Simona Costanzo

IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy · Department of Epidemiology and Prevention.

Background Cardiovascular disease and cancer share modifiable risk factors and, potentially, molecular mechanisms of disease, as postulated by the “common soil” hypothesis. We examined whether the American Heart Association's Life's Simple 7 (LS7) metrics to assess and promote cardiovascular health, is associated with cancer risk, defined as first...

Platelet distribution width (PDW), a marker of platelet size heterogeneity used as a readout of processes leading to platelet production and destruction, was recently reported to tag platelet activation variability. As platelets participate in the pathogenesis of many acute and chronic diseases, we evaluated PDW as a predictor of all-cause and caus...

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 ass...

Background: Nutritional strategies for prevention and management of type 2 diabetes traditionally emphasize dietary patterns reflecting nutrient goals, but the health implications of ultra-processed food (UPF) for patients with type 2 diabetes remain unknown. Objective: To evaluate the association of UPF intake with all-cause and cardiovascular...

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 po...

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 alco...

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...

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 pre...

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 an alternative. This paper aims to study RFM and BMI association with mortality in a general Italian population and potential mediators of such association. Method...

Background Several studies revealed an implication of air pollution in neurodegenerative disorders, although this link and the potential underlying mechanisms remain unclear. Objectives To analyze the impact of air pollution on neurodegenerative risk by testing multiple pollutants simultaneously, along with other potential risk/protective factors,...

Background: Olive oil is a key component of a traditional Mediterranean Diet and its with cancer mortality is less robust, and it remains unclear whether the health advantages of olive oil may be accounted for by specific biological mechanisms. We therefore sought to investigate the relationship between olive oil consumption with cancer mortality i...

Aims: The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. Methods: We used individual-level data of 95,292 individuals of the European population harmonized i...

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6 . Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural an...

Chronological age (CA) may not accurately reflect the health status of an individual. Rather, biological age (BA) or hypothetical underlying “functional” age has been proposed as a relevant indicator of healthy aging. Observational studies have found that decelerated biological aging or Δage (BA-CA) is associated with a lower risk of disease and mo...

Late eating is reportedly associated with adverse metabolic health, possibly through poor diet quality. We tested the hypothesis that meal timing could also be linked to food processing, an independent predictor of health outcomes. We analysed data on 8688 Italians (aged > 19years) from the Italian Nutrition & HEalth Survey (INHES) established in 2...

Introduction: Cardiovascular (CV) disease, the leading cause of death globally, is largely preventable through targeting modifiable risk factors. Scores of modifiable CV risk factors able to collect the combined effect of all the included components were mainly developed in US populations, or do not include nutritional aspects. Hypothesis: We asses...

Introduction: Vegetarian diets are characterized by the absence of some animal foods (e.g. red and processed meats), and a high consumption of plant-based foods. However, plant-based foods can include foods with varying nutritional value and divergent health effects. Hypothesis: We assessed the hypothesis that three different pro-vegetarian (PVG) f...

Introduction: Body mass index (BMI) has J-shaped associations with all-cause mortality, but it is unclear whether diet can modify the impact of BMI on mortality. Hypothesis: We tested the hypothesis that a large dietary share of ultra-processed food (UPF) can act as an effect modifier of this association. Methods: Longitudinal analysis on 22,836 wo...

Introduction: Epidemiologic studies suggest that heavy alcohol drinking is associated with unhealthy profile, whereas its light to moderate intake is associated with reduced hazard of total mortality as compared with lifetime abstention, a result largely driven by a reduction in cardiovascular mortality. Up to date, there is no agreement on a possi...

Epidemiological data on the association between fibrinogen levels and mortality are scarse and controversial. Longitudinal analyses were performed, separately by sex, on 17,689 individuals from the Moli-sani study [53% women, ≥35 years, free from cardiovascular disease (CVD) or cancer at enrolment], to evaluate the association between plasma fibrin...

Evidence on what people eat globally is limited in scope and rigour, especially as it relates to children and adolescents. This impairs target setting and investment in evidence-based actions to support healthy sustainable diets. Here we quantified global, regional and national dietary patterns among children and adults, by age group, sex, educatio...

Aims: Atrial fibrillation (AF) is becoming increasingly common. Traditional cardiovascular risk factors (CVRF) do not explain all AF cases. Blood-based biomarkers reflecting cardiac injury such as high-sensitivity troponin I (hsTnI) may help close this gap. Methods: We investigated the predictive ability of hsTnI for incident AF in 45,298 partic...

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 pathophysiologi...

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...

Polyphenols are naturally occurring compounds endowed with antioxidant and anti-inflammatory properties. We sought to examine the association of dietary polyphenols with the risk of severe lumbar spinal stenosis (LSS), a condition possibly characterized by a high inflammatory component. A case-control study included 156 patients with LSS and indica...

Background The relationship between diet and central nervous system (CNS) tumours was almost exclusively focused on food composition. We evaluated the relationship of different degrees of food processing with risk of CNS tumours. Methods The study sample included 44 CNS tumours cases (20 non-malignant and 24 malignant) recruited from the Neurosurg...

Background: There is little knowledge on the association of changes over time in adherence to a Mediterranean diet (MD) with changes in modifiable cardiovascular disease (CVD) risk factors and of markers of low-grade inflammation. Objective: To evaluate the association between long-term changes in MD adherence and concurrent changes in establish...

Background A healthy diet plays a major role in supporting the immune system which is critical to protect the host from pathogenic organisms. To date, evidence on the relationship between dietary habits and the risk of SARS-CoV-2 infection is still scarce. Methods Analyses on 1,096 participants from the Moli-sani Study (2005-2010) who were re-exam...

Background Ultra-processed food (UPF) is a major public health concern being reportedly associated with increased risk of non-communicable diseases and lower survival. However, most of the epidemiological evidence has been almost exclusively provided by research conducted in populations of youths or middle-aged adults. We tested the hypothesis that...

Background Depression has been associated with increased hospitalization and mortality risk, especially for cardiovascular causes. We previously found a composite circulating inflammation score (INFLA-score) to explain part of this link, although the role of its component and of depressive symptoms domains in this relationship is unexplored. Metho...

Background Studies revealed an implication of air pollution in neurodegenerative disorders, although this link remains unclear. Here, we investigated this testing multiple pollutants simultaneously. Methods In the Moli-sani cohort (N = 24,325; ≥35 years; 51.9% women, baseline 2005-2010), we estimated yearly levels of exposure to nitrogen oxides (N...

Background Vegetarians diets are characterized by the absence of some animal foods (e.g. red and processed meats), and a high consumption of plant-based foods. However, plant-based foods can include foods with varying nutritional value and health effects. We examined the association of three different pro-vegetarian (PVG) food patterns defined as g...

Background Patients with cancer are commonly characterized by abnormalities in laboratory coagulation tests, underlying a subclinical hypercoagulable condition. Due to the involvement of the hemostatic system in cancer patients, some of its biomarkers, such as fibrinogen, could be a useful tool in predicting cancer risk. We performed a case-cohort...

Background Major depressive disorder is a mental illness associated with chronic conditions like cardiovascular disease (CVD). Circulating inflammation has been proposed as a potential mechanism underlying this link, although the role of specific biomarkers, gender, and symptom domains is not well elucidated. Methods We performed multivariable Cox...

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 individ...

Background Thrombosis is common in subjects suffering from cardiovascular diseases (CVD) and cancer. Hypercoagulation plays a pivotal role in the pathophysiology of thrombosis. Therefore, the inactivation of thrombin, the key enzyme in coagulation, is tightly regulated via antithrombin (AT). AT deficiency is related to thrombosis and cardiovascular...

Objective To 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. Design Prospective cohort study. Setting Moli-sani Study, Italy 2005-10. Participants 22 895 participants (mean age 55 (SD 12)...

Background & Aims 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 associatio...

Background/Objectives 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,...

Background The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods For this analysis,...

Supplementary data

The coagulation system can be assessed by the thrombin generation (TG) assay, and increased TG peak height, endogenous thrombin potential (ETP), and velocity index are associated with an increased risk of thrombosis. Obesity had been reported to increase TG and is associated with dyslipidemia, which also predisposes to atherosclerotic cardiovascula...

PurposeNutrition is an important, modifiable, environmental factor affecting human health by modulating epigenetic processes, including DNA methylation (5mC). Numerous studies investigated the association of nutrition with global and gene-specific DNA methylation and evidences on animal models highlighted a role in DNA hydroxymethylation (5hmC) reg...

PurposeTo examine the relationship between psychological distress resulting from the COVID-19 lockdown and dietary changes.Methods Cross-sectional analysis from 2 retrospective Italian cohorts recruited from May to September 2020: (1) The Moli-LOCK cohort consists of 1401 participants from the Moli-sani Study (n = 24,325) who were administered a te...

Background Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood. Methods and Results In pooled multivari...

Asbtract Background and aims 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 relation...

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...

Introduction: Psychological resilience (PR) is understood as the capacity to adapt positively in face of adverse events. Its role as an independent protective factor for health has been increasingly acknowledged in recent years. Hypothesis: We tested the hypothesis that psychological resilience could act as a protective factor towards disease, in p...

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 mortal...

Background Positive psychosocial factors can play an important role in the development of cardiovascular disease (CVD). Among them, psychological resilience (PR) is defined as the capacity of responding positively to stressful events. Our aim was to assess whether PR is associated with CVD or metabolic disturbances through a systematic review. Met...

Objectives: To estimate psychological distress experienced during the Italian lockdown (March-May 2020) by assessing, in the transition period of the pandemic (June-September 2020), participants’ recalling of their psychological state. Methods: Cross-sectional analysis on 1,880 adults (mean age 48.9 ± 14.5 years) from the web-based ALT RISCOVID-19...

The prevalence, determinants, and clinical significance of vitamin D deficiency in the population are debated. The population-based study investigated the cross-sectional associations of several variables with serum 25-hydroxyvitamin D (calcidiol) measured using standardized calibrators. The study cohort consisted of 979 persons of the Moli-sani st...

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 environmen...

The lockdowns resulting from the first wave of the COVID-19 pandemic impacted deeply on all life activities, including diet. We performed a systematic review to investigate changes in food intake, eating behaviours and diet quality during lockdown as compared to before. A literature search was performed using three electronic databases from incepti...

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-f...

Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries...

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...

Aims Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. The aim of this study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. We also included an assessm...

Background Economic downturns may have detrimental effects on mental health. We investigated whether economic hardship resulting from the late 2000s great recession is associated with long-term changes in mental health over 12.8 years of follow up. Methods We analysed data on 2,001 participants from the CASSIOPEA Study, a sub-cohort of the larger...

Background The confinement due to COVID-19 pandemic had adverse effects on mental health, but the relation between psychological distress resulting from lockdown measures and dietary habits needs to be elucidated. Methods We analysed 2,741 subjects (mean age 58.1±15.3 y) pooled from 2 retrospective Italian cohorts recruited from May to September 2...

Background The Nutri-Score front-of-pack label rates foods according to their nutritional quality while the NOVA classification is focused on degree of processing; both systems separately predicted mortality in epidemiological contexts. We evaluated whether ultra-processed food (UPF) modifies the association of the Nutri-Score with mortality. Meth...

Background Data on milk and other dairy products intake with health outcomes are inconsistent. We investigated the association of milk and total dairy consumption with the risk of all-cause and cause-specific mortality in a Mediterranean population. Methods We performed a longitudinal analysis on 22,889 men and women (mean age 55.4±11.7 y; 52.3% w...

Defined as an index of platelet size heterogeneity, the platelet distribution width (PDW) is still a poorly characterized marker of platelet function in (sub)clinical disease. We presently validated PDW as a marker of P-selectin dependent platelet activation in the Moli-family cohort. Platelet-bound P-selectin and platelet/leukocyte mixed aggregate...

Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This...

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....

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a...

The results presently available from randomised clinical trials and their meta-analysis indicate that Hydroxychloroquine is not associated in COVID-19 patients with either decreased mortality or clinical worsening. Thus, the use of Hydroxychloroquine in COVID-19 patients cannot at present be encouraged. However, the hypothesis that Hydroxychloroqui...