Association of perceived mental health with mortality, and analysis of potential pathways in Italian men and women: Prospective results from the Moli-sani Study cohort.

BACKGROUND: Perceived mental health (PMH) was reportedly associated with mortality in general populations worldwide. However, little is known about sex differences and pathways potentially linking PMH to mortality. We explored the relationship between PMH and mortality in Italian men and women, and analysed potential explanatory factors. METHODS: We performed longitudinal analyses on 9045 men and 9467 women (population mean age 53.8 ±â€¯11.2 years) from the Moli-sani Study. Baseline PMH was assessed through a self-administered Short Form 36-item questionnaire. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (95%CI) of death across sex-specific quartiles of PMH, controlling for age, chronic health conditions, and perceived physical health. Socioeconomic, behavioural, and physiological factors were examined as potential explanatory factors of the association between PMH and mortality. RESULTS: In women, HRs for the highest (Q4) vs. bottom quartile (Q1) of PMH were 0.75 (95%CI 0.60-0.96) for all-cause mortality and 0.59 (0.40-0.88) for cardiovascular mortality. Part of these associations (25.8 % and 15.7 %, for all-cause and cardiovascular mortality, respectively) was explained by physiological factors. In men, higher PMH was associated with higher survival (HR = 0.82; 0.69-0.98, for Q4 vs. Q1) and reduced hazard of other cause mortality (HR = 0.67; 0.48-0.95). More than half of the association with all-cause mortality was explained by physiological factors. LIMITATIONS: PMH was measured at baseline only. CONCLUSIONS: PMH was independently associated with mortality in men and women. Public health policies aimed at reducing the burden of chronic diseases should prioritize perceived mental health assessment along with other interventions.

Alcohol: a cardiovascular friend or foe?

This review comprehensively explores the multifaceted implications of alcohol consumption on health. While acknowledging the potential cardiovascular benefits of moderate alcohol intake, concerns arise with excessive use, especially related to some specific cancer types. The detailed evidence emphasizes the importance for healthcare professionals to convey a balanced message, advocating moderation for cardiovascular benefits while acknowledging potential cancer risks linked to excessive consumption. Regarding moderate consumption, the overall balance favors intake, supported by studies like the Global Burden of Disease Study 2020. The intricate risk-benefit ratio of alcohol use demands tailored explanations based on individual characteristics and habits, considering overall risk profiles for cardiovascular diseases, alcohol-related cancers (for example, breast cancer has been associated with moderate alcohol consumption, although the evidence is not conclusive), and other health issues. Factors such as age, pregnancy, cognitive tasks, and personal history influencing the likelihood of alcohol abuse should inform personalized advice on moderate alcohol consumption. Collaborative efforts among stakeholders, including government agencies and healthcare organizations are crucial for providing up-to-date, comprehensive information. Clinical guidelines stress the complexities of the alcohol-heart healthy relationship, advocating moderation and individualized advice. Within personalized advice, the significance of moderate alcohol consumption, particularly in the form of wine within a Mediterranean diet, is highlighted. Wine is seen as a fundamental component of a wholesome diet, aligning with healthy dietary patterns, rather than a medicinal remedy. Acknowledging wine's integration into sound nutrition contributes to heart-healthy lifestyles, in line with Mediterranean dietary traditions. Healthcare professionals play a pivotal role in guiding patients on alcohol intake, considering specific health status and risk factors. Public health campaigns focus on educating individuals to make informed choices about alcohol consumption in the broader context of cardiovascular health. In conclusion, achieving cardiovascular health without undue risks necessitates a balanced and personalized approach to alcohol consumption, guided by healthcare professionals and public health recommendations.

Olive oil consumption is associated with lower cancer, cardiovascular and all-cause mortality among Italian adults: prospective results from the Moli-sani Study and analysis of potential biological mechanisms.

BACKGROUND: Olive oil consumption has been reportedly associated with lower mortality rates, mostly from cardiovascular diseases, but its potential impact on cancer death remains controversial. Moreover, biological mechanisms possibly linking olive oil consumption to mortality outcomes remain unexplored. METHODS: We longitudinally analysed data on 22,892 men and women from the Moli-sani Study in Italy (follow-up 13.1 y), to examine the association of olive oil consumption with mortality. Dietary data were collected at baseline (2005-2010) through a 188-item FFQ, and olive oil consumption was standardised to a 10 g tablespoon (tbsp) size. Diet quality was assessed through a Mediterranean diet score. Multivariable-adjusted Cox proportional hazard models, also including diet quality, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The potential mediating role of inflammatory, metabolic, cardiovascular and renal biomarkers on the association between olive oil intake and mortality was evaluated on the basis of change-in-estimate and associated p values. RESULTS: Multivariable HRs for all-cause, cancer, cardiovascular and other cause mortality associated with high (>3 tbsp/d) versus low (≤1.5 tbsp/d) olive oil consumption were 0.80 (0.69-0.94), 0.77 (0.59-0.99), 0.75 (0.58-0.97) and 0.97 (0.73-1.29), respectively. Taken together, the investigated biomarkers attenuated the association of olive oil consumption with all-cause and cancer mortality by 21.2% and 13.7%, respectively. CONCLUSIONS: Higher olive oil consumption was associated with lower cancer, cardiovascular and all-cause mortality rates, independent of overall diet quality. Known risk factors for chronic diseases only in part mediated such associations suggesting that other biological pathways are potentially involved in this relationship.

Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort.

Background: Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk. Objective: To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk. Methods: In a large Italian population cohort - the Moli-sani study (N=23,437; age ≥ 35 years; 52% women) - we carried out both Cox Proportional Hazards regressions modelling ΔPhenoAge as exposure and incident PD as outcome, and linear models testing prevalent PD as exposure and ΔPhenoAge as outcome. All models were incrementally adjusted for age, sex, education level completed and other risk/protective factors previously associated with PD risk in the same cohort (prevalent dysthyroidism, hypertension, diabetes, use of oral contraceptives, exposure to paints, daily coffee intake and cigarette smoking). Results: No significant association between incident PD risk (209 cases, median (IQR) follow-up time 11.19 (2.03) years) and PhenoAging was observed (Hazard Ratio [95% Confidence Interval] = 0.98 [0.71; 1.37]). However, a small but significant increase of ΔPhenoAge was observed in prevalent PD cases vs healthy subjects (ß (Standard Error) = 1.39 (0.70)). An analysis of each component biomarker of PhenoAge revealed a significant positive association of prevalent PD status with red cell distribution width (RDW; ß (SE) = 0.46 (0.18)). All the remaining markers did not show any significant evidence of association. Conclusion: The reported evidence highlights systemic effects of prevalent PD status on biological aging and red cell distribution width. Further cohort and functional studies may help shedding a light on the related pathways altered at the organism level in prevalent PD, like red cells variability, inflammatory and oxidative stress mechanisms.

Underrated aspects of a true Mediterranean diet: understanding traditional features for worldwide application of a "Planeterranean" diet.

Over the last decades, the Mediterranean diet gained enormous scientific, social, and commercial attention due to proven positive effects on health and undeniable taste that facilitated a widespread popularity. Researchers have investigated the role of Mediterranean-type dietary patterns on human health all around the world, reporting consistent findings concerning its benefits. However, what does truly define the Mediterranean diet? The myriad of dietary scores synthesizes the nutritional content of a Mediterranean-type diet, but a variety of aspects are generally unexplored when studying the adherence to this dietary pattern. Among dietary factors, the main characteristics of the Mediterranean diet, such as consumption of fruit and vegetables, olive oil, and cereals should be accompanied by other underrated features, such as the following: (i) specific reference to whole-grain consumption; (ii) considering the consumption of legumes, nuts, seeds, herbs and spices often untested when exploring the adherence to the Mediterranean diet; (iii) consumption of eggs and dairy products as common foods consumed in the Mediterranean region (irrespectively of the modern demonization of dietary fat intake). Another main feature of the Mediterranean diet includes (red) wine consumption, but more general patterns of alcohol intake are generally unmeasured, lacking specificity concerning the drinking occasion and intensity (i.e., alcohol drinking during meals). Among other underrated aspects, cooking methods are rather simple and yet extremely varied. Several underrated aspects are related to the quality of food consumed when the Mediterranean diet was first investigated: foods are locally produced, minimally processed, and preserved with more natural methods (i.e., fermentation), strongly connected with the territory with limited and controlled impact on the environment. Dietary habits are also associated with lifestyle behaviors, such as sleeping patterns, and social and cultural values, favoring commensality and frugality. In conclusion, it is rather reductive to consider the Mediterranean diet as just a pattern of food groups to be consumed decontextualized from the social and geographical background of Mediterranean culture. While the methodologies to study the Mediterranean diet have demonstrated to be useful up to date, a more holistic approach should be considered in future studies by considering the aforementioned underrated features and values to be potentially applied globally through the concept of a "Planeterranean" diet.

Breakfast quality and its sociodemographic and psychosocial correlates among Italian children, adolescents, and adults from the Italian Nutrition & HEalth Survey (INHES) study.

BACKGROUND: Breakfast quality, together with regularity of breakfast, has been suggested to be associated with cardiometabolic health advantages. We aimed to evaluate the quality of breakfast and its socioeconomic and psychosocial correlates in a large sample of the Italian population. METHODS: Cross-sectional analyses on 7,673 adult and 505 children/adolescent regular breakfast eaters from the Italian Nutrition & Health Survey (INHES; 2010-2013). Dietary data were collected through a single 24-h dietary recall. Breakfast quality was assessed through the Breakfast Quality Index (BQI) combining intake of ten food groups, energy, and nutrients of public health concern, and potentially ranging from 0 to 10. The association of sociodemographic and psychosocial factors with BQI were analyzed by multivariable-adjusted linear regression models. RESULTS: The average BQI was 4.65 (SD ± 1.13) and 4.97 (SD ± 1.00) in adults and children/adolescents, respectively. Amongst adults, older age (ß = 0.19; 95%CI 0.06 to 0.31 for > 65 vs. 20-40 years) and having a high educational level (ß = 0.13; 0.03 to 0.23; for postsecondary vs. up to elementary) were independent predictors of better breakfast quality, while men reported lower BQI (ß = -0.08; -0.14 to -0.02 vs. women). Perceived stress levels at home and work and financial stress were inversely associated with BQI. Children/adolescents living in Central and Southern Italian regions had lower BQI compared to residents in Northern Italy (ß = -0.55; -0.91 to -0.19 and ß = -0.24; -0.47 to -0.01, respectively). CONCLUSIONS: In adults, breakfast quality was associated with age, sex, and educational level. Perceived stress levels were inversely associated with the quality of breakfast. In children/adolescents, a north-south gradient in breakfast quality was observed.

Long-Term Risk of Arterial Thrombosis After Intracerebral Hemorrhage: MUCH-Italy.

BACKGROUND: The identification of patients surviving an acute intracerebral hemorrhage who are at a long-term risk of arterial thrombosis is a poorly defined, crucial issue for clinicians. METHODS: In the setting of the MUCH-Italy (Multicenter Study on Cerebral Haemorrhage in Italy) prospective observational cohort, we enrolled and followed up consecutive 30-day intracerebral hemorrhage survivors to assess the long-term incidence of arterial thrombotic events, to assess the impact of clinical and radiological variables on the risk of these events, and to develop a tool for estimating such a risk at the individual level. Primary end point was a composite of ischemic stroke, myocardial infarction, or other arterial thrombotic events. A point-scoring system was generated by the ß-coefficients of the variables independently associated with the long-term risk of arterial thrombosis, and the predictive MUCH score was calculated as the sum of the weighted scores. RESULTS: Overall, 1729 patients (median follow-up time, 43 months [25th to 75th percentile, 69.0]) qualified for inclusion. Arterial thrombotic events occurred in 169 (9.7%) patients. Male sex, diabetes, hypercholesterolemia, atrial fibrillation, and personal history of coronary artery disease were associated with increased long-term risk of arterial thrombosis, whereas the use of statins and antithrombotic medications after the acute intracerebral hemorrhage was associated with a reduced risk. The area under the receiver operating characteristic curve of the MUCH score predictive validity was 0.716 (95% CI, 0.56-0.81) for the 0- to 1-year score, 0.672 (95% CI, 0.58-0.73) for the 0- to 5-year score, and 0.744 (95% CI, 0.65-0.81) for the 0- to 10-year score. C statistic for the prediction of events that occur from 0 to 10 years was 0.69 (95% CI, 0.64-0.74). CONCLUSIONS: Intracerebral hemorrhage survivors are at high long-term risk of arterial thrombosis. The MUCH score may serve as a simple tool for risk estimation.

High alpha-2-macroglobulin levels are a risk factor for cardiovascular disease events: A Moli-sani cohort study.

BACKGROUND: α2-macroglobulin (α2M) is a versatile endopeptidase inhibitor that plays a role in cell growth, inflammation and coagulation. α2M is an inhibitor of key coagulation enzyme thrombin. Hypercoagulability due to an excess of thrombin production can cause thrombotic events. Therefore, we investigated the association of α2M levels and cardiovascular events in a subset of the general Italian population. METHODS: We determined α2M levels in the baseline samples of a prospective cohort (n = 19,688; age: 55 ± 12 years; 47.8 % men) of the Moli-sani study and investigated the association with the cardiovascular events (n = 432, 2.2 %) in the median follow-up period of 4.3 years. Hazard ratios (HR) with 95 % confidence intervals (CI) were calculated by multivariable Cox regression and adjusted for a large panel of confounding factors. RESULTS: α2M levels above the 90th percentile were significantly associated with cardiovascular disease (CVD) events after full adjustment for age, sex, current smoking, BMI, oral contraceptive use, cardiovascular diseases, hypertension, hypercholesterolemia, diabetes and history of cancer (HR: 1.36; CI: 1.06-1.74). Moreover, high α2M was associated with coronary heart disease (CHD; HR: 1.47; CI: 1.12-1.91), but not stroke. Stratification for CVD at baseline showed that high α2M levels are associated with CHD events in subjects without CVD at baseline (HR: 1.40; CI: 1.00-1.95) and subjects with CVD at baseline (HR: 1.58; CI: 1.02-2.44). CONCLUSION: We show in a prospective cohort that high levels of α2M could be a risk factor for cardiovascular events, especially coronary heart disease events.

Dietary indices underpinning front-of-pack nutrition labels and health outcomes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Nutrient profiling systems are increasingly used to characterize the healthfulness of foods for front-of-package (FOP) labeling, which have been proposed as an effective public health strategy to help people make healthier food choices. OBJECTIVE: This study aimed to review available evidence from cohort studies that evaluated the association of dietary indices underpinning FOP nutrition labels with all-cause mortality and incidence of cardiovascular diseases (CVDs) or cancer. METHODS: PubMed, Web of Science, and Scopus were systematically searched up to October 2023. We included articles if they were prospective cohort studies, if the exposure was any dietary index underpinning FOP nutrition labels [e.g., the modified Food Standard Agency-Nutrient Profiling System (FSAm-NPS) and the Health Star Rating System], and if outcomes were all-cause mortality or incidence of or mortality due to CVD and cancer. Random-effects models were used to calculate the pooled hazard ratios (HRs) and 95% CIs. RESULTS: We identified 11 records (7 unique prospective studies), which were included in the systematic review. The meta-analysis comprised 8 studies analyzing the FSAm-NPS dietary index (DI) as exposure. The pooled HRs associated with a 2-unit increase in the FSAm-NPS DI of all-cause mortality, CVD, and cancer risk were 1.06 (95% confidence interval [CI]: 0.99, 1.13; I2: 80%), 1.08 (95% CI: 1.00, 1.18; I2: 70%), and 1.09 (95% CI: 1.00, 1.19; I2: 77%), respectively. The Chilean Warning Label score and the Health Star Rating systems were examined by 1 study each and were significantly associated with the outcomes. CONCLUSIONS: DIs underpinning most common FOP nutrition labels and reflecting nutrient-poor diets show a tendency toward an increased incidence of CVD and cancer, but the observed effects are quite modest in magnitude. Further studies at the population level are needed to support the widely shared hypothesis that FOP labels, possibly in conjunction with other interventions, may contribute to reduce noncommunicable disease risk. This meta-analysis was registered at PROSPERO as CRD42021292625.

Identifying brain tumor patients' subtypes based on pre-diagnostic history and clinical characteristics: a pilot hierarchical clustering and association analysis.

Introduction: Central nervous system (CNS) tumors are severe health conditions with increasing incidence in the last years. Different biological, environmental and clinical factors are thought to have an important role in their epidemiology, which however remains unclear. Objective: The aim of this pilot study was to identify CNS tumor patients' subtypes based on this information and to test associations with tumor malignancy. Methods: 90 patients with suspected diagnosis of CNS tumor were recruited by the Neurosurgery Unit of IRCCS Neuromed. Patients underwent anamnestic and clinical assessment, to ascertain known or suspected risk factors including lifestyle, socioeconomic, clinical and psychometric characteristics. We applied a hierarchical clustering analysis to these exposures to identify potential groups of patients with a similar risk pattern and tested whether these clusters associated with brain tumor malignancy. Results: Out of 67 patients with a confirmed CNS tumor diagnosis, we identified 28 non-malignant and 39 malignant tumor cases. These subtypes showed significant differences in terms of gender (with men more frequently presenting a diagnosis of cancer; p = 6.0 ×10-3) and yearly household income (with non-malignant tumor patients more frequently earning ≥25k Euros/year; p = 3.4×10-3). Cluster analysis revealed the presence of two clusters of patients: one (N=41) with more professionally active, educated, wealthier and healthier patients, and the other one with mostly retired and less healthy men, with a higher frequency of smokers, personal history of cardiovascular disease and cancer familiarity, a mostly sedentary lifestyle and generally lower income, education and cognitive performance. The former cluster showed a protective association with the malignancy of the disease, with a 74 (14-93) % reduction in the prevalent risk of CNS malignant tumors, compared to the other cluster (p=0.026). Discussion: These preliminary data suggest that patients' profiling through unsupervised machine learning approaches may somehow help predicting the risk of being affected by a malignant form. If confirmed by further analyses in larger independent cohorts, these findings may be useful to create potential intelligent ranking systems for treatment priority, overcoming the lack of histopathological information and molecular diagnosis of the tumor, which are typically not available until the time of surgery.

Scientific evidence supporting the newly developed one-health labeling tool "Med-Index": an umbrella systematic review on health benefits of mediterranean diet principles and adherence in a planeterranean perspective.

BACKGROUND: Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed. METHODS: MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%). RESULTS: A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high. CONCLUSION: In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.

Pro-Vegetarian Food Patterns and Cancer Risk among Italians from the Moli-Sani Study Cohort.

Besides the Mediterranean diet, there is a paucity of studies examining plant-based diets in relation to cancer outcomes in Mediterranean populations. We analyzed 22,081 apparently cancer-free participants (mean age 55 ± 12 year) from the Moli-sani study (enrollment period 2005-2010; Italy). A general pro-vegetarian food pattern was computed by assigning positive or negative scores to plant- or animal-derived foods, respectively from a 188-item FFQ. A priori healthful or unhealthful pro-vegetarian food patterns distinguished between healthy plant foods (e.g., fruits, vegetables) and less-healthy plant foods (e.g., fruit juices, refined grains). Cancer incidence was defined as the earliest diagnosis of cancer from hospital discharge records over a median follow-up of 12.9 years. In multivariable-adjusted analyses, a general pro-vegetarian food pattern was associated with a lower rate of cancer incidence (HR = 0.85; 95%CI 0.75-0.97 for Q5 vs. Q1); no association was observed between the healthful or unhealthful pro-vegetarian food patterns and overall cancer incidence. A healthful pro-vegetarian pattern, however, was inversely associated with digestive cancer (HR = 0.76; 95%CI 0.58-0.99 for Q5 vs. Q1), while the unhealthful pro-vegetarian pattern was directly linked to respiratory cancer (HR = 1.68; 95%CI 1.06-2.68 for Q5 vs. Q1). Our findings in a Mediterranean population support the hypothesis that some, but not all pro-vegetarian diets, might prevent some cancers.

Diet Quality and Risk of SARS-CoV-2 Infection or COVID-19: A Systematic Review of Observational Studies.

The COVID-19 pandemic highlighted the importance of healthy diets in the management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19. Evidence suggests the influence of diet and dietary patterns during post-COVID-19, and the impact of the COVID-19 pandemic on dietary habits and quality. However, limited evidence lies on the association between a healthy diet, and risk of SARS-CoV-2 infection or COVID-19. This study aimed to conduct a systematic review of observational studies to examine the association between diet quality, and the risk of SARS-CoV-2 infection or COVID-19 among adult populations. 6158 research articles from Scopus, EMBASE, PubMed, and MEDLINE databases were identified for eligibility. Only observational studies were included. Study quality was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Thirteen studies were included (4 with SARS-CoV-2 infection and 9 with COVID-19 as the outcome); 3 were case-control, 3 were cross-sectional, and 7 were prospective studies. Adherence to Mediterranean diet was examined as exposure in 7 studies, and was associated with decreased risk of SARS-CoV-2 infection in 2 studies, with estimates varying from 12% to 22%, while COVID-19 risk or severity was found to be reduced in 3 studies with odds ratios (ORs) ranging from 36% to 77%. The Dietary Approaches to Stop Hypertension diet was inversely associated with COVID-19 hospitalization (OR: 0.19; 95% CI: 0.07, 0.55), whereas a healthy plant-based diet had an inverse association with both COVID-19 infection (hazard ratio [HR]: 0.91; 95% CI: 0.88, 0.94) and severity (HR: 0.59; 95% CI: 0.47, 0.74). Studies examining individual food groups generally found lower risk of infection or COVID-19 in association with larger dietary intakes of fruits, vegetables, and fiber. The overall findings of the observational studies in this review support the concept that nutritious diets might lower the risk of SARS-CoV-2 infection or COVID-19. This study was registered at PROSPERO as CRD42023397371.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.

BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).

The Moli-sani risk score, a new algorithm for measuring the global impact of modifiable cardiovascular risk factors.

BACKGROUND: Cardiovascular (CV) disease is preventable through interventions targeting modifiable factors. Most algorithms based on modifiable CV risk factors (CV-rf) have been developed in US populations and do not account for the role of diet. We aimed to assess an algorithm based on modifiable CV-rf including diet, using data from an Italian population. METHODS: To derive the Moli-sani Risk Score (MRS), we used data on 16,656 men and women (age ≥ 35 y) from the population of the Moli-sani Study. The Risk-and-Prevention-Study, Italy (N = 8606) acted as external validation cohort and the Life's-Simple-7 score was used as benchmark. The MRS targeted at fatal or non-fatal CV events and included 9 common modifiable CV-rf. RESULTS: After 8.1 years (median) of follow-up, 816 events occurred in the derivation cohort. The MRS was calculated as a weighted sum of its 9 components, with weights reflecting the strength of the association. In comparison with individuals in the first, those in the fourth quartile of the score had hazard ratio (HR) for CV events equal to 3.18 (95%CI: 2.54-3.97). One more point in the score was associated with 7% (6%-8%) and 4% (3%-5%) higher hazard of events in the derivation and validation cohort, respectively. The MRS performed better than the Life's Simple-7 for discrimination. CONCLUSION: We propose the Moli-sani Risk Score, a validated, performing algorithm able to measure the combined impact that modifiable CV-rf have on CV risk. The score can be used to design preventive interventions, quantify the effectiveness of interventions, and compare different preventive strategies.

Ultraprocessed food consumption is associated with all-cause and cardiovascular mortality in participants with type 2 diabetes independent of diet quality: a prospective observational cohort study.

BACKGROUND: Nutritional strategies for prevention and management of type 2 diabetes traditionally emphasize dietary patterns reflecting nutrient goals, but the health implications of ultraprocessed food (UPF) for patients with type 2 diabetes remain unknown. OBJECTIVES: This study aimed to evaluate the association of UPF intake with all-cause and cardiovascular disease (CVD) mortality among participants with type 2 diabetes from the Moli-sani Study in Italy (enrollment 2005-2010). METHODS: This was a prospective observational cohort study on 1065 individuals with type 2 diabetes at baseline, followed up for 11.6 y (median). Food intake was assessed by a 188-item food-frequency questionnaire. UPF was defined following the Nova classification and calculated as the ratio (weight ratio; %) between UPF (g/d) and total food eaten (g/d). Overall diet quality was assessed through the Mediterranean Diet Score (MDS). Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS: The average UPF consumption was 7.4% (±5.0%). In multivariable-adjusted Cox analyses, greater UPF intake (Q4, ≥10.5% and ≥9% of total food eaten for females and males, respectively), as opposed to the lowest (Q1, UPF <4.7% and <3.7% for females and males, respectively), was associated with higher hazards of both all-cause (HR: 1.70; 95% CI: 1.25, 2.33) and CVD mortality (HR: 2.64; 95% CI: 1.59, 4.40); inclusion of the MDS into the model did not substantially alter the magnitude of these associations (HR: 1.64; 95% CI: 1.19, 2.25 and HR: 2.55; 95% CI: 1.53, 4.24 for all-cause and CVD mortality, respectively). A linear dose-response relationship of UPF intake with both all-cause and CVD mortality was also observed. CONCLUSIONS: In participants with type 2 diabetes at study entry, higher UPF consumption was associated with reduced survival and higher CVD mortality rate, independent of diet quality. Besides prioritizing the adoption of a diet based on nutritional requirements, dietary guidelines for the management of type 2 diabetes should also recommend limiting UPF.

Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project.

The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1-10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74-1.02), 11% (HR = 0.89; 0.84-0.95) and 5% (HR = 0.95; 0.89-1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82-1.25), 10% (HR = 1.10; 1.02-1.19) and 17% (HR = 1.17; 1.09-1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.

Habitual adherence to a traditional Mediterranean diet and risk of SARS-CoV-2 infection and Coronavirus disease 2019 (COVID-19): a longitudinal analysis.

Evidence on habitual Mediterranean diet (MD) and risk of SARS-CoV-2 infection, and COVID-19 is limited. 1,520 participants from the Moli-sani Study (2017-2020) were tested during January-September 2021 and adherence to MD was ascertained through the Mediterranean Diet Score (MDS). SARS-CoV-2 infection cases were determined through serology, and previous clinical diagnosis of COVID-19 disease was self-reported. Results were presented as odd ratios (OR) with 95% confidence intervals (CI). The MDS was not associated with the likelihood of SARS-CoV-2 infection (OR= 0.94; 95% CI: 0.83-1.06) and COVID-19 (OR= 0.82; 95% CI: 0.62-1.10) diagnosis. High consumption of cereals was associated with lower odds of SARS-CoV-2 infection (OR = 0.91; 95% CI: 0.83-1.00; for each 25 g/d increase). Likelihood of having being diagnosed with COVID-19 disease decreased in association with increasing olive oil intake (OR= 0.10; 95% CI: 0.01-0.79; for each additional 10 g/d), moderate alcohol consumption (OR= 0.18; 95% CI: 0.04-0.82) and higher intakes of fruits and nuts (OR = 0.89; 95% CI: 0.79-0.99). Our findings emphasise the adoption and maintenance of a balanced MD as a key strategy to reduce the risk of future SARS-CoV-2 infections and COVID-19.

Risk and protective factors in Parkinson's disease: a simultaneous and prospective study with classical statistical and novel machine learning models.

BACKGROUND: Several environmental/lifestyle factors have been individually investigated in previous Parkinson's disease (PD) studies with controversial results. No study has prospectively and simultaneously investigated potential risk/protective factors of PD using both classical statistical and novel machine learning analyses. The latter may reveal more complex associations and new factors that are undetected by merely linear models. To fill this gap, we simultaneously investigated potential risk/protective factors involved in PD in a large prospective population study using both approaches. METHODS: Participants in the Moli-sani study were enrolled between 2005 and 2010 and followed up until December 2018. Incident PD cases were identified by individual-level record linkage to regional hospital discharge forms, the Italian death registry, and the regional prescription register. Exposure to potential risk/protective factors was assessed at baseline. Multivariable Cox Proportional Hazards (PH) regression models and survival random forests (SRF) were built to identify the most influential factors. RESULTS: We identified 213 incident PD cases out of 23,901 subjects. Cox PH models revealed that age, sex, dysthyroidism and diabetes were associated with an increased risk of PD. Both hyper and hypothyroidism were independently associated with PD risk. SRF showed that age was the most influential factor in PD risk, followed by coffee intake, daily physical activity, and hypertension. CONCLUSION: This study sheds light on the role of dysthyroidism, diabetes and hypertension in PD onset, characterized to date by an uncertain relationship with PD, and also confirms the relevance of most factors (age, sex, coffee intake, daily physical activity) reportedly shown be associated with PD. Further methodological developments in SRF models will allow to untangle the nature of the potential non-linear relationships identified.