Hyperlipidemias: Italy

Potena L, Valantine HA. · Institute of Cardiology, Academic Hospital S.Orsola-Malpighi, via Massarenti 9, Building 21, 40138 Bologna, Italy. · Endocrinol Metab Clin North Am. · Pubmed #17983931 No free full text.

Abstract: Cardiac allograft vasculopathy (CAV) is a major cause of death in patients surviving more than 1 year after heart transplantation. An important cluster of CAV risk factors occurs as a consequence of insulin resistance and manifests as part of the metabolic syndrome. This article summarizes the pathologic features of CAV and reviews the contribution of the major components of insulin resistance in CAV development and progression. It focuses on the few studies that have analyzed the impact of the individual metabolic abnormalities and inflammation and on therapeutic strategies to minimize the clinical manifestation of insulin resistance after heart transplantation.

Iughetti L, Predieri B, Balli F, Calandra S. · Department of Pediatrics, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy. · J Endocrinol Invest. · Pubmed #17923804 No free full text.

Abstract: Atherosclerosis represents a disease that begins in childhood and in which LDL cholesterol plays a pivotal role for the development of the pathology. Children and adolescents with high cholesterol levels are more likely than their peers to present cholesterol elevation as adults. The identification of genetic dyslipidemias associated with premature cardiovascular disease is crucial during childhood to delay or prevent the atherosclerotic process. Guidelines for the diagnosis and treatment of hypercholesterolemia during pediatric age are available from the National Cholesterol Education Program. A heart-healthy diet should begin at the age of 2 yr and a large number of studies have demonstrated no adverse effects on nutritional status, growth, pubertal development, and psychological aspects in children and adolescents limiting total and saturated fat intake. Pharmacotherapy should be considered in children over 10 yr of age when LDL cholesterol concentrations remain very high despite severe dietary therapy, especially when multiple risk factors are present. The only lipid-lowering drugs recommended up to now for childhood and adolescence are resins reported to be effective and well tolerated, although compliance is very poor because of unpalatability. The use of statins is increasing and seems to be effective and safe in children, even if studies enrolled a small number of patients and evaluated efficacy and safety for short-term periods. Recently, an interesting drug represented by ezetimibe has been found that may provide cholesterol-lowering additive to that reached with statin treatment. This review provides an update on recent advances in the diagnosis, therapy, and follow-up of familial hypercholesterolemia during pediatric age and adolescence.

Borrelli F, Capasso R, Izzo AA. · Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy. · Mol Nutr Food Res. · Pubmed #17918162 No free full text.

Abstract: Garlic (Alllium sativum L., Fam Liliaceae) is used medicinally mainly for the treatment of hypercholesterolemia and prevention of arteriosclerosis. Clinical trials have consistently shown that "garlic breath" and body odor are the most common (and well-documented) complaints associated to garlic intake. Case reports have highlighted the possibility that garlic use may cause allergic reactions (allergic contact dermatitis, generalized urticaria, angiedema, pemphigus, anaphylaxis and photoallergy), alteration of platelet function and coagulation (with a possible risk of bleeding), and burns (when fresh garlic is applied on the skin, particularly under occlusive dressings). Consumption of garlic by nursing mothers modifies their infant's behavior during breast-feeding. Finally, garlic may enhance the pharmacological effect of anticoagulants (e. g. warfarin, fluindione) and reduce the efficacy of anti-AIDS drugs (i. e. saquinavir).

Arca M, Gaspardone A. · Department of Clinical and Therapeutic Medicine, La Sapienza University of Rome, Rome, Italy. · Drugs. · Pubmed #17910519 No free full text.

Abstract: Atorvastatin has been extensively studied in the primary and secondary prevention of cardiovascular events, and may have some clinical advantages over various other statins in these respects. The principal primary prevention study of atorvastatin, ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm), revealed that atorvastatin reduced the relative risk of primary coronary heart disease (CHD) events by 36% (p = 0.0005) compared with placebo in patients with hypertension. Much published data confirm the secondary preventive benefits of atorvastatin in various clinical settings. The IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) and TNT (Treating to New Targets) trials demonstrate the preventive efficacy of atorvastatin in patients with stable CHD. Relative to simvastatin (in the IDEAL trial) and low-dosage atorvastatin (in the TNT trial), intensive atorvastatin therapy (80 mg/day) reduced the risk of nonfatal myocardial infarction (MI) by 17-22% (p < or = 0.02). Furthermore, the ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) and GREACE (GREek Atorvastatin and Coronary-heart-disease Evaluation) trials highlight the benefits of atorvastatin in the 'real world' setting in patients with stable CHD. Compared with 'usual' care, atorvastatin reduced the risk of nonfatal MI by 47-59% (p < or = 0.0002).Moreover, the MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), PROVE-IT (PRavastatin Or atorVastatin Evaluation and Infection Therapy) and IDEAL-ACS (Acute Coronary Syndromes) studies outline the benefits of high-dosage atorvastatin therapy started within 24-96 hours, 10 days or 2 months, respectively, of an acute coronary syndrome. Relative to placebo, pravastatin and simvastatin, atorvastatin reduced the risk of death or major cardiovascular events by 16-18% (p < or = 0.048). In patients undergoing revascularisation procedures, the AVERT (Atorvastatin VErsus Revascularisation Treatment) study revealed that 18 months' administration of atorvastatin 80 mg/day was at least as effective as angioplasty plus usual care in reducing the risk of ischaemic events in low-risk patients with stable coronary artery disease. Furthermore, the ARMYDA (Atorvastatin for Reduction in MYocardial DAmage during angioplasty) and ARMYDA-3 trials showed that 7 days' administration of atorvastatin 40 mg/day before coronary intervention significantly reduced the risks of periprocedural myocardial damage (ARMYDA), postprocedural MI (p = 0.025; ARMYDA) and atrial fibrillation (p = 0.003; ARMYDA-3) versus placebo. In addition, it has been reported that C-reactive protein levels and the combined incidence of cardiovascular events (death, MI and target segment revascularisation during the 6-month follow-up) were significantly higher in coronaropathic patients undergoing non-surgical revascularisation procedures (stent implantation) not receiving statin therapy compared with those treated with atorvastatin (80mg). Overall, therefore, the marked efficacy of atorvastatin in the primary and secondary prevention of cardiovascular events underscores the pivotal place that this statin has in general cardiovascular disease management, and suggests even greater potential clinical utility for the drug in some clinical settings.

Lombardi F, Terranova P. · Cardiologia, Dipartimento di Medicina, Chirurgia e Odontoiatria, Osp. San Paolo, University of Milan, Milan, Italy. · Curr Med Chem. · Pubmed #17691948 No free full text.

Abstract: Omega-3 fatty acids (Poly-Unsaturated Fatty Acids or PUFA n-3) have been initially found to reduce plasma levels of triglycerides and to increase levels of high-density lipoprotein in patients with marked hypertriglyceridemia. However, in both bench research studies and clinical trials, omega-3 fatty acid intake has recently been associated with an anti-arrhythmic efficacy. At experimental level, n-3 PUFA administration produces several actions on ionic channels regulating transmembrane action potential. At clinical level, the most significant finding was the reduction in the incidence of sudden death in survivors of MI in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevention trial and the subsequent recommendation for administration of fish oil as part of the post-infarction regimen in European guidelines. More recently, Omega-3 fatty acids administration has been associated with a lower incidence of atrial fibrillation in patients who underwent cardiac surgery. Contrasting results have been instead reported in patients with implantable cardioverter defibrillators. This article reviews in detail the basic and clinical research studies of fish oil as an anti-arrhythmic entity, the types of arrhythmias that have been beneficially affected by fish oil administration, and the presumed and known mechanisms by which the beneficial actions are exerted.

Galioto A, Dominguez LJ, Pineo A, Ferlisi A, Putignano E, Belvedere M, Costanza G, Barbagallo M. · Geriatric Section, Department of Internal Medicine and Emerging Pathologies, University of Palermo, Viale Fco. Scaduto 6/c, 90144 Palermo, Italy. · Exp Gerontol. · Pubmed #17689040 No free full text.

Abstract: Several studies have shown that centenarians have better cardiovascular risk profiles compared to younger old people. Some reports have revealed that cardiovascular diseases (i.e. hypertension, diabetes, angina and/or myocardial infarction) are less common in centenarians respect to 70 and 80 years old persons. In order to explain this evidence, there is a growing number of hypothesis that consider a combination of genetic factors and lifestyle aspects to elucidate the exceptional longevity of centenarians, able to overcome the most frequent mortality cause, which is a cardiovascular event. It has been suggested that a role on this better cardiovascular risk profile may be played by the increasing use of pharmacologic treatments in the elderly population (specially for hypertension and dyslipidemia), but the contribution of drug treatments to promote extreme longevity is not confirmed. Furthermore, centenarians in general have needed fewer drugs at younger ages due to a healthy lifestyle. The importance of the genetic contribution is demonstrated by the inheritance of low-risk cardiovascular profiles in centenarian offspring and lower prevalence of cardiovascular diseases in this population as compared with their spouses or with age-matched subjects without centenarian parents. Another advantage in centenarians' offspring seems to be a delay in the onset for cardiovascular diseases, respect to age- and sex-matched controls. Cardiovascular risk factors mirror the factors that contribute to longevity. Hence, it is not surprising that these risk factors are less prevalent in centenarians when compared to younger old individuals.

Rizzo M, Rini GB, Berneis K. · Department of Clinical Medicine and Emerging Diseases, University of Palermo, Italy. · Adv Ther. · Pubmed #17660166 No free full text.

Abstract: Increasing evidence suggests that the quality-rather than just the quantity-of low-density lipoproteins (LDLs) exerts a great influence on cardiovascular risk. LDLs comprise multiple subclasses with discrete size and density, and different physicochemical composition, metabolic behaviors, and atherogenicity. Individuals generally cluster into 2 broad subgroups. Most have a predominance of large LDLs, and some have a higher proportion of small particles. Small, dense LDLs are good predictors of cardiovascular events and progression of coronary artery disease. Their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. Several studies have shown that therapeutic modulation of LDL size and subclass is of great benefit in reducing the risk of cardiovascular events. This seems particularly true for statins and fibrates when they are administered to higher-risk patients, such as those with type 2 diabetes or vascular disease. Data reporting outcomes with the use of rosuvastatin, the latest statin molecule introduced to the market, and ezetimibe, a cholesterol absorption inhibitor, are promising.

Bosello O, Zamboni M. · Division of Geriatrics, University of Verona, Italy. · Eat Weight Disord. · Pubmed #17644862 No free full text.

This publication has no abstract.

Littarru GP, Langsjoen P. · Institute of Biochemistry, Polytechnic University of the Marche, Via Ranieri, 60131 Ancona, Italy. · Mitochondrion. · Pubmed #17482884 No free full text.

Abstract: Statins are drugs of known and undisputed efficacy in the treatment of hypercholesterolemia, usually well tolerated by most patients. In some cases treatment with statins produces skeletal muscle complaints, and/or mild serum CK elevation; the incidence of rhabdomyolysis is very low. As a result of the common biosynthetic pathway Coenzyme Q (ubiquinone) and dolichol levels are also affected, to a certain degree, by the treatment with these HMG-CoA reductase inhibitors. Plasma levels of CoQ10 are lowered in the course of statin treatment. This could be related to the fact that statins lower plasma LDL levels, and CoQ10 is mainly transported by LDL, but a decrease is also found in platelets and in lymphocytes of statin treated patients, therefore it could truly depend on inhibition of CoQ10 synthesis. There are also some indications that statin treatment affects muscle ubiquinone levels, although it is not yet clear to which extent this depends on some effect on mitochondrial biogenesis. Some papers indicate that CoQ10 depletion during statin therapy might be associated with subclinical cardiomyopathy and this situation is reversed upon CoQ10 treatment. We can reasonably hypothesize that in some conditions where other CoQ10 depleting situations exist treatment with statins may seriously impair plasma and possible tissue levels of coenzyme Q10. While waiting for a large scale clinical trial where patients treated with statins are also monitored for their CoQ10 status, with a group also being given CoQ10, physicians should be aware of this drug-nutrient interaction and be vigilant to the possibility that statin drugs may, in some cases, impair skeletal muscle and myocardial bioenergetics.

Sirtori CR, Eberini I, Arnoldi A. · Department of Pharmacological Sciences, University of Milano, Italy. · Br J Nutr. · Pubmed #17408521 No free full text.

Abstract: In 1995, Anderson et al. published a meta-analysis, derived from most of the clinical studies on soya proteins given to individuals with varying levels of cholesterolaemia that had been reported up to that time. The meta-analysis clearly indicated that cholesterolaemias were generally reduced by diets with soya given as a partial or total substitution of animal proteins, with final mean total and LDL-cholesterol reductions of 23.2 mg/dl and 21.7 mg/dl, respectively. These findings were recently strongly criticised, based on the evaluation of later studies, frequently involving individuals with normal or moderately elevated cholesterolaemias. In the present paper, these more recent studies were re-evaluated using a 'nomogram' prepared on the basis of the quartiles of initial cholesterol concentrations in the Anderson meta-analysis and their corresponding CI for net cholesterol change. The five studies belonging to the first quartile and thirteen out of the fourteen belonging to the second quartile gave results perfectly in line with the nomogram. Out of the fourteen studies belonging to the third quartile, ten agreed with the nomogram and two gave lower cholesterol reductions, whereas two gave higher reductions. Unfortunately, none of the recent studies belonged to the fourth quartile as treatment with statins or other lipid-lowering drugs is now mandatory in the presence of very high cholesterol levels. The re-evaluation thus shows that the thirty-three studies published in the past 10 years are in agreement with the Anderson meta-analysis and confirm its validity.

Zaninotto M, Mion MM, Novello E, Altinier S, Plebani M. · Department of Laboratory Medicine, University-Hospital of Padova, Italy. · Clin Chim Acta. · Pubmed #17400202 No free full text.

Abstract: BACKGROUND: Evaluation of patients presenting to hospital with chest pain or other signs or symptoms suggesting acute coronary syndrome (ACS) is problematic, time-consuming and sometimes expensive, even if new biochemical markers, such as troponins, have improved the ability to detect cardiac injury. However, patients with normal troponin values are not necessarily risk-free for major cardiac events. METHODS: Recent investigations indicate that the overall patient risk may be assessed earlier than before, thanks to new knowledge acquired concerning the pathobiology of atherosclerosis and molecular events involved in the progression of disease, thus allowing the development of new biochemical markers. Some selected markers are released during the different phases of development of cardiovascular disease and may be useful for the diagnosis of patients with cardiovascular disease. In particular, the identification of emerging markers that provide relevant information on the inflammatory process, and the development of biomarkers whose circulating concentrations suggest the status of plaque instability and rupture, seems to be of particular value in prognosis and risk stratification. The overall expectations for a cardiovascular biochemical marker are not only its biological plausibility but also the availability at a reasonable cost of rapid, high quality assays, and their correct interpretation by clinicians using optimal cut-offs. CONCLUSION: The crossing from bench to bedside for each new marker discovered, must be associated with concurrent advances in the characterization of analytical features and the development of routine assay, in the assessment of analytical performance and in interpretative reporting of test results as well as in the training of physicians to use the array of biomarkers available appropriately and to interpret them correctly. This approach calls for the coordinated support of clinicians, technology experts, statisticians and the industry so that new biochemical developments can be of optimal value.

Ferroni P, Basili S, Santilli F, Davì G. · Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele, Rome, Italy. · Pathophysiol Haemost Thromb. · Pubmed #16877882 No free full text.

Abstract: Elevated low-density lipoprotein (LDL) cholesterol (LDL-C) levels represent one of the most important risk factors for atherosclerosis and therefore cardiovascular morbidity and mortality. LDL-C operates at different levels and through various classic and non-classic mechanisms. In particular, increased or modified LDL enhances platelet function and increases sensitivity of platelets to several naturally occurring agonists. Agents that lower LDL-C in hypercholesterolemic patients have been shown to interfere with platelet function. Several studies, in fact, suggested that statins exert anti-thrombotic effects largely as a result of an anti-platelet activity. Among the other LDL-C-lowering agents those acting by interfering with cholesterol reabsorption from the gut (cholestyramine, colestipol) do not appear to interfere with platelet function, whereas peroxisome proliferator-activated receptor agonists (such as fibrates) can inhibit platelet function. The full potential of these drugs in vascular protection is only just being realized. Further studies are still needed to elucidate the full therapeutic benefits of these agents in plaque stabilization and thrombosis.

Parnetti L, Caso V, Lanari A, Saggese E, Sebastianelli M, Tayebati SK, Amenta F. · Department of Neuroscience, University of Perugia, Perugia, Italy. · Clin Exp Hypertens. · Pubmed #16833043 No free full text.

Abstract: Randomized trials with statins have shown a modest but significant absolute reduction in the incidence of stroke in patients with a previous myocardial infarction. The reasons for the positive statin effect on stroke endpoint are unclear, because a link between serum cholesterol level and stroke never has been established. However, positive results of statin trials were mainly obtained in patients with an average or a low serum cholesterol level. Statins have a good overall safety profile. Statins reduced stroke incidence in high-risk (mainly coronary heart disease, diabetics, and hypertensives) population even with a normal baseline blood cholesterol level. In patients with prior strokes, statins reduce the incidence of coronary events, but it is not yet proven if drugs of this class actually reduce the incidence of recurrent strokes in terms of secondary prevention.

De Lorenzo A, Maiolo C, D'Agostino G, Arcudi G. · Cattedra di Alimentazione e Nutrizione Umana, Dipartimento di Neuroscienze, Facoltà di Medicina e Chirurgia, Università "Tor Vergata", Roma, Italia. · Clin Ter. · Pubmed #16817504 No free full text.

Abstract: BACKGROUND: Obesity, is one of the most common nutritional disorder in developed countries. The association with several health disorders (i.e., type 2 diabetes mellitus, hypertension, hyperlipidemias, cholelithiasis, obstructive sleep apneas, coronary heart disease, cancer) is frequently present. DESIGN: Obesity is, actually, measured using body mass index (BMI) determination. However, BMI isn't useful to predict body fat content. Skin-fold thickness, bioelectrical impedance analysis and/or dual energy x ray absorptiometry are specific tools with different capability to measure body composition (i.e., fat mass and fat-free mass). All these methods need a large data-base of age, sex and population reference values. CONCLUSIONS: Obesity management (dietary treatment, monitoring of weight loss, pharmacologic approach, and surgery ) is associated with several complications and errors.

Pinti M, Salomoni P, Cossarizza A. · Department of Biomedical Sciences, Section of General Pathology, University of Modena and Reggio Emilia School of Medicine, via Campi 287, 41100 Modena, Italy. · Biochim Biophys Acta. · Pubmed #16782042 No free full text.

Abstract: Several drugs are currently used that can significantly prolong the course of the infection with the human immunodeficiency virus (HIV), the cause of the acquired immunodeficiency syndrome (AIDS). Among these drugs, the nucleosidic inhibitors of viral reverse transcriptase can alter mitochondrial (mt) function by inhibiting the mitochondrial DNA polymerase gamma (the enzyme responsible for the replication of mtDNA). Decreased mtDNA content provokes a diminished synthesis of respiratory chain enzymes, leading to alterations in mt function. These are in turn responsible for a variety of side effects frequently observed in HIV+ patients, that range from hyperlactatemia and lactic acidosis to lipodystrophy, a pathology characterized by accumulation of visceral fat, breast adiposity, cervical fat-pads, hyperlipidemia, insulin resistance and fat wasting in face and limbs. In this paper, data concerning the effects of different compounds on mitochondria, their role in the pathogenesis of lipodystrophy, and problems related to studies on the mt toxicity of antiviral drugs are reviewed and thoroughly discussed.

Federico A, Trappoliere M, Loguercio C. · 2nd University of Naples, Gastroenterology Unit, via Pansini 5, Naples 80131, Italy. · Dig Liver Dis. · Pubmed #16750661 No free full text.

Abstract: Non-alcoholic fatty liver disease is considered a component of the metabolic syndrome associated with obesity. Problems still exist concerning non-alcoholic fatty liver disease patients in clinical practice, for example: (a) how to diagnose non-alcoholic fatty liver disease and its type; (b) how to select patients candidate to treatment; (c) how to treat selected patients. Non-alcoholic fatty liver disease includes steatosis and non-alcoholic steatohepatitis, but only non-alcoholic steatohepatitis evolves into cirrhosis and the absolute risk of mortality for non-alcoholic fatty liver disease is low. As yet, no tools, other than liver biopsy, are available to differentiate the various types of non-alcoholic fatty liver disease. Many drugs are, currently, under study to treat non-alcoholic fatty liver disease, even if well-performed trials are until necessary to define the best treatment. At the moment, the entity of the problem and the characteristics of patients frequently put the physician, in clinical practice, to choose the therapeutic approach arbitrarily which is considered more effective for each individual patient. Probably the future will consider the possibility of treating non-alcoholic fatty liver disease with more than one drug, by considering the various aspects and degree of this syndrome. Actually each physician should select the individual treatment on the basis of his/her knowledge and experience, by never forgetting the old saying 'primum non nocere'. However, the epidemiological entity of the problem, the characteristics of the patients, generally young, the frequent lack of clinical evidence of involvement of the liver, are all the factors that require vast well-performed clinical trials in order to define the best therapeutic approach for each individual patient.

Testino G. · Unità Operativa Dipartimentale Epato-Gastroenterologia, Dipartimento Trapianti di Organo, Azienda Ospedaliera Ospedale San Martino e Cliniche Universitarie Convenzionate, Genova. · Recenti Prog Med. · Pubmed #16496750 No free full text.

Abstract: Steatosis and hepatitis C are two common liver diseases. Epidemiological and experimental data indicate that hepatitis C predisposes to non alcoholic fatty liver disease and the prevalence of coexistent hepatitis C and steatosis is two-three times higher than it would be expected if these were completely independent processes. Two conditions have been defined in course of hepatitis C: the "metabolic fat", characterized by a correlation between steatosis and metabolic alterations and the "viral fat", characterized by a direct action of HCV. Actually, "mixed forms" are often present. Up to today, most of the authors believe that the presence of steatosis accelerates the progression of fibrosis, and therefore the progression to cirrhosis, increases the risk of developing hepatocellular carcinoma, and decreases the antiviral therapy response percentage. The treatment must associate the common antiviral therapy with all the measures fit for facing the metabolic problems, with particular reference to the antioxidant therapy.

Napoli C, Pignalosa O, Gallo L, Graziano G, Carotenuto F, Fiorito C, Mita L, Botti C, de Nigris F, Sica V. · Centro di Eccellenza nella Ricerca sulle Malattie Cardiovascolari e Cattedra di Patologia Clinica, Dipartimento di Patologia Generale, II Università di Napoli. · Recenti Prog Med. · Pubmed #16491768 No free full text.

Abstract: The prodromal stage of atherosclerotic lesions is already formed during human fetal development. The presence of infections during childhood may increase synergistically the progression of atherogenesis. After delivery, especially those children exposed to severe maternal hypercholesterolemia should be followed up for the onset and development of acute and chronic infections and be included in clinical and noninvasive examinations of vascular function.

Morelli F, Carlier P, Giannini G, De Luigi MC, Dejana AM, Ruzzenenti MR. · Hypertriglyceridemia Department, Immunohematology Services, San Martino University Hospital, Genova--Italy. · Int J Artif Organs. · Pubmed #16288441 No free full text.

Abstract: Several trials have assessed the link between low-density lipoprotein cholesterol (LDL) and the development of coronary heart disease (CHD). LDL apheresis provides an effective role in treating patients with familial hypercholesterolemia (FH) and in preventing the progression of coronary artery disease (CAD). Five different techniques of LDL apheresis are in current use: immunoadsorption (IMA), dextran sulphate-cellulose adsorption (DSA), heparin extracorporeal LDL precipitation system (HELP), double filtration plasmapheresis (DFPP) or lipidfiltration and direct adsorption of lipoprotein using hemoperfusion (DALI). All methods are efficient,but their cost restricts LDL apheresis to the treatment of FH. Indications could include other diseases, but controlled trials are still lacking.

Giannini G, Valbonesi M, Morelli F, Carlier P, De Luigi MC, Dejana AM, Ruzzenenti MR. · Department of Immunohematology, Immunohematology Services, S. Martino University Hospital, Genova--Italy. · Int J Artif Organs. · Pubmed #16288440 No free full text.

Abstract: Patients with extremely high triglyceride levels and associated lipemia are at high risk for acute pancreatitis. Two factors can increase triglyceride-rich lipoproteins; one is overproduction and other is a defect in clearance. Either mechanism can cause hypertriglyceridemia and both may exist simultaneously. Causes can be either primary or secondary. Plasmapheresis is efficacious for severe Hypertriglyceridemia in patients who have not responded to previous therapies. We have treated 15 cases of hypertriglyceridemia complicating the course of patients receiving Cyclosporin A after bone marrow transplantation. Five patients were treated with plasmapheresis, the other ten with cascade filtration. The removal rate for triglycerides was 58.0% for patients treated by cascade filtration and 63.5% for patients treated by plasmapheresis. The removal rates for triglycerides were low possibly as a consequence of early saturation of the filter.

Calabrò P, Yeh ET. · Division of Cardiology, University of Naples Federico II Naples, Italy. · Curr Opin Cardiol. · Pubmed #16234628 No free full text.

Abstract: PURPOSE OF REVIEW: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the most widely prescribed drugs worldwide for lowering cholesterol levels. In use for more than 15 years, they have demonstrated efficacy, safety, and tolerability across a broad range of patients. This class of drugs has been designed to lower the cholesterol level by competitively inhibiting the enzyme responsible for its biosynthesis and thereby to play a major role in reducing cardiovascular risk. However, both basic evidence and clinical evidence also supports the idea that reductions in cardiovascular risk are dependent on mechanisms beyond cholesterol reduction alone, such as the reduction of endothelial dysfunction, inhibition of inflammatory responses, stabilization of atherosclerotic plaques, and modulation of procoagulant activity and platelet function. RECENT FINDINGS: In fact, as shown in several clinical trials, the beneficial effects of statin treatment begin earlier than its cholesterol-lowering effect. These other mechanisms could act in concert with the potent low-density lipoprotein cholesterol-lowering effects of this class of drugs to exert early and lasting cardiovascular protective effects. Recently, several studies have shown that an intensive lipid-lowering regimen with a statin provides greater protection against death or major cardiovascular events than does a standard regimen. SUMMARY: This review summarizes the new findings in these pleiotropic effects and describes their impact on vascular processes.

Bertolotti M, Maurantonio M, Gabbi C, Anzivino C, Carulli N. · Dipartimento di Medicine e Specialità Mediche, Università di Modena e Reggio Emilia, Modena, Italy. · Aliment Pharmacol Ther. · Pubmed #16225468 links to  free full text

Abstract: Hyperlipidaemia represents a determinant for the development of atherosclerosis and an important risk factor for cardiovascular disease, particularly in the context of the insulin resistance syndrome. This is characterized by alterations in the profile of plasma lipoprotein including high triglyceride levels, low high-density lipoprotein cholesterol concentrations and the appearance of qualitatively modified, small-dense low-density lipoproteins. Many charts and algorithms have been developed to estimate the entity of coronary and cardiovascular risk as related to dyslipidaemia, on the basis of additional individual risk factors and conditions: most include age and gender, smoking status, hypertension and diabetes. They should preferably be utilized in consistent patient populations, in terms of geographical areas and general risk profile. Pharmacological treatment of dyslipidaemia, in particular with statin drugs, was shown to greatly improve cardiovascular morbidity and mortality. A body of evidence also underlines the need for a multidisciplinary approach, integrating non-pharmacological lifestyle and diet interventions, as well as treatment of concomitant diseases (hypertension and diabetes).

Davì G, Falco A. · Center of Excellence on Aging, G d'Annunzio Foundation, University of Chieti, G d'Annunzio School of Medicine, Chieti, Italy. · Lupus. · Pubmed #16218483 No free full text.

Abstract: Low-grade inflammation, enhanced oxidant stress and lipid peroxidation have been shown in association with increased cardiovascular risk associated with cardiovascular events. It has been hypothesized that the low-grade inflammatory state characterizing metabolic disorders such as obesity, hypercholesterolemia, type 2 diabetes mellitus and homozygous homocystinuria may be the primary trigger of thromboxane-dependent platelet activation mediated, at least in part, through enhanced lipid peroxidation. Interestingly, as the clinical course of systemic lupus erythematosus (SLE), in particular in the presence of antiphospholipid antibodies, may be complicated by vascular disease, several mechanisms contributing to vascular complications have been documented also in this setting, including enhanced lipid peroxidation and thromboxane biosynthesis. Although epidemiological studies show an inverse relationship between antioxidant vitamin intake and cardiovascular disease, several clinical trials have obtained conflicting results on the effects of vitamin E on the risk of cardiovascular events. The availability of analytical tools for measuring F2-isoprostane biosynthesis in man has improved our understanding of the interplay between lipid peroxidation and low-grade inflammation. The use of F2-isoprostane as a biochemical end-point for dose-finding studies may allow reassessing the adequacy of vitamin supplementation in different clinical settings.

Violi F, Cangemi R. · IV Divisione di Clinica Medica, Viale del Policlinico 155, Roma 00161, Italy. · Curr Opin Investig Drugs. · Pubmed #16187689 No free full text.

Abstract: Oxidative stress appears to play a key role in the pathogenesis of atherosclerosis. Agents that prevent the oxidation of low-density lipoprotein have reduced the development and progression of this disease in a range of in vitro experiments and animal models. In the last decade, many trials of antioxidants in patients with cardiovascular disease have been conducted, but the results have been ambiguous. The reason for the disappointing findings is unclear, but one possible explanation is the lack of identification criteria for patients who are potential candidates for antioxidant treatment. This review analyzes data reported to date, in order to determine whether these clearly support the premise that patients at risk of cardiovascular disease may be candidates for this therapeutic option.

Buemi M, Nostro L, Crascì E, Barillà A, Cosentini V, Aloisi C, Sofi T, Campo S, Frisina N. · Department of Internal Medicine, University of Messina, Messina, Italy. · Med Res Rev. · Pubmed #16075407 No free full text.

Abstract: The nephrotic syndrome is characterized by metabolic disorders leading to an increase in circulating lipoproteins levels. Hypertriglyceridemia and hypercholesterolemia in this case may depend on a reduction in triglyceride-rich lipoproteins catabolism and on an increase in hepatic synthesis of Apo B-containing lipoproteins. These alterations are the starting point of a self-maintaining mechanism, which can accelerate the progression of chronic renal failure. Indeed, hyperlipidemia can affect renal function, increase proteinuria and speed glomerulosclerosis, thus determining a higher risk of progression to dialysis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the rate-limiting enzyme in cholesterol synthesis from mevalonate and its inhibitors, or statins, can therefore interfere with the above-mentioned consequences of hyperlipidemia. Statins are already well known for their effectiveness on primary cardiovascular prevention, which cannot be explained only through their hypolipemic effect. As far as kidney diseases are concerned, statin therapy has been shown to prevent creatinine clearance decline and to slow renal function loss, particularly in case of proteinuria, and its favorable effect may depend only partially on the attenuation of hyperlipidemia. Statins may therefore confer tissue protection through lipid-independent mechanisms, which can be triggered by other mediators, such as angiotensin receptor blockers. Possible pathways for the protective action of statins, other than any hypocholesterolemic effect, are: cellular apoptosis/proliferation balance, inflammatory cytokines production, and signal transduction regulation. Statins also play a role in the regulation of the inflammatory and immune response, coagulation process, bone turnover, neovascularization, vascular tone, and arterial pressure. In this study, we would like to provide scientific evidences for the pleiotropic effects of statins, which could be the starting point for the development of new therapeutical strategies in different clinical areas.