Mariarosaria Persichillo

Adherence to the traditional Mediterranean diet and mortality in subjects with diabetes. Prospective results from the MOLI-SANI study

Background Adherence to the Mediterranean diet is associated with lower mortality in a general population but limited evidence exists on the effect of a Mediterranean diet on mortality in subjects with diabetes. We aim to examine the association between the Mediterranean diet and mortality in diabetic individuals. Design Prospective cohort study on 1995 type 2 diabetic subjects recruited within the MOLI-SANI study. Methods: Food intake was recorded by the European Project Investigation into Cancer and Nutrition food frequency questionnaire. Adherence to the Mediterranean diet was appraised by the Greek Mediterranean diet score. Hazard ratios were calculated using multivariable Cox-proportional hazard models. Results During follow-up (median 4.0 years), 109 all-cause including 51 cardiovascular deaths occurred. A 2-unit increase in Mediterranean diet score was associated with 37% (19%–51%) lower overall mortality. Data remained unchanged when restricted to those being on a hypoglycaemic diet or on antidiabetic drug treatment. A similar reduction was observed when cardiovascular mortality only was considered (hazard ratio = 0.66; 0.46–0.95). A Mediterranean diet-like pattern, originated from principal factor analysis, indicated a reduced risk of overall death (hazard ratio = 0.81; 0.62–1.07). The effect of Mediterranean diet score was mainly contributed by moderate alcohol drinking (14.7% in the reduction of the effect), high intake of cereals (12.2%), vegetables (5.8%) and reduced consumption of dairy and meat products (13.4% and 3.4% respectively). Conclusions The traditional Mediterranean diet was associated with reduced risk of both total and cardiovascular mortality in diabetic subjects, independently of the severity of the disease. Major contributions were offered by moderate alcohol intake, high consumption of cereals, fruits and nuts and reduced intake of dairy and meat products.

Decline of the Mediterranean diet at a time of economic crisis. Results from the Moli-sani study

BACKGROUND AND AIMS Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. METHODS AND RESULTS Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. CONCLUSION Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn.

Adherence to the Mediterranean diet is associated with lower platelet and leukocyte counts: results from the Moli-sani study

Platelet (PLT) and white blood cell (WBC) counts are 2 markers of inflammation and have been linked to the risk for cerebrovascular and coronary heart disease. A Mediterranean diet (MD) has been associated with reduced inflammation and mortality for major chronic diseases. We aimed at evaluating the association between the MD and both PLT and WBC counts. This cross-sectional analysis in a population-based cohort study included 14,586 healthy Italian citizens enrolled within the Moli-sani study. Adherence to MD was appraised by either the MD Score (MDS) or the Italian Mediterranean Index (IMI). PLT and WBC counts were both inversely related to MD adherence (MDS: P < .0001 and P = .008, respectively). As compared with those with poorer MD adherence, subjects with greater adherence had both reduced odds of being in the highest PLT-count group (MDS: odds ratio = 0.50; 95% confidence interval, 0.31-0.80) and increased odds of being in the lowest WBC-count group (IMI: odds ratio = 1.41; 95% confidence interval, 1.07-1.86). The association between WBC count and MDS disappeared when further adjusted for PLT count, whereas the association between PLT count and the MD was not affected by adjustment for WBCs. Food antioxidant and dietary fiber content modified the inverse association between MDS and WBC count and partially accounted for the association with PLTs.

Distribution of short and lifetime risks for cardiovascular disease in Italians.

Background: Guidelines for primary prevention recommend calculation of lifetime risk for cardiovascular disease (CVD) in addition to short-time risk. We aimed at evaluating the distribution of CVD lifetime risk and the percentage of Italians having low short-term, but high lifetime, risk. Design: Cross-sectional general population-based cohort study. Methods: We included 8,403 (46% men) cardiovascular disease-free individuals aged 35–50 years, among those randomly recruited in the framework of the MOLI-SANI cohort. Participants were stratified into three groups: low short-time (10-year) (≤3% and non diabetic)/low lifetime, low short-time/high lifetime, and high short-time risk. Short-time risk was evaluated by the equation provided by the Italian CUORE project. Lifetime risk was evaluated using the algorithm derived from the Framingham cohort. Results: High short-time risk was prevalent in 16% population (32% of men and 2% of women). Among individuals with low short-time risk, 80% had high lifetime risk (82% men and 78% women). The proportion of individuals with very low lifetime risk due to all optimal risk factors was 4.1% only (1.5% men and 6.3% women). Conclusions: A large proportion of Italian adults not qualified for CVD primary prevention because of their very low short-time predicted CVD risk, are in fact at high risk to develop a CVD event in their lifetime; therefore population-based approaches should be sought to modify the overall distribution of individual risk factors. These findings offer helpful information for policy makers involved in contrasting the burden of CVD, especially in women and young men.

Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study.

Elevated D-dimer levels are reportedly associated with higher risk of total mortality in patients with different diseases. We investigated whether a similar association could be found in a large, apparently healthy population. A large sample of individuals (N=17,359, 47% men, age ≥35 years) free of clinically recognized cardiovascular and cancer disease, for whom baseline D-dimer level was available, were studied within the MOLI-SANI cohort, randomly recruited from the general adult population of Southern Italy. The cohort was followed for a median of 4.2 years (73,807 person-years). D-dimer was measured in fresh citrated plasma by an automated latex-enhanced immunoassay. Hazard ratios were calculated using three Cox-proportional hazard models. Two hundred and eighty deaths were recorded. When modeled as a continuous variable, D-dimer level at baseline showed a non-linear association with mortality, whose incidence increased only in the upper quartile of the distribution (D-dimer ≥221 ng/mL). Thus, the group of individuals with D-dimer <221 ng/mL (75% of the population) acted as the reference group, while the remaining individuals were subdivided in tertiles and compared with the former group. Multivariable hazard ratios for mortality were 1.06, 1.45 and 1.97, respectively (P for trend <0.0001) across the three categories of increasing D-dimer concentration. The association was slightly attenuated, but still highly significant (P for trend 0.0002), after further adjustment for white blood cell count and C-reactive protein. In conclusion, Elevated D-dimer levels were independently associated with increased risk of death from any cause in an apparently healthy adult population.

Consumption of healthy foods at different content of antioxidant vitamins and phytochemicals and metabolic risk factors for cardiovascular disease in men and women of the Moli-sani study.

Background/Objectives:To categorize healthy food groups into categories of low-antioxidant (LAC) or high-antioxidant vitamins and phytochemicals content (HAC) and comparatively associate them with metabolic risk factors for cardiovascular disease (CVD).Subjects/Methods:A total of 6879 women (55±12 years) and 6892 men (56±12 years) were analyzed from the Moli–sani cohort, randomly recruited from the general population. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The antioxidant content of each food group was evaluated using Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione and United States Department of Agriculture (USDA) food composition tables. Healthy foods, according to a Mediterranean dietary pattern, were categorized into HAC or LAC; total food antioxidant content (FAC) score was constructed for a comparative evaluation of the consumption of these two groups.Results:In men, an increase in FAC score, which represents an increased consumption of HAC with respect to LAC foods, was associated with a decrease in systolic blood pressure, diastolic blood pressure and C-reactive protein (CRP) (β=−0.5, P=0.02, β=−0.3, P=0.02 and β=−0.03, P=0.03, respectively). Logistic regression analyses showed that in men 15% (30 units) increase in FAC score was associated with 6% decrease in the likelihood of having hypertension (odds ratio (OR)=0.94, 95% confidence interval (CI) 0.91–0.98) and 3% decrease in the likelihood of having a high CRP risk level (OR=0.97, 95% CI 0.94–0.99). No significant associations were observed in women.Conclusions:A possible greater protective role of healthy HAC as compared with healthy LAC foods on hypertension and inflammation was detected in men. These results stress the importance of studying healthy foods according to their content in antioxidant vitamins and phytochemicals, in primary prevention of CVD.

Polyphenol intake is associated with low-grade inflammation, using a novel data analysis from the Moli-sani study

The association of polyphenol content of human diet with low-grade inflammation is not yet fully understood. It was the objective of this study to evaluate the association of flavonoid and lignan intake with frequently used and easily applicable in clinical practice low-grade inflammation biomarkers, in a novel holistic approach. A total of 5,948 women and 5,965 men (aged ≥ 35 years) were analysed from the Moli-sani cohort, randomly recruited from the general population. The EPIC-FFQ was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated using Eurofir eBASIS and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of diet in these nutrients. CRP levels, WBC and PLT count and granulocyte to lymphocyte ratio were conceived as low-grade inflammation biomarkers. INFLA-score was constructed summarizing synergistic effects of these biomarkers. The INFLA-score was negatively associated with PAC-score in different levels of adjustment, in both genders (for all β-coef<0, P<0.05). 10 units increase in PAC-score was associated with 5-8% decrease in the likelihood of higher low-grade inflammation status (i.e. higher quartile of INFLA-score) in men and women (odds ratio [ORs] 0.92 to 0.95, p<0.05). The total variation of INFLA-score that was explained by PAC-score was estimated to be 16.7% in women and 9.1% in men (%R²=16.7 and 9.1). In conclusion, polyphenol content of diet evaluated in a holistic approach was negatively associated with a score of low-grade inflammation biomarkers in a large population based study. For the first time low-grade inflammation was evaluated in a holistic way through INFLA-score and was associated with polyphenol content of diet.

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.

Nut consumption is inversely associated with both cancer and total mortality in a Mediterranean population: Prospective results from the Moli-sani study

Nut intake has been associated with reduced inflammatory status and lower risk of CVD and mortality. The aim of this study was to examine the relationship between nut consumption and mortality and the role of inflammation. We conducted a population-based prospective investigation on 19 386 subjects enrolled in the Moli-sani study. Food intake was recorded by the Italian version of the European Project Investigation into Cancer and Nutrition FFQ. C-reactive protein, leucocyte and platelet counts and the neutrophil:lymphocyte ratio were used as biomarkers of low-grade inflammation. Hazard ratios (HR) were calculated using multivariable Cox proportional hazard models. During a median follow-up of 4·3 years, 334 all-cause deaths occurred. As compared with subjects who never ate nuts, rare intake (≤2 times/month) was inversely associated with mortality (multivariable HR=0·68; 95 % CI 0·54, 0·87). At intake ≥8 times/month, a greater protection was observed (HR=0·53; 0·32, 0·90). Nut intake (v. no intake) conveyed a higher protection to individuals poorly adhering to the Mediterranean diet (MD). A significant reduction in cancer deaths (HR=0·64; 95 % CI 0·44, 0·94) was also observed, whereas the impact on CVD deaths was limited to an inverse, but not significant, trend. Biomarkers of low-grade inflammation were reduced in nut consumers but did not account for the association with mortality. In conclusion, nut intake was associated with reduced cancer and total mortality. The protection was stronger in individuals with lower adherence to MD, whereas it was similar in high-risk groups (diabetics, obese, smokers or those with the metabolic syndrome), as compared with low-risk subjects. Inflammation did not explain the observed relationship.

A score of low-grade inflammation and risk of mortality: prospective findings from the Moli-sani study

Low-grade inflammation is associated with an increased risk of chronic degenerative disease, but its relationship with mortality is less well explored. We aimed at evaluating, at a large epidemiological level, the possible association of low-grade inflammation, as measured by a composite score, with overall mortality risk. We conducted a population-based prospective investigation on 20,337 adult subjects free from major hematological disease and acute inflammatory status, randomly recruited from the general population of the Moli-sani study. A low-grade inflammation score was obtained from the sum of 10-tiles of plasmatic (C-reactive protein) and cellular (leukocyte and platelet counts, granulocyte/lymphocyte ratio) biomarkers of low-grade inflammation; higher levels indicated increased low-grade inflammation. Hazard ratios were calculated using multivariable Cox proportional hazard models with 95% confidence intervals. At the end of follow-up (median 7.6 years), 837 all-cause deaths were recorded. As compared to subjects in the lowest quartile of the low-grade inflammation score, those in the highest category had a significantly increased risk in overall mortality (HR=1.44; 1.17–1.77), independently of possible confounders, including the presence of chronic diseases and a number of health-related behaviors. The magnitude of the association of low-grade inflammation with mortality was relatively higher in type 2 diabetic patients (HR=2.90; 1.74–4.84) and in individuals with a history of cardiovascular disease (HR=2.48; 1.50–4.11) as compared to their counterparts who were free from the disease. In conclusion, an elevated degree of low-grade inflammation, as measured by a composite score of inflammatory biomarkers, is an independent risk factor for total mortality in an apparently healthy adult general population.