Mediterranean diet and all-cause mortality: A cohort of Italian men.

BACKGROUND AND AIMS: The present study analyzes the relation between diet and all-cause mortality in a cohort of Italian men residing in different regions of Italy. METHODS AND RESULTS: The cohort was established using the members of the Associazione Nazionale Alpini, a voluntary organization that enlists individuals who have served in the Alpine troup; a mountain warfare infantry corps of the Italian Army. For the purpose of these analyses a total of 5049 participants were followed for an average of seven years. At baseline information was collected regarding age, education, life style habits, with special emphasis on diet (with the use of a validated dietary questionnaire), smoking and alcohol use. A total of 190 deaths were ascertained. In multivariate analyses the consumption of a Mediterranean type diet was inversely associated with mortality. Additional findings of relevance include: an inverse association between mortality and intake of vegetable fats and proteins, monounsaturated (MUFA) fats of vegetable origins, starch and folic acid. Positive association were evident between mortality and intake of animal fats, MUFA of animal origins and sugar. CONCLUSIONS: This study, focusing on a homogenous cohort characterized by a varied intake and high intake of monounsaturated fats, confirms the inverse association between a Mediterranean type diet and mortality and points out that the nature of the MUFA may be relevant for their effects on health. In addition, the study confirms that fats of animal origins and dietary sugar are associated with an overall deleterious effect on mortality.

Corrigendum to "Sequence Analysis of the UCP1 Gene in a Severe Obese Population from Southern Italy".

[This corrects the article DOI: 10.1155/2011/269043.].

Treat-to-target versus dose-adapted statin treatment of cholesterol to reduce cardiovascular risk.

Clinical guidelines should be based on the best available evidence and are of great importance for patient care and disease prevention. In this respect, the 2013 American College of Cardiology/American Heart Association report is highly appreciated and well-recognized. The report included critical questions concerning hypercholesterolaemia, but its translation into a clinical guideline initiated intense debate worldwide because of the recommendation to switch from a treat-to-target approach for low-density-lipoprotein-cholesterol to a statin dose-based strategy.

The FTO gene polymorphism (rs9939609) is associated with metabolic syndrome in morbidly obese subjects from southern Italy.

Gene variants in MC4R, SIRT1 and FTO are associated with severe obesity and metabolic impairment in Caucasians. We investigated whether common variants in these genes are associated with metabolic syndrome (MetS) in a large group of morbidly obese young adults from southern Italy. One thousand morbidly obese subjects (62% women, mean body mass index 46.5 kg/m(2), mean age 32.6 years) whose families had lived in southern Italy for at least 2 generations were recruited. Single-nucleotide polymorphisms (SNPs) rs12970134, rs477181, rs502933 (MC4R locus), rs3818292, rs7069102, rs730821, rs2273773, rs12413112 (SIRT1 locus) and rs1421085, rs9939609, 9930506, 1121980 (FTO locus) were genotyped by Taqman assay; blood parameters were assayed by routine methods; the Fat Mass, Fat Free Mass, Respiratory Quotient, Basal Metabolic Rate (BMR) and waist circumference were also determined. Binomial logistic regression showed that the TA heterozygous genotype of SNP rs9939609 in the FTO gene was associated with the presence of MetS in our population [OR (95% CI): 2.53 (1.16-5.55)]. Furthermore, the FTO rs9939609 genotype accounted for 21.3% of the MetS phenotype together with total cholesterol, BMR and age. Our results extend the knowledge on genotype susceptibility for MetS in relation to a specific geographical area of residence.

Haplogroup T is an obesity risk factor: mitochondrial DNA haplotyping in a morbid obese population from southern Italy.

Mitochondrial DNA (mtDNA) haplogroups have been associated with the expression of mitochondrial-related diseases and with metabolic alterations, but their role has not yet been investigated in morbid obese Caucasian subjects. Therefore, we investigated the association between mitochondrial haplogroups and morbid obesity in patients from southern Italy. The mtDNA D-loop of morbid obese patients (n = 500; BMI > 40 kg/m(2)) and controls (n = 216; BMI < 25 kg/m(2)) was sequenced to determine the mtDNA haplogroups. The T and J haplogroup frequencies were higher and lower, respectively, in obese subjects than in controls. Women bearing haplogroup T or J had twice or half the risk of obesity. Binomial logistic regression analysis showed that haplogroup T and systolic blood pressure are risk factors for a high degree of morbid obesity, namely, BMI > 45 kg/m(2) and in fact together account for 8% of the BMI. In conclusion, our finding that haplogroup T increases the risk of obesity by about two-fold, suggests that, besides nuclear genome variations and environmental factors, the T haplogroup plays a role in morbid obesity in our study population from southern Italy.

Predictors of resistant hypertension in an unselected sample of an adult male population in Italy.

Prevalence, incidence and predictors of resistant hypertension (RH), (defined as blood pressure persistently above goal in spite of the concurrent use of three antihypertensive agents of different classes) in the general population remain largely unknown. A complete database including anthropometric and biochemical data was collected in 1994-1995 (baseline examination) in 1,019 participants (mean age 51.8, range: 25-79 years) and again in 2002-2004 in 794 male participants of the Olivetti Heart Study (OHS) in southern Italy. The incidence of RH over the average follow-up time of 7.9 years was 4.8% (38/794) in the whole study population and 10.1% (31/307) among hypertensive participants. Basal blood pressure (systolic, diastolic or pulse pressure), cholesterol and urinary albumin/creatinine ratio (ACR) significantly predicted the risk of developing RH using a logistic regression model that also included age as covariates. If in the same model we added basal pharmacological treatment, the fractional excretion of sodium (FENa) also became a statistically significant predictor, and this last model explained nearly 25% of the risk of developing RH. In this unselected sample of an adult male population, ACR (an early marker of organ damage), an elevated FENa (a proxy for dietary sodium intake), cholesterol and a higher basal blood pressure level were independent predictors of RH.

Sequence Analysis of the UCP1 Gene in a Severe Obese Population from Southern Italy.

Brown adipose tissue, where Uncoupling Protein 1 (UCP1) activity uncouples mitochondrial respiration, is an important site of facultative energy expenditure. This tissue may normally function to prevent obesity. Our aim was to investigate by sequence analysis the presence of UCP1 gene variations that may be associated with obesity. We studied 100 severe obese adults (BMI > 40 kg/m(2)) and 100 normal-weight control subjects (BMI range = 19-24.9 kg/m(2)). We identified 7 variations in the promoter region, 4 in the intronic region and 4 in the exonic region. Globally, 72% of obese patients bore UCP1 polymorphisms. Among UCP1 variants, g.IVS4-208T>G SNP was associated with obesity (OR: 1.77; 95% CI = 1.26-2.50; P = .001). Further, obese patients bearing the g.-451C>T (CT+TT) or the g.940G>A (GA+AA) genotypes showed a higher BMI than not polymorphic obese patients (P = .008 and P = .043, resp.). In conclusion, UCP1 SNPs could represent "thrifty" factors that promote energy storage in prone subjects.

Associations of selenium status with cardiometabolic risk factors: an 8-year follow-up analysis of the Olivetti Heart study.

OBJECTIVE: High selenium status has been associated with adverse cardiometabolic outcomes in selenium-replete populations such as the US. In populations with lower selenium status such as in Italy, there is little epidemiological evidence about the association of selenium with cardiometabolic risk factors. We therefore examined cross-sectional and prospective relationships of serum selenium concentrations with cardiometabolic risk factors including blood pressure, diabetes and blood lipids in the Olivetti Heart Study. METHODS: The study population consisted of 445 adult male individuals for whom baseline serum selenium measurement and cardiometabolic risk factors at baseline (1994-1995) and follow-up examination (2002-2004: average follow-up=8 years) were available. Serum selenium was measured by atomic absorption spectrophotometry. RESULTS: Average serum selenium concentration at baseline was 77.5 ± 18.4 µg/L. In cross-sectional analyses, serum selenium levels were positively associated with serum total cholesterol (p for trend <0.0001) and prevalent diabetes (p for trend <0.05). In prospective analysis, serum selenium at baseline was likewise a strong predictor of serum total cholesterol (p=0.002) and LDL-cholesterol (p=0.001) at follow-up, after adjustment for age, BMI, cigarette smoking, physical activity, and lipid-lowering medication. These associations, however, were no longer significant after additional adjustment for baseline blood lipids. Selenium at baseline did not predict changes in total cholesterol levels between the baseline and follow-up examinations [ß-coefficient (± SE)= 0.09 ± 0.12 (p=0.46)]. CONCLUSION: These findings corroborate previous cross-sectional associations of high selenium status with adverse blood lipid profile and diabetes. However, prospective analyses do not support the causality of these relations. Randomized and experimental evidence is necessary to clarify the mechanisms underlying the observed cross-sectional associations.

Is the current therapeutic armamentarium in diabetes enough to control the epidemic and its consequences? What are the current shortcomings?

The prevalence of diabetes is expected to rise together with an increase in morbidity and a reduction in life expectancy. A leading cause of death is cardiovascular disease, and hypertension and diabetes are additive risk factors for this complication. Selected treatment options should neither increase cardiovascular risk in patients with diabetes, nor increase risk of hyperglycaemia in patients with hypertension. The efficacy of present antihyperglycaemic agents is limited and new therapies, such as incretin-targeted agents, are under development. Even though most patients do not achieve glycated haemoglobin targets, trial data show that such interventions reduce the incidence of macrovascular events; however, intensive lowering may be detrimental in patients with existing cardiovascular disease. Currently available oral drugs do not address the key driver of type 2 diabetes--loss of functional beta-cell mass. In the future, new oral treatments must improve this, whilst providing durable blood glucose control and long-term tolerability.

Relationships of PAI-1 levels to central obesity and liver steatosis in a sample of adult male population in southern Italy.

To analyse the relationship of PAI-1 plasma levels to echographically determined liver steatosis and cardiometabolic risk factors in a randomly selected sample of 254 adult male participants of the Olivetti Heart Study. Accounting for age and ongoing pharmacological treatment, PAI-1 levels were directly (P < 0.005) associated with body mass index (BMI), waist circumference (WC), serum triglyceride (TG), total cholesterol, insulin, homeostasis model assessment index, gamma-glutamyl transpeptidase and peritoneal fat. At multiple linear regression (MLR) analysis, measures of adiposity and TG exerted significant and quantitatively similar effects on PAI-1 levels. A progressive rise in PAI-1 level was detected with increasing degree of steatosis. A stepwise MLR model was used to evaluate the relative power of cardiometabolic risk factors and liver steatosis on PAI-1 levels. Adjusting for alcohol intake, BMI, WC and peritoneal fat were alternatively included in the model with other variables found to be significantly associated with plasma PAI-1 level. Liver steatosis, serum TG and various indexes of adiposity each had a significant independent impact on PAI-1 plasma level and explained overall 23% of its variability. Abdominal fat, liver steatosis and serum TG levels were significant and independent determinants of PAI-1 plasma level in an unselected sample of adult male population upon adjustment for age and therapy.

Burden of smoking and occupational exposure on etiology of chronic obstructive pulmonary disease in workers of Southern Italy.

OBJECTIVE: This study evaluates the burden of smoking and occupational exposure on chronic obstructive pulmonary disease (COPD). METHODS: Two thousand nineteen workers underwent a diagnostic protocol for COPD at the baseline and after 5 and 10 years. Taking into account individual and occupational exposures the sample was divided in four groups. Prevalence, incidence of COPD, differences among groups, and logistic regression were calculated. RESULTS: Higher COPD prevalence and incidence were observed in the group with combined exposures. Smoking habits and occupational exposure were confirmed as risk factors for COPD and an interaction between smoking and occupational exposure was found. CONCLUSIONS: Workers exposed to both risk factors have to be considered in COPD high-risk class. Smoking cessation programs could play an important role particularly in activities where effects of smoking have a positive interaction with occupational exposure.

Diagnostic criteria for metabolic syndrome: a comparative analysis in an unselected sample of adult male population.

This analysis compares the performance of 7 different diagnostic criteria of metabolic syndrome (MS) with regard to the prevalence of the syndrome, the characteristics of subjects with a positive diagnosis, and the ability to correctly identify individuals at high calculated cardiovascular (CV) risk or with signs of systemic inflammation or early organ damage. The diagnostic criteria proposed by the World Health Organization (1998); European Group for the Study of Insulin Resistance (EGIR) (1999); Adult Treatment Panel III (ATP III) (2001); American Association of Clinical Endocrinologists (AACE) (2003); ATP III (2004); International Diabetes Federation (IDF) (2005); and American Heart Association/National Heart, Lung, and Blood Institute (2005) were applied to the population of 933 men aged 59.5 years (range, 33-81 years) attending the 2002-2004 examination of the Olivetti Heart Study. Standardized measurements were available for body mass index, waist circumference, blood pressure, fasting serum total and high-density lipoprotein cholesterol, triglyceride, glucose, insulin, high-sensitivity C-reactive protein, and microalbuminuria. Insulin resistance was estimated by the homeostasis model assessment index; and CV risk, by the Prospective Cardiovascular Munster algorithm. The MS prevalence ranged from 8.6% (AACE) to 44.5% (IDF). Among MS-positive subjects, insulin resistance ranged from 94.8% (EGIR) to 49.2% (IDF), whereas type 2 diabetes mellitus (excluded by EGIR and AACE criteria) rated 59.9% by World Health Organization and 22% to 24% by ATP III, IDF, or American Heart Association/National Heart, Lung, and Blood Institute. By most criteria, MS-positive subjects had greater calculated CV risk than MS-negative subjects; but in general, the ability to correctly identify individuals at high CV risk was dampened by limited sensitivity (maximum 60%). Lowering the cutoff for abdominal adiposity (waist circumference <94 cm by IDF) did not improve the performance in this regard but identified a larger number of individuals with microalbuminuria (56%) and elevated C-reactive protein (53%).

Circulating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study.

BACKGROUND: Because high circulating plasma leptin is associated with many features of the metabolic syndrome (MS), such as abdominal obesity, insulin resistance and high blood pressure (BP), we analysed the ability of plasma leptin concentration to predict the risk of developing MS in a prospective investigation of adult male participants of the Olivetti Heart Study (OHS). METHODS AND RESULTS: Three hundred and sixty out of 907 men participating in the 1994-95 and 2002-04 OHS examinations (mean age at baseline 50.4 years, range 25-73 years) were free of MS at first visit according to NCEP-ATP III criteria (modified for the lack of high-density lipoprotein cholesterol measurement at baseline). During an average follow-up period of 8 years, there were 52 incident cases of MS (14.5%) due, in particular, to a rise in the prevalence of high BP (+42.4%), abdominal obesity (+16.4%) and impaired fasting glucose (IFG, +6.1%). In multivariate analyses, a one standard deviation difference in baseline plasma leptin concentration was associated with a 1.58-fold greater risk of developing MS (95% confidence interval = 1.10-2.30, P = 0.016) accounting for age, waist circumference, homeostatic assessment model index, smoking, alcohol consumption and physical activity. In particular, plasma leptin was positively associated with the risk of developing high BP (0.006) and IFG (0.014), after adjustment for confounders. CONCLUSION: In this sample of an adult male population free of MS at baseline, circulating plasma leptin was a significant predictor of the risk of MS and, in particular, of its high BP and IFG components, independently of potential confounders.

Incidence of hypertension in individuals with different blood pressure salt-sensitivity: results of a 15-year follow-up study.

OBJECTIVE: To evaluate the incidence of hypertension and the rate of decline in renal function in a sample of 47 Olivetti Heart Study (OHS) participants whose blood pressure (BP) salt-sensitivity and renal tubular sodium handling had been assessed in 1987-88. METHODS: During the 2002-04 OHS follow-up examination, medical history, physical examination and blood and urine sampling were performed in 36 of the 47 participants to the baseline study (age 60 +/- 6 years; average follow-up = 15.1 +/- 0.6 years). The renal length was measured in 23 participants by kidney ultrasonography. Based on the baseline salt-sensitivity evaluation, the subjects were classified into a lower salt-sensitivity (LSS, n = 20) and a higher salt-sensitivity group (HSS, n = 16). RESULTS: In comparison with the LSS group, HSS participants had a significantly higher incidence of hypertension (87.5 versus 50.0%, P = 0.02), a higher glomerular filtration rate (median, first to fourth quartile: 81.9, 72.3-95.2 versus 72.3, 59.9-81.2 ml/min; P = 0.03) and greater kidney length (median, first to fourth quartile: 68.2, 63.3-72.1 versus 61.9, 58.7-62.7 mm/m of height; P = 0.003). The incidence of hypertension remained significantly higher in HSS individuals after adjustment for age, intercurrent changes in body mass index and baseline blood pressure on low sodium diet (P = 0.04). CONCLUSION: Our findings indicate that individuals with higher BP salt-sensitivity have a higher rate of incident hypertension and suggest an altered renal tubular sodium handling involving a trend to increased glomerular filtration rate and blood pressure over time as a possible mechanism.

Bioelectrical impedance analysis and age-related differences of body composition in the elderly.

BACKGROUND AND AIM: Significant changes in body composition that have important health related effects may occur in the elderly. In this study, we evaluated the bioelectrical characteristics in a large group of apparently healthy Caucasian men in the age range 50-80 years, as a function of age and body mass index. METHODS: We studied 315 men with ages ranging from 50 to 80 years. They were divided into three groups according to body mass index (kg/m(2)): 18.5-24.9 normoweight (NW); 25.0-29.9 overweight (OW); > or =30 obese (OB), and they were classified in nine age subgroups: 50-59 (young-old, YO); 60-69 (old, O); 70-80 (oldest, OS). Fat-free mass, fat mass and body cell mass were investigated using conventional bioelectrical impedance analysis. Body composition was also assessed by bioelectrical impedance vector analysis and the RXc graph method. RESULTS: Body cell mass decreased significantly with age particularly in subgroups of the OW and OB groups (p<0.05). Mean vector displacement followed a definite pattern, with downward migration of the ellipses in the OW and OB groups, after 70 years of age. CONCLUSIONS: Ageing was associated with a pattern of vector bioelectrical impedance analysis indicating decreased soft tissue mass (fat-free mass and body cell mass), particularly in OW and OB-OS healthy men. We suggest 70 years of age as a cut-off for significant quantitative and qualitative (tissue electrical properties) body composition modifications. This bioelectrical impedance vector analysis pattern associated with ageing and across the different body mass index categories, may be useful for clinical purposes and can be used in geriatric routine to accurately assess the body composition modifications occurring in the elderly.

Alcohol drinking pattern and subjective health in a population-based study.

AIMS: Some patterns of alcohol consumption (e.g. binge drinking, drinking outside of meals) have been associated with detrimental effects on health outcomes. Subjective health provides a global assessment of health status and is a strong predictor of total mortality; however, little is known about its relationship with alcohol drinking pattern. The association between several drinking patterns (i.e. drinking intensity and frequency, frequency of intoxication, drinking outside of meals, and beverage type) and subjective health was examined in a random sample of 3586 women and men. DESIGN: A population-based cross-sectional study. METHODS: Subjective health was assessed using the physical and mental health component summaries of the Short Form-36 health survey questionnaire. Alcohol consumption refers to the 30 days before the interview. Analysis of covariance compared gender-specific mean scores across alcohol drinking patterns. FINDINGS: Overall, non-current drinkers reported poorer physical and mental health than life-time abstainers and current drinkers, while no consistent differences were found between life-time abstainers and current drinkers. In female current drinkers, daily drinking, beer and mixed beverage consumption were associated with better mental health. In male current drinkers, moderate alcohol consumption (2-2.9 drinks per day), wine and mixed beverage consumption were associated with better physical health. Intoxication and liquor consumption were associated with poorer mental health in women and poorer physical health in men. No consistent associations were found for drinking outside meals. CONCLUSIONS: Aspects of drinking pattern may affect subjective health differentially in women and men. Overall, intoxication and liquor drinking are associated with poorer self-perceived health status than regular, moderate consumption of other alcoholic beverages.

Abnormalities of renal sodium handling in the metabolic syndrome. Results of the Olivetti Heart Study.

OBJECTIVE: The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy. METHODS: Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25-75 years examined in 1994-1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria. RESULTS: FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without [77.6% (95% confidence interval = 76.7-80.1) versus 74.4% (73.7-75.1), P < 0.001]. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants. CONCLUSION: In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.

[Attitudes and behaviors toward cardiological procedures: results from a multicenter study in Italy]. / Atteggiamenti e comportamenti nei confronti degli interventi cardiologici: risultati di uno studio multicentrico in Italia.

BACKGROUND: In Italy, cardiovascular diseases represent an important cause of disability in the elderly. Therefore, it is necessary to provide effective and appropriate diagnostic and therapeutic procedures to all the interested subjects. The aim of our study was to estimate attitudes and behaviors of health personnel and representatives of citizen associations toward the following procedures: thrombolysis, coronary artery bypass, pacemaker implantation, and aortic valve replacement. METHODS: Within an Italian multicenter study on the relation between age and treatment of cardiovascular diseases, a questionnaire was administered to a stratified sample of medical doctors (cardiologists, heart surgeons, geriatrics, internists), general practitioners in order to show any existing discrimination in care access as regards age, sex and race of patients. RESULTS: The sample included 283 subjects (73.8% men, median age 47 years). In 53% age was a discriminating factor in the distribution of the therapeutic procedures, with higher statistically significant percentages reported by geriatrics and internists (62.5 and 58.6%, respectively) and lower ones by cardiologists and heart surgeons (48.2 and 41.5%, respectively) (chi2 = 29.592, p < 0.0001). The influence of the shortest expectancy of life in the elderly is the reason for discrimination in 19.6% of the participants. Race and gender do not represent a discriminating factor for 81 and 92.1% of responders, respectively. CONCLUSIONS: The results of our study highlight the presence of different attitudes among health personnel about the distribution of cardiological procedures as regards patients' age, in particular when > 75 years old. An easier access should be given to these patients and this may represent the objective of research aimed at developing better treatments for elderly people.

Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial.

Despite the documented antioxidant and chemopreventive properties of selenium, studies of selenium intake and supplementation and cardiovascular disease have yielded inconsistent findings. The authors examined the effect of selenium supplementation (200 microg daily) on cardiovascular disease incidence and mortality through the entire blinded phase of the Nutritional Prevention of Cancer Trial (1983-1996) among participants who were free of cardiovascular disease at baseline (randomized to selenium: n = 504; randomized to placebo: n = 500). Selenium supplementation was not significantly associated with any of the cardiovascular disease endpoints during 7.6 years of follow-up (all cardiovascular disease: hazard ratio (HR) = 1.03, 95% confidence interval (CI): 0.78, 1.37; myocardial infarction: HR = 0.94, 95% CI: 0.61, 1.44; stroke: HR = 1.02, 95% CI: 0.63, 1.65; all cardiovascular disease mortality: HR = 1.22, 95% CI: 0.76, 1.95). The lack of significant association with cardiovascular disease endpoints was also confirmed when analyses were further stratified by tertiles of baseline plasma selenium concentrations. These findings indicate no overall effect of selenium supplementation on the primary prevention of cardiovascular disease in this population.