Hyperlipidemias: France

Ruetsch O, Viala A, Bardou H, Martin P, Vacheron MN. · Centre Hospitalier Sainte-Anne, Secteur 13, 1, rue Cabanis, 75014 Paris. · Encephale. · Pubmed #16389718 No free full text.

Abstract: Weight gain is associated with the use of many psychotropic medications, including antidepressants, mood stabilizers, antipsychotic drugs, and may have serious long term consequences: it can increase health risks, specifically from overweight (BMI = 25-29.9 kg/m2) to obesity (BMI > or =30 kg/m2), according to Body Mass Index (BMI), and the morbidity associated therewith in a substantial part of patients (hypertension, coronary heart desease, ischemic stroke, impaired glucose tolerance, diabetes mellitus, dyslipidemia, respiratory problems, osteoarthritis, cancer); according to patients, psychosocial consequences such as a sense of demoralization, physical discomfort and being the target of substantial social stigma are so intolerable that they may discontinue the treatment even if it is effective. The paper reviews actual epidemiological data concerning drug induced weight gain and associated health problems in psychiatric patients : there is a high risk of overweight, obesity, impaired glucose tolerance, diabetes mellitus, premature death, in patients with schizophrenia or bipolar disorder; and the effects of specific drugs on body weight: Tricyclic Antidepressants (TCA) induced weight gain correlated positively with dosage and duration of treatment, more pronounced with amitriptyline ; Selective Serotonin Reuptake Inhibitors (SSRI) decrease transiently bodyweight during the first few weeks of treatment and may then increase bodyweight; weight gain appears to be most prominent with some mood stabilizers (lithium, valproate); atypical antipsychotics tend to cause more weight gain than conventional ones and weight gain, diabetes, dyslipidemia, seem to be most severe with clozapine and olanzapine. Conceming the underlying mechanisms of drug induced weight gain, medications might interfere with central nervous functions regulating energy balance; patients report about: increase of appetite for sweet and fatty foods or "food craving" (antidepressants, mood stabilizers, antipsychotic drugs) and weight gain despite reduced appetite which can be explained by an altered resting metabolic rate (TCA, SSRI, Monoaminoxidase Inhibitors MAO I). According to current concepts, appetite and feeding are regulated by a complex of neurotransmitters, neuromodulators, cytokines and hormones interacting with the hypothalamus, including the leptin and the tumor necrosis factor system. The pharmacologic mechanisms underlying weight gain are presently poorly understood: maybe the different activities at some receptor systems may induce it, but also genetic predisposition. Understanding of the metabolic consequences of psychotropic drugs (weight gain, diabetes, dyslipidemia) is essential: the insulin-like effect of lithium is known; treatment with antipsychotic medications increases the risk of impaired glucose tolerance and diabetes mellitus. Several management options of weight gain are available from choosing or switching to another drug, dietary advices, increasing physical activities, behavioural treatment, but the best approach seems to attempt to prevent the weight gain : patients beginning maintenance therapy should be informed of that risk, and nutritional assessment and counselling should be a routine part of treatment management, associated with monitoring of weight, BMI, blood pressure, biological parameters (baseline and three months monitoring of fasting glucose level, fasting cholesterol and triglyceride levels, glycosylated haemoglobin). Psychiatrics must pay attention to concomitant medications and individual factors underlying overweight and obesity. Weight gain has been described since the discovery and the use of the firstpsychotropic drugs, but seems to intensify with especially some of the second generation antipsychotic medications ; understanding of the side effects of psychotropic drugs, including their metabolic consequences (weight gain, diabetes, dyslipidemia) is essential for the psychiatrics to avoid on the one hand a risk of lack of compliance, a discontinuation of the pharmacological medication and also a risk of relapse and rehospitalization, and on the other hand to avoid acute life threatening events (diabetic ketoacidocetosis and non ketotic hyperosmolar coma, long term risk complications of diabetes and overweight).

Girardet JP. · Service de gastroentérologie et de nutrition pédiatriques, hôpital Armand-Trousseau, 26, avenue du Docteur-Arnold-Netter, 75571 Paris, cedex 12 France. · Arch Pediatr. · Pubmed #16257193 No free full text.

Abstract: The management of children with hypercholesterolemia (HC) depends on the level of premature atherosclerosis - associated risk. Inherited autosomal-dominant forms of HC (Family HC, Familial deficiency of apolipoprotein B, Family combined dyslipidemia) are at high risk of premature cardiovascular disease. These inherited forms of HC need to be systematically screened during childhood in case of family history and require a long term follow-up in order to prevent adult coronary insufficiency. The first recommended therapy consists in dietary intervention. When necessary, treatment with statin can be used from 8 years old. Before this age, acid-binding resins remain the first step treatment. Plant sterol-esters enriched spreads could be an additional useful treatment.

Rasmusen C, Cynober L, Couderc R. · Laboratoire de biologie de la nutrition EA2498, Faculté de Pharmacie Paris 5. · Ann Biol Clin (Paris). · Pubmed #16230278 links to  free full text

Abstract: Arginine, a semi-essential amino acid, plays a major nutritional and metabolic role. In particular, arginine is the precursor of nitric oxide which is involved in the endothelial function. Several factors, such as hypercholesterolemia, diabetes, ageing and hypertension are established risk factors for atherosclerosis, in particular by decreasing the availability of nitric oxide. Thus, endothelial nitric oxide synthase has a pivotal role against atherosclerosis. A suitable amount of cofactor and a sufficient intake of arginine have been shown to modulate nitric oxide-induced vasodilatation: despite the fact that the intracellular concentration of arginine is well above the Km of endothelial nitric oxide synthase, an arginine supplemented-diet is effective in increasing the production of nitric oxide. Several mechanisms have been proposed to explain this "arginine paradox": co-localization of the arginine transporter with endothelial nitric oxide synthase, intracellular arginine regeneration from citrulline, balance between endothelial arginase and nitric oxide synthase. Statins which are HMG-CoA reductase inhibitors inhibit the synthesis of mevalonate, and thus that of cholesterol. In addition, statins increase the stabilization of endothelial nitric oxide synthase mRNA. The co-operation between cholesterol synthesis and the upregulation of caveolin-1 on the one hand, and the activation of endothelial nitric oxide synthase on the other hand, is very tight. A depletion of cholesterol in the caveolae induces a decrease in caveolin-1 at the cell surface allowing NOS activation. Thus statins improve nitric oxide production and vasodilatation. In a recent work in the hypercholesterolemic Watanabe rabbit, we have demonstrated that the combination of arginine with a statin, namely atorvastatin, significantly hinders the spreading of atherosclerotic plaques as compared with monotherapies. Such association of a nutriment and a drug open a new area of therapeutic strategy.

Aggoun Y, Szezepanski I, Bonnet D. · Pediatric Cardiology, Hôpital Necker-Enfants Malades, 75015 Paris, France. · Pediatr Res. · Pubmed #16055929 No free full text.

Abstract: Noninvasive assessment of vascular dysfunction in the pediatric population has taken advantage of the development of high-resolution ultrasound techniques. The most frequently used methods are the quantification of flow-mediated endothelium-dependent dilation of the brachial artery and measurement of the intima-media thickening of the carotid artery. Both reduced flow-mediated dilation and increased intima-media thickness have been proven to correlate with late cardiovascular events and/or mortality in adults. As these noninvasive methods can easily be applied in children, there have been recent investigations in high-risk pediatric patients harboring classical cardiovascular risk factors. Endothelial dysfunction and increased thickness of the intima media are currently observed in children with familial hypercholesterolemia, obesity, and type 1 diabetes mellitus. The association of early vascular dysfunction with a known risk factor is an important issue as these anomalies precede the formation of atherosclerotic plaques. Therefore, they may help in stratification of the risk for cardiovascular event and to better tailor therapeutic interventions in at risk children. Finally, these methods have been applied in specific pediatric populations, such as children with end-stage renal disease, chronic parenteral nutrition, HIV infection, and coarctation of the aorta. In these conditions, endothelial dysfunction and vascular remodeling are also present early in life and these data raise new possibilities in the understanding of the pathogenesis of atherosclerosis in these populations.

Staels B, Fruchart JC. · Department of Atherosclerosis, Unité INSERM 545-Institut Pasteur, 1, rue du Professeur Calmette, 59019 Lille Cedex, France. · Diabetes. · Pubmed #16046315 links to  free full text

Abstract: Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPARalpha and -gamma are currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPARalpha. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPARgamma, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPARgamma agonists are therefore used to treat type 2 diabetes. PPARalpha and -gamma agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPARalpha/gamma agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPARdelta, and its potential as a therapeutic target are currently under investigation.

Gervois P, Fruchart JC, Staels B. · Départment d'Athérosclérose, Institut Pasteur de Lille and Faculté de Pharmacie, Université de Lille II, Lille, France. · Int J Clin Pract Suppl. · Pubmed #16035393 No free full text.

Abstract: Cardiovascular disease (CVD) remains the leading cause of mortality in developed countries. Several risk factors are associated with CVD, including type 2 diabetes, obesity, insulin resistance, dyslipidaemia and hypertension. Different pharmacological therapies have been developed to control these risk factors. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which belong to the nuclear receptor superfamily that controls lipid and glucose metabolism as well as inflammatory risk factors for CVD. PPARalpha agonists, such as the fibrates, correct dyslipidaemia, thus decreasing CVD risk. PPARgamma agonists, such as the glitazones, increase insulin sensitivity and decrease plasma glucose levels in patients with diabetes. Moreover, both PPARalpha and PPARgamma agonists exert anti-inflammatory activities in liver, adipose and vascular tissues. In this review, we focus on the mode of action of PPARalpha and PPARalpha agonists, illustrating the potential of the newly developed dual PPAR agonists for the treatment of global risk in patients with the metabolic syndrome or type 2 diabetes.

Alkofer BJ, Chiche L, Khayat A, Deshayes JP, Lepage A, Saloux E, Reznik Y. · CHU Caen, Transplantation and Liver Surgery, CHU cote de nacre, Caen 14000, France. · Transplant Proc. · Pubmed #15964390 No free full text.

Abstract: Familial hypercholesterolemia (FH) is a dominant inherited disease of low-density lipoprotein (LDL) metabolism caused by mutations of LDL receptors mainly located in the liver. This metabolic disorder is responsible for severe cardiovascular disease, from coronary lesions to chronic heart failure (CHF). Liver transplantation in homozygous FH provides the missing functional LDL receptors and thus partially restores LDL receptor activity to more than 50% of normal. Combined heart and liver transplantation was successfully performed in a homozygous FH patient with end-stage heart failure. Herein we report our experience with a heterozygous male patient with terminal CHF, and review data from the literature on short- and long-term results of such procedures.

Launay-Vacher V, Izzedine H, Deray G. · Department of Nephrology, Pitie-Salpetriere Hospital, 83, boulevard de l'hopital, 75013 Paris, France. · Int J Cardiol. · Pubmed #15860377 No free full text.

Abstract: Dyslipidemia is frequent in patients with renal failure and in transplant recipient patients. This lead to a wide use of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with impaired renal function or in patients treated with cyclosporine as post-transplantation immunosuppressive therapy. As a result, it is crucial for those patients' physicians to be aware of how to handle these drugs when renal function is impaired and/or when cyclosporine is co-administered. Most statins have an extensive hepatic elimination and the renal route is usually a minor elimination pathway. However, pharmacokinetic alterations have been described for some of these drugs in patients with renal insufficiency. Cyclosporine is a widely used immunosuppresive therapy in solid organ transplant patients and drug-drug interactions are likely to occur when statins and cyclosporine are administered together. Those interactions may theoretically result in increased statins and/or cyclosporine serum levels with potential muscle and/or renal toxicity. As a result, caution is warranted if concurrent administration is performed. In this review, we synthesized the data from the literature on (1) the pharmacokinetics and dosage adjustment of atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin in patients with renal failure and (2) the potential drug-drug interactions between these drugs and cyclosporine in transplant recipient patients.

Vergès B. · Service Endocrinologie-Diabétologie et Maladies Métaboliques, Hôpital du Bocage, Dijon, France. · Curr Med Res Opin. · Pubmed #15811197 No free full text.

Abstract: BACKGROUND: Lipid abnormalities in people with diabetes are likely to play an important role in the development of atherogenesis. These lipid disorders include potentially atherogenic quantitative (increased triglyceride levels and decreased high-density lipoprotein-cholesterol [HDL-C] levels) and qualitative abnormalities of lipoproteins (changes in lipoprotein size, increase in triglyceride content of low-density lipoprotein (LDL) and HDL, glycation of apoproteins and increased susceptibility of LDL to oxidation). Guidelines from the two main diabetes organizations, the International Diabetes Federation and the American Diabetes Association, recommend the aggressive management of diabetic dyslipidaemia to reduce the risk of cardiovascular disease (CVD). Statins are the first choice pharmacological therapy to address diabetic dyslipidaemia due to their effectiveness at lowering LDL-C levels in patients with diabetes. Fibrates (peroxisome proliferator-activated receptor [PPAR]alpha ligands) target another aspect of dyslipidaemia by lower ing triglycerides (to a greater extent than statins) and raising HDL-C levels, especially when baseline levels are low. The PPARgamma agonist, pioglitazone appears to affect lipid metabolism by decreasing plasma triglycerides, increasing HDL-C and decreasing the number of small, dense atherogenic LDL particles. SCOPE: This paper provides a review of the current literature (based on searches of MEDLINE and EMBASE from 1985 to 2005, inclusive) supporting the recommendations for the management of dyslipidaemia among patients with type 2 diabetes, including new strategies involving drug combinations that achieve good glycaemic and lipidaemic control that could potentially reduce the morbidity and mortality associated with type 2 diabetes.

Bruckert E. · Unité d'exploration métabolique pour la prévention des maladies cardiovasculaires, Hôpital Pitié-Salpêtrière, Paris (75), France. · Presse Med. · Pubmed #15798540 No free full text.

Abstract: The management of hypercholesterolemia has rapidly progressed with the large clinical trials mainly on statins. Over the past 15 years, it has been demonstrated that the principle target was LDL-cholesterol and that treatment with statins decreased cardiovascular morbidity and global mortality. The studies have progressively targeted patients with increasingly lower cholesterol levels but always at high risk. Recent data are in favour of the so-called "aggressive" strategy aimed at reducing cholesterol to very low levels. The emergence of new therapies with stronger statins and the concept of combining lipid-lowering treatments has improved the chances of reaching this aim. Prompted by this progress, the transposition of this aggressive strategy to clinical practice is confronted with many problems, which stem from practitioners' and patients' reticence and fears (raising the question of compliance to treatment) and, more generally, the problem of cost. In this perspective, therapeutic education is one of the tools that would promote compliance. New treatments in the field of HDL would further support the progress made in such prevention.

Neau JP, Moumy H, Mathis S, Gil R. · Clinique Neurologique, CHU La Milétrie, 86021 Poitiers cedex 05. · Rev Neurol (Paris). · Pubmed #15798527 No free full text.

Abstract: Statins have become a leading prescription drug in France. Indications have been greatly extended over the last five years subsequent to publication of many multicentric prospective trials. Besides their preventive properties for coronary artery disease, their efficacy for the prevention of stroke also appears to be demonstrated in coronary patients (CARE and LIPID studies) and in subjects at risk (HPS and ASCOT-LLA studies) irrespective of the serum cholesterol level, the relative risk of stroke being decreased by 30 percent compared with placebo. This preventive capacity would involve pathways other than cholesterol and/or LDL-cholesterol lowering mechanisms, and would probably involve a direct effect on inflammation, coagulation, modulation of certain atherogenic processes, and endothelial function. There remains however certain questions concerning the exact role of statins on secondary prevention of stroke (SPARCL study), their real usefulness in the elderly subject (PROSPER study), and the relative superiority of individual statins.

Vergès B. · Service endocrinologie, diabétologie et maladies métaboliques, CHU Dijon, hôpital du Bocage, Dijon, France. · Arch Mal Coeur Vaiss. · Pubmed #15669365 No free full text.

Abstract: The effectiveness of statins in the treatment of hypercholesterolaemia and the reduction in cardiovascular risk have now been clearly demonstrated. While their beneficial effects on the reduction of atherosclerosis and its clinical manifestations occur mainly due to the reduction in LDL-cholesterol, some pleiotropic actions which are independent of LDL-cholesterol have frequently been put forward in recent years. In effect, an improvement in endothelial function (increased vasodilatation in particular), an in vitro reduction in smooth muscle cell proliferation, a reduction in thrombosis, promotion of fibrinolysis and positive effects on atheromatous plaque stabilisation have been observed. Elsewhere, some anti-oxidant and anti-inflammatory properties have been attributed to statins. However, many of the described 'pleiotropic' effects are not due to the direct action of statins, but occur with the reduction in LDL-cholesterol. Furthermore, certain in vitro effects only occur at much higher than therapeutic doses. These considerations have therefore caused doubt about the clinical significance of the statins' pleiotropic effects. Finally, analysis of the results of human clinical trials on statins have proved that their effectiveness relies on the reduction in LDL-cholesterol and that the pleiotropic effects do not actually have a clinical implication.

Riviere D. · Service d'Exploration de la Fonction Respiratoire et de Médecine du Sport, Hôpital Larrey, 24 chemin de Pouvourville, TSA 30030, 31059 Toulouse 9. · Bull Acad Natl Med. · Pubmed #15651421 No free full text.

Abstract: Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

Vincelet C, Bruckert E, Le Corff J, Boisson M, Foucault C. · Centre d'examens de santé de l'enfant, 96-98 rue Amelot, 75011 Paris, France. · Presse Med. · Pubmed #15611671 No free full text.

Abstract: INTRODUCTION: There is a need to dispose of normal cholesterol levels in young children. In view of the paucity of such data in France, we analysed the results of screening conducted in children. METHOD: We analysed the cholesterol levels of 4697 children, with a mean age of 4.3 years, attending a medical check-up in a Child Health Unit in a National Health Scheme centre in Paris. All the children were recruited consecutively during the year 2002. RESULTS: The mean cholesterol level was of 4.4 mmol/L +/- 0.75. We detected a slight gender-related variation (the mean in girls and boys were of 4.5 +/- 0.76 and 4.4 +/- 0.74 respectively). The 95 percentile in girls and boys were 5.7 and 5.6 mmol/L, respectively. DISCUSSION: For the first time in France, we now have access to data on normal cholesterol levels in a large cohort of 4 year-old children. Screening for hypercholesterolaemia in children provides the opportunity to discuss dietary counselling.

Gueguen Y, Ferrari L, Batt AM. · INSERM U525, Université Henri Poincaré--Nancy 1, Nancy, France. · Therapie. · Pubmed #15559550 No free full text.

Abstract: This article summarises the mechanisms responsible for the hyperlipidaemia observed after immunosuppressive treatment. Much progress has been achieved in the treatment of organ transplantation over the last 10 years, in particular because of the use of new immunosuppressive drugs with less nephrotoxicity. However, hypercholesterolaemia and hypertriglyceridaemia persist among many patients, who are thus more likely to develop cardiovascular diseases. We first reviewed the effects of immunosuppressive drugs on biliary acid biosynthesis, which is the main pathway of cholesterol degradation. The inhibition of this biosynthesis pathway, and especially of some key cytochrome P450s (CYP) such as CYP27A1, could contribute to the increased cholesterolaemia. Immunosuppressive drugs may also modify the activity of lipoprotein receptors or the expression of different apolipoproteins involved in cholesterol and triglyceride transport by lipoproteins. Finally, the fact that hypertriglyceridaemia is more frequently observed after certain immunosuppressive treatments may be partly caused by changes in the synthesis and elimination of triglycerides involving lipoprotein lipase or some apolipoproteins which serve as its cofactors (apoCII or apoCIII).

Dallongeville J, Ferrières J, Schuster H, Farnier M, Lepen C. · INSERM U508, Institut Pasteur, Lille, France. · Presse Med. · Pubmed #15523276 No free full text.

This publication has no abstract.

Schlienger JL, Vinzio S, Pradignac A, Grunenberger F, Goichot B. · Service de médecine interne et nutrition, hôpital de Hautepierre, 67098 Strasbourg cedex, France. <> · Rev Med Interne. · Pubmed #15501349 No free full text.

Abstract: INTRODUCTION: The rationale for the treatment of hypercholesterolemia in the elderly is less clear than in middle-aged patients because of several conceptual, epidemiological, economical facts, a higher prevalence of polypathology and a weaker relation between hypercholesterolemia and cardiovascular risk when age increases. CURRENT KNOWLEDGE AND KEY POINTS: However, cardiovascular events-stroke and myocardial infarction occur mainly in people aged more than 65 years. The data of recent randomised clinical trials have demonstrated that the use of statins in the elderly remained associated to a reduced all-cause mortality, cardiovascular mortality and stroke. Statins were effective in elderly with average LDL-cholesterol in primary and secondary prevention trials. The drug tolerance was as good as in middle-aged patients. However, convincing data concerning subjects over 80 are lacking. CONCLUSION: On the basis of disponible data it may be considered that statins are useful in older persons with a serum LDL cholesterol level above 1.3 g/l and or a high cardiovascular risk, with or without cardiovascular disease, when their life expectancy is consequent.

Levy-Marchal C, Jaquet D. · INSERM U457, Robert Debré Hospital, Paris, France. · Pediatr Diabetes. · Pubmed #15450010 No free full text.

Abstract: This review highlights the evidence of linking small for gestational age (SGA) with metabolic/cardiovascular disturbances (dysmetabolic syndrome) in later life. The metabolic and cardiovascular complications associated with in utero undernutrition have been identified during the past 10 yr. Reduced fetal growth is independently associated with an increased risk of the development of cardiovascular diseases, the insulin-resistance syndrome, or one of its components: hypertension, dyslipidemia, impaired glucose tolerance, or type 2 diabetes. All of them appear to result from the initial development of insulin-resistance which appears as a key component underlying the metabolic complications. Although the mechanism remains unclear, there is some evidence that argues in favor of an active contribution of the adipose tissue in the emergence of insulin-resistance associated with in utero undernutrition, but this hypothesis remains to be further documented. From a broader point of view, several hypotheses have been proposed over the past 10 yr to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. Although not confirmed, the hypothesis suggesting that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive.

Claudel T, Sturm E, Kuipers F, Staels B. · Unité de Recherche 545, Institut National de la Santé et de la Recherche Médicale, Département d'Athérosclérose, Institut Pasteur de Lille and the Faculté de Pharmacie, Université de Lille II, Lille, France. · Expert Opin Investig Drugs. · Pubmed #15330745 No free full text.

Abstract: Bile acids are end products of cholesterol metabolism. They are exclusively synthesised by the liver and subsequently secreted via the bile duct into the intestine to facilitate the absorption of dietary fat and fat-soluble vitamins. Nuclear receptors are ligand-activated transcription factors. The farnesoid X receptor (FXR) has recently been identified as a bile acid-activated nuclear receptor. FXR controls bile-acid synthesis, conjugation and transport, as well as lipid metabolism. Recent advances in FXR biology demonstrate that FXR may represent a valuable target for the identification of novel drugs to treat dyslipidaemia and cholestasis. However, for therapeutic purposes the development of selective FXR modulators, which only activate or inhibit specific FXR target genes and as such induce specific responses, will be required.

Amarenco P, Tonkin AM. · Department of Neurology and Stroke Center, Bichat University Hospital and Medical School, Denis Diderot University-Paris VII, 46 rue Henri Huchard, 75018 Paris, France. · Circulation. · Pubmed #15198966 links to  free full text

Abstract: The occurrence of stroke increases with age, particularly affecting the older elderly, a population also at higher risk for coronary heart disease (CHD). Epidemiological and observational studies have not shown a clear association between cholesterol levels and all causes of stroke. Nonetheless, large, long-term statin trials in patients with established CHD or at high risk for CHD have shown that statins decrease stroke incidence in these populations. Combined data from 9 trials including 70,070 patients indicated relative and absolute risk reductions for stroke of 21% and 0.9%, respectively, with statins. The number of strokes prevented per 1000 patients treated for 5 years in patients with CHD is 9 for statins, compared with 17.3 for antiplatelet agents. Statins have not yet been shown to reduce stroke risk in the typical general population without known CHD, nor have they been shown to prevent recurrent stroke in patients with prior stroke. Potential reasons for the effects of statins on stroke and the non-cholesterol-lowering mechanisms that may be involved are discussed. Treatment strategies based on global cardiovascular risk may be most effective. Additional studies in patients representative of the typical stroke population are needed.

Fruchart JC, Nierman MC, Stroes ES, Kastelein JJ, Duriez P. · Departement de Recherche sur les Lipoproteines et l'Atherosclerose,Pasteur de Lille, Inserm U545 et Faculté de Pharmacie, Université du Droit et de la Santé de Lille 2, Lille, France. · Circulation. · Pubmed #15198961 links to  free full text

Abstract: Advances in our understanding of the ways in which the traditional cardiovascular risk factors, including standard lipid (eg, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and nonlipid (eg, hypertension) risk factors, interact to initiate atherosclerosis and promote the development of cardiovascular disease have enhanced our ability to assess risk in the individual patient. In addition, the ongoing identification and understanding of so-called novel risk factors may further improve our ability to predict future risk when these are included along with the classic risk factors in assessing the global risk profile. This review briefly summarizes the evidence that some newer risk factors, including impaired fasting glucose, triglycerides and triglyceride-rich lipoprotein remnants, lipoprotein(a), homocysteine, and high-sensitivity C-reactive protein, contribute to an increased risk of coronary and cardiovascular diseases.

Lefebvre P, Raingeard I, Renard E, Bringer J. · Service des maladies endocriniennes, hôpital Lapeyronie, 371, avenue du Doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France. · Gynecol Obstet Fertil. · Pubmed #15123116 No free full text.

Abstract: The prevalence of the polycystic ovaries syndrome (PCOS) is high but it is a heterogeneous disorder with implications in numerous medical domains. Abdominal obesity and insulin resistance, which are the main metabolic disorders, are strong links between hormonal abnormalities and long-term medical consequences. The latter begin to be better understood. Some studies suggest that PCOS may increase the risk for several conditions, including type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease and some cancers.

Tellier P. · Centre de Médecine nucléaire de l'Artois, Clinique Sainte Catherine 62223 Arras. · Ann Endocrinol (Paris). · Pubmed #15067249 No free full text.

Abstract: LDL-cholesterol (LDL-C) is a key factor in primary and secondary prevention of coronary heart disease. Statins have become a mainstay in the first-line treatment of hypercholestorelomia. Nevertheless, in clinical practice, there is a major gap between treatment guidelines and real life treatment patterns. It is not uncommon that statins lack sufficient efficacy in the most severe cases of dyslipidemia, even when the highest doses are used. Therapy combining statins with other cholesterol-lowering agents is often used, although it may be poorly tolerated. These limitations have directed research towards new mechanisms of action, additive to those of statins which inhibit the hepatic biosynthesis of cholesterol. Ezetimibe is the first once-daily potent and selective inhibitor of cholesterol absorption which has been shown to reduce the overall delivery to the liver, with a subsequent reduction of serum LDL-C. As monotherapy, mean decrease in LDL-C with ezetimibe was 19.1% versus placebo, whereas in addition to ongoing statin therapy, there was a 21.8% incremental reduction of LDL-C (p<0.001) and a 11.1% of triglycerides (p<0.001) with an increase of HDL-C of about 1.7% (p<0.05). Phase III factorial co-administration studies with various statins at increasing dosages have shown a mean supplementary decrease of LDL-C (-12.1 to -13.8%) and triglycerides (-7.4 to -10.5%) and raising HDL-C (+1.4 to 4.5%) (versus pooled statins). Co-administration of ezetimibe (10 mg once a day) with a statin permits a degree of LDL-C lowering similar to that achieved with the highest doses of statins. The efficacy of ezetimibe has also been demonstrated in familial homozygous hypercholesterolemia and sistosterolemia. In both monotherapy and combination studies, clinical and biological safety of ezetimibe was good.

Constans J. · Service de médecine interne et pathologie vasculaire, hôpital Saint-André, 1, rue Jean-Burguet, 33075 Bordeaux, France. · Ann Cardiol Angeiol (Paris). · Pubmed #15038528 No free full text.

Abstract: Endarteriectomy may be of some benefit for those patients who have asymptomatic carotid stenosis above 80%. Duplex echography is a useful non-invasive diagnosis method, and the detection of asymptomatic carotid stenosis is questionable. Detection in the whole population seems inefficient since most stenosis are found in patients who experience other locations of atherosclerosis or who have several risk factors. The conditions where detection seems useful are the patients above 55 years with lower limb occlusive arterial disease or aortic aneurysm, and the subjects who have three of the four following conditions: age above 65 years, hypercholesterolemia, tobacco, and ischaemic cardiopathy.

Levy-Marchal C, Jaquet D, Czernichow P. · INSERM Unit 457, Robert Debré Hospital, 75019 Paris, France. · Semin Neonatol. · Pubmed #15013477 No free full text.

Abstract: This article reviews the evidence for fetal and early origins of type 2 diabetes, insulin resistance, dyslipidaemia and obesity. Particular emphasis is given to the role of adipose tissue in catch-up growth and long-term metabolic complications following restricted fetal growth. To date, several pathways have been proposed to explain the development of insulin resistance following restricted fetal growth, but no precise mechanisms have been demonstrated. It appears that early postnatal growth may also be a critical step.