Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

2015

Objective: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and apolipoprotein B (apoB) below the 5 th percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. Methods: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clin…

Clinical utility of novel biomarkers for cardiovascular disease risk stratification

2012

Over the past few decades, a number of coronary artery disease (CAD) and cardiovascular disease (CVD) risk factors have been identified. The predictive power of "conventional" risk factors have been validated by observational, prospective and intervention studies. Nevertheless, all attempts to exactly predict the individual risk for CAD have failed, biased by a large number of incorrectly risk-classified subjects. To improve cardiovascular (CV) risk prediction, a large number of genetic and/or non-genetic biomarkers have been discovered and tested against the "classical" risk factors for their power to predict CV risk. Only few of them had a significant improvement over the predictive model…

Statins and metabolic syndrome

2003

Abstract Metabolic syndrome (MS) is a multifactorial condition that represents a risk factor for the development of diabetes mellitus (DMII) and cardiovascular disease (CVD). Statins may play a role on some modifiable clinical features of MS; in fact, whereas therapeutic lifestyle changes are mandatory for MS with a 10-year coronary heart disease (CHD) risk 20% and to correct the other associated lipid and non-lipid abnormalities. In fact, they have a VLDL lowering action in hypertriglyceridemia, they reduce the amount of small and dense LDL, they increase the HDL-C, they reduce the atherogenic lipoproteins, and they decrease the inflammatory marker levels.

Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal insufficiency: a possible role in glucocorticoid deficiency

2015

Backgrounds and aims: Adrenal insufficiency (AI) has been reported in patients with stable cirrhosis. A lack of substrates has been suggested as a possible contributing pathogenic mechanism leading to glucocorticoid deficiency in these subjects. To better explore this hypothesis, we studied lipoproteins in cirrhotics with and without AI. Methods. A total of 81 cirrhotic patients and 30 normal volunteers were enrolled. The severity of liver disease was graded by Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI) levels were evaluated. HDL subfractions were measured by gradient gel electrop…

Characterization of a mutant form of human apolipoprotein B (Thr26_Tyr27del) associated with familial hypobetalipoproteinemia

2016

We have previously identified a deletion mutant of human apoB [apoB (Thr26_Tyr27del)] in a subject with primary hypobetalipoproteinemia. The present study determined the effect of Thr26_Tyr27del mutation on apoB secretion using transfected McA-RH7777 cells. Transient or stable transfection of apoB-48 containing the Thr26_Tyr27del mutation showed drastically reduced secretion of the mutant as compared to wild-type apoB-48. No lipoproteins containing the mutant apoB-48 were secreted into the medium. Incubation of transfected cells in a lipid-rich medium in the presence of cycloheximide showed rapid turnover of cell-associated mutant apoB-48 as compared to that of wild-type apoB-48. Immunofluo…

Diagnostic use of fructosamine assay in the control of type II diabetes mellitus.

1988

In an attempt to evaluate the usefulness of fructosamine assay in monitoring type II diabetes, 142 diabetic patients were investigated. Fructosamine values were found to be higher in patients on insulin treatment than on oral hypoglycemic agents. In order to evaluate the metabolic control by using the correlated variations of F, Gm and HbAlc, the patients were subdivided into many control classes: mean values of fructosamine were higher in poorly controlled patients. Fructosamine however correlated better with glycemia in patients with recent variations in metabolic state than HbAlc. It was concluded that fructosamine is a good index for short-term metabolic control, and if used in an integ…

No association between the cystatin C gene polymorphism and Alzheimer's disease: a case-control study in an Italian population.

2005

Cystatin C is an amyloidogenic protein found together with beta-amyloid in cerebral arteriolar walls of both patients with Alzheimer's Disease (AD) and conghopilic amyloid angiopathy. Several findings implicate cystatin C in the pathogenesis of vascular diseases. Recent genetic association studies proposed cystatin C gene (CST3) as a susceptibility factor for AD, although other reports did not replicate this finding. We conducted a case-control study including 192 probable AD cases and 192 age- and sex-matched controls to test the association between CST3 and AD. Possible interaction between CST3 and age at onset of AD or apolipoprotein E (APOE) was also examined. No significant differences…

The C(-260)T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.

2003

CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients …

Familial HDL deficiency due to ABCA1 gene mutations with or without other genetic lipoprotein disorders

2004

Mutations in ABCA1 have been shown to be the cause of Tangier disease (TD) and some forms of familial hypoalphalipoproteinemia (HA), two genetic disorders characterized by low plasma HDL levels. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of which are previously unreported. Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1. Two subjects found to be compound heterozygotes for ABCA1 mutations did not have overt clinical manifestations of TD. Three subjects, all with prema…

Multiple food hypersensitivity as a cause of refractory chronic constipation in adults

2006

Chronic constipation that is unresponsive to laxative treatment is a severe illness, but children unresponsive to laxatives have been successfully treated with an elimination diet. We report the first cases of refractory chronic constipation caused by food hypersensitivity in adults. Four patients with refractory constipation who were unresponsive to high doses of laxatives were put on an oligo-antigenic diet and underwent successive double-blind, placebo-controlled, food challenges (DBPFC). Routine laboratory tests, immunological assays, colonoscopy, esophago-gastroduodenoscopy and rectal and duodenal histology were performed. While on an elimination diet, bowel habits normalized in all pa…

Automated untargeted stable isotope assisted lipidomics of liver cells on high glucose shows alteration of sphingolipid kinetics

2020

Abstract Untargeted lipidomics is a powerful tool to discover new biomarkers and to understand the physiology and pathology of lipids. The use of stable isotopes as tracers to investigate the kinetics of lipids is another tool able to supply dynamic information on lipid synthesis and catabolism. Coupling the two methodology is then very appealing in the study of lipid metabolism. The main issue to face is to perform thousands of calculations in order to obtain kinetic parameters starting from the MS raw data. An automated computerized routine able to do accomplish such task is presented in this paper. We analyzed the lipid kinetics of palmitic acid (PA) in hepatoma liver cells cultured in v…

Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.

2006

Patients homozygous or Compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels. more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype. We sequenced Apo B and PCSK9 genes in two patients with the clinical diagnosis of homozygous FH who were heterozygous for LDLR gene mutations. Proband Z.P. (LDL-C 13.39 mmol/L and pCAD) was heterozygous for an LDLR mutation (p.E228K) inherited from her father (LD…

Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

2016

Abstract Background and aims Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. Methods and results As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric haz…

Metabolic disturbances and risk of cancer in the 25 years follow-up of the “Ventimiglia Heart Study” epidemiological project

2016

Modification of the lipidic and coagulative pattern in postmenopause women: effect of hormone replacement therapy.

2010

AIM: We evaluated the changes of lipidic and coagulative pattern during menopause and the influence of hormone replacement therapy (HRT) on these parameters. METHODS: We considered 158 patients divided into 2 groups: Group I consisted of 127 women in physiological/surgical menopause and Group II of 31 women with childbearing potential. Subsequently, we considered a group III formed of 34 patients from menopausal women (group I) who underwent three months of HRT. We evaluated total-cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG), lipoprotein (a) (Lpa), fibrinogen, antithrombin III (ATIII), factor VII (FVII) and tissue factor pathway inhibitor (TFPI). RE…

The Atrial Natriuretic Peptide Genetic Variant rs5068 Is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population

2013

OBJECTIVE We hypothesized that the minor allele of the atrial natriuretic peptide (ANP) genetic variant rs5068 is associated with a favorable cardiometabolic phenotype in a general Mediterranean population. RESEARCH DESIGN AND METHODS We genotyped a random sample of the residents of Ventimiglia di Sicilia, Sicily, for rs5068. RESULTS Genotype frequencies of rs5068 are AA, 93.5%; AG, 6.4%; and GG, 0.1%. All subsequent analyses are AA versus AG+GG. After adjusting for age and sex, the minor G allele is associated with lower BMI (estimate [SE]: −1.7 kg/m2 [0.8], P = 0.04). In the AG+GG group, males with HDL cholesterol levels <40 mg/dL are less frequent (P = 0.05) and obesity tends to …

Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients

2022

Background and aims: Familial hypercholesterolemia (FH) is the most relevant genetic cause of early cardiovascular disease (CVD). FH is suspected when low density lipoprotein cholesterol (LDL-C) levels exceed the 95th percentile of the population distribution. Different diagnostic scoring systems have been developed, as the Dutch Lipid Clinic Network (DLCN) score, used worldwide. The aim of the study is to describe the characteristics of FH patients of a large cohort of more than eight hundred genotyped subjects enrolled in an Italian Lipid Clinic, and evaluate the DLCN score performance applied retrospectively to the case study. Methods: 836 hypercholesterolemic patients with LDL-C > 4.…

eNOS Activation by HDL Is Impaired in Genetic CETP Deficiency.

2014

Mutations in the CETP gene resulting in defective CETP activity have been shown to cause remarkable elevations of plasma HDL-C levels, with the accumulation in plasma of large, buoyant HDL particles enriched in apolipoprotein E. Genetic CETP deficiency thus represents a unique tool to evaluate how structural alterations of HDL impact on HDL atheroprotective functions. Aim of the present study was to assess the ability of HDL obtained from CETP-deficient subjects to protect endothelial cells from the development of endothelial dysfunction. HDL isolated from one homozygous and seven heterozygous carriers of CETP null mutations were evaluated for their ability to down-regulate cytokine-induced…

Gelatinases and their tissue inhibitors in metabolic syndrome

2014

P1502Open-label ODYSSEY APPRISE study: interim data from the first 843 participants

2017

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

2006

In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could co…

Lipid and Apoprotein Profile in Renal Transplant Recipients

1991

Lipid and apoprotein profiles of renal transplant recipients were compared with that of a group of uremic patients on hemodialytic treatment. Total cholesterol, HDL-cholesterol, apo AI and apo B were higher and triglycerides, apo CII, apo CIII and apo E lower in renal transplant patients. Type IIa and IIb were the prevalent phenotypes in renal transplant recipients.

CETP levels rather than polymorphisms as markers of coronary risk: Healthy athlete with high HDL-C and coronary disease—effectiveness of probucol

2006

Identification of a novel mutation of MTP gene in a patient with abetalipoproteinemia.

2011

Abetalipoproteinemia (ABL), or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder of lipoprotein metabolism, characterized by fat malabsorption, hypocholesterolemia retinitis pigmentosa, progressive neuropathy and acanthocytosis from early infancy. We describe the clinical and molecular characterization of a 6-month-old infant born of consanguineous, apparently healthy parents from Iran. The patient was hospitalized because of failure to thrive, greasy stool and vomiting. The patient's serum lipid profile, the clinical phenotype and the duodenal histology suggested the clinical diagnosis of ABL. The MTP gene analysis by direct sequencing revealed a novel homozygous mutation (…

Prevalence of overweight and obesity in a rural southern Italy population and relationships with total and cardiovascular mortality: the Ventimiglia …

2001

OBJECTIVE: We investigated the prevalence of overweight and obesity and their relationships with the main cardiovascular risk factors in the population of Ventimiglia di Sicilia, a rural village in Southern Italy characterized by low cholesterol levels and by a low incidence of early coronary heart disease mortality. We related all deaths to body weight and fat distribution during an 8 y follow-up. DESIGN: Cross-sectional and prospective observational study. SUBJECTS: A total of 835 free-living individuals, 363 males and 472 females, of age between 20 and 69 y. MEASUREMENTS: In all participants body weight, waist-to-hip ratio (WHR), cardiovascular risk factors and plasma lipids were measure…

Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercho…

2013

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels (≥100 and ≤160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to th…

The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia – A post-h…

2015

AbstractObjectiveLomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide.MethodsExisting lipid-lowering therapy, including apheresis, was to remain stable from Week −6 to Week 26. Lomitapide dose was escalated on the basi…

Albumin versus solvent/detergent-treated pooled plasma as replacement fluid for long-term plasma exchange therapy in a patient with primary hypertrig…

2015

BACKGROUND Chylomicronemia syndrome is a metabolic condition characterized by severe fasting hypertrigliceridemia (≥1000 mg/dL) and other clinical features including chronic abdominal pain and recurrent acute pancreatitis. In patients with acute or recurrent pancreatitis, plasma exchange (PEx) is indicated for the treatment of acute disease and prevention of recurrence. The use of plasma instead of albumin as replacement fluid has been suggested for its putative ability to replace the deficient enzyme possibly leading to better clinical improvement. CASE REPORT A 40-year-old man with chylomicronemia syndrome due to a newly identified loss-of-function mutation in the lipoprotein lipase (LPL)…

Mutation in candidate genes account for a small minority of hypobetalipoproteinemias and NGS analysis support polygenicity in mutation-negative patie…

2020

Prevalence Of familial hypercholeSTerolaemia (FH) in Italian Patients with coronary artERy disease: The POSTER study

2020

Background and aims: Familial hypercholesterolaemia (FH) is a powerful risk factor for cardiovascular (CV) events. High levels of low-density lipoprotein cholesterol (LDL-C) since birth are linked to the early onset of atherosclerotic disease. A genetic mutation determining FH is present in about one subject out of 250; FH should be more represented among subjects with a documented diagnosis of coronary artery disease (CAD). The POSTER Study evaluated the prevalence of FH in Italian patients with a recent CAD event. Methods: Eighty-two cardiology centres enrolled patients with a documented CAD event; CV risk profile, drug therapy and biochemical parameters were collected. Dutch Lipid Clinic…

Rapid degradation of ABCA1 protein following cAMP withdrawal and treatment with PKA inhibitor suggests ABCA1 is a short-lived protein primarily regul…

2020

Objectives: ATP-binding cassette transporter A1 (ABCA1) is a key player in the reverse cholesterol transport (RCT) and HDL biogenesis. Since RCT is compromised as a result of ABCA1 dysfunction in diabetic state, the objective of this study was to investigate the regulation of ABCA1 in a stably transfected 293 cells expressing ABCA1 under the control of cAMP response element. Methods: To delineate transcriptional and posttranscriptional regulation of ABCA1, 293 cells were stably transfected with the full length ABCA1 cDNA under the control of CMV promoter harboring cAMP response element. cAMP-mediated regulation of ABCA1 and cholesterol efflux were studied in the presence of 8-Br-cAMP and af…

Statin therapy in patients with aortic stenosis after the ASTRONOMER trial: is there still any space?

2011

Analysis of sterols by high-performance liquid chromatography/mass spectrometry combined with chemometrics

2006

A newly developed high-performance liquid chromatography/mass spectrometry (HPLC/MS) method has been successfully used to analyze plasma concentrations of various phytosterols (cholestanol and beta-sitosterol) and cholesterol metabolites (desmosterol and lathosterol). This was based on an unusual solvent combination of water/methanol vs. methanol/acetone/n-hexane applied on a Purospher Star RP-18e (125 x 2 mm, 3 microm) column, which proved excellent for the separation, identification and quantification of plasma sterols. Simple solid-phase extraction preparation of plasma samples was performed, followed by the developed fast and robust HPLC separation. Results on four groups of people were…

Protein oxidation in a group of subjects with metabolic syndrome.

2013

Abstract Aims To examine the protein oxidation, marker of the oxidative stress, in metabolic syndrome (MS). Methods We enrolled 106 subjects (45 women and 61 men) with MS of which 43 (14 women and 27 men) were with diabetes mellitus and 63 (31 women and 32 men) were without diabetes mellitus, and 54 subjects (19 women and 35 men) as control group. The protein oxidation, expressed as carbonyl groups, was measured by an enzyme-like immunosorbent assay (ELISA) kit (BioCell PC test kit, Enzo Life Sciences AG, Switzerland). Results In the whole group of MS subjects, in comparison with control group, a significant increase in carbonyl groups was present. The same datum was also evident between co…

Obesity and the metabolic syndrome in a student cohort from Southern Italy

2009

Abstract Background and aim Cardiovascular (CV) risk factors present in childhood predict future CV events. Few data regarding the metabolic syndrome (MS) prevalence are available in adolescents from Mediterranean areas where obesity is becoming a social emergency. This study presents data of MS prevalence in a student cohort from southern Italy. Methods and results 1629 students between 7 and 14 years of age underwent anthropometric measurements and a blood sample was obtained to assess biochemical parameters. MS risk factors were calculated based on age and gender adjusted percentiles of parameter distributions. MS prevalence rate was 0.022 using paediatric, age-adjusted criteria; the rat…

Interleukin 6 plasma levels predict with high sensitivity and specificity coronary stenosis detected by coronary angiography

2007

SummaryIn recent years new biomarkers able to measure the coronary atherosclerotic burden have been investigated. The aim of the present study was: i) to measure plasma levels of four biomarkers: C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), 8-isosprostane (8-ISO),in a series of patients undergoing coronary angiography; ii) to assess the power of the biomarkers to predict critical coronary stenosis detected by angiography. The study population consisted of a group of 438 subjects undergoing coronary angiography; 160 patients with 0, 1, 2, or 3 critical vessels were selected, and biomarkers plasma levels were measured in plasma samples o…

Two Italian kindreds carrying the Arg136--Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsi…

2003

Abstract Background and Aims: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cy Background and Aims: 12, Cy Background and Aims: 58). Apo E2-Christchurch (Arg136→Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia. Methods and Results: This is the first report of two Italian kindreds carrying the Arg136→Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previo…

Homozygous familial hypercholesterolemia in Italy: Clinical and molecular features

2020

Abstract Background and aims Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated plasma levels of low density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease (ASCVD). HoFH is caused by pathogenic variants in several genes, such as LDLR, APOB and PCSK9, responsible for autosomal dominant hypercholesterolemia (ADH), and LDLRAP1 responsible for autosomal recessive hypercholesterolemia (ARH). Aim of this study was the review of the clinical and molecular features of patients with HoFH identified in Italy from 1989 to 2019. Methods Data were collected from lipid clinics and laboratories, …

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia identified in the lipigen centre of Palermo

2017

Changes in plasma lipids and low-density lipoprotein peak particle size during and after acute myocardial infarction

2002

In summary, LDL peak particle size variations occur very early after AMI, and therefore this parameter, which may be considered a genetically determined risk factor, must be measured not before 2 to 3 months after the acute event.

Thyroid function and release of thyroid-stimulating hormone and prolactin from the pituitary in human obesity

1991

Thyroid function, basal serum thyroid-stimulating hormone (TSH) and prolactin concentrations, and the effects of 200 micrograms TSH-releasing hormone (TRH) given intravenously on TSH (delta TSH) and prolactin (delta prolactin) were investigated in 25 euthyroid obese subjects and 20 lean controls. No significant differences in serum thyroid hormone concentrations, glucose metabolism parameters, or basal TSH and prolactin concentrations were detected between groups, but a significant (P less than 0.01) increase in delta TSH and a significant (P less than 0.01) decrease in delta prolactin were observed in obese subjects. No significant differences in basal TSH and prolactin were observed in ob…

Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement

2020

Genome sequencing and gene-based therapies appear poised to advance the management of rare lipoprotein disorders and associated dyslipidaemias. However, in practice, underdiagnosis and undertreatment of these disorders are common, in large part due to interindividual variability in the genetic causes and phenotypic presentation of these conditions. To address these challenges, the European Atherosclerosis Society formed a task force to provide practical clinical guidance focusing on patients with extreme concentrations (either low or high) of plasma low-density lipoprotein cholesterol, triglycerides, or high-density lipoprotein cholesterol. The task force also recognises the scarcity of qua…

Fatty liver in familial hypobetalipoproteinemia: triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis

2003

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 +/- 11.5 and 3.3 +/- 2.9 (mean +/- SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar…

Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells

2005

Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating nor…

Novel LDL-cholesterol lowering therapies: A step forward a personalized medicine

2023

Molecular diagnosis of hypobetalipoproteinemia: an ENID review.

2007

Abstract Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-3…

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syn…

2011

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with ( n=368) and without ( n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effect…

Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

2014

Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), nitric oxide metabolites (nitrite + nitrate) expressed asNOx, and TBARS/NOxratio in a group of subjects with metabolic syndrome (MS). In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS) and nondiabetic (NDMS) and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C) index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS andNOxlevels and a decrease in TBARS/NOxratio in comparison with normal controls. Regarding all these …

Clinical and genetic features of 2 patients with severe hypertriglyceridemia due to a mutation in GPIHBP1 gene

2017

Effect of aspirin on renal disease progression in patients with type 2 diabetes: A multicenter, double-blind, placebo-controlled, randomized trial. T…

2017

Background Type 2 diabetes mellitus (T2DM) is one of the most common causes of chronic kidney disease and kidney failure. It has been estimated that the annual decline of estimated glomerular filtration rate (eGFR) among patients with T2DM is approximately 2.0-2.5 mL min−1 y−1. Cyclooxygenase-dependent eicosanoids, such as 11-dehydro-thromboxane (Tx)B2, are increased in T2DM patients and are potentially involved in the regulation of renal blood flow. Animal models showed that cyclooxygenase inhibitors, such as aspirin, are associated with improvements in renal plasma flow and eGFR values. Hypothesis The primary end point of the LEDA trial is to evaluate the 1-year decline of eGFR in T2DM pa…

Beyond Statins: New Lipid Lowering Strategies to Reduce Cardiovascular Risk

2014

Statins are the first-line therapy in LDL-Cholesterol (LDL-C) reduction and its clinical use has contributed to significant prevention and treatment of atherosclerotic vascular disease. Yet, a significant proportion of patients remain at high risk. Recently, a number of new therapies have been developed to further lower LDL-C. These agents may provide clinical benefit on top of statin therapy in patients with high residual risk, severe hypercholesterolemia or as an alternative for patients who are intolerant to statins. We review four novel approaches based on the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein-B100 (apoB), Cholesteryl ester transport pro…

Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year foll…

2009

Abstract Background and aims Epidemiological prospective data on cardiovascular (CV) events in elderly subjects from Mediterranean populations are lacking. We aimed to investigate 15-year incidence of CV events and to evaluate the association with CV risk factors in an elderly Mediterranean population. Methods and results The population of a small Sicilian village were enrolled, visited and a blood sample was drawn at baseline. CV events were recorded in the 15 years of follow-up. From 1351 subjects (75% of the resident population); 315 were in the age range 65–85 years; 266 subjects free from CV disease were analysed. Seventy-seven CV events were recorded in 73 out of 266 subjects, with a …

Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians.

1998

In order to assess the role of HDL on longevity, we studied HDL subfraction distribution in centenarian women compared with a group of weight- and gender-matched healthy normolipidemic controls. We did not find any significant difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the contrary, in spite of similar HDL-cholesterol concentrations (1.32 ± 0.41 mmol/l in centenarians vs. 1.32 ± 0.25 mmol/l in controls, p = not significant), HDL<sub>2b</sub> and HDL<sub>3a</sub> levels were, respectively, significantly increased and significantly reduced in centenarians in comparison with controls (HDL<sub>2b</sub> 32.4 ± 9.2% in centenarian…

Normal intestinal dietary fat and cholesterol absorption, intestinal apolipoprotein B (ApoB) mRNA levels, and ApoB-48 synthesis in a hypobetalipoprot…

1997

Abstract The purpose of this study was to characterize intestinal apolipoprotein B (apoB) metabolism in subjects with familial hypobetalipoproteinemia (FHBL), where segregation analysis supports linkage to the apoB gene but no apoB truncations are present. We investigated cholesterol and fat absorption, intestinal apoB mRNA synthesis and editing, as well as apoB-48 synthesis. Plasma triglycerides (TG) and retinyl palmitate in the chylomicron fractions were analyzed after 12 hours of fasting and then repeatedly for 14 hours after ingestion of a vitamin A—containing high-fat meal. Cholesterol absorption was assessed using a dual stable-isotope method. Mean peak times and concentrations and ar…

Thrombin-antithrombin III complexes in type II diabetes mellitus.

1992

Several studies suggest that diabetes is associated with a hypercoagulable state. Therefore determination of thrombin-antithrombin complex (TAT) could represent a sensitive parameter for specific detection of a latent activation of the clotting system. The present study documents increased plasma TAT in a heterogeneous group of non-insulin-dependent diabetic patients. The finding of increased TAT levels both in diabetic patients with vascular complications and in vascular disease patients without diabetes suggests a relationship between existing vascular disease and the hemostatic mechanism that produces augmented thrombin activity. In acute vascular occlusions the presence of diabetes seem…

Effects of gemfibrozil in hyperlipidemic patients with or without diabetes

1993

Abstract Four hundred sixty-one hyperlipidemic men and women, aged 23 to 73 years, with (n = 200) or without (n = 261) non-insulin-dependent diabetes mellitus were included in a study designed to evaluate the efficacy and tolerability of 1,200 mg of gemfibrozil given once daily for 24 weeks. All lipid values improved significantly in both diabetic and nondiabetic patients during treatment. The number of patients with the atherogenic predictor ratio of low-density:high-density lipoprotein cholesterol (HDL-C:LDL-C) >5 decreased by 95% in both patient groups. The number of patients in the highest-risk subgroup with the combination risk factors of LDL-C:HDL-C >5 and triglyceride levels >200 mg/…

Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia.

2015

Background: Monogenic hypertriglyceridemia (HTG) may result from mutations in some genes which impair the intravascular lipolysis of triglyceride (TG)-rich lipoproteins mediated by the enzyme Lipoprotein lipase (LPL). Mutations in the LPL gene are the most frequent cause of monogenic HTG (familial chylomicronemia) with recessive transmission. Methods: The LPL gene was resequenced in 149 patients with severe HTG (TG>10mmol/L) and 106 patients with moderate HTG (TG>4.5 and <10mmol/L) referred to tertiary Lipid Clinics in Italy. Results: In the group of severe HTG, 26 patients (17.4%) were homozygotes, 9 patients (6%) were compound heterozygotes and 15 patients (10%) were simple heter…

Relationship of a Body Shape Index and Body Roundness Index with carotid atherosclerosis in arterial hypertension.

2018

Background and aims: A Body Shape Index (ABSI) and Body Roundness Index (BRI) are two new anthropometric adiposity indices that have shown to be associated better than BMI with adipose abdominal tissue, with the onset of diabetes and the risk of premature death. Little is known about the influence of ABSI and BRI on subclinical vascular damage. The study was aimed to assess the relationship between ABSI and BRI with carotid atherosclerosis damage in subjects with arterial hypertension. Methods and results: A total of 468 patients with arterial hypertension (30–80 years old) were enrolled; adiposity indices were calculated (BMI, WC, ABSI, BRI) and carotid ultrasonographic examination was per…

Anti-actin antibodies in celiac disease: correlation with intestinal mucosa damage and comparison of ELISA with the immunofluorescence assay.

2005

The presence in the sera of celiac disease (CD) patients of anti-actin autoantibodies (AAAs) has been suggested as a marker of severe intestinal villus atrophy (1). AAAs have been detected with an immunofluorescence (IF) technique and seem to contribute to villus cytoskeleton damage and to the pathogenesis of intestinal damage in CD (2). The aims of the present study were to evaluate the relationship between the presence of serum IgA AAAs and severity of intestinal mucosa damage in CD patients and to compare the IF assay with a new ELISA for IgA AAA determination. We enrolled 150 individuals in the study. IgA AAAs were assayed in 58 consecutive CD patients diagnosed between January and Dece…

Genotypic and phenotypic characterization of patients with autosomal dominant hypercholesterolemia in sicily

2017

Aim: Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant disorder characterized by high serum low density lipoproteincholesterol (LDL-C) levels. The clinical manifestations of ADH might vary among affected subjects and the phenotype correlates with the severity of mutation and the specific gene involved. The aim of this study was to evaluate the clinical expression and clinical outcomes in a cohort of ADH subjects. Methods: 300 ADH probands with a DUTCH score > 6 were enrolled in this study and the analysis was extended to the family members of these index cases. Anthropometric measures, clinical and biochemical parameters, life style (smoker and/or alcohol habits) and…

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing

2016

Background Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. Objective The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. Methods We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL–10 mmol/L): 4 positive controls in whom pathogenic mutations had pre…

Prothrombotic gene variants as risk factors of acute myocardial infarction in young women

2012

Abstract Background Acute myocardial infarction (AMI) in young women represent an extreme phenotype associated with a higher mortality compared with similarly aged men. Prothrombotic gene variants could play a role as risk factors for AMI at young age. Methods We studied Factor V Leiden, FII G20210A, MTHFR C677T and beta-fibrinogen -455G>A variants by real-time PCR in 955 young AMI (362 females) and in 698 AMI (245 females) patients. The data were compared to those obtained in 909 unrelated subjects (458 females) from the general population of the same geographical area (southern Italy). Results In young AMI females, the allelic frequency of either FV Leiden and of FII G20210A was signif…

Oxidative status in metabolic syndrome

2014

Efficacy and safety of lomitapide in homozygous familial hypercholesterolaemia: the pan-European retrospective observational study

2021

Abstract Aims Lomitapide is a lipid-lowering agent indicated as an adjunct therapy for adult homozygous familial hypercholesterolaemia (HoFH). This study evaluated the medium-term effectiveness and safety of lomitapide in a large cohort of HoFH patients in Europe. Methods and results In a multicentre retrospective, observational study including 75 HoFH patients treated with lomitapide in a real-world clinical setting from 9 European countries, low-density lipoprotein cholesterol (LDL-C) changes, adverse events (AEs), and major adverse cardiovascular events (MACE) were assessed. After a median 19 months (interquartile range 11–41 months) of treatment with a mean dosage of 20 mg of lomitapide…

Effectiveness and safety of lomitapide in a patient with familial chylomicronemia syndrome

2020

Background: Familial chylomicronemia syndrome (FCS) is characterized by severe fasting hypertriglyceridemia, abdominal pain, and recurrent acute pancreatitis. Available triglyceride-lowering drugs are insufficient to avoid pancreatitis. Therefore, there is a significant unmet medical need for effective triglyceride-lowering drugs for patients with FCS. Case report: We report the second case of a patient with FCS and recurrent pancreatitis treated with lomitapide. Lomitapide treatment resulted in a reduction of fasting TG levels from 2897 mg/dL (32.71 mmol/L) to an average of 954 mg/dL (10.77 mmol/L) on the 30 mg lomitapide equating to a 67% reduction from baseline. After 26 months of lomita…

Lipoprotein abnormalities in chronic kidney disease and renal transplantation

2021

Chronic kidney disease (CKD) is one of the most important risk factors for cardiovascular disease (CVD). Despite the kidney having no direct implications for lipoproteins metabolism, advanced CKD dyslipidemia is usually present in patients with CKD, and the frequent lipid and lipoprotein alterations occurring in these patients play a role of primary importance in the development of CVD. Although hypertriglyceridemia is the main disorder, a number of lipoprotein abnormalities occur in these patients. Different enzymes pathways and proteins involved in lipoprotein metabolism are impaired in CKD. In addition, treatment of uremia may modify the expression of lipoprotein pattern as well as deter…

Lp(a): a genetic cause of clinical FH in children

2022

No abstract available

Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles.

2009

BACKGROUND: PCSK9 plays a key role in plasma cholesterol metabolism by modulating the expression of LDL receptors. OBJECTIVE AND METHODS: In this study we investigated the effects of two common polymorphism of the PCSK9 gene (E670G and I474V) on the intima media thickness of the common carotid artery and the possible relation with polymorphisms of apolipoprotein E in 1541 middle aged subjects selected from the general population enrolled in the PLIC study and confirmed the major findings in a second free-living population enrolled in the Ventimiglia study. RESULTS: 670G carriers showed significantly increased plasma total cholesterol, LDL-cholesterol, and Apo levels B while no significant d…

PS166 Efficacy and Safety of Alirocumab According to Smoking Status

2016

Cystatin C levels are decreased in acute myocardial infarction

2005

Background: Cystatin C is the most abundant protease inhibitor in the plasma. Low plasma levels have been found in patients with aortic aneurysms and they seem correlated with the extension of the aortic lesions in early aneurysms detected by ultrasonography. Methods: In this study, plasma levels of cystatin C have been investigated in patients with acute myocardial infarction (AMI), unstable angina and controls. The effect on plasma levels of the G73A polymorphism of the CST3 gene has been also evaluated. Results: Patients with acute myocardial infarction showed significantly lower levels of cystatin C compared to unstable angina and controls, but levels were nearly normal in a week after …

A targeted apoB38.9 mutation in mice is associated with reduced hepatic cholesterol synthesis and enhanced lipid peroxidation.

2006

Familial hypobetalipoproteinemia (FHBL) due to truncation-specifying mutations of apolipoprotein B (apoB), which impair hepatic lipid export in very low-density lipoprotein (VLDL) particles, is associated with fatty liver. In an FHBL-like mouse with the apoB38.9 mutation, fatty liver develops despite reduced hepatic fatty acid synthesis. However, hepatic cholesterol contents in apoB38.9 mice are normal. We found that cholesterogenic enzymes (3-hydroxy-3-methylglutaryl-coenzyme A reductase, sterol-C5-desaturase, and 7-dehydrocholesterol reductase) were consistently downregulated in two separate expression-profiling experiments using a total of 19 mice ( n = 7 each for apob+/+and apob+/38.9, …

Lipase maturation factor 1 is required for endothelial lipase activity

2011

Lipase maturation factor 1 (Lmf1) is an endoplasmic reticulum (ER) membrane protein involved in the posttranslational folding and/or assembly of lipoprotein lipase (LPL) and hepatic lipase (HL) into active enzymes. Mutations in Lmf1 are associated with diminished LPL and HL activities ("combined lipase deficiency") and result in severe hypertriglyceridemia in mice as well as in human subjects. Here, we investigate whether endothelial lipase (EL) also requires Lmf1 to attain enzymatic activity. We demonstrate that cells harboring a (cld) loss-of-function mutation in the Lmf1 gene are unable to generate active EL, but they regain this capacity after reconstitution with the Lmf1 wild type. Fur…

Effects of Mediterranean Diet on Lipid Levels and Cardiovascular Risk in Renal Transplant Recipients

1999

<i>Background:</i> Renal transplant recipients have an increased incidence of cardiovascular disease. These patients present abnormalities of lipoprotein profile which are persistent and involve an increasing number of individuals, suggesting the opportunity of an early therapeutic intervention. <i>Methods:</i> We evaluated the effects of a 10- to 12-week diet based on the American Heart Association step-one diet criteria, modified with an increased intake of monounsaturated fats and alimentary fibers, on lipid profile and lipid-related cardiovascular risk in 78 normolipidemic and hyperlipidemic renal transplant recipients. <i>Results:</i> Diet led to a s…

Long-term efficacy of lipoprotein apheresis and lomitapide in the treatment of homozygous familial hypercholesterolemia (HoFH): a cross-national retr…

2021

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a rare life-threatening condition that represents a therapeutic challenge. The vast majority of HoFH patients fail to achieve LDL-C targets when treated with the standard protocol, which associates maximally tolerated dose of lipid-lowering medications with lipoprotein apheresis (LA). Lomitapide is an emerging therapy in HoFH, but its place in the treatment algorithm is disputed because a comparison of its long-term efficacy versus LA in reducing LDL-C burden is not available. We assessed changes in long-term LDL-C burden and goals achievement in two independent HoFH patients’ cohorts, one treated with lomitapide in Ita…

Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

2015

Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Ill…

Familial hypobetalipoproteinemia due to apolipoprotein B R463W mutation causes intestinal fat accumulation and low postprandial lipemia

2008

Abstract Objective Familial hypobetalipoproteinemia (FHBL) is characterized by inherited low plasma levels of apolipoprotein B (apoB)-containing lipoproteins. In this paper we investigated whether the already described APOB R463W missense mutation, a FHBL mutation able to impair the activity of microsomal triglyceride transfer protein (MTP), may cause intestinal fat accumulation and reduced postprandial lipemia. Methods Four out of five probands harboring APOB R463W mutation were compared with six healthy controls and six patients with celiac disease (CD). An oral fat load supplemented with retinyl palmitate (RP) was administered and a gastro-duodenal endoscopy with biopsy was performed. Re…

Detection of mutations in the apolipoprotein CII gene by denaturing gradient gel electrophoresis. Identification of the splice site variant apolipopr…

1998

AbstractFamilial apolipoprotein (apo) CII deficiency is a rare autosomal recessive inborn error of metabolism clinically resembling lipoprotein lipase deficiency. A number of mutations of the apo CII gene are known to date; they are located in the promoter region, the coding exons, or in the splice junctions. We present a simple assay based on PCR and denaturing gradient gel electrophoresis, which allows scanning of the promoter, the entire coding sequence, and the splice junctions of the apo CII gene for sequence variants. All gene fragments are amplified using a common PCR protocol and are examined for mutations on a single gradient gel. Using this method and direct sequencing, we identif…

Resistive index of ophthalmic artery as an imaging biomarker of hypertension-related vascular and kidney damage

2021

Aim: Resistive index of ophthalmic artery (RI-OA) is associated with atherosclerotic diseases. The aim of this study was to evaluate the association of RI-OA and hypertension-related vascular and kidney damage. Materials and methods: Two-hundred and eighty hypertensive patients underwent evaluation of RI-OA, carotid atherosclerosis and level of 24 h albuminuria. Results: Albuminuria and carotid atherosclerosis were positively associated with RI-OA independently of other cardiovascular risk factors. Receiver-operating characteristic curve analysis allowed us to calculate a cut-off value of RI-OA >0.625, which would be suspicious about the existence of atherosclerotic disease. Conclusion:…

Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred.

2017

Background Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily. Objective The objectives of the study were to improve the molecular diagnosis of familial hypercholesterolemia (FH) and to estimate the frequency of the ARH1 allele in 2 free-living Sicilian pop…

Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study

2020

Abstract Aims To obtain safety and efficacy data of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in a real-life setting in high cardiovascular (CV) risk patients with heterozygous familial hypercholesterolaemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs). ODYSSEY APPRISE was a prospective, single-arm, Phase 3b open-label (≥12 weeks to ≤ 30 months) European/Canadian study with alirocumab. Methods and results Patients received alirocumab 75 or 150 mg every 2 weeks, with dose adjustment based on physician’s judgment. In total, 994 patients were enrolled …

Family hystory, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: a one year follow-up study

2005

BACKGROUND AND AIM: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events. METHODS AND RESULTS: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant re…

Lp(a) levels in patients undergoing aorto-coronary bypass surgery.

1992

The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22…

Is echocardiography mandatory for patients with chronic kidney disease?

2019

This study aims at evaluating the prevalence of left ventricular diastolic dysfunction in a group of 319 hypertensive patients with stage 3b–4–5 chronic kidney disease (according to Kidney Disease Improving Global Outcomes classification), compared with 216 patients with essential hypertension and normal renal function. All patients underwent echocardiographic examination. Patients on stage 1–2–3a chronic kidney disease, dialysis treatment, or with previous manifestations of heart failure or other cardiovascular diseases were excluded. Patients with renal disease had significantly worse diastolic function (both considering trans-mitral flow and tissue Doppler imaging parameters). Diastolic …

Proprotein Convertase Subtilisin Kexin Type 9 Inhibition for Autosomal Recessive Hypercholesterolemia—Brief Report

2016

Objective— Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein (LDL) cholesterol in the vast majority of patients with autosomal dominant familial hypercholesterolemia. Will PCSK9 inhibition with monoclonal antibodies, in particular alirocumab, be of therapeutic value for patients with autosomal recessive hypercholesterolemia (ARH)? Approach and Results— Primary lymphocytes were obtained from 28 genetically characterized ARH patients and 11 controls. ARH lymphocytes treated with mevastatin were incubated with increasing doses of recombinant PCSK9 with or without saturating concentrations of alirocumab. Cell surface LDL receptor expression measured…

Identification Of P.Leu167Del Apoe Gene Mutation By Next Generation Sequencing In A Large Hypercholesterolemic Family

2019

Association of estrogen receptor α gene with Alzheimer's disease: A case-control study

2006

Abstract Recent experimental data have offered the biological background to study the estrogen receptor (ER) alpha gene as a candidate gene for AD. Genetic association studies proposed ERalpha PvuII and XbaI gene polymorphisms as susceptibility factors for AD, although subsequent studies did not replicate this finding. To verify this association in a Caucasian Italian sample, we conducted a case-control study in a dataset of 172 clinic-based probable AD cases and 172 age- and sex-matched controls. Possible interaction between ERalpha polymorphisms and sex, age at onset of AD or apolipoprotein E (APOE) was examined. The xx-genotype of the XbaI polymorphism was associated with the risk of dev…

Long-Term Efficacy and Safety of the Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide in Patients With Homozygous Familial Hypercholeste…

2017

Homozygous familial hypercholesterolemia is a genetic disorder characterized by low-density lipoprotein (LDL)-receptor dysfunction, markedly elevated levels of LDL-cholesterol (LDL-C) and premature atherosclerosis. Patients are often poorly responsive to conventional lipid-lowering therapies that upregulate LDL-receptor expression.1 Lomitapide inhibits microsomal triglyceride transfer protein, which lipidates nascent apolipoprotein (apo)B-containing lipoproteins. In a pivotal 78-week open-label trial, lomitapide, titrated to the maximal tolerable dose, decreased LDL-C by 50% at the end of the efficacy phase (week 26) in patients with homozygous familial hypercholesterolemia.2 The principal …

Differences in cardiac structure and function between black and white patients: Another step in the evaluation of cardiovascular risk in chronic kidn…

2017

Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patien…

2015

OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoi…

POSTPRANDIAL HYPERGLYCEMIA IS A DETERMINANT OF PLATELET ACTIVATION IN EARLY 2 DIABETES MELLITUS

2010

BACKGROUND: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus. OBJECTIVES: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients. METHODS: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandi…

Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients

2010

BACKGROUND: Reducing low-density lipoprotein cholesterol (LDL-C) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease (CHD). METHODS: This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and establishedCHDwhowere taking a stable daily dose of simvastatin 20 mg. Patients were randomized to ezetimibe/simvastatin 10/20 mg (eze/simva; n 5 56) or simvastatin 40 mg (simva; n 5 56) for 6 weeks. Percent change from baseline in LDL-C, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides were assessed by use of the Student t test. The percent of patients achieving L…

Treatment effect of alirocumab according to age group, smoking status, and hypertension: Pooled analysis from 10 randomized ODYSSEY studies

2019

Background: Age, smoking, hypercholesterolemia, and hypertension are major risk factors for atherosclerotic cardiovascular disease. Objective: We examined whether the effects of alirocumab on low-density lipoprotein cholesterol (LDL-C) differed according to age, hypertension, or smoking status. Methods: Data were pooled from 10 Phase 3 ODYSSEY randomized trials (24–104 weeks’ duration) in 4983 people with heterozygous familial hypercholesterolemia (FH) or non–familial hypercholesterolemia (3188 on alirocumab, 1795 on control [620 on ezetimibe and 1175 on placebo]). Most participants received concomitant maximum tolerated statin therapy. In 8 trials, the alirocumab dose was increased from 75…

Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately c…

2009

SUMMARY Aims: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe ⁄simvastatin (EZE ⁄SIMVA) 10 ⁄20 mg vs. rosuvastatin (ROSUVA) 10 mg. Methods: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) ‡ 2.59 and £ 4.92 mmol ⁄l] and with high cardiovascular risk who were taking a stable daily dose of one of several statin medications for ‡ 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation ⁄screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose ⁄potency, patien…

Practical guidance for combination lipid-modifying therapy in high- and very-high-risk patients: A statement from a European Atherosclerosis Society …

2021

International audience; Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.MethodsEvidence-based review.ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-h…

Genetics of familial hypobetalipoproteinemia

2007

Primary hypobetalipoproteinemias include three monogenic disorders: the relatively frequent codominant familial hypobetalipoproteinemia (FHBL), the rare recessive conditions abetalipoproteinemia (ABL) and chylomicron retention disease (CMRD). Approximately 50% of FHBL patients are carriers of mutations in the APOB gene, mostly causing the formation of truncated forms of ApoB. In some kindred, FHBL is linked to a locus on chromosome 3 (3p21), but the candidate gene is still unknown. Recently, a FHBL-like phenotype was observed in carriers of mutations of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene causing loss-of-function of the encoded protein, a proprotein convertase tha…

Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particle…

2016

Background: HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C. Aims: This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a "Mediterranean diet", ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an "in vitro" model of cultured hep…

Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and fam…

2017

Background The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene. Objective A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established. Methods We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and …

APOC-III: a Gatekeeper in Controlling Triglyceride Metabolism

2023

Abstract Purpose of Review Apolipoprotein C-III (ApoC-III) is a widely known player in triglyceride metabolism, and it has been recently recognized as a polyhedric factor which may regulate several pathways beyond lipid metabolism by influencing cardiovascular, metabolic, and neurological disease risk. This review summarizes the different functions of ApoC-III and underlines the recent findings related to its multifaceted pathophysiological role. Recent Findings The role of ApoC-III has been implicated in HDL metabolism and in the development of atherosclerosis, inflammation, and ER stress in endothelial cells. ApoC-III has been recently considered an important player in insulin resistance …

Clinical, pathologic, and genetic features of massive soft tissue neurofibromas in a Sicilian patient

2008

Abstract CONTEXT: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X). OBJECTIVE: The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded. RESULTS: The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and rec…

Effects of a phytosterol-enriched dairy product on lipids, sterols and 8-isoprostane in hypercholesterolemic patients: a multicenter Italian study.

2009

Abstract Background and aims Plant sterols, added to several food sources, lower serum cholesterol concentrations. Plant sterol-induced cholesterol lowering is paralleled by a mild decrease in plasma levels of the antioxidant β-carotene, the amount of this decrease being considered clinically non-significant. Whether the effect on lipid profile of daily consumption of plant sterol-enriched low-fat fermented milk (FM) is paralleled by a concomitant variation in a reliable marker of the oxidative burden like plasma isoprostane levels is unresolved. Methods and results The effect of plant sterol consumption on plasma lipid and isoprostane levels of hypercholesterolemic patients was evaluated i…

Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC)

2021

Background The European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry provides a platform for the global surveillance of familial hypercholesterolaemia through harmonisation and pooling of multinational data. In this study, we aimed to characterise the adult population with heterozygous familial hypercholesterolaemia and described how it is detected and managed globally. Methods Using FHSC global registry data, we did a cross-sectional assessment of adults (aged 18 years or older) with a clinical or genetic diagnosis of probable or definite heterozygous familial hypercholesterolaemia at the time they were entered into the registries. Dat…

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

2014

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these clai…

HDL Subtractions Distribution in Renal Transplant Recipients: Lack of Evidence of a Reduction of HDL&lt;sub&gt;2&lt;/sub&gt; Particles

1996

Since the high rate of cardiovascular disease in renal transplant recipients, alterations of lipoprotein profile in such patients were extensively evaluated, but the HDL subclass profile was not completely clarified. Renal transplant recipients usually show normal to high plasma levels of HDL cholesterol, even if some investigations suggested a persistence of low HDL2 levels: this was not useful in terms of cardiovascular protection. We designed this study in order to evaluate HDL subfractions distribution in renal transplant recipients. We studied 55 renal transplant recipients, treated with prednisone, azathioprine and/or cyclosporine, and 34 healthy normolipidemics as controls. In all su…

Carotid atherosclerosis in renal transplant recipients: Relationships with cardiovascular risk factors and plasma lipoproteins

1999

BACKGROUND: Renal transplant recipients have an increased incidence of cardiovascular disease, but less data exist about cerebrovascular atherosclerosis. In this study, we assessed the prevalence of carotid lesions as evaluated by B-mode ultrasonography in a group of renal transplant recipients, and we evaluated univariate and multivariate relationships between common risk factors and plasma lipoproteins and carotid lesions. METHODS: Fifty-seven renal transplant recipients and 113 age- and gender-matched controls underwent a complete clinical visit for the evaluation of risk factors present. In all subjects, a blood sample was collected for lipoprotein determination, and an ultrasound high-…

Rapid screening of the LDL receptor point mutation FH-Genoa/Palermo

1999

The LDL-receptor gene point mutation FH-Genoa/Palermo is the most frequent mutation responsible for Familial Hypercholesterolemia in Sicily. The mutation does not introduce or abolish any useful restriction site. We establish a GeneComb™-based strategy to identify this mutation in a population of Sicilian unrelated clinically diagnosed FH probands. The method was very sensitive and specific; 12 out of 90 (13.3%) unrelated FH probands were found to carry the FH-Genoa/Palermo mutation. According to these results, the FH-Genoa/Palermo is the more frequent LDL-receptor gene mutation among the Sicilian FH patients. Moreover FH-Genoa/Palermo is the mutation cluster to date more represented in Sou…

Polyvascular subclinical atherosclerosis in familial hypercholesterolemia: The role of cholesterol burden and gender

2019

International audience; BACKGROUND AND AIM:Heterozygous familial hypercholesterolemia (HeFH) is a genetic disease characterized by a heterogeneous phenotype. The assessment of cardiovascular (CV) risk is challenging for HeFH. Cholesterol burden (CB) allows to estimate the lifelong exposure to high levels of cholesterol. The aim of this study was to analyze the distribution of subclinical atherosclerosis and the relationship between atherosclerosis and the CB in a sample of HeFH patients, focusing on sex-related differences.METHODS AND RESULTS:154 asymptomatic HeFH subjects underwent coronary-artery-calcium score (CACs) and Doppler ultrasound of carotid and femoral arteries. Yearly lipid pro…

Chronic constipation and food intolerance: A model of proctitis causing constipation

2005

OBJECTIVE: Chronic constipation in children can be linked to cow''s milk intolerance (CMI) but the existence of a food intolerance-dependent proctitis is still debated. The aim of this study was to evaluate the histologic data in patients with food intolerance-related constipation. MATERIAL AND METHODS: Fifty-two consecutive patients (22 M, median age 4 years) with chronic constipation unresponsive to common treatment were enrolled. All patients were put on a cow''s milk-free diet for 4 weeks and those uncured on this diet underwent a subsequent 4-week period of oligoantigenic diet. In the patients cured on elimination diet, a subsequent double-blind food challenge was performed to confirm …

Oxidative status in nondiabetic middle-aged subjects with metabolic syndrome: preliminary data.

2013

Statin utilization and lipid goal attainment in high or very-high cardiovascular risk patients: insights from Italian general practice

2018

Background and aims: Statin utilization and lipid goal achievement were estimated in a large sample of Italian patients at high/very-high cardiovascular (CV) risk. Methods: Patients aged ≥18 years with a valid low-density lipoprotein cholesterol (LDL-C) measurement in 2015 were selected from the IMS Health Real World Data database; non-high-density lipoprotein cholesterol (non-HDL-C) was assessed in those with available total cholesterol measurements. Index dates were defined as the last valid lipid measurement in 2015. Patients were hierarchically classified into mutually exclusive risk categories: heterozygous familial hypercholesterolemia (primary and secondary prevention), atheroscler…

Diagnostic Accuracy of Fecal Calprotectin Assay in Distinguishing Organic Causes of Chronic Diarrhea from Irritable Bowel Syndrome: A Prospective Stu…

2003

AbstractBackground: Fecal calprotectin (FC) has been proposed as a marker of inflammatory bowel disease (IBD), but few studies have evaluated its usefulness in patients with chronic diarrhea of various causes. We evaluated the diagnostic accuracy of a FC assay in identifying “organic” causes of chronic diarrhea in consecutive adults and children.Methods: We consecutively enrolled 70 adult patients (30 males, 40 females; median age, 35 years) and 50 children (20 males, 30 females; median age, 3.5 years) with chronic diarrhea of unknown origin. All patients underwent a complete work-up to identify the causes of chronic diarrhea. FC was measured by ELISA.Results: In adult patients, FC showed 6…

P233 Efficacité comparative de ézétimibe/simvastatine 10/20 mg et de rosuvastatine 10 mg chez des patients à haut risque en fonction de la présence o…

2010

Introduction L'objectif de cette analyse pos-hoc a ete de comparer l'efficacite de deux traitements (ezetimibe/simvastatine 10/20 mg et rosuvastatine 10 mg) chez des patients a haut risque cardiovasculaire non a l'objectif LDL-cholesterol (LDL-C) sous statine avec ou sans diabete de type 2 (DT2) d'une part et avec ou sans syndrome metabolique (definition NCEP ATP III) d'autre part. Patients et Methodes 618 patients a haut risque avec LDL-C ≥ 1,0 g/l et ≤ 1,6 g/l malgre un traitement par statine ont ete randomises en double-aveugle et traites pendant 6 semaines soit par ezetimibe/simvastatine 10/20 mg, soit par rosuvastatine 10 mg. L'efficacite des deux traitements a ete comparee chez les pa…

Autosomal recessive hypercholesterolemia in a Sicilian kindred harboring the 432insA mutation of the ARH gene

2003

Abstract We describe a Sicilian family presenting a recessive form of hypercholesterolemia harboring a mutation of the autosomal recessive hypercholesterolemia (ARH) gene. In two of the three sibs, a 26-year-old male and a 22-year-old female, a severe hypercholesterolemia was diagnosed with very high levels of plasma cholesterol (15.9 and 12.2 mmol/l, respectively); tendon xanthomatas and xanthelasms were present and in the male proband was documented a diffuse coronary atherosclerotic disease with a rapid and fatal progression. Both the parents had normal or slightly increased levels of plasma cholesterol. All causes of secondary hypercholesterolemia were ruled out as well as an involvemen…

Plasma non-cholesterol sterols: a useful diagnostic tool in pediatric hypercholesterolemia.

2010

Current guidelines strongly recommend the identification of genetic forms of hypercholesterolemia (HC) during childhood. The usefulness of non–cholesterol sterols (NCS) in the diagnosis of genetic HC has not been fully explored. Plasma NCS were measured by gas chromatography/mass spectrometry (GC/MS) in 113 children with hypercholesterolemia affected by: autosomal dominant hypercholesterolemia (ADH), familial combined hyperlipidemia (FCHL), polygenic hypercholesterolemia (PHC), and in 79 controls to evaluate: i) plasma NCS profile in different genetic HC and ii) the usefulness of NCS for the diagnosis of HC beyond current clinical criteria. ADH was characterized by raised lathosterol/total …

Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project.

2002

Knowledge of alimentary habits among populations permits a better definition of appropriate public health interventions. We designed the epidemiological project "Ventimiglia di Sicilia" to characterize the risk profile in a rural village with low total cholesterol levels and low early cardiovascular mortality but with a large prevalence of overweight and obesity, which previously have been significantly associated with total mortality.488 individuals of age 20 to 69 years were included in the dietary survey conducted by a seven-day food record.Alimentary habits were characterized by high consumption of total and complex carbohydrates (respectively 52.5 +/- 7.6% and 46.6 +/- 8.2% of daily en…

Efficacy of Long-Term Treatment of Autosomal Recessive Hypercholesterolemia With Lomitapide: A Subanalysis of the Pan-European Lomitapide Study

2022

Backgroundand aim: Autosomal recessive hypercholesterolemia (ARH) is a rare autosomal recessive disorder of low-density lipoprotein (LDL) metabolism caused by pathogenic variants in the LDLRAP1 gene. Like homozygous familial hypercholesterolemia, ARH is resistant to conventional LDL-lowering medications and causes a high risk of atherosclerotic cardiovascular diseases (ASCVDs) and aortic valve stenosis. Lomitapide is emerging as an efficacious therapy in classical HoFH, but few data are available for ARH.Results: This is a subanalysis carried out on nine ARH patients included in the Pan-European Lomitapide Study. The age at starting lomitapide was 46 (interquartile range (IQR), 39.0–65.5) y…

Diet and Gallstones in Women of a Rural Town of Sicily

1997

To test the possible association between dietary factors and gallstones, we performed a case-control study on the dietary habits of 71 women with gallstones in a rural area of Sicily (mean age 63.2 years) and compared these with 142 women who did not have gallstones (mean age 63.6 years) selected at random from the same general population. The dietary questionnaire, based on data collected over 7 days, was carefully compiled by two dieticians specially trained for the study. The daily calorie intake was higher in the women with gallstones ( p= 0.006) and was equally distributed between fats, carbohydrates and proteins. The intakes of unsaturated fats ( p= 0.03), unrefined sugars ( p= 0.01) …

MOLECULAR CHARACTERIZATION OF PATIENTS WITH AND WITHOUT CORONARY ARTERY DISEASE WITH "EXTREME LDL-C PHENOTYPES"

2020

Efficacy of Lomitapide in the Treatment of Familial Homozygous Hypercholesterolemia: Results of a Real-World Clinical Experience in Italy

2017

Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lomitapide in HoFH patients followed with the usual clinical care. Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lo…

PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.

2019

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradatio…

Transient chylomicronemia preceding the onset of insulin-dependent diabetes in a young girl with no humoral markers of islet autoimmunity

2004

OBJECTIVE: We investigated the possible causes of diabetes in a young child who presented with hyperglycemia associated with severe hypertriglyceridemia (&gt;166 mmol/l), hypercholesterolemia (&gt;38 mmol/l) and fasting chilomicrons. RESULTS: The patient did not have any of the HLA and autoantibody markers typically associated with type 1 diabetes. A glucose clamp failed to demonstrate insulin resistance (peripheral glucose utilization rate (M)=4.3 mg/kg per min) and there was no family history of type 2 diabetes or maturity onset diabetes in youth. Both fasting and stimulated C-peptide levels, including those in response to i.v. glucagon, were below the limit of detection. This is consiste…

Inverse association between type 2 diabetes and aortic root dimension in hypertensive patients

2017

Background Some data support the concept that aortic root diameter (ARD) in hypertension may be regarded as a marker of subclinical organ damage. The impact of type 2 diabetes mellitus (DM) on cardiac structure and function is known, although the relationship between DM and ARD is not clear. The aim of our study was to evaluate the influence of DM on ARD in hypertensive patients. Methods We enrolled 1693 hypertensive patients (aged 63.7 ± 9.6 years). The population was divided into two groups: the first one with DM (n = 747) and the second one without DM (n = 946). ARD was measured by echocardiography at level of Valsalva's sinuses using echocardiography M-mode tracings. It was considered a…

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

2017

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major…

Switching from statin monotherapy to ezetimibe/simvastatin or rosuvastatin modifies the relationships between apolipoprotein B, LDL cholesterol, and …

2011

OBJECTIVE: To evaluate relationships between apolipoprotein B (Apo B), LDL cholesterol (LDL-C), and non-HDL-C in high-risk patients treated with lipid-lowering therapy. DESIGN AND METHODS: This post-hoc analysis calculated LDL-C and non-HDL-C levels corresponding to an Apo B of 0.9 g/L following treatment with 1) statin monotherapy (baseline) and 2) ezetimibe/simvastatin 10/20mg or rosuvastatin 10mg (study end). The percentages of patients reaching LDL-C, non-HDL-C, and Apo B targets were calculated at study end. RESULTS: After switching to ezetimibe/simvastatin or rosuvastatin, the LDL-C and non-HDL-C corresponding to Apo B=0.9 g/L were closer to the more aggressive LDL-C and non-HDL-C goa…

Novel mutations of CETP gene in Italian subjects with hyeralphalipoproteinemia

2009

Abstract Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that catalyses the transfer of cholesteryl esters from HDL to the other plasma lipoproteins. Genetic deficiency of CETP is one of the known causes of elevation of plasma HDL-C (primary hyperalphalipoproteinemia, HALP). We sequenced CETP gene in a group of 24 Italian subjects with primary HALP (HDL-C>80 mg/dl) suspected to have CETP deficiency. Two unrelated subjects both coming from the same geographical district, were found to be heterozygous for a nucleotide substitution in exon 6 (c.544C>T) and another subject was found to be heterozygous for a C>T transition in exon 9 (c.802C>T). Both mutations introduce a prema…

Replication of linkage of familial hypobetalipoproteinemia to chromosome 3p in six kindreds

2002

Familial hypobetalipoproteinemia (FHBL) is a genetically heterogeneous condition characterized by very low apolipoprotein B (apoB) concentrations in plasma and/or low levels of LDL-cholesterol (LDL-C) with a propensity to developing fatty liver. In a minority of cases, truncation-specifying mutations of the apoB gene (APOB) are etiologic, but the genetic basis of most cases is unknown. We previously reported linkage of FHBL to a 10 cM region on 3p21.1-22 in one kindred. The objectives of the current study were to identify other FHBL families with linkage to 3p and to narrow the FHBL susceptibility region on 3p. Six additional FHBL kindreds unlinked to the APOB region on chromosome 2 were ge…

Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia.

2002

Background and Aim: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH. Methods and Results: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" …

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.

2005

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even…

Effectiveness of cascade filtration plasmapheresis in two patients affected by familial hypercholesterolemia

1995

Hypercholesterolemia has been recognised as a primary risk factor for coronary heart disease. Reduction of plasma levels of total and LDL cholesterol has been shown to decrease coronary atherosclerosis. Plasmapheresis represents an useful non-pharmacological tool to treat severe hypercholesterolemias. We have evaluated the effectiveness of a system of plasmapheresis using a cascade filtration method in two young male subjects (aged 16 and 26 years) with homozygous familial hypercholesterolemia. Both showed severe coronary atherosclerosis as determined by angiography. Procedures were performed at intervals of 7 days in each case. We observed a mean reduction of plasma levels of total cholest…

Italian familial defective apolipoprotein B patients share a unique haplotype with other Caucasian patients.

2001

Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one f…

Therapeutic options for homozygous familial hypercholesterolemia: the role of Lomitapide

2020

Background:Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine.Aims:The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH.Results:The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol …

ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiova…

2017

Atherosclerotic cardiovascular disease still represents the leading cause of death in western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proven effective in improving clinical outcomes. This document is focused on the clinical management of hypercholesterolemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors have considered with particular attention the role of hypercholesterole…

Individual analysis of patients with HoFH participating in a phase 3 trial with lomitapide: The Italian cohort

2015

Abstract Background and aims The efficacy and safety of lomitapide as adjunct treatment for adults with homozygous familial hypercholesterolaemia (HoFH) have been confirmed in a phase 3 trial. Given the small number of patients (N = 29), and variations in patient characteristics, examining individual cases provides additional details regarding patient management with lomitapide. Here, we examine the details of the Italian patient cohort in the phase 3 trial. Methods and results The methodology of the multinational, single-arm, open-label, 78-week, dose-escalation, phase 3 trial has been previously reported. The current report details the Italian cohort of six patients (three males, three fe…

A Novel Loss of Function Mutation of PCSK9 Gene in White Subjects With Low-Plasma Low-Density Lipoprotein Cholesterol

2007

Objectives— The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol. In African-Americans two nonsense mutations resulting in loss of function of PCSK9 are associated with a 30% to 40% reduction of plasma low-density lipoprotein cholesterol. The aim of this study was to assess whether loss of function mutations of PCSK9 were a cause of familial hypobetalipoproteinemia and a determinant of low-plasma low-density lipoprotein cholesterol in whites. Methods and Results— We sequenced PCSK9 gene in 18 familial hypobetalipoproteinemia subjects and i…

Autosomal Recessive Hypercholesterolemia

2018

Abstract Background Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. Objectives Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH. Methods Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol. Results We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years…

Comparison of anti-transglutaminase ELISAs and an anti-endomysial antibody assay in the diagnosis of celiac disease: A prospective study

2002

Abstract Background: Most studies of anti-transglutaminase (anti-tTG) assays have considered preselected groups of patients. This study compared the sensitivity, specificity, and predictive value of an immunofluorescence method for anti-endomysial antibodies (EmAs) and two anti-tTG ELISAs, one using guinea pig tTG (gp-tTG) and the other human tTG (h-tTG) as antigen, in consecutive patients investigated for suspected celiac disease (CD). Methods: We studied 207 consecutive patients (99 men, 108 women; age range, 17–84 years) who underwent intestinal biopsy for suspected CD. Patients presented with one or more of the following: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia,…

Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide

2015

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disease characterised by markedly elevated plasma levels of low-density lipoprotein-cholesterol (LDL-C). Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor approved as an adjunct to other lipid-lowering therapies (LLTs), with or without lipoprotein apheresis (LA), for the treatment of adult HoFH. Diet with &lt;20% calories from fat is required. Due to a varying genetic and phenotypic profile of patients with HoFH, individual patients may respond to therapy differently; therefore examining individual cases in a &apos;real-world&apos; setting provides valuable information on the effective day-to-day manag…

Evaluation of nitric oxide metabolites in a group of subjects with metabolic syndrome.

2012

Abstract Aim To evaluate the concentration of metabolites (NO2−, NO3−) of nitric oxide (NO) in metabolic syndrome (MS). Materials and methods We enrolled 106 subjects (45 women and 61 men) with MS of which 43 (14 women and 27 men) with diabetes mellitus and 63 (31 women and 32 men) without diabetes mellitus, and 54 subjects (19 women and 35 men) as control group. The nitric oxide metabolites (nitrite + nitrate = NOx) were evaluated employing the Griess reagent. Results In the whole group of MS subjects was evident, in comparison with control group, a significant increase in NOx. The same finding was also present between control group and diabetic subjects with MS and between control group a…

Unexplained Elevated Serum Pancreatic Enzymes: A Reason to Suspect Celiac Disease

2006

BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastas…

Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm,…

2013

Summary Background Patients with homozygous familial hypercholesterolaemia respond inadequately to existing drugs. We aimed to assess the efficacy and safety of the microsomal triglyceride transfer protein inhibitor lomitapide in adults with this disease. Methods We did a single-arm, open-label, phase 3 study of lomitapide for treatment of patients with homozygous familial hypercholesterolemia. Current lipid lowering therapy was maintained from 6 weeks before baseline through to at least week 26. Lomitapide dose was escalated on the basis of safety and tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in levels of LDL cholesterol from baseline …

Role of Nutraceuticals in Hypolipidemic Therapy.

2015

Nutraceuticals are food components or active ingredients present in foods and used in therapy. This article analyzes the characteristics of the molecules with a lipid-lowering effect. The different nutraceuticals may have different mechanisms of action: inhibition of cholesterol synthesis primarily through action on the enzyme HMG-CoA reductase (policosanol, polyphenols, garlic and, above all, red yeast rice), increase in LDL receptor activity (berberine), reduction of intestinal cholesterol absorption (garlic, plant sterols, probiotics), and also the ability to interfere with bile metabolism (probiotics, guggul). Based on the different mechanisms of action, some nutraceuticals are then abl…

Corrigendum to "Molecular diagnosis of hypobetalipoproteinemia: An ENID review" [Atherosclerosis 195 (2) (2007) 19-27].

2016

Novel LMF1 nonsense mutation in a patient with severe hypertriglyceridemia

2009

Context: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X).Objective: The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded.Results: The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and recurrent epis…

Behavior of the total antioxidant status in a group of subjects with metabolic syndrome.

2014

AIM: Our purpose was to examine the total antioxidant status (TAS) in subjects with metabolic syndrome (MS) subdivided according to the presence or not of diabetes mellitus. METHODS: We enrolled 106 subjects (45 women, 61 men) with MS subsequently subdivided in diabetics (14 women, 29 men) and nondiabetics (31 women, 29 men). TAS was obtained using an Assay kit which relies on the ability of plasma antioxidant substances to inhibit the oxidation of 2,2'-azino-bis(3-ethylbenzthiazoline sulfonic acid) to the radical ABTS+. RESULTS: In the group of MS subjects a significant decrease in TAS (p<0.05) in comparison with normal controls was evident. This difference was present between normal subje…

Determinants of enhanced thromboxane biosynthesis in renal transplantation

2001

Determinants of enhanced thromboxane biosynthesis in renal transplantation.BackgroundDespite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths.MethodsWe investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant.ResultsThe rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithr…

A novel mutation of the DHCR7 gene in a sicilian compound heterozygote with Smith-Lemli-Opitz Syndrome

2005

Introduction: Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol biosynthesis, resulting from deficient 7-dehydrocholesterol reductase (3β-hydroxysterol Δ7-reductase) activity, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. SLOS is most common among people of European descent, with a reported incidence of 1 per 20 000–60 000 newborns, depending on the diagnostic criteria and the reference population. More than 80 different mutations have been identified in several hundred patients. In Italy, SLOS appears to be a rare condition, probably because of underdiagnosis. Method: We analyzed by direct sequencing the 7-dehydrocholesterol…

Microsomal triglyceride transfer protein gene mutations in Turkish children: A novel mutation and clinical follow up.

2016

Abetalipoproteinemia (ABL; OMIM 200100) is a rare autosomal recessive disease that affects the absorption of dietary fats and fat soluble vitamins. Here, we describe the clinical and genetic characteristics of three patients with ABL. Two patients (patients 1 and 2) who were carriers of the c.398-399delAA mutation (previously known mutation) had developmental delay and hepatic steatosis developed at the age of five in patient 1. Patient 3 was the carrier of a novel mutation (g.10886-10902delAAGgtaagtttgtgttg in intron 3 and c.506A>T exon 5) in microsomal triglyceride transfer protein (MTP) gene and had hepatic steatosis.

Dietary cholic acid lowers plasma levels of mouse and human apolipoprotein A-I primarily via a transcriptional mechanism

2000

To induce dietary atherosclerosis in mice, high-fat/high-cholesterol (HF) diets are frequently supplemented with cholic acid (CA). This diet produces low plasma levels of high-density lipoprotein (HDL) and high levels of low-density lipoprotein (LDL). However, HF diets without any added CA, which more closely resemble human diets, increase levels of both HDL and LDL, suggesting that CA may be responsible for the lowering of HDL. Our aim was to examine the potential mechanism responsible for the lowering of HDL. Nontransgenic (NTg) C57BL mice and apoA-I-transgenic (apoAI-Tg) mice, with greatly increased basal apoA-I and HDL levels, were used. Mice were fed the following four diets: control (…

Atorvastatin but not pravastatin impairs mitochondrial function in human pancreatic islets and rat β-cells. Direct effect of oxidative stress

2017

AbstractStatins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study …

Lomitapide does not alter PCSK9 and Lp(a) levels in homozygous familial hypercholesterolemia patients: analysis on cytokines and lipid profile

2021

Abstract Lomitapide, a drug for the treatment of homozygous familial hypercholesterolemia patients, reduced total and LDL cholesterol but no significant changes were observed on PCSK9 and Lp(a) plasma levels. Some changes of inflammatory mediators were also observed, including hsCRP, which may suggest an anti-inflammatory effect.

Down regulation of CD11b and CD18 expression in children with hypercholesterolemia: A preliminary report.

2009

BACKGROUND AND AIM: Cell adhesion molecules play an important role in the development of atherosclerosis mediating the attachment of monocytes to the endothelium. The aim of our study was to assess the cell surface expression of CD11b/CD18 integrin on the phagocytes of children affected by hypercholesterolemia. METHODS AND RESULTS: Twenty-six children with hypercholesterolemia (15 males, mean age 8.3, range 2-18) with a family history of early cardiovascular disease, as well as 26 children with normocholesterolemia matched for gender and age (15 males, mean age 8.3) were studied. Cell surface expression of CD11b/CD18 on peripheral blood mononuclear cells (PBMC) were analyzed by flow cytomet…

Plasma lipid, apolipoprotein and Lp(a) levels in elderly normolipidemic women: Relationships with coronary heart disease and longevity

1995

The relation between plasma lipids and coronary heart disease (CHD) in the elderly is still debated, as well as the proposed role of lipoproteins as markers of longevity. In this study both normolipidemic elderly and middle-aged women with CHD showed higher triglycerides and apolipoprotein B levels and lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels in comparison with age-matched subjects without CHD. In the middle-aged group, hypertension and HDL-cholesterol levels and, in the elderly group, only HDL-cholesterol levels were independently associated with CHD. No significant difference was found between a group of healthy centenarians and elderly and middle-age…

Effect of the -420C/G variant of the resistin gene promoter on metabolic syndrome, obesity, myocardial infarction and kidney dysfunction.

2007

. Objective.  Resistin is an adipokine that has been suggested to be correlated with markers of inflammation and to be predictive of coronary atherosclerosis and type II diabetes in humans. A common single nucleotide polymorphism (SNP) (−420C/G) in the promoter of resistin is associated with increased resistin plasma levels and susceptibility to type II diabetes. The aim of this study was to investigate the association of the -420C/G polymorphism with metabolic syndrome, obesity, myocardial infarction and kidney disease. Design and results.  First we studied 1542 subjects from the PLIC study (a population based cohort). GG carriers showed an higher prevalence of obesity and metabolic syndro…

Low-density lipoproteins generated during an oral fat load in mild hypertriglyceridemic and healthy subjects are smaller, denser, and have an increas…

2005

Triglyceride-rich lipoproteins generated during the postprandial phase are atherogenic. Large very low-density lipoproteins (LDLs) or chylomicrons (CMs) are not as atherogenic as their remnants (Rem). Small and dense LDLs are associated with cardiovascular disease. Low-density lipoprotein size is partly under genetic control and is considered as a relatively stable LDL feature. In this article, we present data on retinyl palmitate kinetics correlated with the modification of LDL features in terms of size, density, and in vitro receptor binding affinity after an oral fat load. Six nondiabetic, hypertriglyceridemic (HTG) patients and 6 healthy controls were examined. Low-density lipoprotein s…

Apolipoprotein profile in type II diabetic patients with and without coronary heart disease.

1990

Diabetes mellitus is frequently associated with lipid metabolism abnormalities. In the present study the lipid and apolipoprotein profiles have been compared in type II diabetic subjects with (n = 30) and without (n = 30) coronary heart disease (CHD). All subjects were studied after good metabolic control had been achieved. Significant differences in plasma lipids and apolipoproteins were seen in diabetic patients with CHD in comparison with diabetics without CHD. Patients with CHD presented higher total cholesterol, triglyceride, LDL-cholesterol, apo B, apo CII and apo CIII levels and total cholesterol/HDL-cholesterol and LDL-cholesterol HDL-cholesterol ratios and lower HDL-cholesterol val…

Lack of Correlation of Plasma HDL With Fecal Cholesterol and Plasma Cholesterol Efflux Capacity Suggests Importance of HDL Functionality in Attenuati…

2018

A number of clinical findings suggested HDL-raising as a plausible approach to treat residual risk of CVD. However, lack of CVD risk reduction by elevated HDL cholesterol (HDL-C) through cholesterol ester transfer protein (CETP) inhibition and enhanced risk reduction in apolipoprotein A-I Milano (apoAI-M) individuals with low HDL-C shifted the focus from HDL-C level to HDL function. In the present study, we investigated correlations between HDL-C, HDL function, fecal cholesterol excretion, and ex vivo plasma cholesterol efflux capacity (CEC) in animal models using two HDL modulators, LXR and PPAR-α agonists. In C57Bl mice, LXR agonist, T1317, raised HDL-C by 30%, while PPAR-α agonist, fenof…

Prevalence of biliary lithiasis in the elderly people of a small town in Sicily

1992

The aim of the present study was to determine the prevalence of biliary lithiasis (BL) and its major associated factors in the elderly people of a small town in Sicily. All inhabitants over the age of 65 were interviewed and underwent a general physical examination, blood tests and ultrasonography of the gallbladder and biliary tracts. The final group included 328 subjects (162 men and 166 women), representing 63.1% of the population asked to participate, with a mean age of 74.3 +/- 6.8 years (range 65-95). The prevalence of BL (lithiasis in progress + subjects cholecystectomized for previous calculosis) was 18.6%. No male subject had been cholecystectomized. Prevalence was higher in women …

We-P11:264 Use of stents with sirolimus is significantly associated with a reduction in mortality and cardiovascular morbidity at 6- and 12-months po…

2006

C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery d…

2009

Abstract Objectives One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. Design and methods Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. Re…

Lack of phenotypic additive effect of familial defective apolipoprotein B3531 in familial hypercholesterolaemia.

2020

Familial defective apolipoprotein (apo) B (FDB) and familial hypercholesterolaemia (FH) are the two common genetic conditions that cause hypercholesterolaemia. R3531C mutation of the APOB gene is a rare cause of FDB. Individuals with both FDB and FH are rare. A 51-year-old man with hypercholesterolaemia (11.4 mmol/L) and his family were studied. Low-density lipoprotein (LDL) receptor (LDLR) and APOB genes were analysed by direct sequencing. LDL of four subjects were studied in a fibroblast LDL receptor-binding displacement assay. We found a mutation of the LDLR gene (p.Y398X) in the proband and in four other family members: the p.R3531C APOB gene mutation was also found in the proband, his …

An irregular atrial tachycardia : What is the underlying mechanism?

2017

Under-prescription of statins in patients with non-alcoholic fatty liver disease

2017

Abstract Background and Aim Non-alcoholic fatty liver disease (NAFLD) is a common disease associated with high cardiovascular risk. Management of dyslipidaemia plays a pivotal role in the prevention of CV events and statins have proved to be safe in these patients. However, in everyday clinical practice statin prescription is sometimes limited because of the concern of physicians about side-effects. The aim of the study was to investigate if the presence of NAFLD affects the prescription of lipid-lowering treatment in a large series of patients with cardio-metabolic disorders. Methods and Results Cardiovascular risk and LDL-C targets were defined according to ESC/EAS Guidelines in 605 conse…

Variable phenotypic expression of chylomicron retention disease in a kindred carrying a mutation of the Sara2 gene

2010

Chylomicron retention disease is a recessive inherited disorder characterized by fat malabsorption and steatorrhea and is associated with failure to thrive in infancy. We describe a kindred carrying a mutation of Sara2 gene causing a chylomicron retention phenotype. The proband was a 5-month-old baby, born of consanguineous, apparently healthy parents from Morocco, with failure to thrive. There was a large quantity of fats in feces and malabsorption of fat-soluble vitamins. Intestinal biopsies showed a diffused enterocyte vacuolization with large cytosolic lipid droplets. Chylomicron retention disease or Anderson disease was hypothesized, and the Sara2 gene was analyzed by direct sequencing…

Liver and Statins: A Critical Appraisal of the Evidence.

2019

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatoto…

Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an "FCS score".

2018

Familial chylomicronaemia syndrome (FCS) is a rare, inherited disorder characterised by impaired clearance of triglyceride (TG)-rich lipoproteins from plasma, leading to severe hypertriglyceridaemia (HTG) and a markedly increased risk of acute pancreatitis. It is due to the lack of lipoprotein lipase (LPL) function, resulting from recessive loss of function mutations in the genes coding LPL or its modulators. A large overlap in the phenotype between FCS and multifactorial chylomicronaemia syndrome (MCS) contributes to the inconsistency in how patients are diagnosed and managed worldwide, whereas the incidence of acute hypertriglyceridaemic pancreatitis is more frequent in FCS. A panel of Eu…

Estrogen up-regulates apolipoprotein E (ApoE) gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor alpha-mediate…

1998

The antiatherogenic property of estrogens is mediated via at least two mechanisms: first by affecting plasma lipoprotein profiles, and second by affecting the components of the vessel wall. Raising plasma apolipoprotein E (apoE) in mice protects them against diet-induced atherosclerosis (Shimano, H., Yamada, N., Katsuki, M., Gotoda, T., Harada, K., Murase, T., Fukuzawa, C., Takaku, F., and Yazaka, Y. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 1750-1754). It is possible that estrogen may be antiatherogenic at least in part by increasing plasma apoE levels. Therefore, we studied the regulation of apoE by estrogen. A survey of 15 inbred strains of mice showed that some mouse strains responded …

The ANP Genetic Variant RS5068 is Associated With a Favorable Cardiometabolic Phenotype in a Mediterranean Population

2012

Introduction: Atrial natriuretic peptide (ANP) possesses cardiorenal protective properties including natriuresis, aldosterone suppression and vasodilation. Importantly, ANP also exerts lipolytic effects in vitro and in vivo. Previous studies reported that the ANP genetic variant rs5068 is associated with increased plasma levels of ANP, lower blood pressure values, and reduced risk of hypertension. We recently reported that in a random sample of the general population from Olmsted County, MN the G allele of rs5068 was associated with increased levels of ANP, lower blood pressure and BMI, waist circumference, reduced prevalence of obesity and metabolic syndrome. To date, these associations ha…

Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart diseas…

2013

AIMS: The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).METHODS AND RESULTS: Of the theoretical estimated prevalence of 1/500 for heterozygous FH, &lt;1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prev…