A.B. Cefalù

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

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≥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.

Low‐density‐lipoprotein peak particle size in a Mediterranean population

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.

Lipoprotein (a) Levels in End-Stage Renal Failure and Renal Transplantation

Some previous studies have documented an increase in lipoprotein (a) [Lp(a)] levels in renal diseases. Here, we report data in subjects with end-stage renal failure treated with hemodialysis (HD) or with continuous ambulatory peritoneal dialysis (CAPD) and in renal transplant recipients (RTR), compared with a group of normolipidemic controls (C). Lp(a) levels were significantly increased in HD and CAPD patients in comparison with C, while they were only slightly increased in RTR. Both HD and CAPD patients showed Lp(a) levels higher than in RTR, but no difference was found between the subjects of the two dialysis procedures. The prevalence of Lp(a) levels > 25 mg/dl was significantly higher in HD and CAPD patients, but not in RTR, in comparison with C. Moreover, Lp(a) levels did not change after HD. When patients were divided according to their fasting lipid levels in normolipidemics and hyperlipoproteinemics, no difference was found for Lp(a) levels in any group. Mechanisms underlying the increase in Lp(a) levels in these patients are not known. It is possible to suggest an active role of the kidney in the Lp(a) metabolism or that uremic plasma contains some factors affecting Lp(a) metabolism.

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

Background: 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. Methods: 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. Results: Diet led to a significant reduction in total cholesterol levels by 10%, triglycerides by 6.5%, low-density lipoprotein (LDL)-cholesterol by 10.4% and LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol ratio by 10%, whereas HDL-cholesterol levels remained unchanged. Dividing renal transplant recipients into risk classes according to the National Cholesterol Expert Program guidelines and LDL-cholesterol levels, we observed a progressively increasing reduction in total cholesterol and LDL-cholesterol levels among ‘desirable LDL-cholesterol’, ‘borderline high-risk LDL-cholesterol’ and ‘high-risk LDL-cholesterol’ patients, while HDL-cholesterol levels did not change in any group and the LDL-cholesterol/HDL-cholesterol ratio significantly decreased in ‘borderline high-risk LDL-cholesterol’ and in ‘high-risk LDL-cholesterol’ patients (respectively by 6.8%, p < 0.05, and by 21.1%, p < 0.0001). Reduction in triglyceride levels was statistically significant only in subjects with ‘desirable LDL-cholesterol’ (by 12.3%, p < 0.01). Patients in the ‘desirable LDL-cholesterol’ class increased from 28 (35.9% of total patients) before diet to 45 (57.7% of total patients, p < 0.01), while subjects in the ‘high-risk LDL-cholesterol’ class reduced from 24 (30.8% of total patients) to 8 (10.2% of total patients, p < 0.005). Conclusion: These data suggest the possibility of a nutritional hypolipidemic approach in renal transplant recipients, even if normolipidemic. Dietetic treatment determined an inversion in the typical trend of renal transplant recipients, reducing instead of increasing the number of subjects with hypercholesterolemia, permitting the selection of individual candidates for further pharmacological treatment by carefully evaluating risk/benefit costs.

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

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.

ApoE polymorphism in a small Mediterranean island: Relationships with plasma lipids, lipoproteins and LDL particle size

Polymorphisms of apoE gene are able to modulate lipoprotein metabolism at different steps and to influence LDL-cholesterol (LDL-C) levels and also other lipoproteins features. Population studies documented large differences in the frequency of apoE alleles which could be even related to the prevalence of cardiovascular disease. In this study we evaluated the apoE genotypes and allele frequency in 576 subjects living in a small island in the Tyrrhenian Sea and the relative contribution of apoE polymorphism on plasma lipid and lipoprotein profile, including LDL particle size. We found a cumulative frequency of 0.073, 0.866 and 0.061 for ε2, ε3 and ε4 alleles respectively. Moreover ε3 subjects had only triglyceride levels significantly lower and LDL-C and lipoprotein (a) (Lp(a)) levels higher than ε2 carriers. LDL-particle size was significant smaller in ε2 subjects than both ε3 and ε4 carriers, but the difference disappeared when data were adjusted for triglycerides. In conclusion we have provided further evidence of a low prevalence of ε4 allele in a Mediterranean population which may represent a genetic protective factor of these populations. Environmental factors, such as diet, occurring in this area may have attenuated the influence of this gene on plasma lipoproteins.

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

Abstract.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.

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

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.

Hypertension and diabetes mellitus are associated with cardiovascular events in the elderly without cardiovascular disease. Results of a 15-year follow-up in a Mediterranean population.

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.

A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily.

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.