Association between body mass index, waist circumference, and relative fat mass with the risk of first unprovoked venous thromboembolism.

BACKGROUND AND AIMS: Obesity defined by body mass index (BMI) is independently associated with venous thromboembolism (VTE). Abdominal obesity, defined by waist circumference, is a predictor of cardiovascular events. Recently, relative fat mass (RFM) was proposed as a marker of cardiovascular risk. We assessed the role of three different measures of obesity to predict unprovoked VTE in a longitudinal study. METHODS AND RESULTS: Moli-sani is a prospective cohort study carried out in the general population of the Molise region, Italy. A total of 23,538 individuals (48% men, age 55.4 years) enrolled between 2005 and 2010 were eligible. Patients on anticoagulant treatment were excluded. BMI ≥30 kg/m2 defined obesity, waist circumference >102 cm for men or 88 cm for women defined abdominal obesity, tertiles of RFM were compared. The long-term incidence of first unprovoked VTE during follow-up was assessed. Overall, 29.6% individuals were obese and 44.2% had abdominal obesity. A total of 66 first unprovoked VTE events were diagnosed during a median follow-up of 8.2 years. After multivariable Cox regression analysis, the risk of unprovoked VTE was significantly higher in obese participants (HR 1.89, 95% CI 1.16-3.07) than in participants with BMI <30; in subjects with abdominal obesity than with normal waist circumference (HR 2.19, 1.26-3.81); and in subjects with third vs first RFM tertile index (HR 2.46, 1.15-5.28). The areas under the curves for the models including the three obesity indexes were comparable. CONCLUSIONS: Three indexes of obesity based on BMI, waist circumference or RFM similarly predict first occurrence of unprovoked VTE.

Correction of QRS voltage for body mass index does not improve the prediction of fatal and nonfatal cardiovascular events. The Moli-sani study.

BACKGROUND AND AIMS: The diagnosis of LVH by ECG may particularly difficult in obese individuals. The aim of this study was to prospectively investigate whether the correction for body mass index (BMI) might improve the prognostic significance for cerebro and cardiovascular events of two electrocardiographic (ECG) criteria for left ventricular hypertrophy (LVH) in a large cohort of Italian adults. METHODS AND RESULTS: In 18,330 adults (54 ± 11 years, 55% women) from the Moli-sani cohort, obesity was defined using the ATPIII criteria. The Sokolow-Lyon (SL) and Cornell Voltage (CV) criteria were used for ECG-LVH. In overweight and obese subjects, as compared with normal weight, the prevalence of ECG-LVH by the SL index was lower. During follow-up (median 4.3 yrs), 503 cerebro and cardiovascular events occurred. One standard deviation (1-SD) increment in uncorrected and in BMI-corrected SL index and CV was associated with an increased risk of events (HR 1.12, 95% CI 1.02-1.22 and HR 1.16, 95% CI 1.06-1.26 and HR 1.12, 95% CI 1.03-1.23 and HR 1.17, 95% CI 1.07-1.27, respectively for SL and CV). In obese subjects, 1-SD increment in uncorrected CV and in BMI-corrected CV was not associated to a significant risk of events (HR 1.05, 95% CI 0.910-1.22 and HR 1.08, 95% CI 0.95-1.23 respectively). Uncorrected SL index showed a significant association with events, which was marginally stronger with BMI-corrected SL voltage (HR 1.18, 95% CI 1.02-1.37 and HR 1.17, 95% CI 1.04-1.33 respectively, Akaike information criterion change from 3220 to 3218). CONCLUSIONS: BMI correction of ECG LVH voltage criteria does not significantly improve the prediction of cerebro and cardiovascular events in obese patients in a large cohort at low cardiovascular risk.

Obesity and ECG left ventricular hypertrophy.

AIM: Our aim was to investigate the prevalence and the prognostic significance for fatal and nonfatal cerebrovascular and cardiovascular events of different ECG criteria for left ventricular hypertrophy (LVH) in normal weight, overweight and obese patients in an adult Italian population. METHODS: A total of 18 330 adults (mean age 54 ±â€Š11 years, 55% women, 53% hypertensive patients) were analyzed from the Moli-sani cohort. Obesity was defined using the ATPIII criteria. ECG-LVH was defined according to 2013 ESC-ESH guidelines. RESULTS: The age and sex adjusted prevalence of ECG-LVH did not differ from normal weight patients to class 1-3 obesity patients, when Cornell-voltage criterion was used. In overweight and obese patients, as compared with normal weight patients, a progressively lower prevalence of ECG-LVH was observed when the Sokolow-Lyon index was used, whereas a higher prevalence was shown by using the aVL R-wave voltage (>11 and >5.7 mm) and the Cornell-voltage-QRS duration product. The incidence of cardiovascular events was significantly greater in patients with ECG LVH diagnosis by the Cornell voltage [hazard ratio 1.89, 95% confidence interval (CI) 1.05-3.39] and the Cornell product (hazard ratio 1.87, 95% CI 1.31-2.67). After adjusting for different confounders (age, sex, cigarette, hypertension, hypercholesterolemia, diabetes, income, education, occupational class and physical activity) and for BMI categories, only the Cornell product remained significantly associated with a higher incidence of cardiovascular events (hazard ratio 1.66; 95% CI 1.16-2.38). The predictive significance of different LVH criteria was assessed across BMI categories; after adjusting for confounders, no LVH criteria were significantly associated with an increased risk of cardiovascular events in obese patients; Cornell-product LVH remained an independent predictor of events in normal weight and overweight individuals (hazard ratio 2.63; 95% CI 1.10-6.28 and hazard ratio 2.72; 95% CI 1.52-4.25, respectively). CONCLUSION: Our results confirm that ECG LVH prevalence may differ according to the criteria used across BMI categories in a low cardiovascular risk cohort. The use of different LVH criteria according to BMI categories may improve cardiovascular risk stratification in a general population independently of several confounding factors.

Development of a pilot project on data sharing among partners of the Italian Hub of Population Biobanks (HIBP): association between lipid profile and socio-demographic variables.

The Italian Hub of Population Biobanks (HIBP) includes both ongoing and completed studies that are heterogeneous in both their purpose and in the specimens collected. The heterogeneity in starting conditions makes sharing study data very difficult because of technical, ethical, and collection rights issues that hamper collaboration and synergy. With the aim of overcoming these difficulties and establishing the "proof-of-concept" that sharing studies is achievable among Italian collections, a data-sharing pilot project has been agreed to by HIBP members. Participants agreed to the general methodology and signed a shared Data Transfer Agreement. The biobanks involved were: EURAC (Micros study), CIG (GEHA project), CNESPS (FINE, MATISS, MONICA, OEC1998, ITR (Italian Twin Register), and IPREA studies, and MOLIBANK (Moli-Sani project). Biobank data were uploaded into a common database using a dedicated informatics infrastructure. Demographic data, and anthropometric and hematochemical parameters were shared for each record. Each biobank uploaded into the common database a dataset with a minimum of 1000 subjects, for a total of 5071 records. After a harmonization process, the final dataset included 3882 records. Subjects were grouped into three main geographic areas of Italy (North, Center, and South) and separate analyses were performed for men and women. The 3882 records were analyzed through multivariate logistic regression analysis. Results were expressed as odds ratios with 95% confidence interval. Results show several geographical differences in the lipidemic pattern, mostly regarding cholesterol-HDL, which represents a strong basis for further, deeper sample-based studies. This HIBP pilot study aimed to prove the feasibility of such collaborations and it provides a methodological prototype for future studies based on the participation in the partnership of well-established quality collections.

Relation between pulmonary function and 10-year risk for cardiovascular disease among healthy men and women in Italy: the Moli-sani Project.

BACKGROUND: Pulmonary dysfunction could influence the onset and the evolution of cardiovascular disorders. This study evaluated whether pulmonary dysfunction based on spirometry, plethysmography and carbon monoxide diffusion test is associated with the estimated risk of cardiovascular disease in 10 years. DESIGN: We performed a cross-sectional general population-based cohort study. METHODS: The Moli-sani Project is a population-based cohort study of subjects aged ≥35 years, randomly recruited from the general population in Italy. Cardiovascular risk in 10 years was predicted by the CUORE score which provides an estimate of the probability of a first coronary or cerebrovascular event in the next 10 years, based on a risk equation derived from Italian cohorts. Out of 12,933 subjects with high-quality flow/volume manoeuvre, 8,132 subjects had suitable plethysmography and 3,422 carbon monoxide diffusion (carbon monoxide alveolar diffusion test [DLCO]). RESULTS: In multivariate analyses, reduced pulmonary function expressed by forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and total lung capacity (TLC) were inversely associated with CUORE score both in men and in women, independently of other risk factors such as age, height, smoking habits, total cigarettes exposure (pack-years), pulmonary disease, body mass index, social status and physical activity. In contrast, there was no association between FEV1/FVC ratio, residual volume, DLCO and CUORE risk score. CONCLUSIONS: In both genders from an adult general Italian population, pulmonary function decline is associated with increased cardiovascular risk. These results suggest that pulmonary monitoring could be useful to more accurately predict cardiovascular risk.

Standardized sample preparation phases for a quantitative measurement of plasma peptidome profiling by MALDI-TOF.

A growing body of literature defines MALDI-TOF MS as a technique for studying plasma and serum, thus enabling the detection of proteins, and the generation of reproducible protein profile mass spectra, potentially able to discriminate correctly different biological systems. In this work, the different steps of the pre-analytical phase that may affect the reproducibility of plasma proteome analysis have been carefully considered. The results showed that the method is highly accurate (9.1%) and precise (8.9%) and the calibration curve for the ACTH (18-39), in human plasma, gave a good correlation coefficient (r>0.99 and r(2)>0.98). The limit of detection (LOD) and the limit of quantification (LOQ), relative intensity, were of 0.5 x 10(-)(9)M and 1.0 x 10(-)(9)M respectively. Thus, an assay has been developed for the detection of low-abundant and low molecular weight proteins, from human plasma, aiming at the identification of new potential biomarkers. The method was tested on plasma from patients with a first diagnosis of pelvic mass. Statistical analysis of plasma profile generated a sub-profile of 17 peptides with their relative abundance able to discriminate patients bearing malignant or benign tumors. The sensitivity and specificity were 85.7% and 80.0% respectively.

Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).

This chapter describes the pharmacology of approved parenteral anticoagulants, including the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin factor Xa and other clotting factors. Heparin also binds to cells and other plasma proteins, endowing it with unpredictable pharmacokinetic and pharmacodynamic properties, and can lead to nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and have a lower risk of nonhemorrhagic side effects. LMWHs can be administered once or twice daily by subcutaneous injection, without anticoagulant monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin; therefore, HIT and osteoporosis are unlikely to occur. Fondaparinux has excellent bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without anticoagulant monitoring. Three parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in HIT patients.

-344C/T Variant in the promoter of the aldosterone synthase gene (CYP11B2) is associated with metabolic syndrome in men.

BACKGROUND: The -344C/T variant in the promoter of the aldosterone synthase gene (CYP11B2) has been associated with hypertension and may influence glucose homeostasis and body mass in humans. We assessed the association between this genetic variant and metabolic syndrome in a large sample of European population. METHODS: Eight hundred two male/female couples, recruited in the framework of the IMMIDIET study, a survey on cardiovascular risk in Italy, UK, and Belgium, had standardized measurements of body mass index, waist circumference, blood pressure (BP), serum total and HDL-cholesterol, triglycerides, and glucose and were genotyped for the -344C/T variant of CYP11B2. Metabolic syndrome was defined according to the International Diabetes Federation criteria. RESULTS: The prevalence of the metabolic syndrome was 23.9% in men and 14.0% in women. The C allele of the variant was associated with metabolic syndrome in men (P = .002) but not in women. At logistic regression analysis, the odds ratio of metabolic syndrome increased progressively with the number of copies of the C allele (CT: 1.54, 95% CI from 1.01 to 2.35; CC: 2.25, 95% CI from 1.38 to 3.66) as compared with the TT homozygotes, taken as reference genotype. CONCLUSIONS: The C allele of -344C/T variant of CYP11B2 increases susceptibility to metabolic syndrome in European men, but not in women, suggesting a pleiotropic role for this gene in modulating cardiovascular risk.

Lipid levels and their genetic regulation in patients with familial hypercholesterolemia and familial defective apolipoprotein B-100: the MEDPED Slovakia Project.

We examined, from a cohort of 165 families, 529 individuals for familial hypercholesterolemia (FH). Utilising clinical criteria for diagnosis, we identified 122 patients (n=41 families) as having FH. With PCR testing, 31 individuals (n=12 families) were found to have familial defective Apo B-100 (FDB). From the cohort, 102 normolipidemic (NL) individuals served as a control group. Patients with FH had the highest levels of total cholesterol (TC), LDL-cholesterol (LDL-C) and apolipoprotein B (Apo B), followed by FDB patients and the normolipidemic relatives had the lowest levels (P<0.0001 for all parameters). We did not find any effect of Apo E genotypes on lipid levels in the NL or FH group. Therefore, other genetic and/or environmental factors may be responsible for the diversity in the clinical expression in these populations.

The mediterranean lecture: wine and thrombosis--from epidemiology to physiology and back.

The protective effect of moderate alcohol consumption on the risk of cardiovascular disease has been consistently shown in many epidemiological studies. Antiatherogenic alterations in plasma lipoproteins, particularly increase in high-density lipoprotein (HDL) cholesterol,are considered as the most plausible mechanism of the protective effect of alcohol consumption on coronary artery disease (CHD). Other potential mechanisms contributing to the cardio-protective effects of moderate alcohol consumption include anti-thrombotic down regulation of blood platelet function, as well as of the coagulation and fibrinolysis balance. Since the proposal of a "French paradox" in the early Nineties, the possibility that consuming alcohol in the form of wine might confer a protection against CHD above that expected from its alcohol content, has made the topic"wine and health" increasingly popular. Many epidemiological studies have explored such a possibility, by comparing specific alcoholic beverage types (wine,beer, liqueur) in respect to their relative capacity to reduce the risk of CHD. In parallel, experimental studies have been done, in which wine and wine-derived products have been tested for their capacity to interfere with molecular and cellular mechanisms relevant to the pathogenesis of CHD. Wine might indeed conceivably have other ethanol unrelated beneficial effects. The biological rationale for such a hypothesis has been linked to the enrichment in grape-derived, non-alcoholic components, that possibly make it peculiar in respect to other alcoholic beverages. In fact, while the mechanisms underlying the effects of alcohol on cardiovascular disease have been limited to lipid metabolism and the haemostatic system, those related to wine consumption have also been extended to specific anti-inflammatory, antioxidant and nitric oxide related vaso-relaxant properties of its polyphenolic constituents. The effect of wine consumption has been carefully investigated to account for potential confounding of several conditions (inappropriate use of abstainers as control population, correlation between wine or total alcohol consumption and markers of healthy lifestyle and socioeconomic factors, diet, etc.). Strong evidence indicates that moderate wine consumption rather than confounders reduces both fatal and non fatal CHD events. In spite of the fact that the healthy effect of moderate intake of wine is by now well accepted, important issues remain to be resolved about the relationship between wine, alcohol and alcoholic beverages, the (possibly different) optimal amount of alcohol intake in men and women, the individual or environmental modulation of the alcohol related effect and the pattern of drinking. Some of these issues have been recently addressed in a large meta-analysis, in which the relationship between wine or beer consumption and CHD risk was quantitatively evaluated. We shall summarize here the experimental and epidemiological studies with wine or wine-derived products aimed at finding biological explanations for the supposed superior cardio-protective effects of wine consumption and to discuss some open questions about wine and vascular disease as approached in epidemiological studies.