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51. Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods

Author: Betül Toprak, Stephanie Brandt, Jan Brederecke, Francesco Gianfagna, Julie K K Vishram-Nielsen, Francisco M Ojeda, Simona Costanzo, Christin S Börschel, Stefan Söderberg, Ioannis Katsoularis, Stephan Camen, Erkki Vartiainen, Maria Benedetta Donati, Jukka Kontto, Martin Bobak, Ellisiv B Mathiesen, Allan Linneberg, Wolfgang Koenig, Maja-Lisa Løchen, Augusto Di Castelnuovo, Stefan Blankenberg, Giovanni de Gaetano, Kari Kuulasmaa, Veikko Salomaa, Licia Iacoviello, Teemu Niiranen, Tanja Zeller, and Renate B Schnabel
Subjects: Kardiologi, Epidemiology, Physiology (medical), Machine learning, Cardiac and Cardiovascular Systems, Community, Cardiology and Cardiovascular Medicine, Risk Prediction, Atrial fibrillation, Biomarkers
Abstract: Aims To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. Methods and results In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82–2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13–1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10–1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02–1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index. Conclusion Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.
Published: 2023

52. Joint association of food nutritional profile by Nutri-Score front-of-pack label and ultra-processed food intake with mortality: Moli-sani prospective cohort study

Author: Marialaura, Bonaccio, Augusto, Di Castelnuovo, Emilia, Ruggiero, Simona, Costanzo, Giuseppe, Grosso, Amalia, De Curtis, Chiara, Cerletti, Maria Benedetta, Donati, Giovanni, de Gaetano, Licia, Iacoviello, and Livia, Rago
Subjects: Adult, Male, Eating, Cardiovascular Diseases, Humans, Fast Foods, Female, General Medicine, Prospective Studies, Nutrients, Middle Aged
Abstract: ObjectiveTo jointly analyse two food dimensions, the Food Standards Agency Nutrient Profiling System (FSAm-NPS), used to derive the Nutri-Score front-of-pack label, and the NOVA classification in relation to mortality.DesignProspective cohort study.SettingMoli-sani Study, Italy 2005-10.Participants22 895 participants (mean age 55 (SD 12) years; 48% men).Main outcomes measuresAssociations between dietary exposures and mortality risk, assessed using multivariable cause specific Cox proportional hazard models controlled for known risk factors.ResultsA total of 2205 deaths occurred during 272 960 person years of follow-up. In the highest quarter of the FSAm-NPS index compared with the lowest quarter, multivariable adjusted hazard ratios for all cause and cardiovascular mortality were 1.19 (95% confidence interval 1.04 to 1.35; absolute risk difference 4.3%, 95% confidence interval 1.4% to 7.2%) and 1.32 (1.06 to 1.64; 2.6%, 0.3% to 4.9%), respectively. The hazard ratios were 1.19 (1.05 to 1.36; absolute risk difference 9.7%, 5.0% to 14.3%) and 1.27 (1.02 to 1.58; 5.0%, 1.2% to 8.8%), respectively, for all cause and cardiovascular mortality when the two extreme categories of ultra-processed food intake were compared. When these two indices were analysed jointly, the magnitude of the association of the FSAm-NPS dietary index with all cause and cardiovascular mortality was attenuated by 22.3% and 15.4%, respectively, whereas mortality risks associated with high ultra-processed food intake were not altered.ConclusionsAdults with the lowest quality diet, as measured using the FSAm-NPS dietary index (underpinning the Nutri-Score), and the highest ultra-processed food consumption (NOVA classification) were at the highest risk for all cause and cardiovascular mortality. A significant proportion of the higher mortality risk associated with an elevated intake of nutrient poor foods was explained by a high degree of food processing. In contrast, the relation between a high ultra-processed food intake and mortality was not explained by the poor quality of these foods.
Published: 2022

53. Association between BMI, RFM and mortality and possible mediators: prospective findings from the Moli-sani study

Author: Anwal Ghulam, Francesco Gianfagna, Marialaura Bonaccio, Simona Costanzo, Augusto Di Castelnuovo, Amalia De Curtis, Alessandro Gialluisi, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, and Licia Iacoviello
Abstract: Background Body mass index (BMI) is the most frequently used adiposity measure, yet it is unable to differentiate fat mass from lean mass. Relative fat mass (RFM) has been proposed as alternative. The aim of this paper is to study RFM and BMI association with mortality in a general Italian population and potential mediators. Methods 20,587 individuals from the Moli-sani cohort were analysed (mean age = 54 ± 11, 52% women, median follow up = 11.2years, interquartile range 1.96 years). Cox regressions were used to assess BMI, RFM and their interactive association with mortality. Dose-response relationships were assessed with spline regression, mediation analysis was performed. All analyses were separated for men and women. Results Men and women with BMI > 35 kg/m2 and men in the 4th quartile of RFM showed an independent association with mortality (HR = 1.71, 95%CI = 1.30–2.26 BMI in men, HR = 1.37, 95%CI = 1.01–1.85 BMI in women, HR = 1.37 CI95%=1.11–1.68 RFM in men), that was lost once adjusted for potential mediators. Cubic splines showed a U-shaped association for BMI in men and women, and for RFM in men. Mediation analysis showed that 46.5% of the association of BMI with mortality in men was mediated by glucose, C reactive protein, forced expiratory volume in 1 second (FEV1) and cystatin C; 82.9% of the association of BMI in women was mediated by HOMA index, cystatine C and FEV1; lastly 55% of RFM association with mortality was mediated by glucose, FEV1 and cystatin C. Regression models including BMI and RFM showed that RFM drives most of the risk in men, but is not predictive in women. Conclusions The association between anthropometric measures and mortality is U shaped and it is largely dependent on sex. Associations were mediated by glucose metabolism, renal and lung function. Public health should mainly focus on severely obese people, or people with impaired metabolic, renal, or respiratory function.
Published: 2022

54. Increased Adherence to a Mediterranean Diet Is Associated With Reduced Low-Grade Inflammation after a 12.7-Year Period: Results From the Moli-sani Study

Author: Marialaura Bonaccio, Simona Costanzo, Augusto Di Castelnuovo, Alessandro Gialluisi, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, and Licia Iacoviello
Subjects: Nutrition and Dietetics, Change in diet quality, Mediterranean diet, Inflammatory markers, General Medicine, Cardiovascular disease risk factors, Food Science
Abstract: There is little knowledge on the association of changes over time in adherence to the 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 MD was estimated by a Mediterranean Diet Score ranging from 0 to 9 points, and the exposure was change in this score measured after a median 12.7-y period.This study included a sub-group 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 9 established CVD risk factors (e.g. serum lipids, blood pressure) and 4 inflammatory markers (including C-reactive protein), respectively, were measured both at enrolment and after the same 12.7-y 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 -0.025), but had little or no impact on the CVD risk score (β=-0.200; 95%CI -0.752, 0.351), as compared to 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, as compared to the reduced consumption group.An increased adherence to a traditional Mediterranean Diet 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.
Published: 2023

55. The tenth anniversary as a UNESCO world cultural heritage: an unmissable opportunity to get back to the cultural roots of the Mediterranean diet

Author: Licia Iacoviello, Giovanni de Gaetano, Marialaura Bonaccio, and Maria Benedetta Donati
Subjects: 0301 basic medicine, Economic growth, Food intake, Mediterranean diet, Population, Biodiversity, Medicine (miscellaneous), 030209 endocrinology & metabolism, Consumption (sociology), Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Humans, education, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, Nutritional epidemiology, digestive, oral, and skin physiology, Feeding Behavior, Diet, Cultural heritage, Anniversaries and Special Events, UNESCO, Geography, Chronic Disease, Food systems
Abstract: In 2010, the Mediterranean diet was awarded the recognition of UNESCO as an Intangible Heritage of Humanity because of its complex interplay between several factors, including skills, knowledge, processing, cooking, and particularly the sharing and consumption of food. Also, the Mediterranean way of eating emphasizes local food, seasonality and biodiversity. Actually, all these aspects are almost completely neglected by the current nutrition research, which rather focuses on amount of food consumed by an individual or a given population but rarely simultaneously considers how foods are matched, whether they are locally-grown or consumed convivially. Basically, nutritional epidemiology usually ends up with classifying populations as highly or poorly adhering to a Mediterranean diet on the basis of the quantity of food consumed with poor or little knowledge on other features of this eating model. As such, this approach is likely to miss important information that could turn out to be as crucial for health as the traditional analysis of food intake. Since a global industrial food system has emerged, traditional diets are facing a global food challenge threating their own survival in the next decades. To transmit the Mediterranean heritage to future generations, it is important to get back to its roots by disentangling the complexity of this diet, which is not merely a healthful model to defeat chronic diseases and improve survival. The Mediterranean diet is a cultural heritage strictly tied to its people and territories. Nutritional epidemiology is now challenged to account for all these aspects in future health research.
Published: 2021

56. Association of nutritional glycaemic indices with global DNA methylation patterns: results from the Moli-sani cohort

Author: Fabrizia, Noro, Federica, Santonastaso, Annalisa, Marotta, Marialaura, Bonaccio, Sabatino, Orlandi, Alfonsina, Tirozzi, Simona, Costanzo, Amalia, De Curtis, Francesco, Gianfagna, Augusto, Di Castelnuovo, Furio, Brighenti, Chiara, Cerletti, Maria Benedetta, Donati, Giovanni, de Gaetano, Licia, Iacoviello, Alessandro, Gialluisi, Benedetta, Izzi, and Americo, Bonanni
Subjects: Male, Glycaemic index, Hydroxymethylation, Metabolic disorders, DNA Methylation, Glycaemic load, Methylation, Diet, Glycemic Index, Genetics, Linear Models, Humans, Female, Molecular Biology, Genetics (clinical), Developmental Biology
Abstract: Background High dietary glycaemic index (GI) and load (GL) have been associated with increased risk of various cardiometabolic conditions. Among the molecular potential mechanisms underlying this relationship, DNA methylation has been studied, but a direct link between high GI and/or GL of diet and global DNA methylation levels has not been proved yet. We analyzed the associations between GI and GL and global DNA methylation patterns within an Italian population. Results Genomic DNA methylation (5mC) and hydroxymethylation (5hmC) levels were measured in 1080 buffy coat samples from participants of the Moli-sani study (mean(SD) = 54.9(11.5) years; 52% women) via ELISA. A 188-item Food Frequency Questionnaire was used to assess food intake and dietary GI and GL for each participant were calculated. Multiple linear regressions were used to investigate the associations between dietary GI and GL and global 5mC and 5hmC levels, as well as the proportion of effect explained by metabolic and inflammatory markers. We found negative associations of GI with both 5mC (β (SE) = − 0.073 (0.027), p = 0.007) and 5hmC (− 0.084 (0.030), p = 0.006), and of GL with 5mC (− 0.14 (0.060), p = 0.014). Circulating biomarkers did not explain the above-mentioned associations. Gender interaction analyses revealed a significant association of the gender-x-GL interaction with 5mC levels, with men showing an inverse association three times as negative as in women (interaction β (SE) = − 0.16 (0.06), p = 0.005). Conclusions Our findings suggest that global DNA methylation and hydroxymethylation patterns represent a biomarker of carbohydrate intake. Based on the differential association of GL with 5mC between men and women, further gender-based separate approaches are warranted.
Published: 2022

57. Different Anticoagulant Regimens, Mortality, and Bleeding in Hospitalized Patients with COVID-19: A Systematic Review and an Updated Meta-Analysis

Author: Giovanni de Gaetano, Licia Iacoviello, Simona Costanzo, Maria Benedetta Donati, Augusto Di Castelnuovo, and Roberta Parisi
Subjects: medicine.medical_specialty, medicine.drug_class, Hemorrhage, heparin, 030204 cardiovascular system & hematology, Disease-Free Survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, medicine, Humans, Hospital Mortality, 030212 general & internal medicine, coagulation, Survival rate, SARS-CoV-2, business.industry, Anticoagulant, Anticoagulants, COVID-19, Retrospective cohort study, bleeding, mortality, Hematology, Intensive care unit, Confidence interval, COVID-19 Drug Treatment, Hospitalization, Survival Rate, Clinical trial, Relative risk, Meta-analysis, Cardiology and Cardiovascular Medicine, business
Abstract: We conducted a systematic review and a meta-analysis to assess the association of anticoagulants and their dosage with in-hospital all-cause mortality in COVID-19 patients. Articles were retrieved until January 8, 2021, by searching in seven electronic databases. The main outcome was all-cause mortality occurred during hospitalization. Data were combined using the general variance-based method on the effect estimate for each study. Separate meta-analyses according to type of COVID-19 patients (hospitalized or intensive care unit [ICU] patients), anticoagulants (mainly heparin), and regimens (therapeutic or prophylactic) were conducted. A total of 29 articles were selected, but 23 retrospective studies were eligible for quantitative meta-analyses. No clinical trial was retrieved. The majority of studies were of good quality; however, 34% did not distinguish heparin from other anticoagulants. Meta-analysis on 25,719 hospitalized COVID-19 patients showed that anticoagulant use was associated with 50% reduced in-hospital mortality risk (pooled risk ratio [RR]: 0.50, 95% confidence interval [CI]: 0.40–0.62; I 2: 87%). Both anticoagulant regimens (therapeutic and prophylactic) reduced in-hospital all-cause mortality, compared with no anticoagulation. Particularly in ICU patients, the anticoagulant therapeutic regimen was associated with a reduced in-hospital mortality risk (RR: 0.30, 95% CI: 0.15–0.60; I 2: 58%) compared with the prophylactic one. However, the former was also associated with a higher risk of bleeding (RR: 2.53, 95% CI: 1.60–4.00; I 2: 65%). Anticoagulant use, mainly heparin, reduced all-cause mortality in COVID-19 patients during hospitalization. Due to the higher risk of bleeding at therapeutic doses, the use of prophylactic dosages of anticoagulant is probably to be preferred in noncritically ill COVID-19 patients.
Published: 2021

58. Egg consumption and risk of all-cause and cause-specific mortality in an Italian adult population

Author: Ruggiero, E, Di Castelnuovo, A, Costanzo, S, Persichillo, M, De Curtis, A, Cerletti, C, Donati, Mb, de Gaetano, G, Iacoviello, L, Bonaccio, M, Moli-sani Study Investigators: Licia Iacoviello, Giovanni de Gaetano, Maria Benedetta Donati, Marialaura, Bonaccio, Americo, Bonanni, Chiara, Cerletti, Simona, Costanzo, Amalia De Curtis, Augusto Di Castelnuovo, Francesco, Gianfagna, Mariarosaria, Persichillo, Teresa Di Prospero, Jos, Vermylen, Ignacio De Paula Carrasco, Antonio, Spagnuolo, Deodato, Assanelli, Vincenzo, Centritto, Marco, Olivieri, Teresa, Panzera, Marialaura Bonaccio Simona Costanzo Simona Esposito, Gialluisi, A, Emilia, Ruggiero, Sara, Magnacca, Benedetta, Izzi, Annalisa, Marotta, Fabrizia, Noro, Roberta, Parisi, Alfonsina, Tirozzi, Francesca, Bracone, Francesca De Lucia, Cristiana, Mignogna, and Livia, Rago
Subjects: Adult, Male, Mediterranean diet, Eggs, Medicine (miscellaneous), Physiology, Blood lipids, Disease, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Cause of Death, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Mortality risk, Cause of death, Nutrition and Dietetics, business.industry, Hazard ratio, Original Contribution, Dietary cholesterol, Diet, Italy, Cardiovascular Diseases, Cohort, Female, business, Cohort study
Abstract: Purpose Dietary guidelines recommend to limit egg consumption to 4 servings per week but the relation between egg intake and health outcomes is still controversial. To evaluate the association of egg consumption and mortality risk in Italian adults and to investigate nutritional factors and serum lipids as potentially explaining such associations. Methods Longitudinal analysis on 20,562 men and women aged ≥ 35y, free from cardiovascular disease (CVD) and cancer belonging to the Moli-sani Study cohort (enrolled 2005–2010) followed up for a median of 8.2 years. Results In multivariable-adjusted analysis as compared to low intake (> 0 ≤ 1 egg/week), eating > 4 eggs/week led to an increased risk of all-cause (Hazard ratio [HR] = 1.50; 95%CI 1.13–1.99), CVD (HR = 1.75; 1.07–2.87) and cancer mortality (HR = 1.52; 0.99–2.33). Similarly, an intake of 2–4 eggs/week was associated with higher all-cause (HR = 1.22; 1.01–1.46) and CVD mortality risk (HR = 1.43; 1.03–1.97). An increase of 1 egg per week was associated with higher mortality risk among high-risk individuals, such as those with hypertension and hyperlipidaemia. Dietary cholesterol explained about 43.0% and 39.3% (p values e.g., total cholesterol) accounted for a small proportion of egg-mortality relation. Conclusions Among Italian adults, high egg consumption leads to an increased risk of all-cause and CVD mortality, with the risk being evident even at the recommended intake of 2–4 eggs per week. A substantial part of this association was likely due to the egg contribution to dietary cholesterol. Our findings suggest limiting the consumption of eggs in the diet and these results should be considered in the development of dietary guidelines and updates.
Published: 2021

59. Combined influence of depression severity and low-grade inflammation on incident hospitalization and mortality risk in Italian adults

Author: Chiara Cerletti, Augusto Di Castelnuovo, Simona Costanzo, Alessandro Gialluisi, Licia Iacoviello, Francesca Bracone, Amalia De Curtis, Marialaura Bonaccio, Giovanni de Gaetano, Moli-sani Study Investigators, Sara Magnacca, and Maria Benedetta Donati
Subjects: Adult, Male, Mediation (statistics), medicine.medical_specialty, lifestyles, Systemic inflammation, Low grade inflammation, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, cardiovascular disease, Internal medicine, Diabetes mellitus, Humans, cancer, Medicine, hospitalizations, Stroke, Depression (differential diagnoses), diabetes, business.industry, medicine.disease, mortality, stroke, 030227 psychiatry, Hospitalization, Patient Health Questionnaire, Psychiatry and Mental health, Clinical Psychology, Italy, depression, inflammation, Cohort, Female, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background Depression and low-grade systemic inflammation are associated risk factors for hospitalizations and mortality, although the nature of this relationship is under-investigated. Methods We performed multivariable Cox regressions of first hospitalization/mortality for all and specific causes vs depression severity, in an Italian population cohort (N=13,176; age≥35 years; 49.4% men), incrementally adjusting for sociodemographic, health and lifestyle factors. We tested potential mediation, additive and interactive effects of INFLA-score, a composite circulating inflammation index, and potential concurrent mediations of main lifestyles and chronic conditions. Results Over 4,856 hospitalizations (median follow-up 7.28 years), we observed an increased incident risk of events by 24% (CI=17-32%) and 59% (30-90%) for moderate and severe depression, which also showed a 125% (33-281%) increased risk of all-cause mortality (over 471 deaths, 8.24 years). These remained stable after adjustment for lifestyles, health conditions and INFLA-score, which explained 2.1%, 7.6%, 16.3% and 8%, 14.9% and 12% of depression influence on hospitalizations and mortality risk, respectively. These proportions remained substantially stable after reciprocal adjustments. INFLA-score showed significant additive (but not interactive) effects on both hospitalizations and mortality risk. Limitations Depression severity was defined using a sub-version of Patient Health Questionnaire 9, which was validated here. Directionality links among exposures could not be established since they were collected simultaneously. Conclusions These findings suggest a combined influence of depression and low-grade inflammation on health, which is partly intertwined and dependent on lifestyles and chronic conditions. This suggests the existence of pathways other than inflammation through which depression may play its detrimental effect.
Published: 2021

60. Abstract MP73: Ultra-processed Food Intake And All-cause And Cause-specific Mortality In Subjects With Type 2 Diabetes: Longitudinal Findings From The Moli-sani Study

Author: Marialaura Bonaccio, Simona Costanzo, Augusto Di Castelnuovo, Mariarosaria Persichillo, Sara Magnacca, Amalia De Curtis, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, and Licia Iacoviello
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: Excessive consumption of ultra-processed food (UPF) is associated with increased risk of mortality and disease in general populations but its health impact for individuals with type 2 diabetes is poorly defined. Hypothesis: We assessed the hypothesis of an association between elevated UPF intake and all-cause and cause-specific mortality among subjects with type 2 diabetes. We expect that elevated sugar content of UPF is on the pathway of this relation and that established risk factors might act as potential biological mechanisms linking UPF to mortality. Methods: Longitudinal analysis on 1,068 men and women (mean age 65±10 y) with type 2 diabetes, at the moment of their enrolled in the Moli-sani Study( between 2005 and 2010), and followed for 10.7 y (median). Food intake was assessed, at enrolment, by a 188-item food frequency questionnaire. UPF was defined using the NOVA classification according to degree of processing, and categorized as quartiles of the ratio (%) between UPF (g/d) and total food consumed (g/d). The possible mediating effects of 18 inflammatory, metabolic, cardiovascular and renal biomarkers were evaluated on the basis of percentage changes and associated p values. Results: Study participants reported a median UPF intake of 6.3% (interquartile range: 4.1-9.4%). Food mostly contributing to the total of UPF eaten were processed meat (22.4%), crispbread/rusks (16.6%), non-homemade pizza (11.2%), and cakes/pies/pastries (8.8%). In multivariable-adjusted COX analyses, higher intake of UPF (Q4, ≥9.4% of total food eaten), as opposed to the lowest (Q1, UPF Conclusions: An increased dietary share of UPF was associated with higher hazards of all-cause and CVD mortality among individuals with type 2 diabetes, possibly through the high sugar content of these products. Creatinine, as a marker of renal function, was likely on the pathway between UPF and mortality.
Published: 2022

61. Abstract MP33: Ultra-processed Food Attenuates The Association Of Nutri-score Front-of-pack Label With All-cause Mortality Risk In The Moli-sani Study Cohort

Author: Marialaura Bonaccio, Emilia Ruggiero, Augusto Di Castelnuovo, Simona Costanzo, Simona Esposito, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, and Licia Iacoviello
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Introduction: The Nutri-Score front-of-pack label rates foods according to their nutritional quality while the NOVA classification is focused on degree of food processing; both systems are reported to separately predict mortality in population-based studies. Hypothesis: We tested the following hypotheses: a) both the Nutri-Score and ultra-processed food (UPF) classification predict mortality in a cohort of Italians from the general population; b) UPF accounts for a proportion of the excess of all-cause mortality risk associated with increased levels of the Nutri-Score. Methods: Longitudinal analysis on 22,913 Italian men and women (mean age 54±12 y) from the Moli-sani Study (enrolled between 2005 and 2010) followed for 11.2 y (median). Food intake was assessed by a 188-item food frequency questionnaire. The Food Standards Agency nutrient profiling system (FSAm-NPS) score, used to derive the Nutri-Score, was calculated for each food based on its amount of energy, saturated fat, sugar, sodium, fibre, protein, fruits, vegetables, legumes and nuts per 100 g of product. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed: increased values indicated lower nutritional quality of diet at individual level. UPF was defined by the NOVA classification according to degree of processing, and categorized as quartiles of the ratio (%) between UPF (g/d) and total food eaten (g/d). Results: The FSAm-NPS dietary index and UPF moderately correlated (Pearson’s’ correlation coefficient=0.34), suggesting that these two indices likely cover different, although complementary, dimensions. Multivariable-adjusted hazard ratios [HRs] for all-cause mortality were 1.18 (95%CI 1.03-1.36 Q4 vs Q1) and 1.25 (1.08-1.44 Q4 vs Q1) for the FSAm-NPS dietary index and UPF, respectively. When the two indices were analyzed simultaneously, the magnitude of the association between the FSAm-NPS dietary index with mortality was significantly reduced (HR=1.13; 0.97-1.30 Q4 vs Q1) with UPF explaining 27.5% (p Conclusions: The higher all-cause mortality risk associated with excessive intake of nutrient-poor foods, as reflected by the FSAm-NPS dietary index underpinning the NutriScore front-of-pack label, is largely explained by the degree of food processing of these foods. Food labelling systems developed to help consumers make healthier food choices should account for the degree of food processing in addition to nutritional content.
Published: 2022

62. The inflammatory potential of the diet as a link between food processing and low-grade inflammation: An analysis on 21,315 participants to the Moli-sani study

Author: Cristiana Mignogna, Simona Costanzo, Augusto Di Castelnuovo, Emilia Ruggiero, Nitin Shivappa, James R. Hebert, Simona Esposito, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, and Marialaura Bonaccio
Subjects: Inflammation, Nutrition and Dietetics, Food processing, Food Handling, Pro-inflammatory diet, Middle Aged, Critical Care and Intensive Care Medicine, Low-grade inflammation, Dietary inflammatory index, NOVA classification, Diet, C-Reactive Protein, Cross-Sectional Studies, Fast Foods, Humans, Energy Intake
Abstract: Food processing may adversely affect human health through a variety of mechanisms, including the development of a chronic pro-inflammatory state. In this study we aimed to test the hypothesis that an increasing degree of food processing is directly associated with low-grade inflammation, and evaluate to what extent this association is mediated by the inflammatory potential of highly processed foods.Cross-sectional analysis on 21,315 subjects (mean age 55 ± 3 y) from the Moli-sani Study with complete dietary data collected by a validated 188-item food frequency questionnaire. The NOVA classification was used to categorize foods on the basis of industrial processing as: 1) unprocessed/minimally processed foods; 2) processed culinary ingredients; 3) processed foods; 4) ultra-processed foods (UPF). The inflammatory potential of the diet was evaluated through the Energy-adjusted Dietary Inflammatory Index (E-DII™). Low-grade inflammation was assessed by a composite INFLA-score including C-reactive protein, leukocyte and platelet counts and the granulocyte to lymphocyte ratio.In multivariable-adjusted linear regression models, the INFLA-score was positively associated with E-DII (β = 0.15; 0.10, 0.19), processed foods (β = 0.04; 0.01, 0.08) and UPF (β = 0.13; 0.07, 0.19), but inversely associated with minimally processed foods (β = -0.09; -0.13, -0.06). The E-DII score was inversely associated with minimally processed food (β = -0.40; 95%CI -0.41, -0.39 for 5% increment in the weight ratio) but directly with either processed culinary ingredients (β = 0.18; 0.15, 0.21 for 1% increment), processed food (β = 0.28; 0.27, 0.29 for 5% increment) or UPF (β = 0.34; 0.32, 0.36 for 5% increment). The inclusion of the E-DII into the multivariable model explained 88.5% of the association of processed food with the INFLA-score (p 0.0001) and mitigated by 32.6% (p 0.0001) the association with UPF.The association of UPF with low-grade inflammation is only partially explained by the high pro-inflammatory potential of these foods. Further studies are warranted to test whether the observed adverse relationship of UPF with low-grade inflammation could be triggered by mechanisms that are not directly related to the pro-inflammatory potential of highly processed food products.
Published: 2022

63. Associations between systemic inflammation and somatic depressive symptoms: Findings from the Moli‐sani study

Author: Francesca Bracone, Giovanni de Gaetano, Chiara Cerletti, Alessandro Gialluisi, Licia Iacoviello, Maria Benedetta Donati, Augusto Di Castelnuovo, and Amalia De Curtis
Subjects: Adult, medicine.medical_specialty, media_common.quotation_subject, Systemic inflammation, Gastroenterology, tiredness, Leukocyte Count, 03 medical and health sciences, depressive symptoms, 0302 clinical medicine, Internal medicine, medicine, Humans, atypical depression, Atypical depression, C-reactive protein, appetite, granulocyte-to-lymphocyte ratio, systemic inflammation, white blood cells count, Depression (differential diagnoses), media_common, Inflammation, biology, Depression, business.industry, Appetite, medicine.disease, Obesity, 030227 psychiatry, Patient Health Questionnaire, Psychiatry and Mental health, Clinical Psychology, C-Reactive Protein, Cohort, biology.protein, medicine.symptom, business, Biomarkers, 030217 neurology & neurosurgery
Abstract: BACKGROUND The link between systemic inflammation and depression has been deeply investigated, but relatively few studies explored symptom-specific associations, mostly focusing on common inflammatory biomarkers like C-reactive protein (CRP) levels. METHODS We investigated associations of low-grade inflammation with depressive symptoms assessed through a reduced version of Patient Health Questionnaire 9 (PHQ-9) in a large population-based cohort of adult Italians (N = 13 301). We built logistic regressions between each depressive symptom and composite index of systemic inflammation based on four circulating biomarkers, namely CRP, Plt, WBC, and GLR (INFLA)-score, a composite blood-based inflammation index, and with its component biomarkers, namely CRP, platelets count (Plt), white blood cells count (WBC), and granulocyte-to-lymphocyte ratio (GLR). RESULTS We observed a strong association of the altered appetite/eating symptom with standardized INFLA-score (OR [95% CI] = 1.19 [1.12-1.26]; corrected p = 3.0 × 10-7 ), CRP (1.28 [1.20-1.36]; p = 1.9 × 10-13 ), and WBC (1.13 [1.06-1.20]; p = 2.3 × 10-3 ), and of tiredness/low energy with GLR (1.11 [1.05-1.17]; p = 9.4 × 10-3 ). These associations remained stable within nondepressed participants (PHQ-9
Published: 2020

64. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project:a population-based study

Author: Wojciech Drygas, B Thorand, Salim Dabboura, Satu Männistö, Kari Kuulasmaa, Jean Ferrières, Yuri Nikitin, Benedikt Schrage, Frank Kee, Licia Iacoviello, Inger Njølstad, Dirk Westermann, Jean Dallongeville, Giovanni de Gaetano, Abdonas Tamosiunas, Patrick McElduff, Stefan Blankenberg, Simona Costanzo, Marco M Ferrario, Giovanni Veronesi, Stefan Söderberg, Guido Grassi, Augusto Di Castelnuovo, Veikko Salomaa, Tanja Zeller, Emanuela Pettenuzzo, Marialaura Bonaccio, Marie Moitry, Maria Benedetta Donati, Hermann Brenner, Allan Linneberg, Di Castelnuovo, A, Costanzo, S, Bonaccio, M, Mcelduff, P, Linneberg, A, Salomaa, V, Mannisto, S, Moitry, M, Ferrieres, J, Dallongeville, J, Thorand, B, Brenner, H, Ferrario, M, Veronesi, G, Pettenuzzo, E, Tamosiunas, A, Njolstad, I, Drygas, W, Nikitin, Y, Soderberg, S, Kee, F, Grassi, G, Westermann, D, Schrage, B, Dabboura, S, Zeller, T, Kuulasmaa, K, Blankenberg, S, Donati, M, de Gaetano, G, and Iacoviello, L
Subjects: Population, Medicine (miscellaneous), SDG 3 - Good Health and Well-being, cardiovascular mortality, HDL cholesterol, Environmental health, cancer mortality, cohort study, Medicine, Alcohol intake, education, Beroendelära, Alcohol Intake, Cancer Mortality, Cardiovascular Mortality, Cohort Study, Hdl Cholesterol, Mortality, education.field_of_study, business.industry, Substance Abuse, Public Health, Global Health, Social Medicine and Epidemiology, medicine.disease, mortality, Total mortality, Substance abuse, Population based study, Psychiatry and Mental health, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Observational study, business, Alcohol consumption, Cohort study
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50±13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI)=7–14%] reduction in the risk of total mortality, while intake >20 g/day was associated with a 13% (95% CI=7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake >20 g/day was associated with a 22% (95% CI=10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022

65. Incremental monounsaturated to saturated fat ratio and fibre consumption is associated with a reduction in a composite score of modifiable cardiovascular risk factors: Prospective results from the Moli-sani study

Author: Emilia Ruggiero, Augusto Di Castelnuovo, Simona Costanzo, Simona Esposito, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, and Marialaura Bonaccio
Subjects: Male, Dietary Fiber, Nutrition and Dietetics, Cardiovascular Diseases, Risk Factors, Fatty Acids, Medicine (miscellaneous), Humans, Polyphenols, Female, Prospective Studies, Diet, Mediterranean, Dietary Fats
Abstract: Unsaturated fats, fibre-rich foods and polyphenols are distinctive features of a traditional Mediterranean diet and have pleiotropic properties possibly contributing to reduce the long-term risk of non-communicable diseases and mortality associated with this diet. We aimed to evaluate whether changes over time in dietary fats, fibre and polyphenols consumption are associated with modifications in cardiovascular disease (CVD) risk factors.The analytic sample consists of a sub-cohort of 2023 men and women enrolled in the Moli-sani Study (n = 24,325). Dietary and health data were obtained both at baseline (2005-2010) and at re-examination (2017-2020). The exposures were changes in dietary fats, fibre and polyphenols consumption measured after 12.7 years (median), and the outcome was change in a composite score including 13 modifiable CVD risk factors (e.g., blood lipids, C-reactive protein), measured both at enrolment and after the 12.7 years period.In multivariable-adjusted analysis including lifestyles, sociodemographic and clinical factors, an incremental intake of the ratio of monounsaturated to saturated fats or of fibre was associated with a reduction in the composite score of CVD risk factors (β = -0.086; 95%CI -0.150, -0.021 and β = -0.051; 95%CI -0.091, -0.012, respectively). Change in polyphenol intake was not associated with a substantial variation in the CVD risk score (p = 0.15).An incremental consumption over time of monounsaturated versus saturated fats and of fibre was associated with an improvement in modifiable CVD risk factors as reflected by a composite score.
Published: 2022

66. Dietary factors and the risk of lumbar spinal stenosis: A case–control analysis from the PREFACE study

Author: Emilia Ruggiero, Marialaura Bonaccio, Simona Costanzo, Simona Esposito, Augusto Di Castelnuovo, Ettore Carpineta, Chiara Cerletti, Maria Benedetta Donati, Sergio Paolini, Vincenzo Esposito, Giovanni de Gaetano, Gualtiero Innocenzi, Licia Iacoviello, null Licia Iacoviello, Giovanni Cardarelli, Grazia Centore, Mariacristina Cotugno, Marianna Damiano, Michelangelo De Angelis, Arianna de Gregorio, Alessandro D’Elia, Maria Antonietta Di Santo, Cristina Mancarella, Giovanna Santangelo, Piera Sciarra, Rocco Severino, Tommaso Vangelista, Amalia De Curtis, Mariarosaria Persichillo, Marco Olivieri, Marianna Storto, and Sara Magnacca
Subjects: medicine.medical_specialty, Mediterranean diet, Food Handling, Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), Dietary factors, Disease, Lower risk, Diet, Mediterranean, Food group, Spinal Stenosis, Internal medicine, medicine, Humans, Prospective Studies, education, education.field_of_study, Nutrition and Dietetics, business.industry, Lumbar spinal stenosis, Case-control, medicine.disease, Ultra-processed food, Diet, Sample size determination, Case-Control Studies, Fast Foods, Cardiology and Cardiovascular Medicine, business
Abstract: 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.
Published: 2022

67. Mediterranean diet and other dietary patterns in association with biological aging in the Moli-sani Study cohort

Author: Simona Esposito, Alessandro Gialluisi, Simona Costanzo, Augusto Di Castelnuovo, Emilia Ruggiero, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Marialaura Bonaccio, Americo Bonanni, Francesco Gianfagna, Teresa Di Prospero, Jos Vermylen, Ignacio De Paula Carrasco, Antonio Spagnuolo, Deodato Assanelli, Vincenzo Centritto, Marco Olivieri, Teresa Panzera, Sara Magnacca, Benedetta Izzi, Annalisa Marotta, Fabrizia Noro, Roberta Parisi, Alfonsina Tirozzi, Francesca Bracone, Francesca De Lucia, Cristiana Mignogna, Livia Rago, null Direzione Generale per la Salute - Regione Molise, null Azienda Sanitaria Regionale del Molise, null Molise Dati Spa, null Offices of vital statistics of the Molise region, null Ospedale A. Cardarelli – Campobasso, null Ospedale F. Veneziale – Isernia, null Ospedale San Timoteo - Termoli (CB), null Ospedale Ss. Rosario - Venafro (IS), null Ospedale Vietri – Larino (CB), null Ospedale San Francesco Caracciolo - Agnone (IS), null Casa di Cura Villa Maria - Campobasso, null Ospedale Gemelli Molise - Campobasso, and null IRCCS Neuromed - Pozzilli (IS)
Subjects: Adult, Male, Aging, Nutrition and Dietetics, Nordic diet, Polyphenols, Mediterranean, Critical Care and Intensive Care Medicine, Diet, Mediterranean, Diet, Dash diet, Cohort Studies, Biological aging, Cross-Sectional Studies, Palaeolithic diet, Mediterranean diet, Humans, Female
Abstract: 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.
Published: 2021

68. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. 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Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, AGEM - Endocrinology, metabolism and nutrition, ACS - Diabetes & metabolism, APH - Global Health, ARD - Amsterdam Reproduction and Development, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, Gómez Santos, Santiago Felipe, NCD Risk Factor Collaboration (NCD-RisC), Faculdade de Desporto, Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Eye Centre, Harvard TH Chan School of Public Health, Middlesex University, World Health Organization, Ministry of Health, University of Lausanne, Eduardo Mondlane University, Victor Babes University of Medicine and Pharmacy Timisoara, University of Sydney, Health and Nutrition, University of Auckland, Seoul National University, ICMR - National Institute of Nutrition, Capital Medical University Beijing An Zhen Hospital, Universidad Peruana Cayetano Heredia, University Tunis El Manar, University of Oulu, University of Zagreb, University of Ljubljana, Caja Costarricense de Seguro Social, Al-Quds University, National Center of Public Healthcare, Qatar University, Birzeit University, Usmanu Danfodiyo University Teaching Hospital, Instituto Mexicano del Seguro Social, Flinders University, Mahidol University, BRAC James P Grant School of Public Health, University of Copenhagen, Copenhagen University Hospital, Food and Nutrition Research Institute, Urmia University of Medical Sciences, Instituto Nacional de Ciencias Médicas y Nutrición, University of Amsterdam, Shahrekord University of Medical Sciences, Non-Communicable Diseases Research Center, University of Oslo, University of Bremen, Republican Center for Health Promotion, Endocrinology and Genetics, Princess Nourah bint Abdulrahman University, Kuwait Institute for Scientific Research, King Abdulaziz University, Dasman Diabetes Institute, Aldara Hospital and Medical Center, King Abdullah International Medical Research Center, Luxembourg Institute of Health, Bispebjerg and Frederiksberg Hospital, Barcelona Institute for Global Health CIBERESP, World Health Organization Regional Office for the Eastern Mediterranean, Bombay Hospital and Medical Research Centre, Research Center for Social Determinants of Health, UMR CNRS-MNHN 7206 Eco-anthropologie, University of Lille, Lille University Hospital, Western Norway University of Applied Sciences, Norwegian School of Sport Sciences, Madras Diabetes Research Foundation, Zahedan University of Medical Sciences, National Institute of Public Health, Institute of Public Health of the University of Porto, Norwegian Institute of Public Health, University of Massachusetts Amherst, Abt Associates, University of Iceland, University of Yaoundé1, Federal University of Pelotas, University of Medicine 1, Oulu University Hospital, Banska Bystrica Regional Authority of Public Health, Tel- Aviv University, Hebrew University of Jerusalem, University of Porto Medical School, Neyshabur University of Medical Sciences, Research Institute for Endocrine Sciences, Non- Communicable Diseases Research Center, Indian Council of Medical Research, University of Science and Technology, Medical University of Lodz, Medical University of Gdansk, Universidad Autónoma de Madrid CIBERESP, University of Rzeszów, University of Palermo, Pan American Health Organization, Mohammed V University de Rabat, University of Pernambuco, Baqai Institute of Diabetology and Endocrinology, Universidade Federal de Santa Catarina (UFSC), Dalhousie University, Jordan University of Science and Technology, Federal University of Maranhao, Al-Farabi Kazakh National University, University College Dublin, Christian Medical College, Care and Consumer Protection, Cafam University Foundation, Kazakh National Medical University, Lithuanian University of Health Sciences, University of Saõ Paulo, B J Medical College, Chirayu Medical College, Sunder Lal Jain Hospital, The Hospital for Sick Children, Aga Khan University, Shandong University of Traditional Chinese Medicine, Jiao-Tong University School of Medicine, Universidad de la República, Institute of Medical Research and Medicinal Plant Studies, Ufa Eye Research Institute, Nepal Health Research Council, University of Montenegro, University of Southern Denmark, University of Gothenburg, Universidade Federal do Rio de Janeiro (UFRJ), National Institute for Public Health and the Environment, University of Turin, University College London, Liverpool John Moores University, Nanyang Technological University Singapore, German Institute of Human Nutrition, Endocrinology Research Centre, Centro de Educación Médica e Investigaciones Clínicas, IRCCS Neuromed, Toulouse University School of Medicine, University of Zurich, University Hospital KU Leuven, Flemish Agency for Care and Health, Ghent University, FrieslandCampina, Universidad Central de Venezuela, Bielefeld University, World Health Organization Regional Office for Europe, 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, Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , 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Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta 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, Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria 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Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

69. Risk prediction of atrial fibrillation and its complications in the community using high-sensitivity cardiac troponin I: results from the BiomarCaRE Consortium

Author: Licia Iacoviello, Stefan Blankenberg, H.M Den Ruijterg, Kari Kuulasmaa, Stephan Camen, B Geelhoed, Tanja Zeller, Teemu J. Niiranen, BiomarCaRE, Maria Benedetta Donati, M.L Lochenl, C Boerschel, Renate B. Schnabel, S. Soederberg, Veikko Salomaa, and Allan Linneberg
Subjects: medicine.medical_specialty, Cardiac troponin, business.industry, Internal medicine, Cardiology, medicine, Atrial fibrillation, Sensitivity (control systems), Cardiology and Cardiovascular Medicine, medicine.disease, business
Abstract: Aims Atrial fibrillation (AF) is becoming increasingly common and is associated with serious complications. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury may help close this gap. High-sensitivity troponin I (hsTnI) has emerged as a potential predictor. Methods We investigated the predictive ability of hsTnI for incident AF in 29,227 participants (median age 52.6 years, 51.2% men) across four different European community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) consortium in comparison to CVRF and established biomarkers (high-sensitive C-reactive protein (hsCRP), N-terminal pro B-type natriuretic peptide (NT-proBNP)). Results During a median follow-up of 13.8 (lower and upper quartiles 4.5, 21.3) years, 1,509 (5.2%) participants developed AF. Those in the highest fourth of hsTnI values at baseline (≥5.1 ng/L) had a 2.71-fold (95% confidence interval (CI) 2.31, 3.17; P Conclusion hsTnI as a biomarker of myocardial injury does not improve prediction of AF incidence beyond classical CVRFs. However, it is associated with AF complications and mortality after AF onset probably reflecting underlying subclinical cardiovascular impairment. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union Seventh Framework Programme (FP7/2007-2013
Published: 2021

70. Epidemiological and genetic overlap among biological aging clocks: New challenges in biogerontology

Author: Alessandro Gialluisi, Licia Iacoviello, Maria Benedetta Donati, Alfonsina Tirozzi, Giovanni de Gaetano, Aurelia Santoro, Claudio Franceschi, Chiara Cerletti, Gialluisi A., Santoro A., Tirozzi A., Cerletti C., Donati M.B., de Gaetano G., Franceschi C., and Iacoviello L.
Subjects: Epigenomics, Linkage disequilibrium, medicine.medical_specialty, Aging, Multivariate analysis, Epigenomic, Population, Biology, Affect (psychology), DNA methylation clocks, Biochemistry, Biological aging, Blood age, Brain age, Genetics, Mortality, Telomere length, Epigenesis, Genetic, Machine Learning, Genetic, Epidemiology, medicine, Humans, Epigenetics, education, Molecular Biology, Organism, education.field_of_study, DNA Methylation, Neurology, Evolutionary biology, Genetic marker, DNA methylation clock, Biotechnology, Human
Abstract: Estimators of biological age (BA) - defined as the hypothetical underlying age of an organism - have attracted more and more attention in the last years, especially after the advent of new algorithms based on machine learning and genetic markers. While different aging clocks reportedly predict mortality in the general population, very little is known on their overlap. Here we review the evidence reported so far to support the existence of a partial overlap among different BA acceleration estimators, both from an epidemiological and a genetic perspective. On the epidemiological side, we review evidence supporting shared and independent influence on mortality risk of different aging clocks - including telomere length, brain, blood and epigenetic aging - and provide an overview of how an important exposure like diet may affect the different aging systems. On the genetic side, we apply linkage disequilibrium score regression analyses to support the existence of partly shared genomic overlap among these aging clocks. Through multivariate analysis of published genetic associations with these clocks, we also identified the most associated variants, genes, and pathways, which may affect common mechanisms underlying biological aging of different systems within the body. Based on our analyses, the most implicated pathways were involved in inflammation, lipid and carbohydrate metabolism, suggesting them as potential molecular targets for future anti-aging interventions. Overall, this review is meant as a contribution to the knowledge on the overlap of aging clocks, trying to clarify their shared biological basis and epidemiological implications.
Published: 2021

71. T31. A MULTI-TRAIT ASSOCIATION ANALYSIS OF PLATELET TRAITS AND BRAIN DISORDERS IDENTIFIES NOVEL SUSCEPTIBILITY LOCI FOR MAJOR DEPRESSION, ALZHEIMER AND PARKINSON DISEASE

Author: Alfonsina Tirozzi, Miriam Shasa Quiccione, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, and Alessandro Gialluisi
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published: 2022

72. Ultra-processed food consumption and its correlates among Italian children, adolescents and adults from the Italian NutritionHealth Survey (INHES) cohort study

Author: Marialaura Bonaccio, Emilia Ruggiero, Licia Iacoviello, Chiara Cerletti, Inhes Study Investigators, Giovanni de Gaetano, Simona Costanzo, Augusto Di Castelnuovo, Maria Benedetta Donati, and Simona Esposito
Subjects: 0301 basic medicine, Adult, Male, Mediterranean diet, Adolescent, Food Handling, Population, Medicine (miscellaneous), Mediterranean, Diet, Mediterranean, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, education, Eating behaviour, Child, Aged, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, Sleep quality, business.industry, Socio-economic factors, Public Health, Environmental and Occupational Health, General population, Health Surveys, Ultra-processed food, Diet, Cross-Sectional Studies, Psychosocial factors, Early adolescents, Health survey, Fast Foods, Female, business, Psychosocial, Demography, Cohort study
Abstract: Objective:To assess ultra-processed food (UPF) consumption and its socio-demographic, psychosocial and behavioural correlates in a general population of Italian children, adolescents and adults.Design:Cross-sectional telephone-based surveySetting:Italy, 2010–2013.Participants:In total, 9078 participants (5–97 years) from the Italian Nutrition & Health Survey. Dietary intakes were collected by a 1-d 24-h dietary recall. UPF was defined by the NOVA classification and expressed as percentage of total energies.Results:Average energy intake from UPF (95 % CI) was 17·3 % (17·1 %, 17·6 %) among adults and 25·9 % (24·8 %, 27·0 %) in children/adolescents. Top sources of UPF were processed meats (32·5 %) and bread substitutes (16·7 %). Among adults, age (β = −3·10; 95 % CI (−4·40, −1·80) for >65 years v. 20–40 years; βs are dimensionless) and residing in Southern Italy (β = −0·73; 95 % CI (−1·32, −0·14) v. Northern) inversely associated with UPF. Screen view during meals was directly linked to UPF, as well as poor self-rated health (β = 5·32; 95 % CI (2·66, 7·99)), adverse life events (β = 2·33; 95 % CI (1·48, 3·18)) and low sleep quality (β = 2·34; 95 % CI (1·45, 3·23)). Boys consumed two-point percent more UPF of the total energy than girls (β = 2·01; 95 % CI (0·20, 3·82)). For all ages, a Mediterranean diet was inversely associated with UPF (β = −4·86; 95 % CI (−5·53, −4·20) for good v. poor adherence in adults and (β = −5·08; 95 % CI (−8·38, −1·77) for kids).Conclusions:UPF contributes a modest proportion of energy to the diets of Italian adults while being one-quarter of the total energies in children/adolescents. UPF was associated with several psychosocial factors and eating behaviours. Increased adherence to Mediterranean diet would possibly result in lower UPF consumption.
Published: 2021

73. Abstract 025: Mediterranean Diet Trajectories And Changes In Cardiovascular Risk Factors And Inflammation Markers Over A 12.7 Years Follow-up: Prospective Findings From The Moli-sani Study Cohort

Author: Alessandro Gialluisi, Maria Benedetta Donati, Chiara Cerletti, Marialaura Bonaccio, Simona Costanzo, Claudio Tabolacci, Amalia De Curtis, Augusto Di Castelnuovo, Licia Iacoviello, Giovanni de Gaetano, Mariarosaria Persichillo, and Francesco Facchiano
Subjects: medicine.medical_specialty, Mediterranean diet, Diet quality, business.industry, Physiology (medical), Internal medicine, Cohort, Cardiovascular risk factors, medicine, Inflammation, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Introduction: Trends in diet quality worldwide indicate a progressive decline in adherence to Mediterranean diet (MD), but data on longitudinal individual-level changes are still limited, especially in Mediterranean countries. Hypothesis: We assessed the hypothesis of an association, in a Mediterranean population, between life course trajectories in MD and concurrent long-term modifications of risk factors for cardiovascular disease (CVD) and inflammatory markers. Methods: We followed 2,107 men and women (mean age at baseline 54.6±8.8 y) from the Moli-sani Study (Italy) between 2005 and 2020. Dietary data were measured at baseline and at a re-examination (after an average of 12.7 years) and were collected by a 188-item food frequency questionnaire. Adherence to MD was estimated by a Mediterranean diet score based on 9 food groups, ranging from 0 to 9 points. MD trajectories were identified as downward (-6 to -2 points in MDS), relatively stable (-1 to 0) and upward (1 to 6). Inflammation was measured by both an INFLA-score including C-reactive protein and cellular markers ( e.g ., leukocyte count) and a CYTO-score including 14 selected analytes (cytokines, chemokines and growth factors). Regression models were used to examine changes in MDS, CVD risk factors and inflammation markers within the same period. Results: Overall, adherence to MD decreased by an average of 6.5% over follow-up. As opposed to the downward, an upward trajectory in MD adherence was inversely associated with the INFLA-score (β=-0.177; 95%CI -0.296, -0.058) and the CYTO-score (β=-0.311; 95%CI -0.548, -0.073). No significant changes were observed for CVD risk factors, with the exception of an increase in blood glucose (β=0.121; 95%CI 0.001, 0.241) and systolic blood pressure (β=0.110; 95%CI 0.003, 0.217) associated with an upward MD trajectory. Conclusions: In a large sample of Mediterranean individuals, diet quality, as reflected by adherence to an MD, has been declining over the last decade. However, in the group of subjects who improved their adherence to an MD, a significant reduction of markers of an inflammatory status was documented, possibly predisposing to a better duration and quality of life.
Published: 2021

74. Socioeconomic trajectories across the life course and risk of total and cause-specific mortality: prospective findings from the Moli-sani Study

Author: Mariarosaria Persichillo, Amalia De Curtis, Licia Iacoviello, Maria Benedetta Donati, Giovanni de Gaetano, Marialaura Bonaccio, Chiara Cerletti, Simona Costanzo, and Augusto Di Castelnuovo
Subjects: Adult, Male, cumulative socioeconomic disadvantage, Epidemiology, Health Behavior, Population, Disease, 030204 cardiovascular system & hematology, Lower risk, socioeconomic status, 03 medical and health sciences, 0302 clinical medicine, Residence Characteristics, Risk Factors, Cause of Death, Surveys and Questionnaires, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, education, Life Style, Socioeconomic status, life course, socioeconomic trajectories, inflammation, mortality, education.field_of_study, business.industry, Public Health, Environmental and Occupational Health, Cause specific mortality, Middle Aged, Health Surveys, Educational attainment, Italy, Social Class, Socioeconomic Factors, Cardiovascular Diseases, Cohort, Educational Status, Life course approach, Female, business, Demography
Abstract: BackgroundA life course approach has been suggested as the most appropriate to establish the total impact of socioeconomic status (SES) on adult health outcomes; however, such an approach has been poorly used within Mediterranean populations. We aimed to examine the SES trajectories from childhood to adulthood associated with mortality risk in a large general population-based cohort and to test potential pathways (eg, inflammation) underlying such associations.MethodsLongitudinal analyses on 22 194 subjects recruited in the Moli-sani Study, Italy (2005–2010). Low and high SES in childhood, educational attainment (low/high) and SES during adulthood (measured by a score including material resources and dichotomised as low/high) were used to define overall trajectories.ResultsOver 8.3 years of follow-up, 1155 deaths occurred. In the group with poor childhood SES, an upward trajectory in both educational and material circumstances was associated with lower risk of all-cause death (HR=0.64; 95% CI 0.47 to 0.87), as opposed to subjects who remained stably low (low education and adulthood SES). Subjects with high childhood SES, but not educational achievement, were at increased risk of total and cardiovascular disease (CVD) death, although reporting higher material SES in adult life, as compared with the stably high SES group (HR=1.44; 1.02 to 2.02 and HR=1.90; 1.10 to 3.28, respectively). Inflammatory markers marginally accounted for such associations.ConclusionFor individuals with low SES in early life, an educational and material upward trajectory over the life course was associated with lower mortality risk. In the high SES childhood group, lack of a higher educational attainment appeared to be unfavourably associated with survival.
Published: 2019

75. Sex-Specific Epidemiology of Heart Failure Risk and Mortality in Europe

Author: Francesco Gianfagna, Christina Magnussen, Erkki Vartiainen, Renate B. Schnabel, Simona Costanzo, Maria Hughes, Hester M. den Ruijter, Allan Linneberg, Gerard Pasterkamp, Veikko Salomaa, Susana Sans, Pekka Jousilahti, Licia Iacoviello, Martin Bobak, Teemu J. Niiranen, Stefan Söderberg, Stefan Blankenberg, Giovanni de Gaetano, Francisco Ojeda, Kari Kuulasmaa, Torben Jørgensen, Tarja Palosaari, Maria Benedetta Donati, and Tanja Zeller
Subjects: medicine.medical_specialty, business.industry, 030204 cardiovascular system & hematology, medicine.disease, Sex specific, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Heart failure, Epidemiology, Cohort, medicine, 030212 general & internal medicine, Cardiology and Cardiovascular Medicine, business
Abstract: OBJECTIVES This study investigates differences between women and men in heart failure (HF) risk and mortality. BACKGROUND Sex differences in HF epidemiology are insufficiently understood. METHODS I ...
Published: 2019

76. Ultra-processed food intake and all-cause and cause-specific mortality in individuals with cardiovascular disease: the Moli-sani Study

Author: Marialaura Bonaccio, Amalia De Curtis, Chiara Cerletti, Mariarosaria Persichillo, Licia Iacoviello, Giovanni de Gaetano, Augusto Di Castelnuovo, Sara Magnacca, Simona Costanzo, and Maria Benedetta Donati
Subjects: Male, medicine.medical_specialty, Renal function, Processed food intake, Disease, Logistic regression, Eating, Secondary cardiovascular prevention, Internal medicine, Cause of Death, medicine, Humans, Mortality, Biomarkers, Ultra-processed food, Aged, biology, business.industry, Hazard ratio, Middle Aged, Confidence interval, Diet, Cystatin C, Quartile, Cardiovascular Diseases, biology.protein, Fast Foods, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Aims To evaluate the association of ultra-processed food (UPF) intake and mortality among individuals with history of cardiovascular disease (CVD) and analyse some biological pathways possibly relating UPF intake to death. Methods and results Longitudinal analysis on 1171 men and women (mean age: 67 ± 10 years) with history of CVD, recruited in the Moli-sani Study (2005–10, Italy) and followed for 10.6 years (median). Food intake was assessed using a food frequency questionnaire. UPF was defined using the NOVA classification according to degree of processing and categorized as quartiles of the ratio (%) between UPF (g/day) and total food consumed (g/day). The mediating effects of 18 inflammatory, metabolic, cardiovascular, and renal biomarkers were evaluated using a logistic regression model within a counterfactual framework. In multivariable-adjusted Cox analyses, higher intake of UPF (Q4, ≥11.3% of total food), as opposed to the lowest (Q1, UPF Conclusion A diet rich in UPF is associated with increased hazards of all-cause and CVD mortality among individuals with prior cardiovascular events, possibly through an altered renal function. Elevated UPF intake represents a major public health concern in secondary CVD prevention.
Published: 2021

77. Impact of Nationwide Lockdowns Resulting from The First Wave of the COVID-19 Pandemic on Food Intake, Eating Behaviours and Diet Quality: A Systematic Review

Author: Licia Iacoviello, Anwal Ghulam, Marialaura Bonaccio, Giovanni De Gaetano, Cristiana Mignogna, Maria Benedetta Donati, Chiara Cerletti, and Simona Costanzo
Subjects: Nutrition and Dietetics, eating behaviors, pandemic, digestive, oral, and skin physiology, eating behaviours, Medicine (miscellaneous), COVID-19, Review, diet quality, confinement, dietary changes, lockdown, AcademicSubjects/MED00060, Food Science
Abstract: The lockdowns resulting from the first wave of the coronavirus disease 2019 (COVID-19) pandemic impacted deeply on all life activities, including diet. We performed a systematic review to investigate changes in food intake, eating behaviors, and diet quality during lockdown as compared with before the lockdown. A literature search was performed using 3 electronic databases from inception until 13 June 2021. Observational studies evaluating changes in general populations during the COVID-19 pandemic lockdown were eligible. Of 1963 studies retrieved from the search strategy, 95 met inclusion criteria (85 in adults, 10 in children/adolescents), and the majority were of high quality (72.6%). Most of the studies were web-based surveys using convenience sampling, mainly focused on variations in the consumption of foods and eating behaviors during lockdown, whereas only 15 studies analyzed diet quality through dietary indices. On the basis of the definition of a healthful diet as reflected by a traditional Mediterranean diet, an increase in recommended foods such as fruit and vegetables, legumes, cereals, and olive oil was observed, although a sharp decrease in fish intake and an increase in dairy products were documented. Accordingly, a reduction in foods that should be eaten less frequently was reported—namely, red and processed meat. However, a higher consumption of unhealthy foods (e.g., snacks and sweets) was also observed. Results indicated improved diet quality in Europe, especially among Mediterranean countries, with the exception of France, while a switch to poor nutrient patterns was observed in Colombia and Saudi Arabia. Analyses of eating behaviors suggest an increase in food intake, number of daily meals, and snacking. In conclusion, changes in intake of major food groups, apart from fish intake, were in line with the definition of a traditional Mediterranean diet, indicating a consistent moderate improvement in dietary habits worldwide. This review protocol was registered at https://www.crd.york.ac.uk/prospero/ as CRD42020225292., Statement of Significance: This is the first systematic review to conduct a comprehensive analysis of changes in different aspects of nutrition during the COVID-19 nationwide lockdowns. The present study summarizes evidence from studies published until the first half of 2021.
Published: 2021

78. Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes

Author: Erkki Vartiainen, Julie K K Vishram-Nielsen, Stefan Söderberg, Jukka Kontto, Christina Magnussen, Simona Costanzo, Blankenberg Stefan, Augusto Di Castelnuovo, Kari Kuulasmaa, Torben Jørgensen, Wolfgang Koenig, Steen M. Jensen, Stephan Camen, Ellisiv B. Mathiesen, Maja-Lisa Løchen, Veikko Salomaa, Licia Iacoviello, Frank Kee, Giovanni de Gaetano, Francesco Gianfagna, Renate B. Schnabel, Teemu J. Niiranen, Tanja Zeller, Ngoc-Anh Sprünker, Maria Benedetta Donati, and Dora Csengeri
Subjects: medicine.medical_specialty, Epidemiology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Internal medicine, medicine, AcademicSubjects/MED00200, Cardiac and Cardiovascular Systems, Alcohol consumption, 030212 general & internal medicine, Kardiologi, Proportional hazards model, business.industry, Hazard ratio, Atrial fibrillation, Biomarkers, Clnical Research, Epidemiology and Prevention, medicine.disease, 3. Good health, Heart failure, Cohort, Cardiology and Cardiovascular Medicine, Risk assessment, business, Cohort study
Abstract: Aims There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts. Methods and results In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11–1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF. Conclusions In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention., Graphical Abstract Hazard ratio for incident atrial fibrillation for alcohol consumption in gram per day by non-linear Cox regression plotted on the log-scale (N = 92 452). The model uses age as time scale and is sex and cohort stratified. The reference value is 0 g/day.
Published: 2021

79. Circulating inflammation markers partly explain the link between the dietary inflammatory index and depressive symptoms

Author: Francesca Bracone, Chiara Cerletti, Licia Iacoviello, Federica Santonastaso, Marialaura Bonaccio, Alessandro Gialluisi, James R. Hébert, Maria Benedetta Donati, Giovanni de Gaetano, and Nitin Shivappa
Subjects: Immunology, Atypical depression, Circulating inflammation, Depressive symptoms, Dietary inflammatory index, Granulocyte-to-lymphocyte ratio, White blood cells, Physiology, Inflammation, RM1-950, White blood cell, Pathology, RB1-214, Immunology and Allergy, Medicine, Depression (differential diagnoses), Original Research, business.industry, Confounding, medicine.disease, Mood, medicine.anatomical_structure, Cohort, Therapeutics. Pharmacology, medicine.symptom, business, Journal of Inflammation Research
Abstract: Alessandro Gialluisi,1 Federica Santonastaso,2 Marialaura Bonaccio,1 Francesca Bracone,1 Nitin Shivappa,3,4 James R Hebert,3,4 Chiara Cerletti,1 Maria Benedetta Donati,1 Giovanni de Gaetano,1 Licia Iacoviello1,2 On behalf of the Moli-sani Investigators1Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy; 2Department of Medicine and Surgery, University of Insubria, Varese, Italy; 3Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 4Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USACorrespondence: Alessandro GialluisiDepartment of Epidemiology and Prevention, IRCCS Neuromed, Via dellÂ´Elettronica, 86077, Pozzilli, ItalyTel +390865915244Email alessandro.gialluisi@gmail.comBackground: Depression is a mood disorder characterized by a high rate of resistance to pharmacological treatments, which has often been linked to chronic inflammation. This can be influenced by different environmental factors, in particular pro-inflammatory diets. However, a mediating role of circulating inflammation has never been observed.Aim: To test the association between a dietary inflammatory index (DIIÂ®) and continuous depressive symptoms (adapted version of PHQ9) in an Italian population cohort (N=13,301), along with potential explanatory effect of a composite index (INFLA-score) based on four circulating inflammatory biomarkers: C-reactive protein, granulocyte-to-lymphocyte ratio, platelet and white blood cell counts.Results: Significant positive associations were observed between DII and total depressive symptoms (standardized Î² (SE) = 0.038 (0.005), p < 0.001), and with two factors tagging somatic (0.012 (0.003), p < 0.001) and cognitive symptoms (0.012 (0.003), p < 0.001), after adjustment for different potential confounders (socioeconomic status, chronic health conditions and lifestyles). These associations were about twice as strong in women than in men. INFLA-score explained a small but significant proportion of the association with total depressive symptoms (0.90â 2.30%, p < 0.05), which was mainly driven by granulocyte-to-lymphocyte ratio (1.18â 1.65%). This effect was even stronger for the somatic (2.66â 4.66%) but not for the cognitive factor (0%).Conclusion: These findings support a strong link between inflammatory diet and depression, especially with somatic symptoms and within women. Moreover, they provide novel evidence for a potential explanatory role of circulating inflammation in this association, suggesting new paths for prevention and treatment of major and atypical depression.Keywords: dietary inflammatory index, depressive symptoms, atypical depression, circulating inflammation, granulocyte-to-lymphocyte ratio, white blood cells
Published: 2021

80. Dietary selenium intake and risk of hospitalization for type 2 diabetes in the Moli-sani study cohort

Author: Lauren A. Wise, Simona Costanzo, Augusto Di Castelnuovo, Mariarosaria Persichillo, Licia Iacoviello, Marco Vinceti, Marialaura Bonaccio, Moli-sani Study Investigators, Tommaso Filippini, Giovanni de Gaetano, Emilia Ruggiero, Chiara Cerletti, and Maria Benedetta Donati
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Epidemiology, Endocrinology, Diabetes and Metabolism, Population, Medicine (miscellaneous), 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Recommended Dietary Allowances, 03 medical and health sciences, Selenium, 0302 clinical medicine, Risk Factors, Internal medicine, Humans, Medicine, Prospective Studies, education, Prospective cohort study, Aged, Risk assessment, education.field_of_study, Nutrition and Dietetics, business.industry, Hazard ratio, Type 2 Diabetes Mellitus, Cohort study, Diet, Middle Aged, Prognosis, medicine.disease, Hospitalization, Diabetes Mellitus, Type 2, Italy, Quartile, Cohort, Female, Cardiology and Cardiovascular Medicine, business
Abstract: 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.
Published: 2021

81. Changes in the consumption of foods characterising the Mediterranean dietary pattern and major correlates during the COVID-19 confinement in Italy: results from two cohort studies

Author: Chiara Cerletti, Maria Benedetta Donati, Cristiana Mignogna, Mariarosaria Persichillo, Simona Esposito, Simona Costanzo, Emilia Ruggiero, Augusto Di Castelnuovo, Marialaura Bonaccio, Giovanni de Gaetano, and Licia Iacoviello
Subjects: 0301 basic medicine, Mediterranean climate, Adult, Male, 2019-20 coronavirus outbreak, lifestyle, genetic structures, Coronavirus disease 2019 (COVID-19), Physical Distancing, 030209 endocrinology & metabolism, Biology, Diet, Mediterranean, confinement, COVID-19, eating behaviours, Mediterranean dietary pattern, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Environmental health, parasitic diseases, Pandemic, Humans, Eating behaviour, Exercise, Life Style, Pandemics, Aged, Consumption (economics), 030109 nutrition & dietetics, SARS-CoV-2, Body Weight, Age Factors, Feeding Behavior, Dietary pattern, Middle Aged, body regions, Italy, Social Class, Communicable Disease Control, Food, Organic, Diet, Healthy, Food Science, Cohort study
Abstract: We investigated the effect of confinement during the COVID-19 pandemic on the consumption of foods characterising the Mediterranean dietary pattern (MDP) and its major correlates in two Italian population-based cohorts comprising 3161 subjects (mean age 57.7 �� 15.4 y). At population level, 38.8% of participants reported an improvement of diet quality during the first nationwide lockdown. Healthful dietary changes were associated with older age (�� = 0.41; 95% confidence interval [CI] 0.08, 0.73 for 56��65 vs. 18��39 y), greater wealth (�� = 0.45; 0.01, 0.89 for >40,000 �� 60,000 vs. �� 10,000 EUR/y), increased physical activity (�� = 0.52; 0.22, 0.81) and reduced body weight (�� = 0.36; 0.11, 0.62). Switching to healthy eating was also related to increased consumption of organic (�� = 1.24; 0.88, 1.60) and locally-grown food (�� = 0.74; 0.51, 0.96). The first Italian lockdown led, in a substantial part of the population, to higher intake of foods characterising a MDP; this was also accompanied by healthier lifestyle and more sustainable food choices.
Published: 2021
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82. Life Course Socioeconomic Status and Risk of Hospitalization for Heart Failure or Atrial Fibrillation in The Moli-Sani Study Cohort

Author: Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Amalia De Curtis, Mariarosaria Persichillo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, and on behalf of the Moli-sani Study Investigators
Subjects: Epidemiology, business.industry, cumulative socioeconomic disadvantage, Hazard ratio, heart failure, Atrial fibrillation, life course socioeconomic status, Disease, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, hospital admission, 0302 clinical medicine, Increased risk, atrial fibrillation, inflammation, Heart failure, Cohort, medicine, Life course approach, 030212 general & internal medicine, business, Socioeconomic status, Demography
Abstract: We investigated the association of cumulative socioeconomic disadvantage (CSD) and socioeconomic status (SES) trajectories across the life course with the risk of first hospitalization for heart failure (HF) or atrial fibrillation (AF) and tested some biological mechanisms to explain such associations. Longitudinal analysis was conducted of 21,756 people without HF or AF who were recruited for the Moli-sani Study (2005–2010; Italy) and followed up for 8.2 years. CSD was computed using childhood SES, education, and adulthood SES indicators, and the same were used to define overall trajectories. A high level of disadvantage across the life course (CSD ≥ 8) was associated with increased risk of HF (hazard ratio (HR) = 2.58, 95% confidence interval (CI): 1.78, 3.74) or AF (HR = 1.57, 95% CI: 1.05, 2.33), as compared with lower CSD. All explanatory factors accounted for 18.5% and 24% of the excess of HF and AF risks, respectively, associated with CSD. For people with low childhood SES, advancements in education lowered their risk of HF (HR = 0.70, 95% CI: 0.48, 1.02) or AF (HR = 0.50, 95% CI: 0.28, 0.89), whereas achievements of adulthood SES were unlikely to contribute to disease reduction. In conclusion, a life-course–disadvantaged SES is an important predictor of first hospitalization for HF and AF; known risk factors partially explained the SES–disease gradient. Being in an upwardly mobile group is likely to mitigate the effect of poor childhood circumstances, especially through educational advancement.
Published: 2021

83. Skin toxicity following radiotherapy in patients with breast carcinoma: is anthocyanin supplementation beneficial?

Author: Roberto Pilu, Francesco Deodato, Chiara Cerletti, Katia Petroni, Licia Iacoviello, Giovanni de Gaetano, Amalia De Curtis, Maria Benedetta Donati, Mariangela Boccardi, Chiara Tonelli, Simona Costanzo, Augusto Di Castelnuovo, Francesca Bracone, Eu-Athena Trial Investigators, Alessio G. Morganti, Gabriella Macchia, Savino Cilla, Bracone F., De Curtis A., Di Castelnuovo A., Pilu R., Boccardi M., Cilla S., Macchia G., Deodato F., Costanzo S., Iacoviello L., de Gaetano G., Morganti A.G., Petroni K., Tonelli C., Donati M.B., and Cerletti C.
Subjects: 0301 basic medicine, Anthocyanin, medicine.medical_specialty, Skin erythema, medicine.medical_treatment, Breast Neoplasms, 030209 endocrinology & metabolism, Critical Care and Intensive Care Medicine, Placebo, Skin Diseases, Gastroenterology, Anthocyanins, Placebos, 03 medical and health sciences, chemistry.chemical_compound, Basal (phylogenetics), 0302 clinical medicine, Breast cancer, Double-Blind Method, Internal medicine, medicine, Cutometer-mexameter, Humans, Radiation Injuries, Aged, Inflammation, 030109 nutrition & dietetics, Nutrition and Dietetics, Radiotherapy, Cholesterol, business.industry, Lipids, Skin toxicity, food and beverages, Middle Aged, Lipid, medicine.disease, Clinical trial, Radiation therapy, chemistry, Dietary Supplements, Female, business
Abstract: Summary Background 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. Objective To evaluate the role of anthocyanins on RT skin side effects in breast cancer patients. Methods 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. Results 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. Conclusions Anthocyanin supplementation did not prevent RT-induced local skin toxicity. The supplementation was well tolerated and safe.
Published: 2021

84. NMU DNA methylation in blood is associated with metabolic and inflammatory indices: results from the Moli-sani study

Author: Simona Costanzo, Fabrizia Noro, Alessandro Gialluisi, Benedetta Izzi, Licia Iacoviello, Alfonsina Tirozzi, Francesco Gianfagna, Annalisa Marotta, Giovanni de Gaetano, Augusto Di Castelnuovo, Roberta Parisi, Amalia De Curtis, Maria Benedetta Donati, and Chiara Cerletti
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Apolipoprotein B, Population, DNS methylation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, White blood cell, medicine, education, Molecular Biology, education.field_of_study, biology, epigenetics, Cholesterol, C-reactive protein, public health, cardiovascular prevention, Methylation, epidemiology, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, DNA methylation, biology.protein, Research Paper, Lipoprotein
Abstract: Neuromedin U (NMU) is a neuropeptide involved in gut-brain axis, energy balance and immune response. We aimed at analysing the association between NMU epigenetic variability and metabolic indices and the potential mediating role of low-grade inflammation in a general population of Italian adults. NMU Blood DNA methylation levels at two CpG islands (NMU76 and NMU32) were analysed using pyrosequencing in a randomly selected sub-cohort of 1,160 subjects from the Moli-sani study (≥35years; 49.20% men). Multivariable regressions adjusted for age, sex, smoking, alcohol and vegetable consumption were performed to estimate the associations between methylation and metabolic phenotypes (BMI, waist-to-hip ratio, blood pressure, glucose, HOMA-IR, lipids, lipoprotein(a) and apolipoproteins). Mediation analysis was performed to identify the influence of low-grade inflammation in the association using a composite index based on C reactive protein, granulocyte-to-lymphocyte ratio (GLR), platelet and white blood cell counts (INFLA-score). Using principal component analysis four methylation factors were identified: NMU76-F1, NMU76-F2, NMU32-F1 and NMU32-F2. NMU76-F1 was FDR significantly associated with total cholesterol (for 1 SD increase: β = 4.5 ± 1.4 mg/dL of, R(2) = 10.8%, p = 0.001), ApoB (0.03 ± 0.01 g/L, 12.2%, p = 0.0004), with INFLA-score (1.05 ± 0.22, p = 2.7E-6) and GLR (-0.27 ± 0.03, 30.4%, p = 1.3E-20). GLR and lymphocyte numbers mediate the association of NMU76-F1 with cholesterol (24.0% of total effect, Sobel p = 0.013) and ApoB (42.6%, p = 9E-7), respectively. These findings suggest that NMU promoter methylation patterns could mark a pathway linking lipids with haematopoiesis and systemic inflammation.
Published: 2021

85. Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing

Author: Giovanni de Gaetano, Sara Magnacca, Simona Costanzo, Licia Iacoviello, Maria Benedetta Donati, Alessandro Gialluisi, Augusto Di Castelnuovo, Moli-sani Study Investigators, Mariarosaria Persichillo, Marialaura Bonaccio, Chiara Cerletti, Amalia De Curtis, and Enrico Capobianco
Subjects: Estimation, medicine.medical_specialty, Epidemiology, business.industry, Public health, medicine.disease, Obesity, Quality of life, Ageing, Medicine, Liver function, business, Socioeconomic status, Demography
Abstract: Deep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored. Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N = 23,858; age ≥ 35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA–CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage 0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained ~48% of the total variance in Δage, potentially suggesting the existence of a genetic basis. These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences.
Published: 2021

86. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. Monique Verschuren, Catterina Ferreccio, Marta Buoncristiano, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Edward D Janus, Laetitia Huiart, Ala'a Alkerwi, Lorenza Pilotto, Mohannad Al Nsour, Daan Kromhout, Marius B. Bjertness, Oanh T. H. Trinh, Nico Dragano, Angélica Ochoa-Avilés, Ingunn Holden Bergh, Yuki Fujita, Juraci Almeida Cesar, Hajer Aounallah-Skhiri, Maria Dorobantu, Jordi Sunyer, Wolfgang Kratzer, Susanne R. de Rooij, Drude Molbo, Rebecca Goldsmith, Jean Woo, Mohammad El-khateeb, Tiffany K. Gill, Nish Chaturvedi, Benjamin Acosta-Cazares, Erik Lykke Mortensen, Nikhil D. Patel, Francesco Pistelli, Yuan He, Ivana Radic, Yi Zeng, Ilse Khouw, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Isti Ilmiati Fujiati, Charles Sossa Jérome, Ben Schöttker, Mikhail Benet, Anastasia Markaki, Christopher T. Cowell, Bharathi Viswanathan, Renata Kuciene, Jose Eugenio Lozano, Pedro J Ortiz, Delphine De Smedt, Elaine M. Murtagh, Kamel Ajlouni, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Xiangjun Wang, Lars Lind, Macia Enguerran, Marjeta Mišigoj-Duraković, Bo Werner, Jean-Michel Gaspoz, Kyungwon Oh, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Felix Kaducu, Ramon O. Jimenez, Jonathan E. Shaw, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Parvina Mukhtorova, Eha Nurk, Bhawesh Koirala, Óscar Lopes, Ana Jelakovic, Karolina Milkowska, Magda Gasull, Regina Heidinger-Felso, Marcela González-Gross, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Tran Quoc Bao, José Boggia, Daniela Galeone, Josep Redon, Matthias Bopp, Abbas Rezaianzadeh, Dusko Bjelica, Amir Houshang Mehrparvar, Felipe F. Casanueva, Khairil Si-Ramlee, Soheir H Ahmed, Maria Nordendahl, Luciana Zaccagni, Mahboubeh Parsaeian, Rod Jackson, Jorge Motta, Keiu Nelis, Fernando Rigo, Andrzej Pajak, Christa Meisinger, Clara Homs, Namuna Shrestha, Mar Alvarez-Pedrerol, Xun Tang, Johann Willeit, Motahareh Kheradmand, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Diana A. Santos, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Elin Kolle, Jingli Gao, Małgorzata Mossakowska, Isabel O. Oliveira, Giuseppe Grosso, Seongjun Ha, Olfa Saidi, Albina A Fakhretdinova, Oye Gureje, Raluca Pop, Iulia Jurca Simina, Nuno Lunet, Maria Forsner, Peter Bjerregaard, Rachael McLean, Antonio Cabrera de León, Guy De Backer, José A. Casajús, Guang Ning, Emmanuella Magriplis, Laura Censi, Graziella Bruno, Valentina Peterkova, Angelique Chan, Yvonne T. van der Schouw, Charalambos Hadjigeorgiou, Anjani Kumar Jha, Toomas Veidebaum, Thamara Hubler Figueiró, Jana Kratenova, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ya Xing Wang, Oscar Noboa, Romana Roccaldo, Sara Magnacca, Johan Sundström, Peter Stehle, Tania Lopez, Francis Delpeuch, Julianne Williams, Ellisiv B. Mathiesen, Leanne M. Riley, Claudia M. Hormiga, Joanne Katz, Ekaterina Stoyanova, Heloisa Bettiol, Gabriele Nagel, Alireza Khosravi, Lars Bo Andersen, João Breda, Jørgen Meisfjord, Ahmad Faudzi Yusoff, Marjeta Majer, Robert Beaglehole, Caleb Ochimana, Shynar Abdrakhmanova, George S. Stergiou, Blanca Sandra Ruiz-Betancourt, Leon A. Simons, Eng Joo Tan, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Liv Elin Torheim, Seppo Koskinen, Assembekov Batyrbek, Jaakko Tuomilehto, Marjo-Riitta Järvelin, Ming-Hui Zhao, Krista Fischer, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, James E. Bennett, Yuna He, Matsuda Fumihiko, Qi Sheng You, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Thet Thet Mu, Yves Martin-Prével, Rafael N. Pichardo, Gailute Bernotiene, Pietro Amedeo Modesti, Frederick C. W. Wu, Chandini Nekkantti, Daniela Rodrigues, Tandi E. Matsha, Mihai Gafencu, Xingwang Ye, Salar Rahimikazerooni, Trevor S. Ferguson, Christophe Tzourio, Marie Zins, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Lourdes Ribas-Barba, Nalan Uysal, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Iraj Mohebbi, Heiner Boeing, Jorge Mota, Jana Námešná, Maria Tsigga, Zivka Dika, Gulmira Aitmurzaeva, Xu Lin, Valéria Regecová, Herman Schargrodsky, Stevo Popovic, Amelia C. Crampin, Hannu Uusitalo, André Luiz Sena Guimarães, Ali Esmaeili, Catherine Kyobutungi, Virginija Dulskiene, Diego Augusto Santos Silva, David De Ridder, Lizzy M. Brewster, Hashem Jaddou, Eunice Ugel, José Camolas, Azli Baharudin, Idris Guessous, Sok King Ong, Tabara Yasuharu, Ali Ghanbari, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Bruna Gonçalves Cordeiro da Silva, Gonzalo Valdivia, Gyulli M. Kazakbaeva, Takuro Furusawa, Pawel Kurjata, Diego Vanuzzo, Marvin Cervantes-Loaiza, Karen Morgan, Mostafa Qorbani, Rute Santos, Marika Ferrari, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Abu Am Hanif, Balkish M. Naidu, Maria Wany Louzada Strufaldi, Moesijanti Soekatri, Marcia Scazufca, Katharina Maruszczak, Jacqueline Ramke, Elvis Oa Wambiya, Kairit Mikkel, Napoleón Pérez-Farinós, Natalia Nowak-Szczepanska, Miao Li Chee, Jose Sanchez-Abanto, Rajaa Al-Raddadi, Michel Joffres, Vayia Rarra, Ningli Wang, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Manoli Garcia-de-la-Hera, Weili Yan, Dong Wook Shin, Rômulo Araújo Fernandes, Ilona Nenko, Sanjib Kumar Sharma, Alfonso Siani, Indrapal I. Meshram, Imelda A. Agdeppa, Ei Ei K. Nang, Ian Rouse, Avula Laxmaiah, Ana M. B. Menezes, Yih Chung Tham, Ebrahim Eftekhar, María José Tormo, Felicia Cañete, Marie Eliasen, Lutgart Braeckman, Dirk Vanderschueren, Genc Burazeri, Kari Kuulasmaa, Jesús Vioque, Marisa K. Sophiea, Agneta Sjöberg, Katarzyna Dereń, Albertino Damasceno, Jochanan Stessman, Stig E. Bojesen, Aline Meirhaeghe, Else Karin Grøholt, Flávio Danni Fuchs, Robert Lundqvist, Frédéric Gottrand, Jeongseon Kim, Helmut Schröder, Joanna Baran, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Aneta Weres, Hans Concin, Damaskini Valvi, Sari Hantunen, Machi Suka, Elena Sacchini, Norbert Amougou, Ursula Kiechl-Kohlendorfer, Edwige Landais, Viktoria Anna Kovacs, Rosemarie Martin, Kenneth James, Amaneh Shayanrad, Grethe S. Tell, Norazizah Ibrahim Wong, Vedrana Sember, Anelise Reis Gaya, Konrad Jamrozik, Thorkild I. A. Sørensen, Martin Neovius, Urho M. Kujala, Nathalie Michels, Marcel Goldberg, Alexandra Cucu, Liliana Dacica, Adelheid Weber, Hermann Pohlabeln, Sandjaja, Jukka T. Salonen, Patricia Varona-Pérez, Tiina Laatikainen, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Julie Taylor, Anabela Mota-Pinto, Cora L. Craig, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Dominique Cottel, Charumathi Sabanayagam, Andrea Gazzinelli, Mieczysław Litwin, Sadaf G. Sepanlou, Adolfo Rubinstein, Abbas Dehghan, Rildo de Souza Wanderley Júnior, Wenhua Zhao, Aleksandra Piwońska, Yong Tao, Bontha V. Babu, Marc J. Gunter, Harunobu Nakamura, Wojciech Drygas, Eiji Oda, Jia Li Duan, Stefan Söderberg, Anthony Kafatos, Lynell V Maniego, Els Clays, Wei-Yen Lim, Marshall K. Tulloch-Reid, Mariachiara Di Cesare, Mattias Johansson, Simona Costanzo, Margot González-León, Matthias Nauck, Henry Völzke, George Luiz Lins Machado-Coelho, Annette Peters, Rajiv T Erasmus, Juan Francisco Miquel, Andrea Gualtieri, Abdul Hamid Zargar, Kaare Christensen, Peter Willeit, Tanja Stocks, Christine Cameron, Samuel C. Dumith, Janina Petkeviciene, Boyd Swinburn, Magdalena Muc, Sabine Schipf, Tajana Zeljkovic Vrkic, Martin Bobak, Damian K Francis, Veronica Mocanu, Karien Stronks, Antonisamy Belavendra, Artur Mazur, Nagalla Balakrishna, Jardena J. Puder, Mehrdad Azmin, Shelly R. McFarlane, Sara Santos Sanz, Yang Yang, Anneke Blokstra, Rafel Ramos, Ertugrul Celikcan, Jody C Miller, Jesús Ibarluzea, Svetlana A. Shalnova, Maria Elisa Zapata, Guansheng Ma, Fereidoun Azizi, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Ana B. Crujeiras, Zhenyu Zhang, Naser Ahmadi, Abdullatif Husseini, Alun Evans, Jiang He, Edyta Łuszczki, Maria G. Stathopoulou, Alibek Mereke, Mari-Liis Tammesoo, Axel C. Carlsson, Helen Gonçalves, Idowu O Senbanjo, Jim Mann, Rajendra Pradeepa, Juel Jarani, Eva Martos, Eugene Sobngwi, Themistoklis Tzotzas, Vassilis Zafiropulos, Reina Engle-Stone, Atul Trivedi, Hui Cai, Sarah Filippi, Georg Posch, Galina Obreja, Cecily Kelleher, Sareh Eghtesad, Chung T Nguyen, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Yi-Ting Lin, Anil Poudyal, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Annamari Lundqvist, Thor Aspelund, Caroline H.D. Fall, Philippe Amouyel, Kristyna Zejglicova, Argyro Karakosta, Piotr Bandosz, Juvenal Soares Dias-da-Costa, Maria Lazo-Porras, Maung Maung Than Htike, Dalia Luksiene, Jutta Stieber, Augusto Di Castelnuovo, Aryeh D. Stein, Lechaba Tshepo, Judith Benedics, Aletta E. Schutte, Jürgen König, Magdalena Korzycka, Grzegorz Sobek, Dimitrios Trichopoulos, Tai Hing Lam, Yn-Tz Sung, Masanori Iwasaki, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Nimmathota Arlappa, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Shoichiro Tsugane, Kaosar Afsana, Alireza Sadjadi, Myriam Galfo, Jean Claude Mbanya, Bernardo L. Horta, Marleen E. Hendriks, M. Arfan Ikram, Fadia AlBuhairan, Huashuai Chen, Marzieh Katibeh, Sidsel Graff-Iversen, Sahar Saeedi Moghaddam, Larissa Pruner Marques, Louise Eriksen, Aleksandra Gomula, Ricky Eddie, Maciej Banach, Jost B. Jonas, Andrea R. V. R. Horimoto, Slavica Sović, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Aye Aye Sein, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Cecilia Björkelund, Luigi Palmieri, Roya Kelishadi, Jie Mi, Nahla Hwalla, Jing Liu, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, Judith Simons, Sofia Malyutina, Michele Monroy-Valle, Andres Metspalu, Lariane M Ono, Rafaela Rosário, Flora A. Ukoli, Efthymios Kapantais, Enzo Manzato, S. Goya Wannamethee, Alison J Price, Gregorio Varela-Moreiras, Ali Reza Safarpour, Erfan Ghasemi, Janine Clarke, René Charles Sylva, Wan Nazaimoon Wan Mohamud, Zhamyila Usupova, Chaoqiang Jiang, Julio Zuñiga Cisneros, Freja B Kampmann, Wei Cheng Lo, Reza Mohammadpourhodki, Kaspar Staub, Mojtaba Farjam, Vincenzo Solfrizzi, Garry L. Jennings, Fabio Galvano, Monika Zuziak, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Emmanuel Cohen, Snehalatha Chamukuttan, Maria Ruiz-Castell, Karen Sparrenberger, Pedro Plans-Rubio, Wei Zheng, Eldridge Ferrer, Martijn Huisman, Maria Hassapidou, Iris Pigeot, Jakub Stokwiszewski, Domenico Palli, Ewelina Czenczek-Lewandowska, Ramiro Guerrero, Farzad Hadaegh, Han Cg Kemper, Saeid Safiri, Ivan Pećin, Arnaud Chiolero, Niels Møller, Jorge Bezerra, Ulrike Gehring, Iná S. Santos, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Marie Moitry, Nizal Sarrafzadegan, Jacqueline F. Price, Ranko Stevanovic, Sai Yin Ho, Georg Lappas, Alberto Palloni, Malay K. Mridha, Elaine M. Dennison, Jeonghee Lee, Saeid Eslami, Rahman Shiri, Japhet Killewo, Juergen Breckenkamp, Mathilde Kersting, Y Nikitin, Iqbal Bata, Geetha R Menon, Maria Avdicova, Sanjay Rampal, Antônio Augusto Moura da Silva, Kirsten Mehlig, Chien-An Sun, Ramin Heshmat, Violeta Iotova, Stefaan Demarest, Mette Rasmussen, Dirk De Bacquer, San-Lin You, Suzanne N Morin, Martin Gulliford, Maties Torrent, Luc Dauchet, Fred Paccaud, Paibul Suriyawongpaisal, Sherali Rakhmatulloev, Hyeon Chang Kim, Markku Peltonen, Ruth Frikke-Schmidt, Vera Musil, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Gowri Mahasampath, Ulrich Keil, Sérgio Viana Peixoto, Haiquan Xu, Helle-Mai Loit, Valérie Deschamps, Ilpo Huhtaniemi, Lijuan Liu, Marialaura Bonaccio, Altan Onat, Rody G. Sy, José María Huerta, Ko Ko Zaw, Akihiro Yoshihara, Peter Ueda, Belgin Ünal, Rachel Dankner, Andrzej Wiecek, Eman Aly, Ruzena Kubinova, Justina Vaitkeviciute, Hanna Tolonen, Priscilla Duboz, Orn Olafsson, Yin Guo, Chiara Donfrancesco, Salim Mohanna, Dusan Grafnetter, Daniel Weghuber, Ali Ahmadi, Rosemary B. Duda, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Liis Nelis, Badreya Al-Lahou, J. Jaime Miranda, Lèlita Santos, Aroor Bhagyalaxmi, Mohamed Bamoshmoosh, Børge G. Nordestgaard, Jeannette Lee, Ahmad Reza Dorosty, Alain Morejon, Ying-Wei Wang, Jakob Tarp, Rosalba Rojas-Martínez, Luxia Zhang, Bahram Mohajer, Maja Bæksgaard Jørgensen, Jurate Klumbiene, Zhengming Chen, Ambady Ramachandran, Andrea Rodriguez-Martinez, Alisha N. Wade, Suyeon Park, Janne Schurmann Tolstrup, Lucjan Szponar, Krishna Kumar Aryal, Tahir Aris, Mahfuzar Rahman, Dorja Vočanec, Juan P. González-Rivas, Rob M. van Dam, Daniel Bia, Oonagh Markey, Ryutaro Ohtsuka, Kumiko Ohara, Ričardas Radišauskas, Jurate Medzioniene, Tiina Vlasoff, Tania Tello, Suzanne C. Ho, Kodavanti Mallikharjuna Rao, May Soe Aung, Vesselka Duleva, Michael Hobbs, Lutgarde Thijs, Marjolein Visser, Parasmani Dasgupta, Inge Huybrechts, Raimund Erbel, Alice Bonilla-Vargas, Hermann Brenner, Mohammad Reza Fattahi, Jolanda Hyska, Roman Topor-Madry, Ranjit Mohan Anjana, Merike Liivak, Eruke E. Egbagbe, Mathilde Savy, Herculina S. Kruger, Neil Murphy, Vinay Nangia, Cesar G. Victora, Mostafa K. Mohamed, H. Bas Bueno-de-Mesquita, Gabriella Gruden, Marcos André Moura-dos-Santos, Mohammed Rasoul Tarawneh, Maria Teresa Menzano, Francesco Branca, Abdonas Tamosiunas, Elena Bogova, Niveen M E Abu-Rmeileh, Maroje Sorić, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Tatjana Hejgaard, Yves Kameli, Margarita Samoutian, Andreia N. Pizarro, Jin Soo Moon, Frank Claessens, Zulfiqar A Bhutta, Frank Tanser, Nor Azwany Yaacob, Vanina Bongard, Gregor Jurak, Johan G. Eriksson, Christina-Paulina Lambrinou, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Thomas Meinertz Dantoft, Wichai Aekplakorn, Anwar Batieha, Eduardo Capuano, Teresa Haugsgjerd, Jeremy M. Jacobs, Paola Russo, Nguyen D Nguyen, Luis Revilla, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Wan Mohamad Wan Bebakar, Paul Elliott, Denise Eldemire-Shearer, Angela Döring, Giovanni Viegi, Xiaoguang Yang, María-Elena González-Villalpando, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Tomasz Zdrojewski, Carlos P. Boissonnet, Mohamad Hasnan Ahmad, Mahmudur Rahman, Günther Fink, Marcia Makdisse, Dragana P Jovic, Aline Wagner, Coimbatore Subramaniam Shanthirani, Pascal Bovet, Dong Wook Kim, Tom Wilsgaard, Anders Grøntved, Thirunavukkarasu Sathish, Antonia Trichopoulou, Noushin Mohammadifard, Igor Spiroski, Natasja M. van Schoor, Cláudia S. Minderico, Betina H. Thuesen, Queenie Chan, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Line Lund Kårhus, Cihangir Erem, Amina Barkat, Maria Paula Santos, Fernanda Cunha Soares, Constanta Huidumac Petrescu, Allan G. Hill, Honor Bixby, Benoît Salanave, Joana Carvalho, Maigeng Zhou, Ofra Kalter-Leibovici, Roy A Wong-McClure, Kim F. Michaelsen, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, José R. Banegas, Quang Ngoc La, Uruwan Yamborisut, Parinaz Mehdipour, Farhad Pourfarzi, Sudha Ramachandra Rao, Katsuyasu Kouda, Chien-Jen Chen, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Ronald D. Gregor, Rudolf Kaaks, Maria do Carmo Franco, Marta García-Solano, Beata Gurzkowska, Bahman Cheraghian, Stefaan De Henauw, Daniel Ferrante, Johanna A. Otero, Jamila Abubakar Garba, Antonio Pedro Graça, Sumit Bharadwaj, Shiqi Zhen, Xiu-Hua Guo, Prashant Mathur, Raphael Mendes Ritti-Dias, Kouamelan Doua, Esteban Carmuega, Majid Shirani, Przemyslaw Slusarczyk, Petra Rust, Visnja Djordjic, Farahnaz Joukar, Johanna Gunnlaugsdottir, Leila Houti, Nayu Ikeda, Imperia Brajkovich, Amirabbas Momenan, Erik J. Timmermans, Marcin Rutkowski, Biruta Velika, Joana Araújo, Jostein Steene-Johannessen, Christa L. Lilly, Per Tynelius, Michael Tornaritis, Anne Juolevi, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Espen Bjertness, Ana P. Ortiz, Joel G. R. Roy, Himanshu K. Chaturvedi, Michelle Holdsworth, Niels Wedderkopp, Johan Van der Heyden, Mukharram M. Bikbov, Hsien-Ho Lin, Eva Corpeleijn, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tuyen D Le, Teresa Norat, Hana Zamrazilová, Garry Brian, Tien Yin Wong, Rosa Haghshenas, Clive Osmond, Diego Giulliano Destro Christofaro, Mahmood Moosazadeh, Vilma Irazola, Olli T. Raitakari, Marco Aurélio Peres, Terho Lehtimäki, Shuohua Chen, Dimitrios Papandreou, Robert J. Adams, Sigmund A. Anderssen, Peter T. Katzmarzyk, Luisa M Macieira, Félicité Tchibindat, Lital Keinan Boker, Toshiharu Ninomiya, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, N Capkova, Zumin Shi, Maria Turley, Zbigniew Gaciong, Giovanni Veronesi, Martin McKee, Veikko Salomaa, Gilad Twig, Elisabetta L. Romeo, Peter Kristensen, Grazyna Jasienska, Victor Guillermo Sequera, Mario V. Capanzana, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Jonathan Giovannelli, Stela McLachlan, Ellis Owusu-Dabo, Stefania Toselli, Maria Teresa Anselmo Olinto, Senthil K Vasan, Sara Schramm, Xenophon Theodoridis, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Dongfeng Gu, Tomas Vega, Hynek Pikhart, Päivi Mäki, Heba Fouad, Vilnis Dzerve, Christina Howitt, Seyed Mohammad Hashemi-Shahri, Jenny M. Kindblom, Marjolijn C. E. Bragt, G. K. Mini, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Vilmundur Gudnason, Loreto Santa Marina, Kairat Davletov, Afshin Ostovar, Niloofar Peykari, Nicholas J. Wareham, Wilma M. Hopman, Karl-Heinz Jöckel, Jussi Kauhanen, Breige A. McNulty, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Stefan Kiechl, Alicia Matijasevich, Boban Mugoša, Srinivasan Kannan, Jyrki K. Virtanen, Mohan Deepa, Mangesh S. Pednekar, Shahla AlDhukair, Cynthia M. Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020

87. Exploring domains, clinical implications and environmental associations of a deep learning marker of biological ageing

Author: Alessandro Gialluisi, Simona Costanzo, Enrico Capobianco, Augusto Di Castelnuovo, Mariarosaria Persichillo, Maria Benedetta Donati, Licia Iacoviello, Giovanni de Gaetano, Sara Magnacca, Amalia De Curtis, Chiara Cerletti, and Marialaura Bonaccio
Subjects: Estimation, Adult, Male, medicine.medical_specialty, Aging, business.industry, Biological age, Public health, Deep learning, Biology, medicine.disease, Diet, Mediterranean, Obesity, Deep Learning, Ageing, medicine, Educational Status, Humans, Female, Liver function, Artificial intelligence, business, Socioeconomic status, Biomarkers, Demography
Abstract: Deep Neural Networks (DNN) have been recently developed for the estimation of Biological Age (BA), the hypothetical underlying age of an organism, which can differ from its chronological age (CA). Although promising, these population-specific algorithms warrant further characterization and validation, since their biological, clinical and environmental correlates remain largely unexplored.Here, an accurate DNN was trained to compute BA based on 36 circulating biomarkers in an Italian population (N=23,858; age≥35 years; 51.7% women). This estimate was heavily influenced by markers of metabolic, heart, kidney and liver function. The resulting Δage (BA-CA) significantly predicted mortality and hospitalization risk for all and specific causes. Slowed biological aging (Δage0) was associated with smoking and obesity. Together, lifestyles and socioeconomic variables explained □48% of the total variance in Δage, potentially suggesting the existence of a genetic basis.These findings validate blood-based biological aging as a marker of public health in adult Italians and provide a robust body of knowledge on its biological architecture, clinical implications and potential environmental influences.
Published: 2020

88. Comparison of Cardiovascular Risk Factors in European Population Cohorts for Predicting Atrial Fibrillation and Heart Failure, Their Subsequent Onset, and Death

Author: Veikko Salomaa, Christina Magnussen, Julie K K Vishram-Nielsen, Licia Iacoviello, Francisco Ojeda, Erkki Vartiainen, Augusto Di Castelnuovo, Allan Linneberg, Stefan Blankenberg, Benedikt Schrage, Maria Benedetta Donati, Kari Kuulasmaa, Bastiaan Geelhoed, Teemu J. Niiranen, Tanja Zeller, Hugh Tunstall-Pedoe, Stefan Söderberg, Wolfgang Koenig, Jukka Kontto, Torben Jørgensen, Simona Costanzo, Francesco Gianfagna, Renate B. Schnabel, Maria Hughes, Giovanni de Gaetano, and Stephan Camen
Subjects: Male, Epidemiology, heart failure, population, Comorbidity, 030204 cardiovascular system & hematology, 0302 clinical medicine, Cardiovascular Disease, Atrial Fibrillation, Prevalence, risk factors, Cardiac and Cardiovascular Systems, atrial fibrillation, 030212 general & internal medicine, Original Research, 2. Zero hunger, education.field_of_study, Kardiologi, Incidence, Atrial fibrillation, Middle Aged, Prognosis, 3. Good health, Europe, Cardiology, Female, Cardiology and Cardiovascular Medicine, Risikofaktor, Adult, medicine.medical_specialty, Cardiovascular risk factors, Population, Risk Assessment, 03 medical and health sciences, Vorhofflimmern, Internal medicine, medicine, Humans, ddc:610, education, Heart disease risk factors, Herzinsuffizienz, Heart Failure, business.industry, biomarkers, European population, Biomarker, medicine.disease, Heart Disease Risk Factors, Heart failure, business
Abstract: Background Differences in risk factors for atrial fibrillation (AF) and heart failure (HF) are incompletely understood. Aim of this study was to understand whether risk factors and biomarkers show different associations with incident AF and HF and to investigate predictors of subsequent onset and mortality. Methods and Results In N=58 693 individuals free of AF/HF from 5 population‐based European cohorts, Cox regressions were used to find predictors for AF, HF, subsequent onset, and mortality. Differences between associations were estimated using bootstrapping. Median follow‐up time was 13.8 years, with a mortality of 15.7%. AF and HF occurred in 5.0% and 5.4% of the participants, respectively, with 1.8% showing subsequent onset. Age, male sex, myocardial infarction, body mass index, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) showed similar associations with both diseases. Antihypertensive medication and smoking were stronger predictors of HF than AF. Cholesterol, diabetes mellitus, and hsCRP (high‐sensitivity C‐reactive protein) were associated with HF, but not with AF. No variable was exclusively associated with AF. Population‐attributable risks were higher for HF (75.6%) than for AF (30.9%). Age, male sex, body mass index, diabetes mellitus, and NT‐proBNP were associated with subsequent onset, which was associated with the highest all‐cause mortality risk. Conclusions Common risk factors and biomarkers showed different associations with AF and HF, and explained a higher proportion of HF than AF risk. As the subsequent onset of both diseases was strongly associated with mortality, prevention needs to be rigorously addressed and remains challenging, as conventional risk factors explained only 31% of AF risk.
Published: 2020

89. Determinants of serum uric acid levels in an adult general population: results from the Moli-sani Study

Author: Chiara Cerletti, Marco Olivieri, Amalia De Curtis, Licia Iacoviello, Augusto Di Castelnuovo, Maria Benedetta Donati, Sara Magnacca, Moli-sani Study Investigators, Simona Costanzo, and Giovanni de Gaetano
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Population, Blood Pressure, Cerebro-cardio-vascular risk factors, Gastroenterology, Body Mass Index, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rheumatology, Observational study, Internal medicine, medicine, Humans, 030212 general & internal medicine, Risk factor, education, Determinants, Uric acid, Triglycerides, 030203 arthritis & rheumatology, education.field_of_study, Creatinine, biology, business.industry, Albumin, General Medicine, Uric Acid, Cystatin C, chemistry, biology.protein, Population study, Female, Diuretic, business, Body mass index
Abstract: High levels of serum uric acid (UA) are associated with cerebro-cardiovascular disease risk factors. This study aimed at evaluating the main determinants of serum UA levels in relation to biochemical, lifestyle, and clinical variables.The study population included 15,594 participants (48% men, age ≥ 35 years) to the Moli-sani Study, for whom data on serum UA levels were available. Association of UA with dependent variables was investigated by multivariable linear regression analysis separately for men and women.Average serum UA levels were higher in men than in women (6.1 ± 1.3 vs 4.6 ± 1.2 mg/dL, respectively). Cystatin C, creatinine, albumin, triglycerides, body mass index (BMI), and diuretic therapy were the major determinants of the heterogeneity of UA levels. In women, the final model, resulting from the stepwise analysis, explained 41.6% of the UA variability. In particular, cystatin C explained 22.5% of UA variance, followed by BMI (7.2%), albumin (4.0%), and creatinine (1.9%). The final model in men fitted the data less than in women (total RIn a general adult population, the major determinants of serum UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics. Knowledge of its main determinants will be useful to better evaluate the relationship between UA levels and detrimental health outcomes and to clarify if an increase in uricemia is a marker or an independent risk factor. Key Points • Increased serum uric acid (UA) levels are reportedly associated with cardiovascular disease risk factors. • The major determinants of heterogeneity of UA levels are cystatin C, creatinine, BMI, triglycerides, albumin, and the use of diuretics, in a general adult population. • Studying the main determinants associated with high levels of serum uric acid would help better understanding if uric acid is a marker or an independent cardiovascular risk factor.
Published: 2020

90. The CASSIOPEA Study (Economic Crisis and Adherence to the Mediterranean diet: poSSIble impact on biOmarkers of inflammation and metabolic PhEnotypes in the cohort of the Moli-sAni Study): Rationale, design and characteristics of participants

Author: Simona Costanzo, Licia Iacoviello, Cassiopea Study, Marco Olivieri, Giovanni de Gaetano, Mariarosaria Persichillo, Augusto Di Castelnuovo, Maria Benedetta Donati, Marialaura Bonaccio, Moli-sani Study Investigators, Amalia De Curtis, and Chiara Cerletti
Subjects: Research design, Male, Mediterranean diet, Economic crisis, Social Determinants of Health, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Financial Stress, 030204 cardiovascular system & hematology, Diet, Mediterranean, Recession, Socioeconomic disparities, Socioeconomic factors, 0302 clinical medicine, Risk Factors, Prevalence, Medicine, Longitudinal Studies, media_common, Metabolic Syndrome, education.field_of_study, Nutrition and Dietetics, Middle Aged, Economic Recession, Italy, Research Design, Cohort, Income, Female, Diet, Healthy, Cardiology and Cardiovascular Medicine, Risk assessment, Adult, Employment, media_common.quotation_subject, Population, 030209 endocrinology & metabolism, Risk Assessment, 03 medical and health sciences, Humans, Social determinants of health, education, Socioeconomic status, Aged, Inflammation, business.industry, Feeding Behavior, Protective Factors, Socioeconomic Factors, Health Expenditures, business, Risk Reduction Behavior, Biomarkers, Demography
Abstract: 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.
Published: 2020

91. Cardiovascular risk factors control according to diabetes status and prior cardiovascular events in patients managed in different settings

Author: Amalia De Curtis, Simona Costanzo, Maria Masulli, Licia Iacoviello, Marilena Vitale, Gabriele Riccardi, Olga Vaccaro, Giovanni de Gaetano, Maria Benedetta Donati, Angela A. Rivellese, Vaccaro, O., Vitale, M., Costanzo, S., Masulli, M., Riccardi, G., De Curtis, A., Donati, M. B., Rivellese, A. A., de Gaetano, G., and Iacoviello, L.
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, Cardiovascular risk factor, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes management, Risk Factors, Internal medicine, Diabetes mellitus, Cardiovascular risk factors, Model of care, Quality of care, Treatment targets, Internal Medicine, medicine, Humans, 030212 general & internal medicine, education, Aged, education.field_of_study, business.industry, Diabetes status, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Blood pressure, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Heart Disease Risk Factors, Female, business, Treatment target
Abstract: Aims To document in recent cohorts the degree of control of major cardiovascular (CV) risk factors according to diabetes status and prior CV disease in different settings. Methods We studied men and women aged 50–75 years of whom 3028 with type 2 diabetes mellitus (T2DM) managed at diabetes clinics participants of the TOSCA.IT (NCT00700856) study recruited in 2008–2014; 742 with T2DM managed mainly in primary care and 6753 without diabetes participating in the Moli-sani (NCT03242109) study and recruited in 2005–2010 from an adult general population. Results Among people without a prior CV event people with diabetes managed at diabetes clinics have lower LDL-cholesterol and blood pressure and a more frequent use of lipid-lowering and antihypertensive medications as compared to people with diabetes managed mainly in primary care and to people without diabetes. The proportions achieving the recommended treatment targets are respectively 47.4% vs 33.4% vs 29.5% for LDL-cholesterol and 42.6% vs 9.5% vs 47.4% for blood pressure. Figures for the participants with prior CV events were 26.8% vs 15.1% vs 42.5% for LDL-cholesterol and 43.8% vs 8.5% vs 43.6% for blood pressure. Conclusions The study documents that in modern cohorts a large proportion of people with or without diabetes does not achieve the treatment targets for LDL-cholesterol and blood pressure, both in primary and secondary CV prevention. People with diabetes attending diabetes clinics achieve a better control of major CV risk factors than those managed mainly in primary care, thus highlighting the relevant role of a structured model of care.
Published: 2020

92. Socioeconomic determinants of the adherence to the Mediterranean diet

Author: Licia Iacoviello, Marialaura Bonaccio, Giovanni de Gaetano, Maria Benedetta Donati, and Americo Bonanni
Subjects: Limited access, Geography, Healthy food, Mediterranean diet, Diet quality, media_common.quotation_subject, Environmental health, Recession, Socioeconomic status, Diversity (politics), media_common
Abstract: Adherence to the Mediterranean diet has been continuously declining over time, with major drops experienced by Mediterranean countries where socioeconomic disparities in lifestyles have been clearly established in the last decades. It is well-documented that individuals with low socioeconomic status not only tend to consume less healthy foods but also show differentials in other indices of diet quality. Indeed, poor socioeconomic status has found to be associated with reduced diet diversity and limited access to organic foods. It is likely that new disparities are emerging beyond those traditionally linked to the amount of healthy food consumed. Among possible causes the increasing cost of many key foods of the MD is likely to have led people to give up this eating pattern in favor of cheaper unhealthy products. Also, there is reason to believe that the current economic downturn is going to produce unfavorable effects on the dietary lifestyle of people, especially among the less wealthy groups.
Published: 2020

93. Daily Coffee Drinking Is Associated with Lower Risks of Cardiovascular and Total Mortality in a General Italian Population: Results from the Moli-sani Study

Author: Chiara Cerletti, Simona Costanzo, Amalia De Curtis, Giovanni de Gaetano, Moli-sani Study Investigators, Licia Iacoviello, Emilia Ruggiero, Maria Benedetta Donati, Mariarosaria Persichillo, Marialaura Bonaccio, and Augusto Di Castelnuovo
Subjects: Adult, Male, medicine.medical_specialty, Mediterranean diet, medicine.drug_class, Population, Medicine (miscellaneous), Renal function, 030204 cardiovascular system & hematology, Coffee, general population, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, cardiovascular mortality, Internal medicine, Troponin I, Natriuretic peptide, Medicine, Humans, 030212 general & internal medicine, Mortality, education, Prospective cohort study, Aged, coffee consumption, education.field_of_study, Nutrition and Dietetics, business.industry, Proportional hazards model, mortality risk, Middle Aged, Blood pressure, Italy, Cardiovascular Diseases, Female, business
Abstract: 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.
Published: 2020

94. Cardiac Troponin I and Incident Stroke in European Cohorts

Author: Stephan Camen, Tarja Palosaari, Jaakko Reinikainen, Ngoc Anh Sprünker, Teemu Niiranen, Francesco Gianfagna, Julie K.K. Vishram-Nielsen, Simona Costanzo, Stefan Söderberg, Luigi Palmieri, Marco Ferrario, Annette Peters, Erkki Vartiainen, Maria Benedetta Donati, Chiara Donfrancesco, Rossana Borchini, Christin Susanna Börschel, Simona Giampaoli, Augusto Di Castelnuovo, Christina Magnussen, Frank K
Published: 2020
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95. Beyond Haemostasis and Thrombosis: Platelets in Depression and Its Co-Morbidities

Author: Alfonsina Tirozzi, Marc Hoylaerts, Giovanni de Gaetano, Alessandro Gialluisi, Chiara Cerletti, Benedetta Izzi, Licia Iacoviello, and Maria Benedetta Donati
Subjects: 0301 basic medicine, MILD COGNITIVE IMPAIRMENT, Chemistry, Multidisciplinary, MITOCHONDRIAL COMPLEX-I, Disease, Review, Bioinformatics, lcsh:Chemistry, 0302 clinical medicine, cardiovascular disease, Epidemiology, gender, Cardiovascular disease, Depression, Gender, Neurodegenerative disorders, Platelet distribution width, Platelets, Psychiatric comorbidities, Platelet, lcsh:QH301-705.5, Spectroscopy, Depression (differential diagnoses), Neurons, Neurodegenerative Diseases, General Medicine, Thrombosis, 3. Good health, Computer Science Applications, AMYLOID PRECURSOR PROTEIN, ALZHEIMERS-DISEASE, Chemistry, neurodegenerative disorders, Physical Sciences, depression, platelets, CORONARY-ARTERY-DISEASE, Major depressive disorder, Co morbidity, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, ACUTE MYOCARDIAL-INFARCTION, medicine.medical_specialty, NEUROTROPHIC FACTOR BDNF, Context (language use), Catalysis, MONOAMINE-OXIDASE-B, Inorganic Chemistry, 03 medical and health sciences, psychiatric comorbidities, mental disorders, medicine, Humans, platelet distribution width, Physical and Theoretical Chemistry, Molecular Biology, Hemostasis, Science & Technology, business.industry, Organic Chemistry, BLOOD-PLATELETS, MAJOR DEPRESSION, medicine.disease, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Neurodevelopmental Disorders, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: Alongside their function in primary haemostasis and thrombo-inflammation, platelets are increasingly considered a bridge between mental, immunological and coagulation-related disorders. This review focuses on the link between platelets and the pathophysiology of major depressive disorder (MDD) and its most frequent comorbidities. Platelet- and neuron-shared proteins involved in MDD are functionally described. Platelet-related studies performed in the context of MDD, cardiovascular disease, and major neurodegenerative, neuropsychiatric and neurodevelopmental disorders are transversally presented from an epidemiological, genetic and functional point of view. To provide a complete scenario, we report the analysis of original data on the epidemiological link between platelets and depression symptoms suggesting moderating and interactive effects of sex on this association. Epidemiological and genetic studies discussed suggest that blood platelets might also be relevant biomarkers of MDD prediction and occurrence in the context of MDD comorbidities. Finally, this review has the ambition to formulate some directives and perspectives for future research on this topic ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:21 issue:22 pages:1-31 ispartof: location:Switzerland status: published
Published: 2020
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96. Revisiting the link between platelets and depression through genetic epidemiology: new insights from platelet distribution width

Author: Benedetta Izzi, Licia Iacoviello, Augusto Di Castelnuovo, Chiara Cerletti, Giovanni de Gaetano, Alessandro Gialluisi, and Maria Benedetta Donati
Subjects: Blood Platelets, Platelets, Platelet Count, business.industry, Platelet Distribution Width, Hematology, depression, genetic correlation, genetics, platelet distribution width, Bioinformatics, Genetic correlation, Genetic epidemiology, Humans, Medicine, Platelet, Online Only Articles, business, Depression (differential diagnoses)
Published: 2019

97. Association of Psychological Resilience with All-Cause and Cardiovascular Mortality in a General Population in Italy: Prospective Findings from the Moli-Sani Study

Author: Anwal Ghulam, Marialaura Bonaccio, Simona Costanzo, Alessandro Gialluisi, Federica Santonastaso, Augusto Di Castelnuovo, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Francesco Gianfagna, Licia Iacoviello, and on behalf of the Moli-Sani Study Investigators
Subjects: Adult, population study, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Resilience, Psychological, psychological resilience, mortality, cardiovascular mortality, Article, Cohort Studies, Italy, Cardiovascular Diseases, Risk Factors, Humans, Medicine, Prospective Studies
Abstract: Psychological resilience (PR) is the capacity to adapt positively in face of adversity. Its role as an independent protective factor has been acknowledged in recent years. We aimed to test the association of PR with all-cause and cardiovascular disease (CVD) mortality in a general adult population. We performed longitudinal analyses on 10,406 CVD-free individuals from the Moli-Sani cohort (follow up = 11.2 year). PR was assessed by the 25-item Connor and Davidson resilience scale. PR factors were identified through polychoric factor analysis. Associations with mortality were tested using multivariable Cox regressions. Higher levels of PR were associated with reduced all-cause mortality in a model including sex and age (HR = 0.78; 95%CI 0.62–1.00). The association decreased after inclusion of socioeconomic, clinical, and behavioral factors into the model (HR = 0.80; 95%CI 0.62–1.03). No relation was observed with cardiovascular mortality in the fully adjusted model (HR = 0.89; 95%CI 0.56–1.39). An inverse association of Factor 1 (reflecting positive acceptance of change) with all-cause mortality (HR = 0.89; 95%CI 0.82–0.98; p value = 0.01) was found. However, at a borderline non-significant way, PR predicts all-cause mortality in a general population of Italian adults. This is supported by the findings demonstrating a significant association between the PR’s domain reflecting a positive acceptance of change and all-cause mortality.
Published: 2021

98. Age- and sex-based ranges of platelet count and cause-specific mortality risk in an adult general population: prospective findings from the Moli-sani study

Author: Licia Iacoviello, Simona Costanzo, Moli-sani Study Investigators, Maria Benedetta Donati, Giovanni de Gaetano, Augusto Di Castelnuovo, Chiara Cerletti, Amalia De Curtis, and Marialaura Bonaccio
Subjects: Adult, Male, medicine.medical_specialty, Population, Disease, 030204 cardiovascular system & hematology, Age and sex, general population, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Cause of Death, Internal medicine, Epidemiology, medicine, Humans, Platelet, education, Aged, education.field_of_study, epidemiology, mortality, platelet count, Hematology, Thrombocytosis, business.industry, General Medicine, Middle Aged, medicine.disease, Confidence interval, Italy, Population Surveillance, Female, business, Follow-Up Studies, 030215 immunology
Abstract: Platelet count varies by age, sex and ethnicity. However, previous studies have adopted standard ranges to identify subjects with thrombocytopenia or thrombocytosis. The aim of this study was to test the predictive role of age-sex-based cut-offs of platelet count proposed by an Italian collaborative study, towards the risk of cause-specific death. We conducted a prospective analysis on 21,563 adult subjects (mean age 55.6 ± 11.8) randomised from the general population of the Moli-sani study.Hazard ratios (HR) were calculated by multivariable Cox-proportional hazard models with 95% confidence intervals. Over a median follow-up of 8.2 years (interquartile range: 7.3 to 9.2 years; 175,972 person-years), we ascertained and validated 1,130 deaths, 415 of which are from cardiovascular disease, 439 from cancer and 276 from non-vascular/non-cancer causes.As opposed to the normal ranges defined by age and sex (extreme values from 122 to 405 x109/L), lower platelet number (87.7% of values being higher than ...
Published: 2017

99. Moderate Alcohol Consumption Is Associated With Lower Risk for Heart Failure But Not Atrial Fibrillation

Author: Augusto Di Castelnuovo, Simona Costanzo, Marialaura Bonaccio, Livia Rago, Amalia De Curtis, Mariarosaria Persichillo, Francesca Bracone, Marco Olivieri, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano, Licia Iacoviello, Jos Vermylen, Ignacio De Paula Carrasco, Simona Giampaoli, Antonio Spagnuolo, Deodato Assanelli, Vincenzo Centritto, Pasquale Spagnuolo, Dante Staniscia, Francesco Zito, Americo Bonanni, Roberto Lorenzet, Antonio Mascioli, Domenico Rotilio, Francesco Gianfagna, Maurizio Giacci, Antonella Padulo, Dario Petraroia, Federico Marracino, Maria Spinelli, Christian Silvestri, Francesca De Lucia, Branislav Vohnout, Franco Zito, Angelita Verna, Maura Di Lillo, Irene Di Stefano, Agostino Pannichella, Antonio Rinaldo Vizzarri, Agnieszka Pampuch, Antonella Arcari, Daniela Barbato, Carmine Di Giorgio, Sara Magnacca, Simona Panebianco, Antonello Chiovitti, Sergio Caccamo, Vanesa Caruso, Daniela Cugino, Alessandra Ferri, Concetta Castaldi, Marcella Mignogna, Tomasz Guszcz, Romina di Giuseppe, Paola Barisciano, Lorena Buonaccorsi, Floriana Centritto, Antonella Cutrone, Francesca Fanelli, Iolanda Santimone, Anna Sciarretta, Isabella Sorella, Emanuela Plescia, Alessandra Molinaro, Christiana Cavone, Giovanna Galuppo, Dolores D'Angelo, Rosanna Ramacciato, and Amalia de Curtis
Subjects: Male, medicine.medical_specialty, Alcohol Drinking, Mediterranean diet, alcohol consumption, Population, heart failure, 030204 cardiovascular system & hematology, Lower risk, Risk Assessment, atrial fibrillation, Cardiology and Cardiovascular Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, education, Prospective cohort study, education.field_of_study, business.industry, Incidence, Hazard ratio, Atrial fibrillation, Middle Aged, Prognosis, medicine.disease, Surgery, Survival Rate, Italy, Population Surveillance, Cohort, Population study, Female, business, Follow-Up Studies
Abstract: Objectives The aim of this study was to assess the hypothesis that alcohol consumption is associated with onset of atrial fibrillation (AF) and/or heart failure (HF). Background The connection between ethanol intake and AF or HF remains controversial. Methods The study population was 22,824 AF- or HF-free subjects (48% men, age ≥35 years) randomly recruited from the general population included in the Moli-sani study, for whom complete data on HF, AF, and alcohol consumption were available. The cohort was followed up to December 31, 2015, for a median of 8.2 years (183,912 person-years). Incident cases were identified through linkage to the Molise regional archive of hospital discharges. Hazard ratios were calculated using Cox proportional hazard models and cubic spline regression. Results A total of 943 incident cases of HF and 554 of AF were identified. In comparison with never drinkers, both former and occasional drinkers showed comparable risk for developing HF. Drinking alcohol in the range of 1 to 4 drinks/day was associated with a lower risk for HF, with a 22% maximum risk reduction at 20 g/day, independent of common confounders. In contrast, no association of alcohol consumption with onset of AF was observed. Very similar results were obtained after restriction of the analyses to regular or only wine drinkers or according to sex, age, social status, or adherence to the Mediterranean diet. Conclusions Consumption of alcohol in moderation was associated with a lower incidence of HF but not with development of AF.
Published: 2017

100. Reduced pulmonary function, low-grade inflammation and increased risk of total and cardiovascular mortality in a general adult population: Prospective results from the Moli-sani study

Author: Augusto Di Castelnuovo, Simona Costanzo, Alessio Piraino, Sara Magnacca, Licia Iacoviello, Moli-sani Study Investigators, Maria Benedetta Donati, Giovanni de Gaetano, Marialaura Bonaccio, and Chiara Cerletti
Subjects: Adult, Male, Risk, Pulmonary and Respiratory Medicine, Vital capacity, medicine.medical_specialty, General adult population, Vital Capacity, Adult population, Maximal Midexpiratory Flow Rate, Forced vital capacity (FVC), Pulmonary function testing, Low grade inflammation, FEV1/FVC ratio, Risk Factors, Forced Expiratory Volume, Internal medicine, Forced expiratory flow at 25–75% of FVC (FEF25-75), Humans, Medicine, Prospective Studies, Mortality, Lung, Aged, Cardiovascular mortality, Inflammation, business.industry, Forced expiratory volume in the first second (FEV1), Hazard ratio, Age Factors, Middle Aged, respiratory system, FEV1 quotient (FEV1Q), Blood Cell Count, respiratory tract diseases, C-Reactive Protein, Increased risk, Cardiovascular Diseases, Cardiology, Female, business, Follow-Up Studies
Abstract: Aim to investigate the relation of pulmonary function impairment with mortality and the possible mediation by low-grade inflammation in a general adult population. Methods A prospective investigation was conducted on 14,503 individuals from the Moli-sani study (apparently free from lung disease and acute inflammatory status at baseline; 2005–2010). The 2012 Global Lung Function Initiative percent predicted (% pred) value of forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25–75% of FVC (FEF25-75) and FEV1 quotient (FEV1Q) index were used. C-reactive protein and blood cell counts were measured and a score of subclinical inflammation (INFLA-score) was calculated. Results Over a median follow-up of 8.6y, 503 deaths (28.9% cardiovascular) were ascertained. Total mortality increased by 19% for each decrease in 1 standard deviation of FEV1% pred or FVC% pred (Hazard Ratio:1.19; 95% CI:1.11–1.28 and 1.19; 1.10–1.28, respectively). Comparable findings for FEV1Q (1.30; 1.15–1.47) were observed. A statistically significant increased risk in cardiovascular mortality of 23%, 32% and 49% was observed for 1 standard deviation decrease of FEV1% pred, FVC% pred and FEV1Q, respectively. INFLA-score mediated the association of FEV1% pred and FEV1Q with cardiovascular mortality by 22.3% and 20.1%, respectively. Subjects with FEV1, FVC lower than normal limit showed increased risk both in total and cardiovascular mortality. Abnormal FEF25-75 values were associated with 33% (1.33; 1.02–1.74) total mortality risk. Conclusions Obstructive lung function impairment was associated with decreased survival. Low-grade inflammation mainly mediated the association of FEV1 with cardiovascular mortality.
Published: 2021

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