RESUMO
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 hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]. CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits.
Assuntos
Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Neoplasias/epidemiologia , Obesidade/epidemiologia , Idoso , Área Sob a Curva , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Distribuição de Qui-Quadrado , Dieta Saudável , Dieta Mediterrânea , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Resistência à Insulina , Itália/epidemiologia , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Obesidade/diagnóstico , Prevalência , Modelos de Riscos Proporcionais , Fatores de Proteção , Curva ROC , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Lomitapide reduces low-density lipoprotein-cholesterol (LDL-C) but also high-density lipoprotein-cholesterol (HDL-C) levels. The latter may reduce the clinical efficacy of lomitapide. We investigated the effect of lomitapide on HDL-C levels and on cholesterol efflux capacity (CEC) of HDL in patients with homozygous familial hypercholesterolemia (HoFH). METHODS AND RESULTS: Four HoFH patients were treated with increasing dosages of lomitapide. Lomitapide decreased LDL-C (range -34 to -89%). Total HDL-C levels decreased (range -16 to -34%) with a shift to buoyant HDL. ABCA1-mediated CEC decreased in all patients (range -39 to -99%). The changes of total, ABCG1- and SR-BI-mediated CEC were less consistent. CONCLUSION: Lomitapide decreased LDL-C and HDL-C levels. Our report raises the hypothesis that the anti-atherogenic potential of HDL seems to be unaffected as total CEC did not seem to change consistently. Combined with the reduction of atherogenic lipoproteins, the net effect of lomitapide appears to be beneficial in HoFH patients.
Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Benzimidazóis/farmacologia , Lipoproteínas HDL/sangue , Lipoproteínas HDL/efeitos dos fármacos , Adulto , Aterosclerose , Colesterol/metabolismo , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Masculino , Fenótipo , Resultado do Tratamento , Adulto JovemRESUMO
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 females) based on individual patient data, individual patient histories and narratives, and by mean data ± SD. Lomitapide was administered according to the dose-escalation protocol. At Week 78, concentrations of low-density lipoprotein-cholesterol were decreased by a mean of 42.6 ± 21.8% compared with baseline. Lomitapide was similarly well tolerated in the Italian cohort as in the entire study population. The most common adverse events were gastrointestinal symptoms. One patient showed an increase in liver transaminases >5× upper limit of normal that resolved after lomitapide treatment was reduced and maintained at a lower dose. CONCLUSION: The efficacy, safety and tolerability of lomitapide demonstrated in the Italian subgroup of patients are consistent with findings in the entire study population, and illustrate the broad applicability of lomitapide therapy across genotypes and clinical phenotypes. These data also provide an insight into the management of lomitapide use in a cohort of patients within a clinical trial protocol. Clinicaltrials.gov Identifier: NCT00730236.
Assuntos
Anticolesterolemiantes/uso terapêutico , Benzimidazóis/uso terapêutico , Heterozigoto , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Mutação , Receptores de LDL/genética , Adolescente , Adulto , Anticolesterolemiantes/efeitos adversos , Benzimidazóis/efeitos adversos , Biomarcadores/sangue , LDL-Colesterol/sangue , Feminino , Predisposição Genética para Doença , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/genética , Itália , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
To study the mechanism of low levels of full length and truncated apoB in individuals heterozygous for apoB truncation, a non-sense mutation was introduced in one of the three alleles of apob gene of HepG2 cells by homologous recombination. Despite very low levels of apoB-82 (1-2%) in the media, a prominent N-terminal apoB protein of 85 kDa (apoB-15) was secreted that fractionated at d>1.065 in density gradient ultracentrifugation. The mechanism of production of this short protein was studied by (35)S-methionine pulse-chase experiment. Oleate prevented presecretory degradation of apoB-100 in the cell and resulted in increased secretion of newly synthesized apoB-100 with decreases in the apoB-15, suggesting that rescue of pre-secretary intracellular degradation of apoB restricted the production and secretion of apoB-15. Further investigation on the degradation of transmembrane forms of apoB, in the presence and absence of a cysteine protease inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN), showed appearance of detectable levels of newly synthesized apoB-82 in the cell and the media together with increased apoB-100 secretion, and reduction in the secretion of apoB-15. Compared to ER membrane, the levels of apoB were higher in the luminal content, and presence of both oleate and ALLN had additive effect on apoB secretion. These results suggest that the presence of improper folding of apoB during translocation led to the cleavage of both apoB-100 and apoB-82 by ALLN-sensitive protease and generation of 85 kDa N-terminal fragment of apoB.
Assuntos
Apolipoproteínas B/metabolismo , Cisteína Proteases/metabolismo , Hipobetalipoproteinemia Familiar por Apolipoproteína B/metabolismo , Apolipoproteínas B/química , Apolipoproteínas B/genética , Códon sem Sentido , Inibidores de Cisteína Proteinase/farmacologia , Células Hep G2 , Humanos , Hipobetalipoproteinemia Familiar por Apolipoproteína B/genética , Leupeptinas/farmacologia , Dobramento de Proteína , Transporte ProteicoRESUMO
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 rate increased to 0.029 using a 90th percentile criteria for fasting blood glucose instead of >100mg/dL. Using the criteria issued by the International Diabetes Federation the MS prevalence rate dropped to 0.005. The exploratory factor analysis identified four factors: age/fat related, lipids, blood pressure and blood glucose. Family history of type 2 diabetes mellitus was associated with triglyceride [OR=1.55 (1.0-2.3)] and BMI [OR=1.71 (1.2-2.4)] but not to blood glucose by logistic regression analysis. CONCLUSIONS: In a student cohort from Southern Italy, obesity is associated with the features of MS.
Assuntos
Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Estudantes/estatística & dados numéricos , Adolescente , Doenças Cardiovasculares/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Masculino , Sobrepeso/epidemiologia , Prevalência , Fatores de RiscoRESUMO
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 cytometry. The geometric mean percentages of CD11b and CD18 expression were significantly lower in the hypercholesterolemic group [52 (95% confidence intervals, 40-68) and 88 (84-93)] than in the control group [87 (83-91), P<0.0001 and 93 (89-96), P<0.05], respectively. After correction for age, gender, and pubertal status, CD11b cell surface expression on PBMC was inversely and independently correlated with total cholesterol concentrations (r=-0.395; P<0.01) and LDL (r=-0.307; P<0.05), as well as with triglycerides (r=-0.406; P<0.01). CONCLUSIONS: In children with hypercholesterolemia, cell surface expression of CD11b and CD18 on PBMC was significantly decreased. Follow-up studies are necessary to determine the clinical implications of these findings in the context of the natural course and progression of atherosclerosis in high risk children.
Assuntos
Antígeno CD11b/sangue , Antígenos CD18/sangue , Hipercolesterolemia/imunologia , Fagócitos/imunologia , Adolescente , Aterosclerose/sangue , Aterosclerose/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Regulação para Baixo , Feminino , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/complicações , Lipídeos/sangue , Masculino , Projetos PilotoRESUMO
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 19.7% rate (in 10 years). Hypertension (HTN) (hazards ratio=2.1) and diabetes mellitus (DM) (hazards ratio=1.8) were independently associated with CV events. Subjects with both DM and HTN showed a lower survival free of CV events compared to those with DM or HTN. CONCLUSIONS: In a 15-year follow-up of an elderly Mediterranean population free from CV disease, diabetes mellitus and hypertension were related to CV events. The control of risk factors in the elderly needs to be reinforced to achieve better results in terms of CV prevention.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Complicações do Diabetes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/mortalidade , Incidência , Inflamação/sangue , Itália/epidemiologia , Lipídeos/sangue , Masculino , Fatores de Risco , Análise de SobrevidaRESUMO
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 syndrome as well as increased plasma triglycerides levels, BMI, systolic and diastolic blood pressure and cardiovascular risk according to Framingham algorithm (P < 0.05 for all). Next we investigated the presence of the -420C/G resistin polymorphism in a case-control study that included 300 subject with myocardial infarction and 300 age and sex matched controls and then we studied the role of the -420C/G SNP in 88 patients with mild to moderate renal dysfunction. No statistically significant differences in allele frequencies between the PLIC study, the myocardial infarction (MI) cases and the subjects with renal dysfunction were observed. Pro-inflammatory gene expression profiling of peripheral blood mononuclear cells failed to detect any difference between wild type subjects and carriers of the rare allele. CONCLUSION: Our data suggest that the presence of the -420C/G SNP of the resistin gene is associated with increased obesity and metabolic syndrome, although it is not different in subjects at high cardiovascular risk such as patients with myocardial infarction or patients with renal dysfunction compared with controls.
Assuntos
Nefropatias/genética , Síndrome Metabólica/genética , Infarto do Miocárdio/genética , Obesidade/genética , Regiões Promotoras Genéticas/genética , Resistina/genética , Adulto , Idoso , Doença Crônica , Estudos de Coortes , Feminino , Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Nefropatias/sangue , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Obesidade/sangue , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Resistina/biossínteseRESUMO
BACKGROUND: Lipoid proteinosis (LP), also known as Urbach-Wiethe disease, is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LP. OBJECTIVES: We report the molecular analysis of the ECM1 gene in a Sicilian patient with LP in order to extend the mutation spectrum of this genodermatosis. METHODS: We studied a 32-year-old female born from consanguineous parents who was diagnosed at the age of 11 years as having LP. She has a clinical phenotype corresponding to Urbach-Wiethe disease characterized by papules/nodules, indurated plaques and sometimes ulcerated lesions primarily involving the skin and mucous membranes, and extracutaneous features such as epilepsy, hoarseness of the voice and neuropsychiatric abnormalities. Samples of clinically affected skin obtained by biopsies were analysed after staining with haematoxylin and eosin, periodic acid-Schiff (PAS), and PAS-diastase. The whole ECM1 gene was analysed by direct sequencing. RESULTS: We identified a homozygous nonsense mutation in exon 6 of the ECM1 gene, C589T (Q197Ter). CONCLUSIONS: Over 60% of mutations occur in exons 6 and 7. Exon 7 is alternatively spliced and frameshift mutations in exon 7 lead to ablation of the ECM1a transcript, but not the shorter ECM1b transcript that normally lacks this exon. Homozygous nonsense or frameshift mutations in exon 6 are predicted to affect both full-length ECM1a and ECM1b transcripts, whereas ECM1b should be unaffected for similar types of mutation in exon 7. It has been suggested that individuals with mutations in exon 7 have a slightly milder phenotype than those with exon 6 mutations. This is the first report with respect to a novel mutation of the ECM1 gene responsible for recessive LP in Sicily.
Assuntos
Códon sem Sentido , Proteínas da Matriz Extracelular/genética , Proteinose Lipoide de Urbach e Wiethe/genética , Dermatopatias Genéticas/genética , Adulto , Sequência de Bases , Biópsia , Feminino , Humanos , Proteinose Lipoide de Urbach e Wiethe/patologia , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase/métodos , Sicília , Dermatopatias Genéticas/patologiaRESUMO
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 with and acute myocardial infarction 213 healthy controls were included in the study. Genotype frequencies of the C(-260)T polymorphism in the CD14 promoter were determined by polimerase chain reaction and the amplified product was cleaved with HaeIII. The frequency of the T allele was not significantly different in patients compared with controls. In this study we were not able to detect differences of frequency of the allele T (-260) in the promoter of the CD14 receptor gene in survivors of myocardial infarction and controls.
Assuntos
Citosina , Receptores de Lipopolissacarídeos/genética , Infarto do Miocárdio/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Timina , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Valores de Referência , Fatores de Risco , Fumar , Análise de SobrevidaRESUMO
BACKGROUND AND AIMS: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cys112, Cys158). 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 previous myocardial infarction and residual angina, severe carotid atherosclerosis, peripheral arterial vascular disease and arterial hypertension. The other family was identified in Palermo (Sicily, Italy): the proband was an overweight 62-year-old man with a mixed form of hyperlipidemia. The mutation, which was identified by means of Apo E genotyping followed by direct sequencing, co-segregated with the same haplotype in the two families. CONCLUSIONS: The family histories and clinical examinations of these subjects clearly show that the Apo E Arg136-->Ser variant fully expresses a type III phenotype in association with a second allele coding for Apo E2, and only partially in association with a second allele coding for Apo E4.
Assuntos
Apolipoproteínas E/genética , Arteriosclerose/genética , Hiperlipoproteinemia Tipo III/genética , Alelos , Apolipoproteína E2 , Arteriosclerose/etiologia , Sequência de Bases , Feminino , Genótipo , Haplótipos , Humanos , Hiperlipoproteinemia Tipo III/complicações , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Reação em Cadeia da Polimerase , Homologia de SequênciaRESUMO
BACKGROUND: The predominance of small, dense low-density lipoprotein (LDL) particles ('LDL phenotype B') has been associated with a three-fold increased risk of myocardial infarction, but the feasibility of the identification of small, dense LDL as independent predictors of coronary artery disease risk in population studies remains questioned. Design We evaluated the LDL peak particle size and its relation with other established risk factors for coronary heart disease in a group of 156 randomized subjects living on the Mediterranean island of Ustica (71 males and 85 women, range of age 20-69 years), representing approximately 30% of the total population. RESULTS: The prevalence of LDL phenotype B subjects was low (approximately 15% in both men and women) and there was a clear trend for both genders in reducing the LDL peak particle size with age. Moreover, LDL phenotype B subjects had higher BMI values, prevalence of diabetes and plasma triglyceride (TG) levels and lower plasma HDL-C concentrations in comparison with LDL phenotype A individuals; in a multivariate analysis, plasma TG levels were the only variable independently associated with LDL peak particle size. CONCLUSIONS: In this population, which appears to be somewhat protected by premature coronary artery disease, a low prevalence of the LDL pattern B was found in both men and women, and plasma TG could have a key role in regulating the LDL peak particle size. The follow up, still ongoing, will provide useful information on the predictive role of LDL peak particle size on cardiovascular risk, at least in a low-risk population.
Assuntos
Doença das Coronárias/sangue , Lipoproteínas LDL/sangue , Adulto , Idoso , Envelhecimento/sangue , Índice de Massa Corporal , Eletroforese em Gel de Poliacrilamida/métodos , Feminino , Humanos , Lipídeos/sangue , Lipoproteínas LDL/química , Masculino , Ilhas do Mediterrâneo , Pessoa de Meia-Idade , Análise Multivariada , Tamanho da Partícula , Fenótipo , Fatores de Risco , Triglicerídeos/sangueRESUMO
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 involvement of the LDL receptor or apoB genes. Beta-Sitosterol plasma levels were in the normal range. Cultured fibroblasts from skin biopsy from parents and the two probands displayed a normal ability to bind and degrade 125I-LDL. Direct sequencing of ARH gene demonstrated the presence of a 432insA mutation in homozygosis in the two probands; parents were heterozygotes for the same mutation. This mutation is the first report of a mutation of the ARH gene responsible for recessive forms of hypercholesterolemia in Sicily.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Adaptadoras de Transporte Vesicular/genética , Estenose Coronária/genética , Genes Recessivos/genética , Heterozigoto , Hiperlipoproteinemia Tipo II/genética , Mutação Puntual , Adulto , Sequência de Bases , Angiografia Coronária , Estenose Coronária/complicações , Estenose Coronária/diagnóstico por imagem , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Masculino , Dados de Sequência Molecular , Linhagem , RNA Mensageiro/análise , Medição de Risco , Irmãos , Sicília , Resultado do TratamentoRESUMO
The aim of the Epidemiological project "Ventimiglia di Sicilia" is to identify the cardiovascular risk factors in a Sicilian population with a low risk profile and healthy nutritional habits. The risk of cardiovascular mortality in older subjects (over 60 years of age) is presented for an 11 year follow-up. Females showed higher prevalence of diabetes mellitus, hypertension, obesity and higher levels of total, LDL and HDL cholesterol, factor VII activity and fibrinogen compared to males. Cardiovascular mortality was related to hypertension and obesity in males, to high factor VII activity, obesity and diabetes mellitus in females. In a Logistic Regression model the same variables were independently correlated to cardiovascular mortality with the exception of obesity. In conclusion, these findings suggest that in a population with a low risk profile, other factors, such as factor VII activity, may emerge as predictors of cardiovascular mortality.
Assuntos
Doenças Cardiovasculares/mortalidade , Fator VII/análise , Adulto , Fatores Etários , Idoso , Doenças Cardiovasculares/sangue , Estudos de Coortes , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Hipercolesterolemia/epidemiologia , Hiperlipoproteinemia Tipo II/epidemiologia , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Risco , Fatores de Risco , Fatores Sexuais , Sicília/epidemiologia , Fumar/epidemiologiaRESUMO
BACKGROUND AND AIM: The populations of the Mediterranean area have a low incidence of cardiovascular disease (CHD). The aims of this paper are: 1) to present demographic data of the population of Ustica, a small island in the southern part of the Tyrrhenian sea that has reduced communications with the mainland and a diet presumably rich in fish; and 2) to evaluate the distribution of risk factors, plasma lipids, lipoproteins and dyslipidemias in this population. METHODS AND RESULTS: We invited all of the free-living resident population aged more than 14 years (about 800 individuals) to participate in the study; 576 responded, for a participation rate of about 73%. The distribution of cardiovascular risk factors, plasma lipids, lipoproteins and dyslipidemias were evaluated in all of the subjects. More than 60% of the population was out of the normal weight range. Total and low-density lipoprotein cholesterol levels were respectively 207.4 +/- 46.7 and 141.7 +/- 42.4 mg/dL, and similar in males and females. Lipoprotein (a) (Lp[a]) levels presented the classical "skewed" distribution and, among the apolipoprotein(a) isoforms, there was a clear predominance of intermediate-sized kringle IV repeats. Overall, 43% of the subjects had a lipid disorder: the prevalence of hypercholesterolemia was 22.8% (3.2% with severe hypercholesterolemia terolemia > or = 300 mg/dL); low high-density lipoprotein cholesterol levels were found in 22.5%; the so-called lipid triad in 2.1%; and high Lp(a) levels in 6.2%. Large familial clusters were found for some lipid disorders. CONCLUSIONS: A large prevalence of body weight disturbances and high frequency of dyslipidemias are the main characteristics of this population. Ongoing data and future longitudinal studies will better clarify the relative influence of each parameter on CHD risk and total mortality.
Assuntos
Doenças Cardiovasculares/epidemiologia , Hiperlipidemias/epidemiologia , Lipídeos/sangue , Lipoproteínas/sangue , Obesidade/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Dieta Mediterrânea , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/mortalidade , Itália/epidemiologia , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Ilhas do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Fatores de RiscoRESUMO
BACKGROUND AND AIM: Extracranial cerebrovascular atherosclerosis is a common feature of hypercholesterolemia and carotid lesions are good predictors of cardiovascular events in the general population. Factors associated with the carotid damage of hypercholesterolemic patients and their relationships with the occurrence of clinical events are investigated in this study. METHODS AND RESULTS: One hundred and seventeen cardiovascular event-free hypercholesterolemic subjects underwent a complete clinical examination to look for additional risk factors. A blood sample was collected for lipoprotein determination and an ultrasound high resolution B-mode imaging examination of the common carotid arteries was performed. Patients were treated according to the current guidelines during a 4-yr follow-up and all major cardiovascular events were recorded. The prevalence of subjects with increased intima-media thickness and plaque was 21.4% and 29.9% respectively, higher than in normolipidemic controls. Carotid lesions were significantly related to age, hypertension and LDL-cholesterol and HDL-cholesterol levels. The relative risk of developing a major clinical event was 3.92 (95% CI 1.54-9.95, p < 0.004) among categories of carotid status. At multivariate analysis, cardiovascular events were independently related to the diagnosis of familial hypercolesterolemia (FH), baseline carotid score and mean levels of LDL-cholesterol and HDL-cholesterol during the follow-up. CONCLUSIONS: Common risk factors cooperate with plasma lipoprotein levels in increasing the frequency of carotid lesions of hypercholesterolemic patients. Since such lesions are useful predictors of clinical events, B-mode ultrasound evaluation of the carotids should be routinely included in the management of these patients.
Assuntos
Doenças das Artérias Carótidas/etiologia , Artéria Carótida Primitiva/patologia , Hipercolesterolemia/complicações , Fatores Etários , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/epidemiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Colesterol/sangue , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Triglicerídeos/sangue , UltrassonografiaRESUMO
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 measured. During the follow-up, total and cardiovascular deaths were registered. RESULTS: We found a high overall prevalence of subjects with overweight or obesity (respectively 45.0% and 27.7%), with great differences among classes of age. As expected, body weight and fat distribution were associated with diabetes, hypertension, dyslipidemia and with a worsening of lipid profile. During the follow-up we registered 37 total and 11 cardiovascular deaths. All-cause and cardiovascular mortality risks were, respectively, 1.64 (95% CI 0.65-4.15) and 2.71 (95% CI 0.29-25.26) in subjects with a body mass index (BMI) of 27-29.99 kg/m2 and 2.45 (95% CI 1.03-5.87) and 5.36 (95% CI 1.41-62.01) in subjects with a BMI of > or =30 kg/m2 in comparison with participants with a BMI of <27 kg/m2, and 3.48 (95% CI 1.46-8.30) and 4.55 (95% CI 1.12-18.40) in subjects with a WHR higher than the median in comparison with individuals with a WHR lower than the median. CONCLUSION: The Ventimiglia di Sicilia Study highlights the great importance of overweight and obesity as a public health issue in a rural population and indicates that it is necessary to consider the impact of body weight and fat distribution on both total and CHD mortality.
Assuntos
Doenças Cardiovasculares/mortalidade , Lipídeos/sangue , Obesidade/epidemiologia , Adulto , Idoso , Constituição Corporal , Peso Corporal , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Prevalência , Estudos Prospectivos , Fatores de Risco , População RuralRESUMO
Stroke incidence rates in the Mediterranean area are higher compared to northern European countries. In this study, we present the 8-year prospective data from a small rural Sicilian town. This population, consisting of 1351 subjects (622 males and 729 females), is homogeneous for ethnic background with traditional healthy dietary habits and shows low cholesterol mean levels. We found that the risk of stroke was significantly associated with the record of at least one previous neurological symptom (PNS), such as lack of strength, loss of vision or speech or possible drop attacks, and high hematocrit in males, and to high body mass index (BMI) and waist-hip ratio (WHR), diabetes, hypertension, high leukocyte count in females. We also documented age-related differences: stroke was associated in younger subjects (age<65 years) with diabetes, high BMI, high uric acid levels and in older patients (age>/=65 years) with high WHR, hypertension, diabetes, PNS, leukocyte count and hematocrit above the 95th percentile. Multivariate analysis demonstrated an independent association between stroke and age, diabetes, leukocyte count, hypertension and PNS. In conclusion, in this rural Sicilian population, the incidence rate of stroke is 1.72 cases per 1000/year in the subjects between 40 and 75 years of age. The risk factors associated with stroke are different in younger and older subjects. Leukocyte count, as an expression of an undergoing inflammatory process, may have a relevant role at least in the elderly.
Assuntos
Acidente Vascular Cerebral , Adulto , Fatores Etários , Complicações do Diabetes , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , População Rural , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Despite 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. METHODS: We investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant. RESULTS: The 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-antithrombin (TAT) complexes were significantly higher (P < 0.001) in RTRs compared with controls. Urinary 11-dehydro-TXB2 directly correlated with plasma vWF and cholesterol. We next examined the relative influence of cyclosporine A (CsA) on TXA2 biosynthesis and endothelial activation, comparing a group of RTRs not receiving CsA with an age- and sex-matched group of patients treated with CsA. Urinary excretion of 11-dehydro-TXB2 and plasma levels of vWF were significantly increased in RTRs who received CsA compared with those who did not. After an overall follow-up of 120 months, RTRs who experienced cardiovascular events had a higher frequency of abnormal plasma levels of vWF than patients who remained event free. CONCLUSION: Renal transplantation is associated with in vivo platelet activation highly related to endothelial activation. This is particularly evident in CsA-treated patients. Administration of drugs that are able to reduce or eliminate thromboxane-dependent platelet activation in vivo may be beneficial to reduce the risk of cardiovascular events in RTRs.
Assuntos
Transplante de Rim , Tromboxanos/biossíntese , Adulto , Antitrombina III , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Colesterol/sangue , Ciclosporina/uso terapêutico , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Peptídeo Hidrolases/sangue , Período Pós-Operatório , Valores de Referência , Diálise Renal , Fator de von Willebrand/análiseRESUMO
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 from the Liguria region and two from Sicily, and the haplotype of the apo B gene co-segregating with the mutation. By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The Arg3531Cys mutation was not detected in any proband. In the three new families with Arg3500Gln mutation in the present study and in one previously described in Italy, the mutation was associated with a unique apo B haplotype, which is consistent with data previously reported for Caucasian patients [XbaI-, MspI+, EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49-repeat allele of the 3'-VNTR].