between the two. The use of serial capillary measurements in an out-of-hospital situation is an alternative for oral fat loading tests. Daylong TG profiles reflect postprandial lipemia and are increased in conditions like the metabolic syndrome, type 2 diabetes and atherosclerosis. Studies are needed to elucidate the role of postprandial inflammation in atherogenesis and to find new methods in order to reduce selectively the postprandial inflammatory response. Future studies are needed to find new methods in order to reduce selectively the postprandial inflammatory response.

Huijgen R, Vissers MN, Defesche JC, Lansberg PJ, Kastelein JJ, Hutten BA. · Academic Medical Center, Department of Vascular Medicine, Meibergreef 9 (Room F4-146), 1105 AZ, Amsterdam, The Netherlands. · Expert Rev Cardiovasc Ther. · Pubmed #18402545 No free full text.

Abstract: Heterozygous familial hypercholesterolemia is associated with elevated levels of LDL-cholesterol and the development of premature cardiovascular disease. The condition is considerably under-diagnosed and under-treated. Statins are the first choice treatment for all patients with heterozygous familial hypercholesterolemia. For those patients who do not reach their treatment target or who are unable to use adequate statin dose, several alternative treatment modalities can be used, either as add-on therapy or as monotherapy. In this review the various treatment options are discussed.

Hettema ME, Bootsma H, Kallenberg CG. · Division of Rheumatology and Clinical Immunology, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. · Rheumatology (Oxford). · Pubmed #18321944 No free full text.

Abstract: Atherosclerosis is considered to be a chronic inflammatory disorder. Several autoimmune rheumatic diseases are characterized by premature and accelerated atherosclerosis in which both classical and non-classical risk factors contribute to atherogenesis. SSc is characterized by vasculopathy, and microvascular involvement is common. Macrovascular involvement is considered rare, although increased prevalence of macrovascular disease has been reported as well. Here, we review the literature regarding coronary artery disease, cerebrovascular disease and peripheral arterial disease in SSc. An increased prevalence of distal peripheral artery disease in the digits has been found. The prevalence of coronary artery disease and cerebrovascular disease is not increased, although studies using intima-media thickness of the carotid artery as a marker of early atherosclerosis showed discrepant results. Besides traditional risk factors, as present in the general population, non-traditional risk factors are present in SSc as well, such as increased lipoprotein(a), oxidized LDL, inflammation, vasospasm and endothelial dysfunction. Moreover, markers of vascular damage in atherosclerosis, like antibodies to oxidized LDL, and increased levels of soluble vascular adhesion molecules, have been described in association with vascular damage in SSc. Nevertheless, generalized premature atherosclerosis has not been detected in SSc. Therefore, further research is necessary to assess the prevalence of clinically manifest or subclinical early atherosclerosis in SSc.

Hovenkamp E, Demonty I, Plat J, Lütjohann D, Mensink RP, Trautwein EA. · Unilever Food and Health Research Institute, 3130 AC Vlaardingen, The Netherlands. · Prog Lipid Res. · Pubmed #18022398 No free full text.

Abstract: The cholesterol-lowering effect of phytosterols has been extensively studied, and consumption of phytosterols is among the recommendations to lower LDL-cholesterol concentrations. Due to their structural similarity with cholesterol, phytosterols may undergo oxidative processes comparable to those involved in cholesterol oxidation. Consumption of phytosterols could therefore lead to increased systemic concentrations of oxidized phytosterols (oxyphytosterols) via increased dietary intake or in vivo formation from non-oxidized phytosterols. While the biological effects of oxidized cholesterol (oxycholesterol) have been well studied, the amount of biological research on oxyphytosterols is scarce. Most reports on oxyphytosterols cover their quantitative analysis. Whether oxyphytosterols may play similar biological roles as compared to oxycholesterol has not been fully elucidated. The usual perception about oxyphytosterols is that these components present a concern in terms of food quality and health. This perception originates from the parallel that is made with oxycholesterol. Yet, in line with results for oxycholesterol, recent data suggest that oxyphytosterols--depending on the type of oxidation product--may also have beneficial biological properties. Therefore, the objective of this review is to summarise the current understanding of the biological effects, next to identifying future research needs that will help to clarify the possible impact of oxyphytosterols on human health.

El Harchaoui K, van der Steeg WA, Stroes ES, Kastelein JJ. · Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Room F4-159.2, Meibergdreef 9, Postbus 22660, 1105 AZ Amsterdam, The Netherlands. · Curr Atheroscler Rep. · Pubmed #17877921 No free full text.

Abstract: Cholesteryl ester transfer protein (CETP) inhibitors are currently being investigated because of their ability to increase high-density lipoprotein cholesterol levels. In various metabolic settings, the relationship between CETP and lipoprotein metabolism is complex and may depend largely on the concentration of triglyceride-rich lipoproteins. Two CETP inhibitors, JTT-705 and torcetrapib, are in an advanced phase of development. Following hopeful intermediate results, a large endpoint study using torcetrapib has just been discontinued due to increased mortality in torcetrapib-treated subjects. In this review we summarize clinical data on the use of CETP inhibitors.

Dullens SP, Plat J, Mensink RP. · Department of Human Biology, Maastricht University, Universiteitssingel 50, Maastricht, The Netherlands. · Nutr Metab Cardiovasc Dis. · Pubmed #17703927 No free full text.

Abstract: Dyslipidemia leading to coronary heart diseases (CHD) enables venues to prevent or treat CHD by other strategies than only lowering serum LDL cholesterol (LDL-C) concentrations, which is currently the most frequently targeted change. Unlike LDL-C, elevated high-density lipoprotein cholesterol (HDL-C) concentrations may protect against the development of CHD as demonstrated in numerous large-scale epidemiological studies. In this review we describe that besides elevating serum HDL-C concentrations by increasing alpha-HDL particles, approaches to elevate HDL-C concentrations by increasing pre-beta HDL particle concentrations seems more attractive. Besides infusion of apoA-I(Milano), using apoA-I mimetics, or delipidation of alpha-HDL particles, elevating de novo apoA-I production may be a suitable target to functionally increase pre-beta HDL particle concentrations. Therefore, a detailed description of the molecular pathways underlying apoA-I synthesis and secretion, completed with an overview of known effects of pharmacological and nutritional compounds on apoA-I synthesis will be presented. This knowledge may ultimately be applied in developing dietary intervention strategies to elevate apoA-I production and serum HDL-C concentrations and consequently lower CHD risk.

Akdim F, Stroes ES, Kastelein JJ. · Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands. · Curr Opin Lipidol. · Pubmed #17620855 No free full text.

Abstract: PURPOSE OF REVIEW: Antisense oligonucleotides are novel therapeutic agents that reduce the number of specific mRNAs available for translation of the encoded protein. ISIS 301012 is an antisense oligonucleotide developed to reduce the hepatic synthesis of apolipoprotein B-100. Apolipoprotein B-100 is made in the liver, and antisense oligonucleotides preferentially distribute to that organ, so antisense apolipoprotein B-100 may have potential as an efficacious lipid-lowering agent. RECENT FINDINGS: Recently, in healthy volunteers and in mild dyslipidaemic patients, this strategy as monotherapy or in conjunction with statins has shown unparalleled efficacy in reducing apolipoprotein B-100 and LDL-cholesterol. Tolerance for this novel therapy is encouraging and safety concerns currently only relate to mild injection-site reactions and rare liver-function test abnormalities. It should be noted, however, that these safety results were obtained in relatively few individuals. SUMMARY: ISIS 301012 has initially shown promising results in experimental animal models, and in clinical trials in humans. Besides the effect of reducing apolipoprotein B-100 and LDL-cholesterol, this compound also significantly lowers plasma triglycerides. Safety concerns related to the drug include increased liver-function tests. To date no evidence of hepatic steatosis has been reported. Nonetheless, clinical trials of longer duration are required to demonstrate further safety.

Avis HJ, Vissers MN, Stein EA, Wijburg FA, Trip MD, Kastelein JJ, Hutten BA. · Academic Medical Centre, Department of Vascular Medicine, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. · Arterioscler Thromb Vasc Biol. · Pubmed #17569881 links to  free full text

Abstract: OBJECTIVE: Functional and morphological changes of the arterial wall already present in young children with heterozygous familial hypercholesterolemia (HeFH) suggest that treatment should be initiated early in life to prevent premature atherosclerotic cardiovascular disease. The purpose of this study was to assess the efficacy and particularly safety of statin therapy in children with HeFH. METHODS AND RESULTS: We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating statin therapy in children aged 8 to 18 years with HeFH. Six studies (n=798 children) with 12 to 104 weeks of treatment were included. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin- and placebo-treated children with respect to the occurrence of adverse events (RR 0.99; 95% CI: 0.79 to 1.25), sexual development (RR of advancing > or = 1 stage in Tanner classification 0.96; 95% CI: 0.79 to 1.17), muscle toxicity (RR of CK > or = 10 times the upper limit of normal [ULN] 1.38; 95% CI: 0.18 to 10.82), or liver toxicity (RR of > or = 3 times the ULN for ASAT 0.98; 95% CI: 0.23 to 4.26 and for ALAT 2.03; 95% CI: 0.24 to 16.95). We found a minimal difference in growth in favor of the statin group (0.33 cm; 95% CI: 0.03 cm to 0.63 cm). CONCLUSION: In addition to the fact that statin treatment is efficacious, our results support the notion that statin treatment in children with HeFH is safe. Thus, even though further studies are required to assess lifelong safety, statin treatment should be considered for all children aged 8 to 18 with HeFH.

Alipour A, Elte JW, van Zaanen HC, Rietveld AP, Cabezas MC. · Department of Internal Medicine, St Franciscus Gasthuis, Center for Diabetes and Vascular Medicine, PO Box 10900, 3004 BA Rotterdam, The Netherlands. · Biochem Soc Trans. · Pubmed #17511629 No free full text.

Abstract: Postprandial hyperlipidaemia is a common metabolic disturbance in atherosclerosis. During the postprandial phase, chylomicrons and their remnants can penetrate the intact endothelium and cause foam cell formation. These particles are highly atherogenic after modification. People in the Western world are non-fasting for most of the day, which consequently leads to a continuous challenge of the endothelium by atherogenic lipoproteins and their remnants. Furthermore, atherosclerosis is considered a low-grade chronic inflammatory disease. Many studies have shown that the process of atherogenesis in part starts with the interaction between the activated leucocytes and activated endothelium. Postprandial lipoproteins can activate leucocytes in the blood and up-regulate the expression of leucocyte adhesion molecules on the endothelium, facilitating adhesion and migration of inflammatory cells into the subendothelial space. Another inflammatory process associated with postprandial lipaemia is the activation of the complement system. Its central component C3 has been associated with obesity, coronary sclerosis, the metabolic syndrome and fasting and postprandial TAGs (triacylglycerols). Moreover, chylomicrons are the strongest stimulators of adipocyte C3 production via activation of the alternative complement cascade. A postprandial C3 increment has been shown in healthy subjects and in patients with CAD (coronary artery disease) and with FCHL (familial combined hyperlipidaemia). Postprandial lipaemia has been related to TAG and free fatty acid metabolism. All of these mechanisms provide an alternative explanation for the atherogenicity of the postprandial period.

Dullaart RP, Dallinga-Thie GM, Wolffenbuttel BH, van Tol A. · University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. · Eur J Clin Invest. · Pubmed #17217373 No free full text.

Abstract: In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91-106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs.

van der Graaf A, Hutten BA, Kastelein JJ, Vissers MN. · Academic Medical Centre, Dept.Vascular Medicine, Meibergdreef 9 (room F4-159.2) 1105 AZ, Amsterdam, The Netherlands. · Expert Rev Cardiovasc Ther. · Pubmed #16716095 No free full text.

Abstract: Heterozygous familial hypercholesterolemia is associated with elevated low-density lipoprotein cholesterol levels and the development of premature cardiovascular disease. Despite this general statement, data regarding the incidence of cardiovascular disease in young women with familial hypercholesterolemia are lacking. In this review, information of age-specific incidence, risk factors and therapeutic avenues in women with heterozygous familial hypercholesterolemia are discussed.

Lamberts SW, Langeveld CH, Vandenbroucke JP. · Department of Medicine, Erasmus Medical Center, 40 Molenwaterplein, 3015 GD Rotterdam, The Netherlands. · J Clin Epidemiol. · Pubmed #16549257 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Familial hemochromatosis (FHEM), familial hypercholesterolemia (FH), familial mediterranean fever (FMF), and familial thrombophilia (FT) are relatively common genetically determined diseases of (early) adulthood. Chances, shortcomings, and practical aspects of population screening were considered. METHODS: The literature, as well as existing data concerning the treatment of these diseases in The Netherlands, were studied. RESULTS: In these four diseases there are so many modifying genes and environmental and lifestyle influences that accurate predictive testing at the population level is currently not sufficiently effective. The data indicate that the implementation of family clinics for FHEM and FH are necessary. There is need for further sociologic studies in the moslim population of Mediterranean and North African origin about acceptance of DNA diagnostics in relation to consanguinity and into the problem of "pseudodominance." There seems no need for early detection and preventive measures for FT in asymptomatic persons. CONCLUSION: No population screening for these four genetically determined diseases of (early) adulthood is sufficiently effective at the present time. We propose to call these diseases "chronic diseases with a single gene component."

Rodenburg J, Vissers MN, Daniels SR, Wiegman A, Kastelein JJ. · Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, the Netherlands, and Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Ohio, USA. · Pediatr Endocrinol Rev. · Pubmed #16456497 No free full text.

Abstract: In the last decades, there has been an important progression in the development and assessment of various cholesterol-lowering agents. Until recently, in children under age 10, the focus of treatment has been on dietary and lifestyle adjustments. For children older than 10 years, bile acid-binding resins were also recommended if LDL-C levels remained high after dietary adjustment. However, the lipid-lowering effect of bile acid-binding resins is modest at best and long-term compliance is often poor. In contrast, HMG-CoA reductase inhibitors (statins) are currently widely used in adults and are considered the first choice in the treatment of hypercholesterolemia. In the last few years, several randomized trials have shown that statins are also effective in reducing LDL cholesterol levels in children and seem safe at least in the short term. Another novel development is the cholesterol-lowering agent, ezetimibe, which inhibits cholesterol absorption in the intestine. Although efficacy and safety data in children are still lacking, ezetimibe has a good safety profile in adults, either as monotherapy or in combination with a statin. Lastly, two other classes of lipid-lowering drugs include fibrates and nicotinic acid, but most agree that the side effect profile precludes their use in children except in extreme circumstances. Overall, therapeutic options to lower cholesterol levels in children are expanding.

de Leeuw FE, van Norden AG, van der Flier WM, Olde Rikkert MG, Scheltens P. · Universitair Medisch Centrum St Radboud, Huispostnummer 326, Postbus gIoI, 6500 HB Nijmegen. · Ned Tijdschr Geneeskd. · Pubmed #16398165 No free full text.

Abstract: There is increasing evidence that vascular risk factors including hypertension, high cholesterol, hyperhomocysteinaemia and diabetes mellitus are connected to the risk of Alzheimer's disease (AD). The risk of AD may be reduced by the treatment of hypertension prior to onset of cognitive impairment. One small randomised clinical trial has provided some evidence of beneficial effects on cognition of cholesterol-lowering drugs such as the statins in patients with AD. Treatment of hypertension, hyperhomocysteinaemia and diabetes mellitus with the aim of halting the progression of cognitive decline in AD is still under study and results are awaited. For the time being findings from the trials carried out thus far should be interpreted with care due to methodological shortcomings, both in study design and execution. In order to investigate the role of vascular risk factors both in the aetiology and treatment of AD, large prospective randomised trials with long-term follow-up of AD patients who have been diagnosed using revised uniform diagnostic criteria that take the heterogeneity of the disease into account, are necessary.

Kastelein JJ, Sankatsing RR. · Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef, The Netherlands. · Int J Clin Pract. · Pubmed #16351680 No free full text.

Abstract: Ezetimibe/simvastatin (INEGY), a dual inhibitor of both cholesterol production and absorption, is a new approach to the management of hyperlipidaemia. Recent studies have shown that it produces greater reductions in low-density lipoprotein (LDL) cholesterol than the single inhibition of statin therapy, enabling many more patients to achieve their LDL cholesterol treatment goals. With ezetimibe/simvastatin therapy, reductions of up to 61% from baseline have been seen in LDL cholesterol, with clear improvements in other associated lipid fractions. It has been well tolerated across all studies, with a safety profile similar to that of statin therapy. This article will review clinical experience to date with ezetimibe/simvastatin, commenting upon its place and potential value in the prevention of cardiovascular disease.

Nurmohamed SA, Nubé MJ. · Department of Nephrology, VU University Medical Centre, Amsterdam, the Netherlands. · Neth J Med. · Pubmed #16301758 links to  free full text

Abstract: Traditional risk factors, such as high blood pressure (BP), obesity and hypercholesterolaemia, play an important role in the development of cardiovascular disease (CVD), not only in the general population but also in patients with chronic renal disease. In recent years, it has become less clear whether these conventional risk factors are responsible for the extremely high risk of CVD in chronic haemodialysis (CHD) patients. Recent studies have shown that low BP, body mass index (BMI) and serum cholesterol are often correlated with an unfavourable clinical outcome. Thus, whereas traditional risk factors of CVD are correlated with an unfavourable outcome in the general population and patients with chronic renal failure not yet on dialysis, in CHD patients these factors appear to be protective and associated with an improved survival. Therefore, these phenomena have been referred to as 'paradoxical or reverse epidemiology'. The aetiology of this inverse relationship is not clear. Interestingly, in CHD patients, both C-reactive protein, a marker of inflammation, and (pre)albumin, a marker of nutrition, are important independent predictors of mortality. It has been speculated that what is known as the malnutritioninflammation-atherosclerosis complex underlies, at least partly, the phenomenon of reverse epidemiology, since malnutrition causes a low BMI and hypocholesterolaemia. Hence, besides care for adequate nutrition, attempts should be made to reduce inflammation. In this respect, various haemodialysis-related factors, such as the purity of the dialysate and several characteristics of the dialyser, deserve attention.

Fouchier SW, Rodenburg J, Defesche JC, Kastelein JJ. · Department of Vascular Medicine, Academic Medical Centre at the University of Amsterdam, Amsterdam, The Netherlands. · Eur J Hum Genet. · Pubmed #16189547 links to  free full text

Abstract: Inherited, or autosomal dominant, hypercholesterolaemia, with an average global prevalence of one in 500 individuals, is one of the most frequent inherited metabolic disorders. The disorder is associated with a high risk for premature cardiovascular disease (CVD) and death as a consequence of accelerated atherosclerosis. Although the molecular genetic basis is largely elucidated and effective medical treatment, in the form of inhibitors of intracellular cholesterol synthesis, is available, the disorder is severely underdiagnosed and undertreated. On the other hand, with the well-understood aetiology, the accurate diagnosis, the availability of sensitive predictive makers and efficacious therapy, this disorder can serve as a model for disease management: from early presymptomatic diagnosis, accurate prognosis, optimal treatment and large-scale screening to population-based prevention of CVD.