Hyperlipidemias: Spain

Mantilla Morató T, Alonso R, Mata P. · EAP Mar Báltico, Madrid, Spain. · Aten Primaria. · Pubmed #15607060 links to  free full text

This publication has no abstract.

Pujol RM, Muret MP, Bergua P, Bordes R, Alomar A. · Department of Dermatology, Hospital del Mar, IMAS, Barcelona, Spain. · Dermatology. · Pubmed #15604547 No free full text.

Abstract: Oral involvement in cutaneous CD30+ T-cell lymphoid proliferations is rare and has received little attention in the dermatologic literature. The authors report 2 patients with self-healing, recurrent papulonodular eruptions with the classic clinical, histopathological and immunophenotypic features of lymphomatoid papulosis, which developed two ulcerated papules and an ulcerative nodule on the dorsum of the tongue, respectively. The lesions appeared coincident with a new cutaneous relapse of the disease. Histopathological and immunophenotypic features were similar to those of the cutaneous lesions. All lesions regressed spontaneously after several weeks. Since then, and after follow-up periods of 3 and 7 years, respectively, no evidence of extracutaneous involvement has been detected. Oral involvement in lymphomatoid papulosis is an uncommon event, probably without prognostic significance. Previously reported cases are reviewed. The differential diagnosis of atypical T-cell lymphoid infiltrates observed in the oral mucosa is discussed.

Formiguera X, Cantón A. · Obesity Unit, University Hospital Germans Trias i Pujol, Carretera de Canyet s/n. 08916-Badalona. Catalonia, Spain. · Best Pract Res Clin Gastroenterol. · Pubmed #15561643 No free full text.

Abstract: At the beginning of the 21st Century, obesity has become the leading metabolic disease in the World. So much so, that the World Health Organisation refers to obesity as the global epidemic. In fact, obesity is a common disease affecting not only affluent societies but also developing countries. Currently 300 million people can be considered as obese and, due to the rising trend in obesity prevalence, this figure could double by year 2025 if no action is taken against this threat. In terms of health impairment, the importance of obesity lies in the fact that, besides being a disease in itself, it is a risk for many other diseases, mainly from the metabolic and cardiovascular area. Among these, type 2 diabetes, dyslipemia, hyperuricemia, arterial hypertension and cardiovascular disease are the most frequent. Also, respiratory diseases such as obesity hypoventilation syndrome and obstructive sleep apnoea syndrome are strongly associated with obesity.

Martínez E, Tuset M, Milinkovic A, Miró JM, Gatell JM. · Infectious Diseases, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. · Antivir Ther. · Pubmed #15535403 No free full text.

Abstract: Dyslipidaemia associated with the treatment of HIV infection, particularly with the use of protease inhibitors (PIs), can raise cholesterol and triglyceride (TG) levels to the thresholds indicated for intervention. Recent evidence from epidemiological studies has shown that there are correlations between antiretroviral drug use and increased risks for, and incidences of, cardiovascular disease, including myocardial infarction and coronary heart disease. The primary goals of dyslipidaemia therapy for HIV patients are reductions of both low-density lipoprotein cholesterol (LDL-C) and markedly elevated TG levels. Dietary strategies and exercise programs may be tried, although these have shown inconsistent results. The two options for drug therapy are switching antiretroviral agents and using lipid-lowering drugs. Each approach is associated with advantages and limitations, and the need to maintain viral suppression must be balanced with the need to treat abnormal lipid levels. Most drug switches replace the PI component with drugs from another antiretroviral class. Selection of drug therapy for lipid lowering depends on the type of dyslipidaemia predominating and the potential for drug interactions. The use of the statins pravastatin and atorvastatin is recommended for the treatment of patients with elevated LDL-C levels and gemfibrozil or fenofibrate for patients with elevated TG concentrations. Development of new PIs with more favourable effects on the lipid profile should be of benefit.

Sanmarti R, Cañete JD, Salvador G. · Arthritis Unit, Rheumatology Service, Hospital Clinic de Barcelona, Villarroel 170, Barcelona 08036, Spain. · Best Pract Res Clin Rheumatol. · Pubmed #15454124 No free full text.

Abstract: Patients with recurrent or relapsing arthritis are frequently seen in rheumatological practice. Besides crystal arthritis, the most frequent cause of recurrent arthritis, there are several diseases that may present clinically as intermittent mono- or polyarthritis. Palindromic rheumatism is the paradigm of this type of condition, but other diseases such as systemic autoinflammatory disorders (periodic fever syndromes), Whipple's disease, arthritis associated with hyperlipidemia, intermittent hydrarthrosis and other diseases should be taken into account in the differential diagnosis of patients with recurrent arthritis. In this chapter, we discuss recent developments in these diseases with special emphasis on palindromic rheumatism, a common condition whose close relationship with rheumatoid arthritis remains intriguing.

Ascaso JF, Fernández-Cruz A, González Santos P, Hernández Mijares A, Mangas Rojas A, Millán J, Felipe Pallardo L, Pedro-Botet J, Pérez-Jiménez F, Pía G, Pintó X, Plaza I, Rubiés-Prat J, Anonymous00031. · Endocrinology Service, Clinic University Hospital, University of Valencia, Spain. · Am J Cardiovasc Drugs. · Pubmed #15449972 No free full text.

Abstract: In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome.

Gomis Barbará R. · Servicio de Endocrinología, Nutrición y Diabetes, Hospital Clínic, Barcelona. · Rev Med Univ Navarra. · Pubmed #15382615 No free full text.

Abstract: The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

Rodríguez de Fonseca F. · Fundación Hospital Carlos Haya de Málaga. · Rev Med Univ Navarra. · Pubmed #15382609 No free full text.

Abstract: Acylethanolamides are endogenous compounds with lipid structure including anandamide (AEA), palmitoilethanolamide, oleylamide and oleylethanolamide (OEA). AEA binds to the cannabinoid receptor CB1, located at the central nervous system, while OEA is an endogenous ligand for the alpha subtype of peroxisome-proliferator activating receptor (PPARalpha). Since AEA acts on the same receptor which binds marihuana active derivatives, this group of compounds were called endocannabinoids. Besides typical central effects of cannabinoids, CB1 receptor activation leads to hyperphagia, whereas its pharmacological blockade is followed by changes in energy metabolism favouring substrate oxidation. OEA has inhibitory effects on food intake by acting on PPARalpha receptors which modulate the autonomous nervous system. Both acylethanolamides, AEA and OEA, have opposite effects suggesting that they form part of a satiety sensor system. Whereas fasting triggers AEA release and inhibits OEA synthesis, eating has the reverse effect. Additionally OEA is also produced by adipocytes ad has some effects on lipid metabolism. All these data suggest a role for acylethanolamides and the endocannabinoid system in the pathophysiology of obesity, diabetes and atherosclerosis.

Suñer M, Guerrero A, Montes R, Rivera M, Ruiz A, Martínez-García M, Pérez-Valdivia MA, Mateos J. · Servicio de Nefrología, Hospital Universitario Virgen del Rocío, Sevilla. · Nefrologia. · Pubmed #15219089 No free full text.

Abstract: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate. RESULTS: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins. CONCLUSIONS: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.

Pocovi M, Civeira F, Alonso R, Mata P. · Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain. · Semin Vasc Med. · Pubmed #15199435 No free full text.

Abstract: A case-finding program for the identification of patients with familial hypercholesterolemia (FH) has been established in Spain. The program is based on family investigation and molecular genetic testing for mutations in the low-density lipoprotein receptor gene. To assist this program, intensive research into the molecular basis of FH and genotype/phenotype relations is performed. To optimize DNA testing, a DNA-diagnostic platform has been constructed that is composed of systematic mutation screening by single-strand conformation polymorphism (SSCP) analysis, DNA-sequencing, Southern blotting, and the use of microarrays for high-throughput analysis. To date, 161 different mutations leading to inherited hypercholesterolemia have been identified in Spanish patients with FH. In addition, a patient organization was founded to ensure patient support and follow-up. To further facilitate FH case-finding and patient follow-up, we initiated the publication of a set of guidelines for diagnosis and clinical management of FH that can be applied internationally.

Martín-Campos JM, Escolà-Gil JC, Ribas V, Blanco-Vaca F. · Servei de Bioquímica i Institut de Recerca, Hospital de la Santa Creu i Sant Pau, and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. · Curr Opin Lipidol. · Pubmed #15166779 No free full text.

Abstract: PURPOSE OF REVIEW: Apolipoprotein (apo) A-II is the second most abundant HDL apolipoprotein; however its function remains largely unknown. Owing to the lack of consequences of apoA-II deficiency in humans, it has long been considered an apolipoprotein of minor importance. Overexpression of apoA-II in transgenic mice, however, causes combined hyperlipidemia and, in some cases, insulin resistance. This, and the location of the apoA-II gene in chromosome 1q23, a hot region in the search for genes associated with familial combined hyperlipidemia, insulin resistance and type 2 diabetes mellitus, has greatly increased interest in this protein. RECENT FINDINGS: ApoA-II is biochemically and genetically linked to familial combined hyperlipidemia. Given that the chromosome 1q21-q24 region is associated with insulin resistance or type 2 diabetes, this region is a now a focus of interest in the study of these complex, often overlapping diseases. However, no polymorphisms that increase apoA-II levels have been identified to date in humans. Other nonstructural loci may regulate apoA-II plasma concentration. Further, plasma apoA-II concentration is increased by saturated fat intake. Several reports have added to our understanding of the relationship between apoA-II mutations and amyloidosis both in humans and mice. SUMMARY: An increased plasma concentration of apoA-II might contribute to familial combined hyperlipidemia or type 2 diabetes mellitus expression, which emphasizes the need to understand its function and metabolism. Genetic studies in well characterized patients and genomic and proteomic approaches in cell and mouse models may help to achieve this understanding.

Moreno LA, Tresaco B, Bueno G, Fleta J, Rodríguez G, Garagorri JM, Bueno M. · Departamento de Pediatría, Universidad de Zaragoza, C/ Domingo Miral S/N, 50009 Zaragoza, Spain. · J Physiol Biochem. · Pubmed #15000455 No free full text.

Abstract: In children and adolescents from developed countries, obesity prevalence has strongly increased in the last decades and insulin resistance and impaired glucose tolerance are frequently observed. Some dietary components such as low glycemic index foods and dietary fibre could be used in order to improve glucose homeostasis in these children. Psyllium or ispaghula husk (the husk of the seeds of Plantago ovata) is a mixture of neutral and acid polysaccharides containing galacturonic acid with a ratio of soluble/insoluble fibre of 70/30. Some foods could potentially be enriched with psyllium, like breads, breakfast cereals, pasta and snack foods. The aim of this review was to assess the usefulness of psyllium in the management of obese children and adolescents with abnormalities of carbohydrate and lipid metabolism. After psyllium supplementation, the percentage change in postprandial glucose in type 2 diabetes patients, ranged from -12.2 to -20.2%. In hypercholesterolemic children, the effect of psyllium in LDL-cholesterol serum concentrations ranged from 2.78 to -22.8%; the effect in HDL-cholesterol from -4.16 to 3.05%; and the effect on triglycerides from 8.49 to -19.54%. The reviewed evidence seems to show that psyllium improves glucose homeostasis and the lipid and lipoprotein profile; however, more well controlled trials and further studies are needed to clarify it's effects and the mechanisms involved.

Dronda F. · Servicio de Enfermedades Infecciosas. Hospital Ramón y Cajal. Madrid. España. · Enferm Infecc Microbiol Clin. · Pubmed #14757007 links to  free full text

Abstract: Atherosclerosis increases cardiovascular risk and the possibility of developing acute myocardial infarction (AMI) or stroke. Patients infected with human immunodeficiency virus (HIV) often present morphological and metabolic alterations (hypercholesterolemia, hypertriglyceridemia, insulin resistance, diabetes) that can increase vascular risk. The frequent coexistence of classic risk factors (atherogenic diet, smoking, physical inactivity, cocaine abuse), the progressive increase in mean age of HIV-1 infected patients, and the polymedication they receive make it difficult to estimate the direct effect that new therapies may have on cardiovascular risk. Retrospective clinical studies with diverse designs in large cohorts offer contradictory results for cardiovascular risk in the HIV-infected population. Longer observational periods are needed and the effect of other classic risk factors needs to be controlled, in order to establish the possible detrimental effect the new therapies may have on cardiovascular risk in this population.

Roca B. · Unidad de Enfermadades Infecciosas, Hospital General, Castellón. · An Med Interna. · Pubmed #14624657 No free full text.

Abstract: In the last few years, recently developed antirretroviral treatment has allowed a dramatic improvement in the prognosis of HIV disease. As a result, other medical problems are taking increasing relevance in the follow up of the patients infected by such virus. In this article, metabolic disorders associated with HIV, as well as those provoked by antiretroviral therapy, are comprehensively reviewed.

Roca Villanueva B. · Unidad de Enfermedades Infecciosas, Hospital General de Castellón. · Rev Clin Esp. · Pubmed #14622516 No free full text.

This publication has no abstract.

Gil-Núñez AC, Vivancos-Mora J. · Unidad de Ictus, Servicio de Neurología, Hospital General Universitario Gregorio Marañon, Madrid, España. · Rev Neurol. · Pubmed #14606054 links to  free full text

Abstract: INTRODUCTION: Stroke is the primary cause of mortality and incapacity of women in Spain. Current therapeutic guidelines are based on clinical trials in which the number of females taking part is insufficient, and overall benefits are then dangerously extrapolated to women. DEVELOPMENT AND CONCLUSIONS: Strokes in women have important features that distinguish them from those suffered by males, both as regards risk factors and aetiology, and in prevention and the therapeutic treatment that is performed during the fertile stage, pregnancy and menopause. There is, then, a need for further studies and specific clinical trials about strokes in females. Health professionals, society and the authorities, as well as women themselves, also need to be made more aware of the importance of strokes and to be provided with more information. If not, this epidemic will increase, especially if we bear in mind the foreseeable increase in life expectancy, and mortality and loss of independence in women will rise along with it.

Iglesias P, Díez JJ. · Department of Endocrinology, Hospital General, Ctra. de Avila s/n, 40002 Segovia, Spain. · Expert Opin Investig Drugs. · Pubmed #14585054 No free full text.

Abstract: Endogenous and exogenous pathways determine plasma levels of cholesterol and lipoproteins. Plasma cholesterol levels and coronary heart disease risk can be reduced pharmacologically by decreasing cholesterol synthesis, increasing its elimination and/or reducing its absorption from the intestine. The more profound knowledge about cholesterol homeostasis has allowed the development of several lipid-lowering drugs with different mechanisms of action, with the purpose of reducing both morbidity and mortality associated with coronary heart disease. Two new and more potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), also called superstatins (rosuvastatin and pitavastatin), are being studied for their ability to improve lipid profiles. Rosuvastatin is a potent, hepato-selective and relatively hydrophilic statin with a low propensity for muscle toxicity and drug interactions. Pitavastatin is another statin with a high oral bioavailability and minimal propensity for cytochrome p450-mediated drug interactions. Rosuvastatin seems to be more potent than other available statins while pitavastatin presents with a similar potency to that of atorvastatin. Another promising approach for lowering total and low-density lipoprotein cholesterol levels is inhibition of cholesterol absorption. A wide variety of new agents with the capacity for inhibiting the intestinal cholesterol absorption is currently being investigated. Ezetimibe is a selective cholesterol absorption inhibitor whose clinical efficacy has been recently demonstrated both in monotherapy and in combination with other lipid-lowering drugs. Colesevelam, a new bile acid sequestrant, has shown a clinical efficacy similar to that of other resins, with minimal gastrointestinal side effects, improving tolerability and patient compliance. Other lipid-lowering drugs with the ability to act at the enterocyte level, such as avasimibe and implitapide, are currently being investigated in humans.

Sambola A, Fuster V, Badimon JJ. · Servicio de Cardiología, Hospital de Terrassa, Barcelona, España. · Rev Esp Cardiol. · Pubmed #14563295 links to  free full text

Abstract: Recent advances in basic science have linked some systemic risk factors to endothelial dysfunction which gives rise to atherosclerotic disease and triggers the progression of thrombotic complications. Superficial erosion of the stenotic plaque can be observed in one-third of acute coronary syndromes (ACS). In these cases the presence of classic risk factors such as diabetes mellitus, hypercholesterolemia and smoking favor a state of "vulnerable blood" or high risk. Increased thrombogenicity can exacerbate thrombus formation and is able to trigger an ACS. The vessel endothelium regulates contractile, mitogenic and thrombotic activities of the vessel wall. Risk factors impair both homeostasis and hemostasis of the vessel wall and promote inflammatory signals. Platelet and monocyte activation favors the expression of tissue factor (TF), thus triggering the coagulation cascade with thrombin generation and clot formation. Increased blood thrombogenicity linked to classic risk factors may be associated with circulating TF levels which are much higher than those observed in healthy subjects without risk factors. These observations not only emphasize the usefulness of aggressive management of risk factors but open a new avenue for future studies to devise therapeutic strategies to treat ACS by inhibiting TF expression.

Cacabelos R, Fernández-Novoa L, Lombardi V, Corzo L, Pichel V, Kubota Y. · Department of Clinical Neuroscience, EBIOTEC, EuroEspes Biomedical Research Center, Institute for CNS Disorders, Bergondo, Coruña, Spain. · Neurol Res. · Pubmed #14503010 No free full text.

Abstract: Recent evidence indicates that different vascular risk factors are present in Alzheimer's disease (AD) and other prevalent dementia types probably contributing to deterioration of cerebrovascular function, thus enhancing neurodegeneration and premature neuronal death due to a reduction in brain perfusion. Brain blood flow shows a reduced velocity and increased pulsatility (PI) and resistance indices (RI) in different types of dementia and in diabetes and hypertension, as well. High levels of diastolic blood pressure correlate with diminished brain blood flow and elevated PI and RI, accompanied by cognitive deterioration. Nitric oxide (NO) levels are found increased in the sera and brain tissue of AD patients. Vascular risk factors (hyperglycemia, LDL-cholesterol, triglycerides, hypertension) and altered brain hemodynamic parameters correlate with APOE genotypes of which APOE-4/4 carriers represent the AD population with the highest cerebrovascular risk. In addition, the genomic profiles of patients with dementia integrating AD-related genes (APOE, PS1, PS2, cFOS) in a mini-tetragenic haplotype significantly differ from controls with an absolute genetic variation of about 50%-60%. Cerebrovascular dysfunction is a factor common to most types of dementia; however, genetic variation among different dementia types might be determinant for the activation of early vascular events inducing or accelerating neurodegeneration. In this regard, cerebrovascular dysfunction should be considered a potential therapeutic target in dementia.

Mata P, Alonso R, Badimón J. · Lipid Clinic, Internal Medicine Department, Fundación Jiménez Díaz, Madrid, Spain. · Drug Saf. · Pubmed #12908847 No free full text.

Abstract: Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with lipid-lowering therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia.Simvastatin 40-80 mg/day effectively reduces serum low density lipoprotein (LDL)-cholesterol levels. Furthermore, simvastatin reduces triglycerides and mildly raises high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of LDL oxidation and vascular inflammation, have been associated with HMG-CoA reductase inhibitor therapy. Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions.The good safety and tolerability profile of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of therapy are gastrointestinal upset and headache. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon.The overwhelming clinical evidence regarding the long-term use of HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to simvastatin) provide support for the use of this drug as a first-line agent when pharmacological treatment is indicated. Early intervention with simvastatin treatment can be successfully implemented with favourable economic benefits.

QuIlez J, GarcIa-Lorda P, Salas-Salvadó J. · Departament de Tecnologia, Europastry SA Tarragona, Spain. · Clin Nutr. · Pubmed #12880600 No free full text.

Abstract: Over the past decade, the possibility of using phytosterols as ingredients in functional foods has led to numerous research studies in relation to their ability to reduce blood cholesterol. Many different types of carriers have been tested, with good results. The main conclusion is that the effective doses were between 1.5 and 3g/day, leading to reductions between 8% and 15% in LDL-cholesterol. The principal mechanism of action is based on interference with the solubilisation of the cholesterol in the intestinal micelles and, thus, absorption is reduced. Work has also been done on the optimal pattern of administration, and it has been found that ingesting phytosterols in a single dose per day or between meals are equally effective methods. The only side effect is that they can interfere with the absorption of carotenoids, but this can be compensated for in the diet or by adding these compounds in appropriate carriers. It has also been reported that phytosterols have anticancer properties and act as immune system modulators.There are several possible future lines of research: alternative sources with a high phytosterol content must be found, industrial processes must be implemented which minimise their loss, phytosterols must be included in food composition tables, the potential of the different types of phytosterols must be discerned, the genetic bases of their action must be elucidated, synergic effects with other compounds must be studied, side effects must be minimised, and the effects of long-term treatment must be defined precisely.

Clotet B, Negredo E. · HIV Unit and Retrovirology Laboratory, IrsiCaixa Foundation, Hospital Universitari, Germans Trias i Pujol, Carretera del Canyet s/n Badalona, Barcelona, Spain. · AIDS Rev. · Pubmed #12875104 No free full text.

Abstract: Highly active antiretroviral therapy (HAART) significantly prolongs the lives of HIV-infected patients. Current regimens may consist of a protease inhibitor (PI) combined with at least two or more other antiretroviral drugs. PI administration has been shown to be associated with alterations in plasma lipids (i.e. prompt and sustained increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides) and insulin levels that place PI-treated patients at risk for coronary heart disease (CHD). Because PI-associated dyslipidemia is generally asymptomatic and occurs in patients who are often younger than those traditionally at risk for CHD, the need for primary prevention of acute coronary events in these patients is often unappreciated. Statins form a significant component of pharmacotherapy for PI-associated dyslipidemia. However, because PIs and all statins except pravastatin are metabolized by the cytochrome P450 (CYP) system, co-administration of these agents produces a significant risk of drug interactions and statin-induced hepatotoxicity and myopathy. This risk can be greatly reduced by administering a statin not metabolized by CYP. The need for lipid reduction therapy may be minimized with the use of new PIs that are comparable in efficacy to current PIs but do not negatively affect lipid levels.

Fernández-Real JM, Ricart W. · Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona Dr. Josep Trueta, 17007 Girona, Spain. · Endocr Rev. · Pubmed #12788800 links to  free full text

Abstract: Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary heart disease. The similarities of insulin resistance with another inflammatory state, atherosclerosis, have been described only in the last few decades. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, mainly due to the actions of the two major proinflammatory cytokines, TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of these cytokines is associated with metabolic derangement and simultaneously with coronary heart disease. Dysregulation of the inflammatory axis predicts the development of insulin resistance and type 2 diabetes mellitus. The knowledge of how interactions between metabolic and inflammatory pathways occur will be useful in future therapeutic strategies. The effective administration of antiinflammatory agents in the treatment of insulin resistance and atherosclerosis is only the beginning of a promising approach in the management of these syndromes.

Rubiés-Prat J, Pedro-Botet J. · Departamento de Medicina. Universidad Autónoma de Barcelona. Barcelona. España. · Med Clin (Barc). · Pubmed #12636901 No free full text.

This publication has no abstract.

Llaverías G, Laguna JC, Alegret M. · Unitat de Farmacologia, Departament de Farmacologia i Química Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain. · Cardiovasc Drug Rev. · Pubmed #12595916 No free full text.

Abstract: Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration-dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B-containing lipoproteins into plasma. Avasimibe induced cholesterol 7alpha-hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol-fed as well as in non-cholesterol-fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non-HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50-500 mg/day, significantly reduced plasma total triglyceride and VLDL-cholesterol. Although total cholesterol, LDL-cholesterol, and HDL-cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol-lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.