Hyperlipidemias: Spain

Marín R, Goicoechea MA, Gorostidi M, Cases A, Díez J, Escolar G, Fernández-Vega F, Palomar R, Rodrigo E, Martínez I, Segura J, Anonymous00167. · Servicio de Nefrología, Hospital Universitario Central de Asturias, Celestino Villamil, s/n 33006 Oviedo, Asturias. · Nefrologia. · Pubmed #16649424 links to  free full text

This publication has no abstract.

Civeira F, Anonymous00222. · Lipid Unit, Hospital Universitario Miguel Servet, Avda Isabel La Católica 1-3, 50009 Zaragoza, Spain. · Atherosclerosis. · Pubmed #15177124 No free full text.

Abstract: Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism characterized by very high plasma concentrations of low density lipoprotein cholesterol (LDLc), tendon xanthomas and increased risk of premature coronary heart disease (CHD). FH is a public health problem throughout the world. There are 10,000,000 people with FH worldwide, mainly heterozygotes, and approximately 85% of males and 50% of females with FH will suffer a coronary event before 65 years old if appropriate preventive efforts are not implemented. Early identification of persons with FH and their relatives, and the early start of treatment are essential issues in the prevention of premature cardiovascular disease (CVD) and death in this population. However, guidelines for the general population formally exclude FH from their diagnostic and treatment recommendations. These guidelines have been elaborated by a group of international experts with the intention to answer the main questions about heterozygous FH (heFH) subjects that physicians worldwide face in the diagnosis and management of these patients.

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

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

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

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

Sánchez Hernández R. · Servicio de Nefrologia, Hospital General de Segovia, Spain. · Nefrologia. · Pubmed #18847430 No free full text.

Abstract: Chronic kidney disease (CKD) is a public health problem worldwide, not only because of the risk of progression to end-stage kidney disease (ESKD) but also because of the high risk of morbidity and mortality, especially from cardiovascular disease. In recent years, the epidemiological relevance of CKD has not only raised the interest of nephrologists, but of other areas of medicine and in particular of primary care. The primary objectives of this presentation are to assess the impact that CKD has had in recent years as an epidemiological problem in the primary care setting and to describe the strategies that will be used to try to address this problem. Knowledge of the most relevant factors affecting kidney function with age, and specifically glomerular filtration rate (GFR), is essential for defining the patient group at most risk of mortality, cardiovascular complications and progression to ESKD, thereby facilitating overall and individualized management of these patients. Fortunately, we already have clarifying consensus guidelines on a national scale to address this problem jointly. CKD in a mortality amplifying factor, not only in patients with cardiovascular disease but also in patients with chronic infections and in cancer patients. In this regard, the new KDIGO guidelines place particular emphasis on the need to assess renal function in these patients and to perform vigorous cardioprotection from the initial stages of CKD.

Matía Martín P, Lecumberri Pascual E, Calle Pascual AL. · Servicio de Endocrinología y Nutrición, Hospital Clínico San Carlos, Madrid. · Rev Esp Salud Publica. · Pubmed #18274353 No free full text.

Abstract: Sufficient evidence exists in relation to the association in clinical practice between disorders in the metabolism of glucose, lipoproteins, insulin action, arterial hypertension and centrally-distributed obesity. This association is named Metabolic Syndrome. Despite the existence thereof had been questioned by the ADA and EASD, it is a useful tool affording the possibility of identifying individuals at high risk of developing cardiovascular disease. Metabolic syndrome and/or its individual components are associated with a high incidence rate of cardiovascular disease. Obesity and a sedentary lifestyle are underlying risk factors along this syndrome's pathway to disease, changes in living habits therefore being a first-line intervention in the prevention and treatment of insulin resistance, hyperglycemia, aterogenic dyslipemia and arterial hypertension. Weight loss and exercise are the keys to the overall plan, one of the most important non-pharmacological cardiovascular risk reduction strategies however still being diet. Epidemiological studies have found a high intake of simple sugars, of foods having a glycemic index and of diets with a high glycemic load to be associated to insulin resistance, type II diabetes mellitus, hypertriglyceridemia and low HDL-cholesterol figures. Los saturated fat intake in favor of polyunsaturated and monounsaturated fatty acids has been implied in a reduction of the incidence of type II diabetes mellitus and dyslipemia, although the debate is ongoing. Unrefined grain fiber in the diet has been beneficial in reducing the risk of diabetes. Among the diet patterns, the Mediterranean diet has been related to a lower incidence of diabetes and a reduction in the risk of death. Studies for intervention in the prevention of type II diabetes have suggested low-fat diets (reducing saturated and trans-fats), with a high degree of fiber and low glycemic index. Clinical trials have shown diets with small amounts of carbohydrates, low glycemic index and the Mediterranean and DASH diets to be beneficial in reducing aterogenic dyslipemia. There is currently no good evidence for choosing diets with restricted carbohydrates. On the other hand, different guides recommend low-calorie diets with a low content in saturated fats, trans-fats, cholesterol and sugars in favor the eating fruits, green vegetables, unrefined grains and fish.

Castilla Guerra L, del Carmen Fernández Moreno M, López Chozas JM, Jiménez Hernández MD. · Department of Internal Medicine, Hospital de Merced, Osuna, Seville, Spain. · Eur J Intern Med. · Pubmed #18206595 No free full text.

Abstract: Historically, the etiological link between hypercholesterolemia and stroke has been less clear than for coronary heart disease. The lack of association between cholesterol levels and stroke in most epidemiological and observational studies has brought about this controversy. Many recent, long-term clinical studies have confirmed that statin therapy results in a reduced risk of strokes, even in so-called "normocholesterolemic" patients. The magnitude of the effect is great. A large-scale analysis of more than 90,000 individuals showed that every 10% reduction in the concentration of LDL-cholesterol reduces the risk of stroke by 15.6%. The positive effect of statins on stroke depends mainly on LDL cholesterol reduction, but other non-lipid mechanisms, so-called "pleiotropic" effects, have been shown to play a role. This review seeks to summarize the role of statins in stroke prevention. Despite the fact that our understanding of the benefits of statins in stroke prevention is still evolving, we find marked room for improvement in stroke risk factor management. Internists must face this challenge and integrate this new knowledge into their daily clinical practice.

Padial LR. · Cardiac Unit, Hospital Virgen de la Salud, Avda. Barber, 30, 45004 Toledo, Spain. · Expert Rev Cardiovasc Ther. · Pubmed #18095904 No free full text.

Abstract: Ezetimibe is a drug that impairs intestinal cholesterol absorption and decreases blood cholesterol levels. It has been shown that added to statins it can achieve a further reduction of low-density lipoprotein-cholesterol of 18-20%, overcoming the increase in absorption that follow the reduction in cholesterol synthesis by statins. Four major outcome trials are underway to study the effect of ezetimibe plus simvastatin in different subsets of high-risk patients: familiar hypercholesterolemia, degenerative aortic stenosis, chronic kidney disease and acute coronary syndrome. Hopefully, in the next few years the information provided by these trials will allow us to further reduce the increasing burden of cardiovascular disease.

Medrano MJ, Pastor-Barriuso R, Boix R, del Barrio JL, Damián J, Alvarez R, Marín A, Anonymous00066. · Escuela Nacional de Sanidad, Instituto de Salud Carlos III, Madrid, España. · Rev Esp Cardiol. · Pubmed #18082090 links to  free full text

Abstract: INTRODUCTION AND OBJECTIVES: The proportion of the ischemic heart disease (IHD) burden attributable to cardiovascular risk factors in Spain has traditionally been extrapolated from populations in other countries. The aim of this study was to estimate the IHD risk attributable to smoking, hypercholesterolemia, hypertension, diabetes and excess weight using data from studies carried out in the Spanish population. METHODS: Data on the prevalence of cardiovascular risk factors in the general population were obtained from a meta-analysis of 48 cross-sectional studies carried out in Spain, and data on corresponding prevalences among IHD patients were derived from the PRIAMHO II and PREVESE II multicenter hospital registries. Crude and adjusted relative risks of IHD were obtained from follow-up data collected over 5 years in a primary-care cohort of 6124 adults without cardiovascular disease. The crude and adjusted population attributable fractions for various risk factors were calculated for both sexes combined and for men and women separately. RESULTS: Among men, 42.5% (95% confidence interval [CI] 6.8%-59.6%) of the adjusted incidence of IHD was attributable to overweight, 33.9% (95% CI 22.6%-41.0%) to smoking, 19.4% (95% CI 8.2%-26.5%) to hypercholesterolemia, and 15.5% (95% CI 1.6%-24.6%) to hypertension. Among women, 36.5% (95% CI -8.0%-56.3%) of IHD cases were attributable to overweight, 24.8% (95% CI 12.0%-31.9%) to diabetes, and 20.1% (95% CI 6.1%-28.6%) to hypercholesterolemia. CONCLUSIONS: The cardiovascular risk factors found to contribute most to IHD in the Spanish population were excess weight in both sexes, followed by smoking in men.

Alcudia JF, Martinez-Gonzalez J, Guadall A, Gonzalez-Diez M, Badimon L, Rodriguez C. · Centro de Investigacion Cardiovascular, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, c/Antoni Ma Claret 167, 08025 Barcelona, Spain. · Front Biosci. · Pubmed #17981747 No free full text.

Abstract: Lysyl oxidase (LOX) plays a pivotal role in extracellular matrix (ECM) maturation. Furthermore, novel biological functions has been ascribed to LOX, among them cell differentiation, migration, transformation and regulation of gene expression. In this context, it has been suggested that abnormalities of LOX expression could underlie the development of multiple pathological processes including cardiovascular diseases. LOX seems to be crucial in the preservation of endothelial barrier function. In fact, accumulating evidences suggest a role of this enzyme in atherogenesis and endothelial dysfunction triggered by atherosclerotic risk factors and pro-inflammatory cytokines. Indeed, cytokines such as tumour necrosis factor-alpha (TNF-alpha) modulate vascular LOX expression. This cytokine decreases LOX expression and activity in endothelial cells through a transcriptional mechanism that involves TNF receptor-2 and protein kinase C activation. Interestingly, in vivo studies reveal that TNF-alpha causes a down-regulation of vascular LOX expression. Thus, LOX down-regulation seems to be associated to the endothelial dysfunction elicited by multiple pathological factors. LOX rises as a promising target gene for the development of therapeutic strategies in the treatment of cardiovascular diseases.

Tuñón J, Martín-Ventura JL, Blanco-Colio LM, Tarín N, Egido J. · Cardiology Department, Fundación Jiménez Díaz, Autónoma University, Madrid, Spain. · Vasc Health Risk Manag. · Pubmed #17969382 links to  free full text

Abstract: In the last years there has been increasing evidence suggesting that the treatment of cardiovascular risk factors must be done on a global rather than on a separate approach, because they have additive effects and share common pathways leading to atherothrombosis. Of special interest is the relationship between hypertension and dyslipidemia. An excessive activity of the renin-angiotensin system (RAS), that plays an important role in hypertension, contributes to endothelial dysfunction, vascular inflammation and thrombosis. Dyslipidemia induces the same effects through similar mechanisms. In fact, combined therapy with statins and RAS modulators shows synergic beneficial effects in the treatment of atherosclerosis. Then, in the future, the traditional hypertension and dyslipidemia units should probably evolve into global cardiovascular risk management Units. Also, polypills combining antihypertensive and lipid-lowering drugs will make easier the treatment of these conditions. These changes would provide us the necessary tools to treat our patients in accordance with the current strategies of cardiovascular therapy and prevention.

Lopez-Miranda J, Williams C, Lairon D. · Lipids and Atherosclerosis Research Unit, Department of Medicine, Hospital Universitario Reina Sofía, University of Cordoba, Córdoba, Spain. · Br J Nutr. · Pubmed #17705891 No free full text.

Abstract: Most of diurnal time is spent in a postprandial state due to successive meal intakes during the day. As long as the meals contain enough fat, a transient increase in triacylglycerolaemia and a change in lipoprotein pattern occurs. The extent and kinetics of such postprandial changes are highly variable and are modulated by numerous factors. This review focuses on factors affecting postprandial lipoprotein metabolism and genes, their variability and their relationship with intermediate phenotypes and risk of CHD. Postprandial lipoprotein metabolism is modulated by background dietary pattern as well as meal composition (fat amount and type, carbohydrate, protein, fibre, alcohol) and several lifestyle conditions (physical activity, tobacco use), physiological factors (age, gender, menopausal status) and pathological conditions (obesity, insulin resistance, diabetes mellitus). The roles of many genes have been explored in order to establish the possible implications of their variability in lipid metabolism and CHD risk. The postprandial lipid response has been shown to be modified by polymorphisms within the genes for apo A-I, A-IV, A-V, E, B, C-I and C-III, lipoprotein lipase, hepatic lipase, fatty acid binding and transport proteins, microsomal triglyceride transfer protein and scavenger receptor class B type I. Overall, the variability in postprandial response is important and complex, and the interactions between nutrients or dietary or meal compositions and gene variants need further investigation. The extent of present knowledge and needs for future studies are discussed in light of ongoing developments in nutrigenetics.

Martínez M, Labiós M, Gabriel F. · Departamento de Biopatología Clínica, Hospital Universitario La Fe, Valencia, España. · Med Clin (Barc). · Pubmed #17169286 No free full text.

Abstract: Currently it is accepted that deep vein thrombosis is a multifactorial event in which the presence of activated platelets and also plasmatic lipids seems to play a pivotal role that it is not well established in the scientific bibliography. Due to the non consensus state about these topics between the different groups working in these aspects, the topic involving deep vein thrombosis-platelets-lipids, and also their interactions, still is an interesting area of investigation, in which it is necessary to carry out studies with the aim of establishing risk factors, initial diagnostic methods and clinical assays to probe the efficacy of new therapies.

López MM, Valenzuela JE, Alvarez FC, López-Alvarez MR, Cecilia GS, Paricio PP. · Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia, Spain. · Transpl Immunol. · Pubmed #17157211 No free full text.

Abstract: Long-term immunosuppression may produce several severe complications, highlighting cardiovascular complications and de novo malignancies, which are the main causes for late demise not related to graft.

Farriol M, Jordà M, Delgado G. · Centro de Investigación Bioquímica y Biología Molecular, Hospital Vall d'Hebron, Barcelona, Spain. · Nutr Hosp. · Pubmed #16913204 No free full text.

Abstract: The aim was to determine in what areas the therapeutic application of soy predominates in clinical trials and to assess the emerging fields of its use by means of an analysis of bibliographic resources. A search was performed in the MEDLINE database up to 31 december 2004, limited to the Title/Abstract field, and Clinical Trials as the type of publication. The abstracts from the publications selected (n=86) were reviewed and different variables were assessed. A total of 3280 subjects were included: 15% men and 59% women (71% postmenopausal). The studies were performed basically in healthy individuals (71%). Twenty five percent of the studies investigated plasma levels of different metabolites and 21% determined hormone or lipid profiles. After the year 2000 a new population focus was detected, with the publication of two studies in elite gymnasts and judoists, with positive results. The present observations indicate that soy supplementation in the competitive sports elite may be an emerging application.

Morales JM, Domínguez-Gil B, Gutiérrez MJ. · Unidad de Trasplante Renal, Servicio de Nefrología, Hospital Doce de Octubre, Madrid. · Nefrologia. · Pubmed #16808256 links to  free full text

This publication has no abstract.

Herrera E, Amusquivar E, López-Soldado I, Ortega H. · Department of Biochemistry, Molecular and Cellular Biology, University San Pablo-CEU, Madrid, Spain. · Horm Res. · Pubmed #16612115 No free full text.

Abstract: During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may accumulate in maternal fat depots and become available for placental transfer during late pregnancy, when the fetal growth rate is maximal and fetal requirements for LC-PUFAs are greatly enhanced. During this late part of gestation, enhanced lipolytic activity in adipose tissue contributes to the development of maternal hyperlipidaemia; there is an increase in plasma triacylglycerol concentrations, with smaller rises in phospholipid and cholesterol concentrations. Besides the increase in plasma very-low-density lipoprotein, there is a proportional enrichment of triacylglycerols in both low-density lipoproteins and high-density lipoproteins. These lipoproteins transport LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the placenta allows their placental uptake, where they are hydrolysed by lipoprotein lipase, phospholipase A(2) and intracellular lipase. The fatty acids that are released can be metabolized and diffuse into the fetal plasma. Although present in smaller proportions, maternal plasma non-esterified fatty acids are also a source of LC-PUFA for the fetus, their placental transfer being facilitated by the presence of a membrane fatty acid-binding protein. There is very little placental transfer of glycerol, whereas the transfer of ketone bodies may become quantitatively important under conditions of maternal hyperketonaemia, such as during fasting, a high-fat diet or diabetes. The demands for cholesterol in the fetus are high, but whereas maternal cholesterol substantially contributes to fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather than cholesterol transfer from maternal lipoproteins seems to be the main mechanism for satisfying fetal requirements during late pregnancy.

Perona JS, Cabello-Moruno R, Ruiz-Gutierrez V. · Nutrition and Lipid Metabolism Group, Instituto de la Grasa (CSIC), Seville 41012, Spain. · J Nutr Biochem. · Pubmed #16481154 No free full text.

Abstract: The endothelium is involved in many of the processes related to the development of atherosclerosis, which is considered an inflammatory disease. Actually, traditional risk factors for atherosclerosis predispose to endothelial dysfunction, which is manifested as an increase in the expression of specific cytokines and adhesion molecules. There are firm evidence supporting the beneficial effects of olive oil, the most genuine component of the Mediterranean diet. Although the effects of olive oil and other oleic acid-rich dietary oils on atherosclerosis and plasma lipids are well known, the roles of minor components have been less investigated. Minor components constitute only 1-2% of virgin olive oil (VOO) and are composed of hydrocarbons, polyphenols, tocopherols, sterols, triterpenoids and other components usually found in traces. Despite their low concentration, non-fatty acid constituents may be of importance because studies comparing monounsaturated dietary oils have reported different effects on cardiovascular disease. Most of these compounds have demonstrated antioxidant, anti-inflammatory and hypolipidemic properties. In this review, we summarize current knowledge on the effects of these compounds contained in VOO on vascular dysfunction and the mechanisms by which they modulate endothelial activity. Such mechanisms involve the release of nitric oxide, eicosanoids (prostaglandins and leukotrienes) and adhesion molecules, in most cases by activation of nuclear factor kappaB by reactive oxygen species.

Praga M. · Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. · Kidney Int Suppl. · Pubmed #16336567 No free full text.

Abstract: The level of proteinuria is one of the most important risk factors for progressive renal function loss in renal diseases. Any therapeutic measure that reduces proteinuria will slow or halt the progression of proteinuric nephropathies. Blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors or AT1-receptor antagonists (ARA) is currently the most powerful available antiproteinuric treatment. Recent investigations point out that blockade of RAAS at other levels (e.g., aldosterone or renin antagonists) could also induce a significant decrease in proteinuria. Because angiotensin II is also generated from angiotensin I by enzymes other than ACE, ARA would provide a more effective blockade of angiotensin II; however, ACE inhibition increases plasma levels of substances such as bradykinin and N-acetyl-seryl-aspartyl-lysyl-proline, which have strong antifibrotic properties. These differential effects of ACE inhibitors and ARA are the rationale for combined administration of both agents, which in clinical studies has demonstrated a significantly higher antiproteinuric and renoprotective effect than by either drug alone. Salt and protein restriction, as well as cautious use of diuretics, can also increase the antiproteinuric effect of RAAS blockade. Treatment with statins or other lipid-lowering agents leads to reduction in proteinuria levels, as some meta-analyses have demonstrated. Smoking is associated with an increased risk for the appearance of proteinuria, so cessation of smoking should be mandatory in proteinuric renal diseases. Recent studies have highlighted an epidemic increase of obesity-related proteinuric glomerulopathies; weight loss is effective not only in this condition, but also in overweight patients with proteinuric nephropathies of other etiologies.

Cole P, Rabasseda X. · Medical Information Department, Prous Science, Barcelona, Spain. · Drugs Today (Barc). · Pubmed #16082429 No free full text.

Abstract: While therapy with HMG-CoA reductase inhibitors, or statins, has provided the principal pharmacological innovation in the treatment of hypercholesterolemia in recent years, extensive use of these agents has shown that not all patients respond to them and that still greater reductions in low-density lipoprotein (LDL) cholesterol can further protect patients from cardiovascular events. The strategy of increasing the doses of statins is effective but associated with an increase in adverse effects. The combination of statins with other agents has also, in some cases, increased efficacy, but has likewise been limited by toxicity. The administration of a new agent with a novel mechanism of action, ezetimibe, with a well-characterized and effective statin, simvastatin, in a single tablet now appears to provide enhanced treatment without compromising safety. Monotherapy with either ezetimibe or simvastatin has demonstrated the ability to significantly lower LDL cholesterol. Simultaneous administration of the two agents benefits from their two distinct mechanisms of action: inhibition of biliary and dietary cholesterol absorption by ezetimibe and inhibition of hepatic cholesterol synthesis by simvastatin. The two mechanisms have exhibited complementary activity in preclinical evaluation and have demonstrated an absence of pharmacokinetic interaction in humans. Large clinical trials have consistently shown that the addition of ezetimibe to simvastatin produces significantly greater reductions in LDL cholesterol than simvastatin alone, with tolerability similar to statin monotherapy. Ezetimibe/simvastatin has also been associated with other beneficial effects on lipids, and it achieves greater efficacy than monotherapy with the use of lower, safer doses of the statin. These findings indicate that use of the ezetimibe/simvastatin single tablet will allow more patients to meet increasingly stringent LDL cholesterol goals, thereby avoiding negative cardiovascular outcomes.

Corella D, Ordovas JM. · Nutrition and Genomics Laboratory, Jean Mayer-U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111, USA. · Annu Rev Nutr. · Pubmed #16011471 No free full text.

Abstract: Cardiovascular disease (CVD) risk is the result of complex interactions between genetic and environmental factors. During the past few decades, much attention has focused on plasma lipoproteins as CVD risk factors. The current evidence supports the concept that gene-environment interactions modulate plasma lipid concentrations and potentially CVD risk. The findings from studies examining gene-diet interactions and lipid metabolism have been highly promising. Several loci (i.e., APOA1, APOA4, APOE, and LIPC) are providing proof-of-concept for the potential application of genetics in the context of personalized nutritional recommendations for CVD prevention. However, the incorporation of these findings to the clinical environment is not ready for prime time. There is a compelling need for replication using a higher level of scientific evidence. Moreover, we need to evolve from the simple scenarios examined nowadays (i.e., one single dietary component, single nucleotide polymorphism, and risk factor) to more realistic situations involving interactions between multiple genes, dietary components, and risk factors. In summary, there is need for both large population studies and well-standardized intervention studies.

Lima J, Fonollosa V, Chacón P. · Unidad de Lípidos, Servicio de Medicina Interna, Hospital General Vall d'Hebron, 08035 Barcelona, España. · Med Clin (Barc). · Pubmed #15960941 No free full text.

Abstract: Ezetimibe is the first of a new class of lipid-lowering drugs, the 2-azetidinones, which selectively inhibits the absorption of intestinal cholesterol. Ezetimibe's mechanism of action complements that of cholesterol synthesis inhibitors. Ezetimibe as monotherapy or in combination with statins significantly decreases plasma cLDL levels. As monotherapy, ezetimibe is well tolerated with a side-effect profile similar to placebo, whereas in combination with statins no differences in the incidence of myopathy, rhabdomyolysis or elevated liver enzymes are reported.

Carmena R, Betteridge DJ. · Endocrine Service, Hospital Clínico Universitario, University of Valencia, Avda Blasco Ibañez 15, 46010 Valencia, Spain. · Semin Vasc Med. · Pubmed #15861314 No free full text.

Abstract: Lipid abnormalities play an important part in raising the cardiovascular risk in diabetic subjects. The main components of diabetic dyslipidemia are increased plasma triglycerides, low concentration of high-density lipoprotein cholesterol, preponderance of small, dense low-density lipoprotein, and excessive postprandial lipemia. Small, dense low-density lipoprotein, the elevation in remnant triglyceride-rich lipoprotein particles, and the low high-density lipoprotein are the most powerful atherogenic components. The coexistence of these three factors strongly aggravates the lipid accumulation in the arterial wall and the formation of atherosclerotic plaques. The position of diabetes in cardiovascular risk assessment has been recently reviewed in the Harmonized Clinical Guidelines on Prevention of Atherosclerotic Vascular Disease. In general, patients with diabetes carry a high risk for cardiovascular disease, but the absolute risk varies depending on the type of diabetes, age, and population baseline risk. The Adult Treatment Program III (ATP III) and the American Heart Association have designated diabetes as a high-risk condition and recommended intensive risk-factor management. Concerning therapeutic targets, both ATP III and the American Diabetes Association (ADA) guidelines have identified low-density lipoprotein cholesterol as the first priority of lipid lowering, and the optimal level was set at less than 2.6 mmol/L (100 mg/dL). There is strong evidence, coming from landmark secondary prevention studies, that LDL lowering in people with diabetes is associated with significant clinical benefits. The benefits of statin therapy in type 2 diabetics can no longer be questioned. Ongoing clinical trials will help clarify the question of whether increasing high-density lipoprotein cholesterol with fibrates in the presence of low low-density lipoprotein levels (lower than 3.4 mmol/L, or 130 mg/dL) will be more beneficial than statin therapy alone. The new paradigms in risk-reduction therapies for type 2 diabetic subjects are focused on cardiovascular disease prevention, rather than only on glucose or lipid control. Therapeutic lifestyle changes are considered primary therapies for hyperglycemia and coexisting metabolic syndrome, which can be diagnosed in more than half of type 2 diabetes subjects. New perspectives of lipid management in type 2 diabetes should take into account that insulin resistance, increased lipolysis, and overproduction of large, buoyant, very low density lipoprotein particles are at the base of diabetic dyslipidemia. Accordingly, drugs acting in the regulatory steps of very low density lipoprotein assembly should be developed. Activation of peroxisome proliferator activated receptor alpha (PPARalpha), as occurs with fibrates, lowers free fatty acids (FFAs) and triglyceride levels. PPARgamma agonism, as demonstrated by the thiazolidinediones, increases triglyceride lipolysis, FFA transport, and conversion of FFAs to triglycerides. As separate activation of PPARalpha and PPARgamma improves lipid metabolism, the development of new drugs integrating PPARalpha and PPARgamma activity (PPAR-alpha/gamma agonists) is a promising line that may further improve insulin resistance, FFA metabolism, and consequently, atherogenic diabetic dyslipidemia.

Alonso R, Mata N, Mata P. · Fundación Jiménez Díaz, Lipid Clinic, Internal Medicine Department, Madrid 28040, Spain. · Expert Opin Drug Saf. · Pubmed #15794711 No free full text.

Abstract: Familial hypercholesterolaemia (FH) is a frequent inherited monogenic disorder, associated with premature coronary artery disease. Life expectancy of FH patients is reduced by 15 - 30 years unless they are adequately treated with lipid-lowering therapy. Patients with this disorder need long-term drug therapy and the selection of treatment should be strongly based on its long-term safety and tolerability. The introduction of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors has changed the treatment of FH. Simvastatin 40 - 80 mg/day effectively reduces serum low-density lipoprotein cholesterol levels, and also reduces triglycerides with a modest rise in high-density lipoprotein cholesterol levels. Other potentially important effects, such as improvement of endothelial function, reduction of LDL oxidation and vascular inflammation, have been associated with simvastatin therapy in FH. In addition, simvastatin has been shown to abolish the progression, and even facilitate the regression of existing human atherosclerotic lesions. The safety and tolerability of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon. The efficacy and tolerability of simvastatin at doses up to 80 mg/day are well-established, as well as its cost-effectiveness in the management of FH patients.

Esteve E, Ricart W, Fernández-Real JM. · Sección de Diabetes, Endocrinología y Nutrición, Hospital Universitario de Girona "Dr Josep Trueta", Avenida de Francia s/n, 17007 Girona, Spain. · Clin Nutr. · Pubmed #15681098 No free full text.

Abstract: Inflammation leads to changes in lipid metabolism aimed at decreasing the toxicity of a variety of harmful agents and tissue repair by redistributing nutrients to cells involved in host defence. Acute phase response, mediated by cytokines, preserves the host from acute injury. When this inflammation becomes chronic, it might lead to chronic disorders as atherosclerosis and the metabolic syndrome. The activation of the inflammatory cascade will induce a decrease in HDL-cholesterol (HDL-C), with impairment in reverse cholesterol transport, and parallel changes in apolipoproteins, enzymes, anti-oxidant capacity and ATP binding cassette A1-dependent efflux. This decrease in HDL-C and phospholipids could stimulate compensatory changes, as synthesis and accumulation of phospholipid-rich VLDL which binds bacterial products and other toxic substances, resulting in hypertriglyceridemia. The final consequence is an increased accumulation of cholesterol in cells. When the compensatory response (inflammation) is not able to repair injury, it turns into a harmful reaction, and the lipid changes will become chronic, either by repeated or overwhelming stimulus, enhancing the formation of atherosclerotic lesions. Thus, the classical lipid changes associated with the metabolic syndrome (increased triglycerides and decreased HDL-C) may be envisioned as a highly conserved evolutionary response aimed at tissue repair. Under this assumption, the problem is not the response but the persistence of the stimulus.