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The relationship between diet and central nervous system (CNS) tumours was almost exclusively focused on food composition. We evaluated the relationship of different degrees of food processing with risk of CNS tumours. The study sample included 44 CNS tumours cases (20 non-malignant and 24 malignant) recruited from the Neurosurgery Department at the IRCCS Neuromed (Italy), and 88 controls matched 1:2 for sex and age± 10 years, identified from the Moli-sani Study. Dietary intake was assessed using a 188-item FFQ. Food items were grouped according to the NOVA classification on the basis of processing as: (1) unprocessed/minimally processed foods; (2) processed culinary ingredients; (3) processed foods; and (4) ultra-processed food (UPF). Conditional logistic regression models were used to estimate odds ratio (OR) and 95% confidence intervals (95%CI) of dietary contributions from each NOVA group (as weight ratio on the total food eaten) and adjusting for potential confounders. Results : In a multivariable conditional to match logistic regression analysis also controlled for overall diet quality, 1% increment in UPF intake was associated with higher odds of all CNS tumours (OR = 1.06; 1.01–1.13), particularly of malignant CNS tumours (OR = 1.11; 1.02–1.22), while no association with non-malignant CNS tumours was found (OR = 1.06; 0.99–1.15). In contrast, only processed food was inversely associated with risk of both CNS tumours overall (OR = 0.94; 0.90–0.98) and of malignant CNS tumours (OR = 0.90; 0.83–0.96). Increasing UPF intake was associated with higher risk of CNS tumours, especially malignant ones, independently of the overall diet quality, while only processed food (but not UPF) was inversely related to the risk of this disease. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EV) represent a population of small vesicles deriving from all types of cells, generated by the extroflection of the plasma membrane, and released into the circulation. EV can have both pro- and anti-atherothrombotic effects depending on the clinical setting, origin cell, stimuli, and different treatments might affect their levels. The primary endpoint of our study was to compare the amount of circulating EV and specific EV subtypes derived from platelets, endothelial cells, and leucocytes in subject at high CV risk, with and without T2DM, and if any ongoing anti-diabetic drugs could affect the levels of EV. The levels of total EV (d = 0.576; p = 0.049), total Annexin + EV (d = 0.519; p = 0.011), CD41a+/AnnexinV+ platelet derived EV (d = 0.482; p = 0.0187) and CD31 endothelial derived EV (d = 0.590; p = 0.0041) were lower in diabetic patients vs. those without T2DM. Interestingly, after adjustment for variables no significantly different between groups, including HbA1c, differences in EV subtypes were no longer observed. Linear regression analysis showed that HbA1c was inversely related to total EV to (beta coefficients = −10969; p = 0.0170), CD41a+/AnnexinV+ platelet-derived EV (beta coefficients = −352.71125; p = 0.0529) and CD31+ endothelial-derived EV (beta coefficients = −188.01952; p = 0.0095) in all patients. Among subjects with diabetes, CD41+ platelet-derived EV and CD41a+/AnnexinV+ platelet-derived EV (p = 0.0644 and p = 0.0635) were lower in patients on metformin treatment, even after adjustment for gender, hypertension, weight, waist circumference, total cholesterol, diuretics and statins use). Our study showed that, among high CV risk patients, treated with the state-of-the-art preventive strategies, T2DM is associated with lower levels of total, platelet-and endothelial-derived EV, and that this difference may be accounted for, at least in part, by hyperglycemia and ongoing treatment with metformin, the most widely prescribed oral antidiabetic agent. • Extracellular vesicles (EV) can have both pro- and anti-atherothrombotic effects. • DM is associated with lower levels of total, platelet-and endothelial-derived EV. • Platelet-derived AnnexinV + EV are lower in patients on treatment with metformin. • EV number may serve as biomarkers for the response to metformin intervention. [ABSTRACT FROM AUTHOR]

Biological age (BA) is the hypothetical underlying age of an organism and has been proposed as a more powerful predictor of health than chronological age (CA). The difference between BA and CA (Δage) reflects the rate of biological aging, with lower values indicating slowed-down aging. We sought to compare the relationship of four a priori–defined dietary patterns, including a traditional Mediterranean diet (MD) and three non-Mediterranean diets, with biological aging (Δage) among Italian adults. We also examined distinctive nutritional traits of these diets as potential mediators of such associations. Cross-sectional analysis on a sub-cohort of 4510 subjects (aged ≥35 y; 52.0% women) from the Moli-sani Study (enrolment, 2005–2010). Food intake was recorded by a 188-item semi-quantitative food-frequency questionnaire. A Mediterranean diet score (MDS) was used as exposure and compared with non-Mediterranean dietary patterns, i.e. DASH (Dietary Approaches to Stop Hypertension), Palaeolithic and the Nordic diets. A Deep Neural Network based on 36 blood biomarkers was used to compute BA and the resulting Δage (BA-CA), which was tested as outcome in multivariable linear regressions adjusted for clinical factors, lifestyles and sociodemographic factors. In a multivariable-adjusted model, 1 standard deviation increase in the MDS was inversely associated with Δage (β = −0.23; 95%CI -0.40, −0.07), and similar findings were observed with the DASH diet (β = −0.17; 95%CI -0.33, −0.01). High dietary polyphenol content explained 29.8% (p = 0.04) and 65.8% (p = 0.02) of these associations, respectively, while other nutritional factors analysed (e.g. dietary fibre) were unlikely to be on the pathway. No significant associations were found with either the Palaeolithic or the Nordic diets. Increasing adherence to either the traditional MD or the DASH diet was associated with delayed biological aging, possibly through their high polyphenol content. [ABSTRACT FROM AUTHOR]

Background: An inverse relationship between coffee intake and mortality has been observed in several population cohorts, but rarely within Mediterranean countries. Moreover, the biological pathways mediating such an association remain unclear.Objectives: We assessed the associations between coffee consumption and total and cause-specific mortality and examined the mediating roles of N-terminal pro B-type natriuretic peptide (NTproBNP), high-sensitivity Troponin I, blood glucose, lipid metabolism, and selected biomarkers of inflammation and renal function.Methods: We longitudinally analyzed data on 20,487 men and women (35-94 years old at baseline) in the Moli-sani Study, a prospective cohort established in 2005-2010. Individuals were free from cardiovascular disease (CVD) and cancer and were followed-up for a median of 8.3 years. Dietary data were collected by a 188-item semi-quantitative FFQ. Coffee intake was standardized to a 30-mL Italian espresso cup size. HRs with 95% CIs were calculated by multivariable Cox regression.Results: In comparison with no/rare coffee consumption (up to 1 cup/d), HRs for all-cause mortality across categories of coffee consumption (>1 to ≤2, >2 to ≤3, >3 to ≤4 and >4 cups/d) were 0.79 (95% CI, 0.65-0.95), 0.84 (95% CI, 0.69-1.03), 0.72 (95% CI, 0.57-0.92), and 0.85 (95% CI, 0.62-1.12), respectively. For CVD mortality, a nonlinear (P for non-linearity = 0.021) J-shaped association was found (magnitude of the relative reduction = 37%; nadir at 3-4 cups/d). Circulating levels of NTproBNP explained up to 26.4% of the association between coffee and all-cause mortality, while systolic blood pressure was likely to be on the pathway between coffee and CVD mortality, although to a lesser extent.Conclusions: In this large cohort of Italian adults, moderate consumption (3-4 cups/d) of Italian-style coffee was associated with lower risks of all-cause and, specifically, of CVD mortality. Among the known biomarkers investigated here, NTproBNP likely mediates the relationship between coffee intake and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background and Aims: There is a lack of knowledge on the association of dietary factors and Lumbar Spinal Stenosis (LSS). We evaluated the association of a Mediterranean diet (MD), its major food components and ultra-processed food (UPF) with the risk of LSS.Methods and Results: Participants were recruited from the Neurosurgery Department of the IRCCS Neuromed, Italy. The study sample consisted of 156 cases of LSS, and 312 controls matched 1:2 for sex, age (±6 months) and physical activity, without a history or clinical evidence of LSS who were identified from the general population. Adherence to MD was assessed by the Mediterranean Diet Score based on 9 food groups. UPF was defined according to NOVA classification and calculated as the ratio (%) of UPF (g/d) on total food consumed (g/d). In multivariable-adjusted analysis, a 2-point increase in the MD score was not associated with LSS risk (OR: 1.02, 95% CI: 0.72-1.46). An increment of 10 g/d of fruits and nuts, cereals or fish led to lower odds of LSS (OR: 0.97, 95% CI: 0.95-0.99; OR: 0.88, 95% CI: 0.82-0.94; OR: 0.87, 95% CI: 0.76-0.99, respectively). Additionally, 1% increment in the consumption of UPF in the diet was independently associated with higher LSS risk (OR: 1.09, 95% CI: 1.04-1.14).Conclusion: A diet rich in fruits, cereals, fish is associated with lower risk of LSS while a large dietary share of UPF increases the risk of this disease. Further studies with a prospective design and larger sample sizes are warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Diabetes has consistently been shown to increase risk for cognitive decline. Cognitive deficits may occur at the very earliest stages of diabetes. We sought to estimate the determinants of memory function in a group of middle-aged obese subjects with prediabetes or newly-diagnosed type 2 diabetes mellitus.Methods and Results: Sixty-two obese patients in treatment with metformin-with prediabetes (n = 41) or newly diagnosed T2DM (n = 21), were studied. Short- and long-term memory function was assessed through a neuropsychological assessment consisting of two tests and a composite domain z score was calculated. Cardiometabolic variables, such as abdominal MRI quantification of subcutaneous (SAT) and visceral (VAT) adipose tissue content, and of intra-hepatocellular lipid content, as well as insulin sensitivity (Matsuda Index, HOMA-IR) and beta cell performance (Beta Index), by multiple sampling, 8-point oral glucose tolerance test, were also evaluated. Age, non-alcoholic fatty liver disease (NAFLD), and lnHOMA-IR together explained 18% (R square) of the variance in memory domain. Including NAFLD increased the explained variance by 8% and including lnHOMA-IR by 9.1%, whereas the contribution of age and other factors was negligible.Conclusion: Preventing and managing insulin resistance in precocious and possibly earlier stages of diabetes might provide benefit in slowering down future cognitive decline. [ABSTRACT FROM AUTHOR]

Background and Aims: Experimental and non-experimental human studies have consistently shown a positive association between exposure to the trace element selenium, which occurs primarily through diet, and risk of type 2 diabetes mellitus. Plausible biological mechanisms include adverse effects of selenium and selenium-containing proteins on glucose metabolism. However, the levels of exposure above which risk increases are uncertain.Methods and Results: We examined the association between selenium intake and first hospitalization for type 2 diabetes during a median follow-up period of 8.2 years among 21,335 diabetes-free participants in the Moli-sani cohort, Italy. Selenium intake was ascertained at baseline using a food frequency questionnaire, showing a median value of 59 μg/day. During follow-up, we identified 135 incident cases of hospitalization for diabetes, based on population-based hospital discharge data. We used a Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization for diabetes, adjusting for potential confounders. HRs (95% CIs) were 1.01 (0.60-1.70), 1.13 (0.66-1.96) and 1.75 (0.99-3.10) comparing the second, third, and fourth sex-specific quartiles with the first quartile, respectively. Risk was 64% greater in the fourth quartile as compared with the previous three. Spline regression analysis also indicated a steeper increase in risk occurring among men compared with women.Conclusions: In a large population of Italian adults free of type 2 diabetes at cohort entry, high dietary selenium intake was associated with increased risk of hospitalization for diabetes. [ABSTRACT FROM AUTHOR]

Background and Aims: The CASSIOPEA Study was designed to evaluate whether the economic downturn during the late 2000s was a contributing factor to the observed decrease in adherence to Mediterranean diet (MD).Methods and Results: The study protocol consists of two steps: A) recall of 7406 men and women who, between 2005 and 2006, had been randomly recruited in the Moli-sani Study from the general population of Molise, to assess possible economic hardship (EH) related to the economic crisis initiated in 2007; B) re-examination, between 2017 and 2020, of available subjects identified in Step 1 as poorly or harder hit by EH to test the hypothesis that EH is associated with a decrease in MD adherence, possibly resulting in increased inflammation. The results of Step 1 are reported here. From the initial sample of individuals re-examined after 12.6 years (median; IQR = 12.1-13.0 y), 3646 were finally analysed. An Economic Hardship Score (EHS; range 0-14) was obtained by scoring three domains: 1) change in employment status; 2) financial hardship and 3) financial hardship for health expenditures. Overall, 37.8% of the sample reported high EHS (≥3), whilst 32% scored 0 (no EH). Those with high EHS were prevalently women and younger, with low socioeconomic status.Conclusions: High economic hardship was prevalently reported by weaker socioeconomic groups. Longitudinal analysis (step 2) will examine whether the economic crisis had an effect on adherence to Mediterranean diet with consequent potential impact on inflammation, one of the main biological pathways linking MD to health outcomes. CLINICALTRIALS.Gov Identifier: NCT03119142. [ABSTRACT FROM AUTHOR]

The EU-supported ATHENA project stems from a previous study suggesting that moderate wine consumption reduced the side-effects of radiotherapy (RT) in breast cancer patients, an effect possibly due to non-alcoholic anthocyanin fractions of wine. To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. Randomized, controlled, double-blind clinical trial. Patients were assigned to an intensity modulated radiation therapy (IMRT) either for three or five weeks, then randomized to receive three times a day a water-soluble anthocyanin (125 mg)-rich extract of corn cob or a placebo. Supplementation started one week before till the end of RT. Skin characteristics were detected by a standardized, non-invasive Cutometer® dual-MPA580, providing quantitative indices of skin maximal distensibility (R0), elasticity (R2, R5, R7) and viscoelasticity (R6); a Mexameter® MX18 probe evaluated the skin erythema (Er) and melanin (M). Measures were performed before (T0), at the end of RT and of supplementation (T1), and 1, 6 and 12 months after RT (T2-T4). Acute and late skin toxicity were scored according to the RTOG/EORTG scale. Selected biomarkers were measured at T0 and T1. 193 patients previously assigned to 3- or 5-week RT schedules were randomized to either anthocyanin (97) or placebo (96) supplementation. RT induced changes in skin parameters: R0, R2, R5 and R7 decreased, while R6 increased; the changes in R0 and R6 continued in the same direction up to one year, while the others recovered towards basal values; Er and M peaked at T1 and T2, respectively, and returned to basal values at T4. Comparable skin changes were apparent in anthocyanin and placebo groups. A moderate RT-induced increase in total and HDL cholesterol and triglycerides was prevented by anthocyanins. Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe. [ABSTRACT FROM AUTHOR]

Background Consumption of ultra-processed food (UPF) is gaining growing attention in relation to disease/mortality risk, but less is known on the main nutritional factors or biological mechanisms potentially underlying such associations. Objectives We aimed to assess the association between UPF and mortality risk in a large sample of the Italian adult population and test which nutritional factors were on the pathway of this relation. Established risk factors for cardiovascular disease (CVD) were analyzed as potential biological mechanisms linking UPF to mortality. Methods Longitudinal analysis was conducted on 22,475 men and women (mean ± SD age: 55 ± 12 y) recruited in the Moli-sani Study (2005–2010, Italy) and followed for 8.2 y. Food intake was assessed using a semiquantitative FFQ. UPF was defined using the NOVA classification according to degree of processing, and UPF intakes were categorized as quartiles of the ratio (%) of UPF (g/d) to total food consumed (g/d). Results Individuals reporting the highest intake of UPF (Q4, >14.6% of total food), as opposed to the lowest (Q1, UPF < 6.6%), experienced increased risks of CVD mortality (HR: 1.58; 95% CI: 1.23, 2.03), death from ischemic heart disease (IHD)/cerebrovascular disease (HR: 1.52; 95% CI: 1.10, 2.09), and all-cause mortality (HR: 1.26; 95% CI: 1.09, 1.46). High sugar content explained 36.3% of the relation of UPF with IHD/cerebrovascular mortality, whereas other nutritional factors (e.g. saturated fats) were unlikely to be on the pathway. Biomarkers of renal function accounted for 20.1% of the association of UPF with all-cause mortality, and 12.0% for that of UPF with CVD mortality. Conclusions A high proportion of UPF in the diet was associated with increased risk of CVD and all-cause mortality, partly through its high dietary content of sugar. Some established biomarkers of CVD risk were likely to be on the pathway of such associations. These findings should serve as an incentive for limiting consumption of UPF, and encouraging natural or minimally processed foods, as several national nutritional policies recommend. [ABSTRACT FROM AUTHOR]

Background and Aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death.Methods and Results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6-14.7 for age ≥85 vs 18-44 y); HR = 4.7; 2.9-7.7 for estimated glomerular filtration rate levels <15 vs ≥ 90 mL/min/1.73 m2; HR = 2.3; 1.5-3.6 for C-reactive protein levels ≥10 vs ≤ 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses.Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Chili pepper is a usual part of a traditional Mediterranean diet. Yet epidemiological data on the association between chili pepper intake and mortality risk are scarce, with a lack of studies from Mediterranean populations.Objectives: This study sought to examine the association between chili pepper consumption and risk of death in a large sample of the adult Italian general population, and to account for biological mediators of the association.Methods: Longitudinal analysis was performed on 22,811 men and women enrolled in the Moli-sani Study cohort (2005 to 2010). Chili pepper intake was estimated by the EPIC (European Prospective Investigation Into Cancer) Food Frequency Questionnaire and categorized as none/rare consumption, up to 2 times/week, >2 to ≤4 times/week, and >4 times/week.Results: Over a median follow-up of 8.2 years, a total of 1,236 deaths were ascertained. Multivariable hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality among participants in the regular (>4 times/week) relative to none/rare intake were 0.77 (95% confidence interval [CI]: 0.66 to 0.90) and 0.66 (95% CI: 0.50 to 0.86), respectively. Regular intake was also inversely associated with ischemic heart disease (HR: 0.56; 95% CI: 0.35 to 0.87) and cerebrovascular (HR: 0.39; 95% CI: 0.20 to 0.75) death risks. The association of chili pepper consumption with total mortality appeared to be stronger in hypertension-free individuals (p for interaction = 0.021). Among known biomarkers of CVD, only serum vitamin D marginally accounted for such associations.Conclusions: In a large adult Mediterranean population, regular consumption of chili pepper is associated with a lower risk of total and CVD death independent of CVD risk factors or adherence to a Mediterranean diet. Known biomarkers of CVD risk only marginally mediate the association of chili pepper intake with mortality. [ABSTRACT FROM AUTHOR]

For almost a century, the scientific community is aware of the J-shaped curve between alcohol consumption and all-cause mortality. Moderate drinkers seem to live longer than both abstainers and heavy drinkers. These epidemiological observations regarding moderate alcohol consumption and beneficial health effects have been incessantly scrutinised for confounding and bias. This viewpoint discusses previous and recent criticisms regarding the J-shaped curve between alcohol consumption and total mortality risk. The controversies regarding the J-shaped curve between alcohol consumption and mortality are ongoing, as well as the debate among scientists in this area of research, resulting in conflicting messages in media and in different alcohol guidelines. Although it appears quite difficult to come up with a position statement only based on the currently available scientific data, it is imperative to fairly inform the public, without creating confusion and, worst case, disbelief in science. [ABSTRACT FROM AUTHOR]

Abstract Background Statins are prescribed for patients with cardiovascular disease (CVD), along with the recommendation of adopting healthy diets. We evaluated the independent and the combined effect of statins and Mediterranean diet (MD) towards mortality risk in patients with previous CVD by using real-life data from a population-based prospective cohort. Methods Longitudinal analysis on 1180 subjects (mean age 67.7 ± 10) with prior CVD at enrollment in the Moli-sani Study and followed up for 7.9 y (median). Adherence to MD was appraised by a Mediterranean diet score. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated by multivariable Cox regression and competing risk models. Results Multivariable risk estimates associated with a 2-point increase in MD score were 0.84 (95% CI 0.70–1.00), 0.77 (0.61–0.97) and 0.70 (0.52–0.93) for overall, cardiovascular and coronary artery disease (CAD)/cerebrovascular deaths, respectively. Statins were not associated with death risk. Subjects combining statins and average-high adherence to MD had much lower than expected risk of cardiovascular and CAD/cerebrovascular mortality (p for interaction = 0.045 and 0.0015, respectively) as compared to those neither using statins nor having average-high MD. The combination of average-high MD and statins was associated in a likely synergistic way with reduced low-grade inflammation, but not with blood cholesterol. Conclusions MD lowered the risk of all-cause, cardiovascular and CAD/cerebrovascular mortality CVD patients, net of statins. In the same population, statins reduced CVD death risk only in combination with MD. Low-grade inflammation, rather than lipids, is likely to be on the pathway of the interaction between MD and statins towards mortality risk. Highlights • Mediterranean diet (MD) is associated with lower risk of death in CVD patients. • Statins reduce CVD death risk only in combination with Mediterranean diet. • Inflammation is likely to be on the pathway of the interaction of MD and statins. • Combination of MD and statins may be an optimal option for secondary prevention. [ABSTRACT FROM AUTHOR]

Background and aims The orientation of the frontal plane T-wave axis (T axis) is a reliable measure of ventricular repolarisation. We investigated the association between T-axis and the risk of coronary heart disease (CHD), heart failure (HF), atrial fibrillation (AF), stroke and cardiovascular (CVD) mortality. Methods A sample of 21,287 Moli-sani participants randomly recruited from the general adult (≥35 y) Italian population, free of CVD disease, were followed for a median of 4.4 years. T-axis was measured from a standard 12-lead resting ECG. Results After adjusting for CVD risk factors, subjects with abnormal T-axis showed an increase in the risk of both CHD (Hazard Ratio (HR) = 2.65; 95% CI = 1.67–4.21), HF (HR = 2.56; 1.80–3.63), AF (HR = 2.48; 1.56–3.94) and CVD mortality (HR = 2.83; 1.50–5.32). The association with CHD and HF, but not with AF or CVD death, remained significant after further adjustment for ECG abnormalities. Subjects with abnormal T-axis showed higher levels of subclinical inflammation, hs-troponin I and hs-NT-proBNP ( p < 0.001 for all). However, further adjustment for troponin I and/or NT-proBNP determined a reduction of HRs ranging from 12.1 to 24.0% for CHD, while additional adjustment for inflammation markers did not change any association. Conclusions An abnormal T-axis orientation is associated with an increased risk of both CHD and HF, independently of common CVD risk factors and other ECG abnormalities. This association was partially explained by increased hs-troponin I and hs-NT-proBNP levels. [ABSTRACT FROM AUTHOR]

Background Angiotensin receptor blockers (ARBs) are a valuable option to reduce cardiovascular (CV) mortality and morbidity in cardiac patients in whom ACE-inhibitors (ACE-Is) cannot be used. However, clinical outcome data from direct comparisons between ACE-Is and ARBs are scarce, and some data have recently suggested superiority of ACE-Is over ARBs. Methods We performed a Bayesian network-meta-analysis, with data from both direct and indirect comparisons, from 27 randomized controlled trials (RCTs), including a total population of 125,330 patients, to assess the effects of ACE-Is and ARBs on the composite endpoint of CV death, myocardial infarction (MI) and stroke, and on all-cause death, new-onset heart failure (HF) and new-onset diabetes mellitus (DM) in high CV risk patients without HF. Results Using placebo as a common comparator, we found no significant differences between ACE-Is and ARBs in preventing the composite endpoint of CV death, MI and stroke (RR: 0.92; 95% CI 0.78–1.08). When components of the composite outcome were analysed separately, ACEi and ARBs were associated with a similar risk of CV death (RR: 0.92; 95% CI 0.73–1.10), MI (RR: 0.91; 95% CI 0.78–1.07) and stroke (RR: 0.97; 95% CI 0.79–1.19), as well as a similar incident risk of all-cause death (RR: 0.94; 95% CI 0.85–1.05), new-onset HF (RR: 0.92; 95% CI 0.77–1.15) and new-onset DM (RR: 99; 95% CI 0.81–1.21). Conclusions With the limitations of indirect comparisons, we found that in patients at high CV risk without HF, ARBs were similar to ACE-Is in preventing the composite endpoint of CV death, MI and stroke. Compared with ARBs, we found no evidence of statistical superiority for ACE-Is, as a class, in preventing incident risk of all-cause death, CV death, MI, stroke, new-onset DM and new-onset HF. [ABSTRACT FROM AUTHOR]

Objective: Folate status has been associated with neural tube defects and cerebrovascular disease. The aim of this study was to evaluate possible differences in folate status in two European Union countries and to assess their possible association with dietary patterns and/or other lifestyles. Methods: In the framework of the European Union-funded IMMIDIET Project, 1068 individuals (534 male-female pairs), ages 26 to 64 y, were enrolled in Italy and the United Kingdom. One-year-recall food frequency questionnaire was used to evaluate dietary intake. Reduced rank regression analysis was used to derive a dietary pattern better describing high dietary folate intake. Results: Of the total participants, 11.3% of the Italians and 45.1% of the British exceeded the optimal dietary folate intake of 400 µg/d (Recommended Dietary Allowance). Of the women, 66.7% and 22.1% of Italian and British women, respectively, all at childbearing age, had folate serum levels <6.62 ng/mL (P = 0.01). The percentage of total variance of dietary folate intake explained by food group consumption was 14.2% and 16.3% in Italy and the United Kingdom, respectively. Reduced rank regression analysis indicated a healthy pattern that was positively associated with folate serum levels in both countries (for all β-coefficients >0; P < 0.001): 100 mg/d increase in dietary folate intake was associated with 13.8% and 10.5% increase in folate serum levels in the Italian and British population, respectively (for 100 mg/d increase eβ-coef = 1.138 and 1.105; P < 0.001). Smoking habit was negatively but physical activity positively associated with folate serum levels (P < 0.05). Conclusions: An inadequate dietary folate intake and subsequent serum levels were observed in the Italian participants. High consumption of food sources of folate was positively associated with folate serum levels, explaining a good proportion of its variability. [ABSTRACT FROM AUTHOR]

Abstract: Electrocardiographic signs of left ventricular hypertrophy (ECG-LVH) and T-wave axis (TA) deviation are independent predictors of fatal and non fatal events. We assessed the prevalence of ECG-LVH, TA abnormalities and their combination according to the presence or absence of diabetes and/or hypertension in a large sample of the adult general Italian population. Data from 10,184 women (54±11years) and 8775 men (54±11years) were analyzed from the Moli-sani cohort, a database of randomly recruited adults (age >35) from the general population of Molise, a central region of Italy that includes collection of standard 12-lead resting ECG. Subjects with previous myocardial infarction, angina, cerebrovascular disease or left bundle brunch block or missing values for TA or ECG-LVH have been excluded. TA was measured from the standard 12-lead ECG and it was defined as the rotation of the T wave in the frontal plane as computed by a proprietary algorithm (CalECG/Bravo, AMPS-LLC, NY). ECG-LVH was defined as Sokolow Lyon voltage (SLv) >35mm or Cornell voltage duration Product (CP)>=2440 mm*ms. Among subjects with ECG-LVH, prevalence of hypertension was 59.0% and 49.7%, respectively for men and women, whereas that of diabetes was 10.7% and 5.7%. In hypertensives, TA was normal in 72.3% of subjects, borderline in 24.8% and abnormal in 2.9%. In diabetics, TA was normal in 70.4% of subjects, borderline in 26.5% and abnormal in 3.1%. In both hypertensive and diabetic subjects, the prevalence of ECG-LVH, was significantly greater in subjects with borderline or abnormal TA. Hypertension was an independent predictor of abnormal TA (odd ratio: 1.38, P =.025). These results suggest that hypertension might play a relevant role in the pathogenesis of TA deviation. [Copyright &y& Elsevier]

Background: Several randomized clinical trials evaluated whether preoperative supplementation of omega-3 (n-3) polyunsaturated fatty acids protects against postoperative atrial fibrillation after cardiac surgery, a condition associated with increased cardiac and cerebral mortality. However, their efficacy remains still controversial. An updated meta-analysis was performed to clarify if preoperative n-3 polyunsaturated fatty acid supplementation prevents postoperative atrial fibrillation in patients undergoing cardiac surgery. Methods: Articles were retrieved until November 2012 by screening electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials) and cross references. Two of us independently reviewed articles and agreed to select 8 randomized clinical trials. For each study, the incidence of atrial fibrillation in both the intervention and placebo groups was extracted to calculate odd ratio and 95% confidence intervals (CIs). Weighted study-specific estimates were combined using fixed (Mantel-Haenszel method) and random-effects (DerSimonian-Laird method) models. Results: This meta-analysis includes 2687 patients (1337 in the intervention group) who underwent cardiac surgery. Pooled analysis using fixed-effects models showed a significant reduction (average, 16%; 95% CI, 1%-29%) in postoperative atrial fibrillation by preoperative n-3 polyunsaturated fatty acids. There was a low heterogeneity among studies (P = .07 and I2 = 46%). By using a random-effects model, the reduction averaged 25% (odds ratio, 0.75; 95% CI, 0.57-1.00; P = .05). When isolated coronary artery bypass graft surgery was only considered (7 studies), a significant protection averaging 34% was observed in a fixed model (odds ratio, 0.66; 95% CI, 0.50-0.87; P = .003; I2 = 26%, P = .23). Conclusions: A preoperative supplementation of n-3 polyunsaturated fatty acids significantly prevents the occurrence of postoperative atrial fibrillation in patients undergoing cardiac surgery, in particular coronary artery bypass surgery. [Copyright &y& Elsevier]

Abstract: Aim: We aimed at investigating the association between T-wave axis deviation, metabolic syndrome (MetS), its components and estimated risk of cardiovascular disease (CVD) at 10 years in an adult Italian population. Methods: 11,143 women (54 ± 11 years) and 9742 men (55 ± 11 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. MetS was defined using the ATPIII criteria. T-wave axis deviation was measured from the standard 12-lead resting electrocardiogram. CVD risk in ten years was estimated by the CUORE score. Results: 29% of men and 27% of women with MetS showed borderline or abnormal T-wave as compared to 24% and 17% without MetS (p < 0.0001 for both genders). Among components of MetS, elevated waist and blood pressure were strongly associated with T-wave axis deviation, whereas glucose, HDL and triglycerides were only marginally. The odds of having borderline or abnormal T-wave axis deviation in multivariable regression analysis, was 1.38 (95% CI:1.25–1.53) in MetS men and 1.68 (95% CI:1.51–1.87) in MetS women compared to those without. Further adjustment for MetS components completely abolished the associations. Abnormal T-wave axis deviation was associated with an increased risk of CVD in 10 years in men (OR = 4.4; 95% CI:1.10–17.9). Conclusion: T-wave axis deviation is strongly associated with components of the MetS, in particular high waist circumference and blood pressure and with an increased CVD risk, particularly in men. ECG monitoring to identify T-wave axis deviation in obese, hypertensive or MetS subjects can be an early indicator of vascular disease and help in reducing cardiac events. [Copyright &y& Elsevier]

Abstract: Computerized electrocardiogram (ECG) acquisition and interpretation may be extremely useful in handling analysis of data from large cohort studies and exploit research on the use of ECG data as prognostic markers for cardiovascular disease. The Moli-sani project (http://www.moli-sani.org) is a population-based cohort study aiming at evaluating the risk factors linked to chronic-degenerative disease with particular regard to cardiovascular disease and cancer and intermediate metabolic phenotypes such as hypertension, diabetes, dyslipidemia, obesity, and metabolic syndrome. Between March 2005 and April 2010, 24 325 people aged 35years or older, living in the Molise region (Italy), were randomly recruited. A follow-up based on linkage with hospital discharge records and mortality regional registry and reexamination of the cohort is ongoing and will be repeated at prefixed times. Each subject was administered questionnaires on personal and medical history, food consumption, quality of life (FS36), and psychometry. Plasma serum, cellular pellet, and urinary spots were stored in liquid nitrogen. Subjects were measured blood pressure, weight, height, and waist and hip circumferences, and underwent spirometry to evaluate pulmonary diffusion capacity, gas diffusion, and pulmonary volumes. Standard 12-lead resting ECG was performed by a Cardiette ar2100-view electrocardiograph and tracings stored in digital standard communication protocol format for subsequent analysis. The digital ECG database of the Moli-sani project is currently being used to assess the association between physiologic variables and pathophyiosiologic conditions and parameters derived from the ECG signal. This computerized ECG database represents a unique opportunity to identify and assess prognostic factors associated with cardiovascular and metabolic diseases. [Copyright &y& Elsevier]

Abstract: Early recognition of patients at increased cardiovascular risk is a major challenge. The surface electrocardiogram provides a useful platform and it has been used to propose several indexes. T wave axis abnormality is associated with an increased risk of cardiovascular mortality, independently of other risk factors and can be associated with the presence of the metabolic syndrome (MetS). We assessed the prevalence of T axis abnormalities and its relationship with MetS and its components in a large population of Italian adults. Data concerning 11,143 women (54±11years) and 9742 men (55±11years) randomly recruited from a general population (Moli-sani cohort) were analyzed. After excluding subjects with incomplete data and with history of cardiac disease or left ventricular hypertrophy, T-wave axis was normal in 74.5% of men and 80.9% of women, borderline in 23.6% and 17.3% and abnormal in 1.9% and 1.8%. In subjects with MetS, the prevalence of borderline or abnormal T-wave axis deviation was higher than in subjects without MetS (in men: 26.6% vs. 22.1% and 2.5% vs. 1.7%; in women: 25% vs. 15% and 2.4% vs. 1.6%, respectively for borderline and abnormal levels, p<0.0001). Each component of MetS increased the odds of having borderline or abnormal T-wave axis deviation by 1.21 in men and 1.31 in women. T wave axis deviation is associated with MetS and its individual components. These findings confirm previous reported results, expanding them to a large and representative sample of European population of Caucasian ethnicity. [Copyright &y& Elsevier]

Abstract: Daily intake of an anti-thrombotic diet may offer a suitable and effective way of coronary artery disease (CAD) prevention. A diet rich in fruit, vegetables, complex carbohydrates, monounsaturated fat and fish, moderate alcohol consumption but poor in salt, saturated fat and simple sugars, plays an important role in protect against CAD. Chocolate, coffee and tea, unfairly not included in “traditional healthy food basket”, have received much attention over the past few years, if for no other reason than they are consumed worldwide and are important dietary sources of polyphenols (flavonols and cathechins). Several in vitro and in vivo studies have tried to elucidate the role of these foods and a large amount of experimental studies clearly indicated a beneficial effect of polyphenols in influencing CAD. However, data from epidemiological studies are not conclusive. The blood pressure lowering effects and the anti-inflammatory activity of dark chocolate suggests its use as potential prophylactic and therapeutic agent, in particular considering that epidemiological studies suggest that dark chocolate is inversely associated with CAD. Although regular consumption of moderate quantities of coffee and (green) tea seems to be associated with a small protection against CAD, results from randomized clinical trials about their beneficial effects are less evident. As for other diffuse consumption habits, such as that of alcohol, moderation is the key word. In fact, both for coffee and chocolate, the optimal healthy effects on CAD have been observed to be associated with a moderate intake, while healthy outcomes vanish at heavy consumption. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to quantify the relation between alcohol consumption and cardiovascular and total mortality in patients with a history of cardiovascular events. Background: Regular, moderate alcohol consumption by healthy people is associated with lower cardiovascular and all-cause mortality. No extensive meta-analysis is presently available on the possible association of alcohol consumption with secondary events in patients with cardiovascular disease. Methods: Articles were retrieved through October 2009 by search in PubMed and EMBASE. Fifty-four publications were identified, but only 8 were selected for our analyses, including 16,351 patients with a history of cardiovascular disease. Secondary events were cardiovascular or all-cause mortality. All selected studies were prospective. Data were pooled with a weighted, least-squares regression analysis of second-order fractional polynomial models. Results: The meta-analysis on cardiovascular mortality showed a J-shaped pooled curve with a significant maximal protection (average 22%) by alcohol at approximately 26 g/day. In the meta-analysis on mortality for any cause, J-shaped pooled curves were observed in the overall analysis (average maximal protection of 18% in the range of 5 to 10 g/day) and in all subgroups according to either the type of patients or the characteristics of the studies. Conclusions: In patients with cardiovascular disease, light to moderate alcohol consumption (5 to 25 g/day) was significantly associated with a lower incidence of cardiovascular and all-cause mortality. [Copyright &y& Elsevier]

Abstract: Introduction: Moderate alcohol consumption is protective against cardiovascular disease (CAD). ADHs are major enzymes of alcohol metabolism. A polymorphism in the alcohol dehydrogenases 1C gene (ADH1C) was reportedly associated with the protective effect of alcohol consumption on CAD risk and risk factor levels. Aims: The aim of our study was to investigate whether the association of alcohol consumption with metabolic risk factors for CAD is related to ADH1C variants. Methods: IMMIDIET is a cross-sectional study of 974 healthy male–female pairs living together, randomly recruited in Belgium, Italy and England. The rs698 ADH1C polymorphism was genotyped. A 1-year recall food frequency questionnaire was used to estimate alcohol intake. Results: The intake of alcohol did not vary in relation to ADH1C genotypes. BMI, waist circumference (WC), waist-to-hip ratio, blood pressure, HDL or total cholesterol, triglycerides and FVII:ag levels were positively associated with alcohol intake in men (multivariate ANOVA). Regression coefficient for alcohol and BMI or WC was progressively higher in heterozygotes and gamma 2 homozygotes as compared to gamma 1 homozygotes (p =0.006 and p =0.03 for interaction, respectively). No interaction was found for other risk factors. In women, alcohol intake was positively associated with HDL, LDL and FVII:ag levels but no interaction was found between ADH1C polymorphism and any risk factor. Conclusion: Regulation of ADH1C genotype on the association between alcohol consumption, BMI and WC was found in men from different European countries. In men homozygous for the gamma 2 alleles, intake of alcohol was positively associated with both BMI and WC values. [Copyright &y& Elsevier]

Dark chocolate contains high concentrations of flavonoids and may have antiinflammatory properties. We evaluated the association of dark chocolate intake with serum C-reactive protein (CRP). The Moli-sani Project is an ongoing cohort study of men and women aged ⩾35 y randomly recruited from the general population. By July 2007, 10,994 subjects had been enrolled. Of 4849 subjects apparently free of any chronic disease, 1317 subjects who declared having eaten any chocolate during the past year (mean age 53 ± 12 y; 51 % men( and 824 subjects who ate chocolate regularly in the form of dark chocolate only (50 ± 10 y; 55% men( were selected. High sensitivity-CRP was measured by an immunoturbidimetric method. The European Prospective Investigation into Cancerand Nutrition FF0 was used to evaluate nutritional intake. After adjustment for age, sex, social status, physical activity, systolic blood pressure, BMI, waist:hip ratio, food groups, and total energy intake, dark chocolate consumption was inversely associated with CRP (P = 0.0381. When adjusted for nutrient intake, analyses showed similar results (P = 0.016). Serum CRP concentrations [geometric mean (95% Cl)) univariate concentrations were 1.32 (1.26-1.39 mg/LI in nonconsumers and 1.10 (1 .03-1.17 mg/L) in consumers (P< 0.0001). A J-shaped relationship between dark chocolate consumption and serum CAP was observed; consumers of up to 1 serving (20 g) of dark chocolate every 3 d had serum CRP concentrations that were significantly lower than nonconsumers or higher consumers. Our findings suggest that regular consumption of small doses of dark chocolate may reduce inflammation. [ABSTRACT FROM AUTHOR]

Background and Aims: The Mediterranean diet is reportedly a healthy eating pattern with protective effects on chronic diseases. The aim of this study was to assess the relationship between adherence to the Mediterranean diet and anthropometric and metabolic variables in a rural setting in southern Italy, in the context of a health screening initiative.Methods and Results: Five hundred and twenty-two healthy participants from the "Alto Molise" region in southern Italy were studied. Blood pressure, glucose, and total cholesterol were measured using automatic devices. Food intake was evaluated with a semi-quantitative food-frequency questionnaire, and the Mediterranean adequacy index (MAI) was calculated. The median value of MAI in the population studied was 3.0 (1.5-5.4) in men and 2.4 (1.2-5.1) in women. In women, the stronger contributors to MAI were dairy products (42.5%), sweets (29.3%) and meat (19.4%), while in men they were cereals (39.1%), meat (18.6%), dairy products (16.9%) and sweets (16.1%). In multiple linear regression analysis MAI was positively associated with age in both sexes (P=0.0044 in men and P=0.0054 in women) and with systolic blood pressure in women (P=0.012). After stratification of women by age, systolic blood pressure was significantly associated with MAI only in older persons (P=0.040) but not at younger ages (interaction effect P<0.0001).Conclusions: Adherence to the Mediterranean diet depends on age, possibly because in younger people the traditional Mediterranean style diet is decreasing, even in rural areas of southern Italy. Age also influences the association between MAI and metabolic variables such as systolic blood pressure in women. [ABSTRACT FROM AUTHOR]

α 2 -macroglobulin (α 2 M) is a versatile endopeptidase inhibitor that plays a role in cell growth, inflammation and coagulation. α 2 M is an inhibitor of key coagulation enzyme thrombin. Hypercoagulability due to an excess of thrombin production can cause thrombotic events. Therefore, we investigated the association of α 2 M levels and cardiovascular events in a subset of the general Italian population. We determined α 2 M levels in the baseline samples of a prospective cohort (n = 19,688; age: 55 ± 12 years; 47.8 % men) of the Moli-sani study and investigated the association with the cardiovascular events (n = 432, 2.2 %) in the median follow-up period of 4.3 years. Hazard ratios (HR) with 95 % confidence intervals (CI) were calculated by multivariable Cox regression and adjusted for a large panel of confounding factors. α 2 M levels above the 90th percentile were significantly associated with cardiovascular disease (CVD) events after full adjustment for age, sex, current smoking, BMI, oral contraceptive use, cardiovascular diseases, hypertension, hypercholesterolemia, diabetes and history of cancer (HR: 1.36; CI: 1.06–1.74). Moreover, high α 2 M was associated with coronary heart disease (CHD; HR: 1.47; CI: 1.12–1.91), but not stroke. Stratification for CVD at baseline showed that high α 2 M levels are associated with CHD events in subjects without CVD at baseline (HR: 1.40; CI: 1.00–1.95) and subjects with CVD at baseline (HR: 1.58; CI: 1.02–2.44). We show in a prospective cohort that high levels of α 2 M could be a risk factor for cardiovascular events, especially coronary heart disease events. • Alpha 2 -Macroglobulin and cardiovascular events are associated. • High α 2 M is a risk factor for coronary heart disease. • The association is independent of age, sex, and lifestyle. [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

There is little knowledge on the association of changes over time in adherence to a Mediterranean diet (MD) with changes in modifiable cardiovascular disease (CVD) risk factors and of markers of low-grade inflammation. To evaluate the association between long-term changes in MD adherence and concurrent changes in established CVD risk factors and in markers of low-grade inflammation among adult Italians. A prospective cohort study was conducted. Dietary and health data were obtained both at baseline (2005-2010) and at follow-up (2017-2020). Adherence to the MD was estimated by a Mediterranean Diet Score ranging from zero to nine points, and the exposure was change in this score measured after a median 12.7-year period. This study included a subgroup of 897 men and 1,126 women aged ≥35 years at enrolment in the Moli-sani Study (n = 24,325). Changes in two composite z scores, including nine established CVD risk factors (eg, serum lipid levels and blood pressure) and four inflammatory markers (including C-reactive protein), respectively, were measured both at enrolment and after the same 12.7-year period. Multivariable-adjusted linear regression models were used. In a multivariable-adjusted analysis, an increased Mediterranean Diet Score over time was associated with decreased levels in the Inflammatory score (β = –0.372, 95% CI –0.720 to –0.025), but had little or no influence on the CVD risk score (β = –0.200, 95% CI –0.752 to 0.351), compared with individuals who had decreased their MD adherence. Among individual food groups/nutrients included in the Mediterranean Diet Score, an increased intake of monounsaturated over saturated fats over time was associated with lower CVD Risk Score, whereas increased consumption of cereals was inversely linked to the Inflammatory Score, compared with the reduced consumption group. An increased adherence to a traditional MD over time was associated with reduced low-grade inflammation. These findings suggest the potential of a traditional Mediterranean eating pattern to help reduce the long-term risk of inflammation-related chronic diseases in an ageing population. [ABSTRACT FROM AUTHOR]

Inflammatory markers have been demonstrated to be associated with increased risk of cardiovascular events. In this setting, C-reactive protein (CRP) was shown to add predictive value to cholesterol levels. We investigated hypercholesterolemic patients and related their inflammatory variables and their coagulation state focusing on factor VII, a coagulation protein which plays an established role in thrombogenesis. We examined the relationship between factor VII clotting activity (FVIIc), FVII antigen (FVIIAg) and activated FVII (FVIIa) levels against CRP, interleukin-6 soluble receptor (IL-6sR), P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-β1 (TGF-β1), in fifty-eight hypercholesterolemic subjects. Patients were subjected to 6–8 weeks of lipid lowering treatment with diet or diet plus pravastatin (40 mg/day). Univariate analysis showed that FVII levels were positively associated with CRP (FVIIAg: r=0.56, P<0.0001; FVIIc: r=0.57, P<0.0001; FVIIa: r=0.39, P<0.001) and IL-6sR (FVIIAg: r=0.59, P<0.0001; FVIIc: r=0.52, P<0.0001; FVIIa: r=0.47; P<0.001). CRP was still correlated, at the baseline, with FVIIAg and FVIIc levels after multiple stepwise regression analysis (FVIIAg: P<0.0001; FVIIc: P<0.0001, respectively) and with FVIIAg at the end of lipid lowering treatment (P<0.0001). Our data indicate that the FVII level is independently associated with inflammatory variables and suggest their pathophysiological link in hypercholesterolemic patients. [Copyright &y& Elsevier]

Interleukin (IL)-6 plasma levels are predictive of major cardiovascular events. The -174 G/C promoter polymorphism of the IL-6 gene affects basal levels in vivo and transcription rates in vitro, but its association with IL-6 acute phase levels among patients with coronary artery disease has not been investigated. In 111 patients with multivessel coronary artery disease undergoing elective coronary artery bypass graft surgery, we prospectively assessed genotype at position -174 and serial blood levels of IL-6 and other inflammatory indexes. Clinical and surgical characteristics did not differ among genotypic groups. IL-6 levels--measured daily up to 72 hours before surgery, after surgery, and at discharge--showed a mean 17-fold increase, peaking at 24 hours (p <0.0001). IL-6 levels (but not fibrinogen, white-blood cell count, and C-reactive protein values) differed significantly according to the -174 genotype (p = 0.042 for difference between areas under the curve), the 62 GG homozygotes exhibiting higher concentrations than the 49 carriers of the C allele (widest difference at 48 hours, p = 0.015 in multivariate analysis). GG homozygosity was associated with longer stays in the intensive care unit (2.5 +/- 3.4 vs 1.4 +/- 0.9 days, p = 0.02) and in the hospital (6.7 +/- 4.0 vs 5.3 +/- 1.4 days, p = 0.02) than C carriership. Rates of postoperative death, myocardial infarction, and stroke were 8% in GG homozygotes and 2% in C-carriers (p = 0.16). The IL-6-174 GG genotype is associated with higher acute phase levels of IL-6 and with longer stays in the hospital and in the intensive care unit than C allele carriership after surgical coronary revascularization. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Numerous epidemiological studies suggest that exposure to flavonoid-rich fruits has beneficial influence on risk factors for cardiovascular disease. We investigated whether intake of orange juice (OJ) could affect whole blood (WB) procoagulant activity. Methods: 17 healthy subjects (aged 31±1.5 SEM 10 males) were randomized to receive, according to a cross-over design, either red or blond OJ, enriched or free of anthocyanins, respectively. After one week run-in period on a controlled diet, the subjects were randomly allocated to receive either type of OJ for 4weeks, with a 4-week wash-out period. Venous blood was collected on citrate before and at the end of each treatment period. WB was incubated with or without an inflammatory stimulus (tumor necrosis factor-α or bacterial endotoxin LPS). Procoagulant activity was evaluated by a one-stage clotting assay. Tissue factor (TF) and TF pathway inhibitor (TFPI) were measured in plasma by ELISA. Results: Intake of either type of OJ caused a prolongation of unstimulated and stimulated WB clotting times, without any difference between the two treatments. Intake of OJ did not modify TF levels. On the contrary, an increase in circulating TFPI antigen was detected following either treatment. Conclusions: Orange juice intake by healthy volunteers decreases procoagulant activity, possibly through mechanisms independent of its anthocyanin content. [Copyright &y& Elsevier]

Purpose: Given the high cost and side effects of radioprotective agents such as amifostine, attention has been focused on potentially equally effective but less expensive and toxic natural substances. We evaluated the potential radioprotective effects of wine in preventing skin toxicity in patients with breast cancer. Methods and Materials: Before treatment, the medical history and habits of patients were assessed and the information recorded in their clinical folders. Patients were divided into three groups based on the dose/fractionation scheme used: control group, 60.4 Gy (standard technique); Modulated Accelerated Radiotherapy in Adjuvant treatment of breast cancer (MARA)-1 protocol group, 44 Gy (concomitant boost to tumoral bed); and MARA-2 protocol group, 60 Gy (concomitant boost to tumoral bed). The impact of the following variables on acute skin toxicity was evaluated by chart review: radiotherapy protocol, planning target volume (PTV), comorbidity (e.g., hypertension and diabetes), hemoglobin level before therapy, adjuvant hormone therapy, adjuvant chemotherapy, cigarette smoking, and drinking habits. Results: The study population consisted of 348 patients. More severe skin toxicity was significantly associated with the radiotherapy protocol (p < 0.001) and median PTV (p = 0.005). In addition, the incidence of acute toxicity of Grade 2 or greater was higher in patients without alcohol intake (38.4% vs. 22.3%, p = 0.021). The daily amount of alcohol intake also influenced the incidence of skin toxicity, with an incidence of 38.4% in patients with no wine intake, 31.8% in patients drinking half a glass per day, 13.6% in patients drinking one glass per day, and 35.0% in patients drinking two glasses per day. Multivariate analysis showed that wine intake, PTV, and radiotherapy protocol were all significantly correlated with acute toxicity. Conclusions: Our results indicate that wine may have a radioprotective effect; however, prospective studies are needed to confirm this beneficial effect of wine and its components. [Copyright &y& Elsevier]